Amgen Stock

My name is Julianne, and I will be your conference facilitator today for the Amgen Q3 2026 Earnings Conference Call. [Operator Instructions] I would now like to introduce Casey Capparelli, Vice President of Investor Relations. Mr. Capparelli, you may now begin.

Thank you Julianne. Good afternoon, everyone, and welcome to our third quarter of 2026 earnings call. Bob Bradway will lead the call today can be followed by a broader review of our performance by Murdo Gordon, Jay Bradner and Thomas Dittrich.

Through the course of our discussion today, we will use non-GAAP financial measures to describe our performance and have provided appropriate reconciliations within the materials that accompany this call. We will also make some forward-looking statements, which are qualified by our safe harbor statement. And please note that actual results can vary materially.

Over to you, Bob.

Good afternoon, and thank you for joining our call. Our results through the first 3 quarters of the year reflect the strength of our business across a broad range of products and pipeline molecules. This is exactly the candid performance our strategy was designed to achieve. Strong commercial and operations execution and continued innovation from our research and development organization, reinforce our confidence in Amgen's ability to deliver durable long-term growth.

For the latest quarter, total revenues grew a strong 8% year-over-year to $10.4 billion. Our 6 key growth drivers grew 27% year-over-year and represented over 70% of our third quarter product sales. Across the portfolio, products delivered double-digit sales growth and 17 products are now annualizing at more than $1 billion based on third quarter sales. We see significant opportunity to build on this momentum. Many of our medicines address large, underpenetrated disease areas where the majority of patients remain untreated. Repatha, EVENITY and TEZSPIRE are clear examples of that. Our strong financial performance gives us the flexibility to invest in innovation and the capabilities needed to support future growth while delivering attractive returns to shareholders.

In the third quarter, we generated $3.7 billion in free cash flow, increased our investment in research and development by 11% year-over-year and invested another $600 million in the business through capital expenditures. This was another productive quarter for our R&D organization. We reported positive Phase III results from 3 important programs: IMDELLTRA, in small cell lung cancer, where we are working to establish it as the cornerstone therapy; TEZSPIRE, in eosinophilic esophagitis, an area with significant unmet need; and dazodalibep, in Sjogren's disease, where no approved disease-modifying therapies currently exist.

I would note that each of these represents an established or potential first-in-class medicine with the opportunity to make a meaningful difference for patients while providing additional sources of long-term growth for Amgen. Likewise, our progress reflects the strength of our science and our commitment to pursuing novel approaches for serious diseases. That same focus guides our investment in programs such as MariTide, which is advancing through Phase III development. Jay will discuss these programs and our other clinical advances in more detail shortly.

We're also leveraging technology, data-driven insights and artificial intelligence across Amgen to improve the speed and efficiency of how we discover, develop, manufacture and deliver medicine to patients. We're encouraged by our performance this quarter and our broad portfolio, continued investment in advancing pipeline give us confidence in Amgen's ability to deliver durable growth well into the next decade. I want to thank our colleagues around the world for their dedication to our mission to serve patients and for the quality of their work every day.

With that, I'll turn it over to Murdo.

Thanks, Bob. Looking back at the third quarter, what stands out for me is the remarkable progress we've made across our late-stage pipeline and broad in-line portfolio. We've seen important positive clinical readouts, regulatory milestones and record sales performance for several of our key medicines. Consistency of these achievements reflects the breadth and strength of Amgen today and reinforces our confidence in the growth opportunities ahead. .

Our commercial performance reflects this progress. Product sales grew 8% year-over-year, and we have 17 products annualizing at more than $1 billion in sales. All 6 of our key growth drivers delivered double-digit growth in the quarter, together growing 27% year-over-year and now representing more than 70% of product sales. Starting with General Medicine, Repatha delivered $1.1 billion in third quarter sales, growing 37% year-over-year. Repatha's momentum continues to accelerate with U.S. average weekly new-to-brand prescriptions increasing over 60% compared with the prior year. This growth is supported by increased urgency to treat in both secondary prevention and high-risk primary prevention patients. With the Landmark VESALIUS-CV results, Repatha is now the only PCSK9 inhibitor with Phase III cardiovascular outcomes evidence in both primary and secondary prevention.

We're seeing deepening fiction and adoption among cardiologists and accelerating use in primary care and support the use of PCSK9 inhibitors without requiring prior treatment with ezetimibe. The new guidelines supported by Repatha's differentiated outcomes data, strengthen clinical conviction that Repatha should be the first choice when additional LDL-cholesterol lowering is needed beyond statins. This year alone, we expect more than 3 million additional patients globally to start treatment with Repatha. With an estimated 100 million patients worldwide, still above their LDL-C goals, we are only beginning to address the significant unmet need, giving us confidence in Repatha's growth potential into the 2030s.

EVENITY sales increased 39% in the third quarter to $751 million, building on 38% year-over-year growth in the previous quarter. In the United States, robust patient demand continues to drive momentum, supported by an expanding prescriber base and deeper adoption among treating physicians. We're increasing investment to expand our reach among physicians and to help more patients access treatment with EVENITY. The opportunity remains significant, particularly when we consider the devastating consequences of osteoporotic fractures, 1 in 2 patients who experienced a hip fracture do not regain their pre-fracture mobility. This reinforces the importance of earlier intervention and our conviction in EVENITY's potential to help more women at very high fracture risk, including those have not yet experienced a fracture. In Japan, EVENITY maintains leadership in the bone-builder category with nearly 60% volume share. Updated treatment guidelines and increasing use among treatment-naive patients are supporting continued growth and reinforcing EVENITY's important role in osteoporosis care.

Moving to inflammation. TEZSPIRE's sales grew 43% year-over-year, reaching $538 million, driven by strong demand in severe uncontrolled asthma. TEZSPIRE's growth continues to outperform the severe uncontrolled asthma market with U.S. new-to-brand prescriptions growing 15% year-over-year and versus 3% market growth. TEZSPIRE achieved 34% new-to-brand prescription share among allergists in the U.S. and continues to gain share among pulmonologists with substantial room for further adoption. The consistent flow of strong clinical data continues to reinforce TEZSPIRE's differentiated efficacy across inflammatory diseases. Phase III results in chronic rhinosinusitis with nasal polyps demonstrated improvements in disease control and a reduction in need for surgery. More recently, positive Phase III results in eosinophilic esophagitis or EOE demonstrated meaningful improvements in key measures of disease activity and symptoms highlighting another potential new opportunity for TEZSPIRE to help more patients.

Turning to rare disease. This portfolio grew 21% year-over-year to $1.6 billion, reflecting continued momentum from additional indications and disciplined execution of international expansion. We see opportunity to extend the reach of these treatments, improve outcomes for patients and sustain meaningful growth well into the next decade. UPLIZNA sales increased 191% year-over-year to $451 million in the third quarter, driven by strong paying demand across all approved indications. UPLIZNA offers a highly differentiated clinical profile, combining outstanding efficacy that resonates with physicians and convenient twice-yearly dosing that benefits patients. This profile is supported by broad payer coverage and Amgen's comprehensive patient support services, helping physicians initiate treatment and support continuity of care.

In the U.S., UPLIZNA is demonstrating significant growth in generalized myasthenia gravis, or GMG, with new and continuing patients increasing 45% quarter-over-quarter. Adoption is expanding among both biologic-naive patients and those transitioning from other therapies, reinforcing our confidence in the business potential to establish market leadership in this category. In IgG4-related disease, long-term follow-up data from the Phase III mitigations efficacy profile. All patients who continued treatment with UPLIZNA remained flare free through the first year of the open-label extension with more than 70% achieving complete remission without glucocorticoids. These durable results together with growing disease awareness and improved diagnosis support our confidence in the business potential to help many more patients. UPLIZNA continues to expand its reach internationally and is now launched in 25 markets outside the U.S. We see substantial opportunity for continued growth. as we bring UPLIZNA to more patients around the world and advances development across additional autoimmune diseases.

TEPEZZA generated $526 million in third quarter sales, a 6% decline year-over-year, impacted by an inventory build in the third quarter of last year. International adoption continues to build with particularly encouraging uptake in Japan since entering the market last year. TEPEZZA has now launched in more than 20 countries worldwide with 3 additional markets planned for the remainder of 2026. Our biosimilar portfolio delivered 26% year-over-year growth, generating $977 million in sales in the third quarter. PAVBLU or biosimilar to EYLEA increased sales of 41% year-over-year to $300 million in the quarter. Retina specialists recognize the benefits of PAVBLU's convenient prefilled syringe presentation, supported by Amgen's established capabilities and biosimilar manufacturing and supply. Our next wave of biosimilar candidates for EYLEA, HD, OPDIVO, KEYTRUDA and OCREVUS are in late-stage clinical development and represent large market opportunities.

Turning to innovative Oncology. The portfolio grew 21% year-over-year, generating $2.1 billion in sales in the third quarter. BLINCYTO sales increased 27% year-over-year to $496 million in the third quarter. This growth continues to reflect broad prescribing across academic and community settings and increasing international adoption. BLINCYTO's established role in treating B-cell acute lymphoblastic leukemia demonstrates the strength of our bispecific T-cell engager platform and this ability to deliver meaningful outcomes across different cancers. IMDELLTRA sales more than doubled year-over-year to $406 million. Behind this commercial momentum is a medicine with the potential to make a profound difference for patients facing small cell lung cancer. These patients and their families have faced limited treatment options and poor survival outcomes for decades, IMDELLTRA is changing that. landmark DeLLphi-304 trial demonstrated a 40% reduction in the risk of death compared with chemotherapy in second-line treatment. IMDELLTRA also offers convenient every 2-week dosing following initial step-up period.

We're making progress on reducing the burden of treatment. The FDA recently shortened the recommended monitoring period for the first 2 doses from 22 to 24 hours to just 6 to 8 hours. Looking ahead, we are advancing alternative dosing schedules, subcutaneous administration and has the potential to further improve convenience for patients and expand access in community settings. The potential to help patients earlier in their treatment journey is even more exciting. And as Jay will discuss in more detail, we recently presented Phase III results from the DeLLphi-305 study evaluating IMDELLTRA in combination with IMFINZI in first-line maintenance treatment. I was at the European Society for Medical Oncology Congress in Madrid, when these findings were presented, and I was moved by the standing of vision from the audience, the excitement we heard from oncologists about the potential to significantly extend patients' lives was remarkable.

The magnitude of these results is difficult to overstate more than 8 additional months of median overall survival represents an extraordinary advance for patients facing this devastating disease. We're moving with urgency to advance regulatory discussions with health authorities and support timely consideration by clinical guideline organizations, including the NCCN. These findings can translate into clinical practice as rapidly as possible. We believe IMDELLTRA has the potential to transform the treatment of small cell lung cancer and with additional regulatory approvals become a cornerstone therapy across multiple stages of small cell lung cancer. Our portfolio has significant potential for deeper market penetration, additional indications and global expansion. We're confident in our ability to deliver sustained growth well into the next decade while reaching more patients around the world.

And now I'll turn it over to Jay.

Thank you, Murdo, and good afternoon. This quarter, we reported 3 positive Phase III readouts across 3 serious diseases: IMDELLTRA in small cell lung cancer; TEZSPIRE in eosinophilic esophagitis; and dazodalibep in Sjogren's disease. These results reflect our R&D strategy that focuses on first-in-class and best-in-class medicines for serious diseases with high unmet need. Each advance represents meaningful progress for patients and physicians and meaningful potential for long-term growth.

As Murdo introduced, IMDELLTRA is our DLL3 targeted bispecific T cell engager currently approved in second line or later small cell lung cancer and the second approved medicine arriving from our BiTE platform. At the European Society for Medical Oncology Conference, we presented practice-changing results for IMDELLTRA from the DeLLphi-305 study that evaluates IMDELLTRA plus IMFINZI versus IMFINZI alone as first-line maintenance treatment. The combination of IMDELLTRA to IMFINZI brought a median overall survival of 21.1 months versus 12.7 months with IMFINZI alone. The results are notable in a challenging clinical setting where current medicines deliver only a modest improvement in overall survival. Median follow-up at the data cutoff was 15.9 months, and we will report final survival benefit as these data mature. Longer follow-up of 30 months from the Phase Ib first-line maintenance study of IMDELLTRA with anti-PD-L1 therapy was also presented at ESMO, remarkably featuring a median overall survival of 37 months. These results are unprecedented in small cell lung cancer.

The safety profile of IMDELLTRA and DeLLphi-305 was consistent with the clinical experience to date. Cytokine release syndrome and ICANs were primarily low-grade and occurred mostly for the first 2 doses. DeLLphi-305 permitted 1- to 2-hour monitoring time, which could support outpatient administration and broader uptake. Given the transformative benefit observe, we are now working to rapidly file with regulatory authorities around the world. If approved in first-line maintenance, IMDELLTRA could address the needs of 23,000 patients in the U.S. alone, important used earlier in the treatment journey and for a longer duration of therapy. We are pursuing a broad clinical program to establish IMDELLTRA as the cornerstone therapy for patients with small cell lung cancer. This program includes evaluating IMDELLTRA in earlier-stage disease novel combinations, including antibody-drug conjugates and in other DLL3 expressing cancers.

Turning to TEZSPIRE, which targets TSLP, an upstream driver of inflammation in airways and other tissues, we recently presented positive results from the crossing study in eosinophilic esophagitis or EOE. EOE is another epithelial driven eosinophilic inflammatory disease alongside severe asthma, in chronic rhino-sinusitis with nasal polyps. EOE affects more than 470,000 people in the U.S., nearly half of patients with this devastating disease remain inadequately controlled with existing treatments. The Phase III crossing study evaluated TEZSPIRE in adolescents and adults with symptomatic, uncontrolled EOE. At week 24, the study met both primary endpoints demonstrating improved histologic remission and improved swallowing symptoms compared with placebo. These benefits were sustained through week 52. This is the first time sustained efficacy through 52 weeks has been shown for a biologic in a placebo-controlled EOE trial.

Multiple secondary endpoints were also met as TEZSPIRE improved measures of underlying inflammation, swallowing symptoms and endoscopic disease activity. Together with every 4-week dosing, these results support TEZSPIRE's potential as an important treatment option for patients with EOE and to add to the evidence for targeting TSLP across serious diseases driven by eosinophilic inflammation. For patients with Sjogren's disease, we are targeting CD40 ligand signaling with dazodalibep in 2 Phase III trials in systemic and in symptomatic disease. Sjogren's can affect multiple organ systems and cause persistent dryness, fatigue and paid. There are no approved disease-modifying therapies for Sjogren's disease. In systemic Sjogren's disease, we are excited by the positive clinically meaningful results of dazodalubab in the placebo-controlled Phase III OASIS-301 study. The study met its primary endpoint with statistically significant improvement from baseline SDI of 5.6 points with monthly dosing and 5.2 points with quarterly dosing or 1.8 and 1.4 point placebo-adjusted improvement, respectively. The treatment effect was observed as early as week 4 and sustained through the end of study at week 48.

Importantly, dazodalibep also met key secondary endpoints for patient-reported dryness with statistically significant improvements in DASPRI and ESSPRI scores with monthly dosing. Dazodalibep was generally well tolerated, whether administered monthly or quarterly. We'll present the detailed data at ACR on November 11 and await the completion of our second Phase III study in symptomatic shores disease expected later this year. Beyond these 3 important Phase III advances, we recently reported at EADV, the positive Phase II data for Daxdilimab in primary discoid lupus or DLE. Daxdilimab targets ILT7, to reduce plasmacytoid dendritic cells and address type 1 interferon mediated inflammation. DLE can cause permanent scarring, skin pigment changes and hair loss. In this study, both doses of daxdilumab met the primary endpoint with improvement in active skin disease observed as early as week 4 and sustained through week 24. At week 24, daxdilimab improved baseline by 10.2 points at the lower dose and 9.9 points at the higher dose. The corresponding placebo adjusted Class A improvements of 6.0 and 5.7 points, respectively, were both statistically significant.

Daxdilimab was well tolerated with no serious adverse events or gets reported. Based on these results, we are advancing Daxdilimab into Phase III development. As you can see, we've been working hard to execute the late-stage portfolio and enjoyed terrific results this quarter. Elsewhere in the portfolio, we are focused on developing important new medicines in our late-stage pipeline. For patients with prostate cancer, we are rapidly advancing Xaluritamig in both early stage in advanced disease, extending the reach of our T cell engager platform. For individuals with obesity and related conditions, we are advancing our comprehensive Phase III maritime development program. This quarter, we completed enrollment of both Phase III sleep apnea studies our cardiovascular outcome study and initiated the first of 3 Phase III studies in type 2 diabetes. MariTide is emerging as the first monthly therapy for obesity, with the potential for as few as 4 or 6 doses per year. The MARITIME program is designed to establish how individuals can start and stay on MariTide and how others can switch from other GLP-1-based medicines and stay on MariTide. Our goal is to make long-term treatment easier for patients to sustain weight loss and enjoy durable health benefits. I'd like to thank my colleagues across Amgen for their continued focus on patients and their commitment to advancing innovative medicines for serious diseases.

I'll now turn it over to Thomas for the financial update.

Thank you, Jay. As many of you know, this is my second chapter at Amgen. I spent nearly a decade here earlier in my career working with Bob and the team. Since then, I've served as CFO of 3 public companies with responsibilities spanning finance, strategy, transformation and operations. I also gained experience in a more consumer-focused health care environment and in a rare disease setting. So I come back to Amgen knowing the company well, but also looking at it with fresh eyes, informed by my experiences over the past 12 years. Today, I am pleased to join you from our first quarterly earnings call as Amgen's CFO.

I look forward to maintaining Amgen's active engagement with the investment community and the financial discipline that investors expect. My top priorities are straightforward. One, working with my colleagues as a team to drive long-term growth through consistent execution of our strategy and operational efficiency. Two, maintaining Amgen's disciplined approach to capital allocation. You should expect continuity here as we balance investment in the best innovation and future growth with returning capital to shareholders. Let's now turn to our third quarter financial results. Our strong third quarter performance reinforces confidence in our 6 key growth drivers. Together, they reflect the breadth and depth of our business and continue to provide a strong foundation for durable growth well into the next decade. We continue to invest in advancing our pipeline while delivering strong operating results.

In the third quarter, our non-GAAP operating margin was 47%. Non-GAAP R&D spending increased 11% year-over-year, driven by higher spend in research and early pipeline, including business development activity. We continue to invest in the innovation that will drive future growth, including MariTide, dazodalibep and Xaluritamig as well as our marketed medicines, including IMDELLTRA, Repatha and UPLIZNA. SG&A expenses decreased 1% year-on-year, mainly driven by the timing of investments and to a lesser extent, our ongoing productivity efforts. We generated $3.7 billion in free cash flow, reflecting continued momentum across the business and enabling us to continue investing for future growth. Capital expenditures were $600 million in the quarter, including investments across our U.S. manufacturing sites in North Carolina, Ohio and Puerto Rico. We continue to expect capital expenditures of approximately billion in 2026 to scale manufacturing capacity for commercial growth and to prepare for a potential MariTide launch. In addition, we returned capital to shareholders through attractive dividend payment of $2.52 per share, representing a 6% increase compared to the third quarter of 2025.

Turning now to the outlook for the business for the remainder of 2026. We are pleased with the strength of our execution and are raising our 2026 guidance ranges for both revenue and non-GAAP EPS. We now expect 2026 total revenues in the range of $38.9 billion to $39.7 billion and non-GAAP earnings per share between $22.90 and $23.70. And let me highlight several additional guidance items. We now anticipate non-GAAP other income and expense to be in the range of $2 billion to $2.1 billion of expense in 2026. We continue to expect the full year non-GAAP operating margin as a percentage of product sales to be roughly 45% to 46%. And -- as we look to the fourth quarter, we expect a meaningful sequential increase in operating expenses, consistent with our established pattern of higher spending in the final quarter of the year. Specifically, we expect a sequentially higher cost of sales margin due to changes in our sales mix and higher profit share expenses and higher SG&A expense due to the aforementioned timing of investments in the third quarter and continued investment in our marketed products.

We expect other revenue to be approximately $1.9 billion for the full year. We expect a non-GAAP tax rate in the range of 15% to 16.5%. We expect share repurchases not to exceed $3 billion. Looking ahead to 2027, we do not anticipate a step-down in operating margin compared with our 2026 guidance. We will continue to allocate resources efficiently, balancing investment in growth with disciplined expense management. As we close out the year, we remain focused on executing our strategy, advancing our growth drivers investing in the best innovation and maintaining our rigorous financial discipline that supports our ability to deliver durable growth well into the next decade. I am grateful to work with all our colleagues worldwide in our mission to serve patients. This concludes our financial update.

I will now hand it over to Bob for Q&A.

Okay. Let's open up the line for questions. And why don't you remind our callers of the procedure.

[Operator Instructions] Our first question comes from Salveen Richter from Goldman Sachs.

On the back of the positive Phase III results in systemic Sjogren's disease, could you help us think about the confidence or kind of handicap how we should think about the readout here in the symptomatic patients and then speak to the regulatory path for this program overall.?

Thanks, Salveen. This is Jay. We're delighted by the results of the systemic study 301 and the efficacy that we observed for both the primary endpoint on SI, placebo-adjusted as well as the impact on secondary dryness are quite encouraging. It is hard to read through, though, from 301 into 303, the systemic to the symptomatic. These are different patient populations. They are being studied separately. And this is important to tease out. the possibility of impact on these 434 patients in the 303 study. So we'll have more to say shortly after we see data in Q4 of this year. Regarding the regulatory path going forward, this is a very competitive space of late, which is good for patients because for years, there was very little progress. so really represents the first therapeutic to show efficacy in the systemic setting also on symptoms and durable out to end of study. So we have nothing to say here today, but we look forward to a consideration of these data. .

Our next question comes from Terence Flynn from Morgan Stanley.

Great. Congrats on all the progress. I know, Thomas, you talked about some of the CapEx investments that you guys are making for ahead of the Maritime launch. Is there any consideration to maybe ramping down the biosimilars business to make even more capacity for that for that launch? Would that also be on the table? And then the kind of related question is, can you tell us, Jay, if you guys have access to the blinded tolerability data from the ongoing MariTide Phase III trials?

I can answer that for you, Terence, it's Bob. Obviously, we consider all options when it comes to managing capacity. But we feel very confident about our ability to continue to be a reliable supplier of high-quality biosimilars. So that's not strain for us and our capacity expansion is really designed for larger quantities of protein than what you're referring to with the biosimilars program. On the other question, Jay, do you want to take a shot?

Sure. Thanks, Terence, for the question. We are, in 2026 just now is down with disciplined data generation on MariTide, and the MariTide studies are being carried out with a total adherence to good clinical practices. We'll have more share around the efficacy and tolerability of MariTide at the time that these studies read out.

Our next question comes from Akash Tewari from Jefferies.

Hearing your team talk about the Phase III Sjogren's data versus Phase II in systemic. I think one of the things I've noticed is your team was surprised with the onset of effect, and it might have been better than what you saw in Phase II. Can you talk about what we are seeing on onset of effect with the systemic trial? And how that reads across to the symptomatic study that's coming up -- and then just any comment on the MARITIME PEN study. I know you just started a study looking at miratide with an at-home auto-injector, what gave you the confidence to start that study now? And do we have any visibility on what auto-injector dose you would be having in that trial?

Thanks. I'll take the question. This is Jay. As I shared a moment ago, we were delighted, but maybe not surprised by the impact of dazodalibep in Sjogren's disease, we were building on a very strong Phase II data set after all. The significant 1.8 placebo-adjusted improvement with monthly dosing on the SDI and 1.4 on the Q12 week are in line with our expectations and strong results. and the effect on dryness as well. We were hoping and expecting to see as well. The read-through, I think I've already covered a moment ago, but you asked about onset. And here is a potential advantage of something that targets active inflammatory signaling like CD40 and CD40 ligand. We got a lot of experience at this company with B cell depletion. And with B-cell depletion, there can be a delay in onset in some circumstances, though many diseases, we haven't experienced that with UPLIZNA.

So to see effect at week 4 is highly consistent with our mechanistic thesis, that as an inhibitor of CD40 ligand CD40 signaling, you have this chance for an immediate inhibition on B-cell-driven inflammation. But moreover, as CD40 is also highly expressed on salivary gland ductal epithelial cells and can, therefore, drive local inflammation through interaction with activated T cells or otherwise, it could be sensible that dazodalibep would work as early as 4 weeks where we saw statistically significant improvement already that prove durable through the end of study. So thanks for calling out that feature. It is a nice feature of a molecule directed at an active signaling pathway that it might, in some circumstances, work faster.

Akash asked the second question about the auto-injector. Obviously, we've got a ton of experience with auto-injectors, Akash. So I don't think there's anything particularly interesting about the study that you're referencing. But Jay, feel free to add anything more if you'd like.

No. We've been pretty consistent in sharing that MariTide expected ultimately to be delivered in a patient-friendly single-chamber handheld auto-injector. We have significant experience as Bob shared. We've taken a fairly standard approach to its development and going well so far.

Okay. Let's go to the next question and maybe just remind our callers so that we can try to get to everybody tonight, if you could hold yourself to one question, that would be great. Casey and his team will be around and all of us are available if you have other questions you need to get in front of us later in the day.

Our next question comes from Michael Yee from UBS.

One question for Bob. Bob, Amgen has been quieter, I guess, on the M&A front in a period of record M&A bill making. Could you just comment about your perspective about what you think is going on? Is your desperation factor not high, you're very busy. Maybe you're just more excited about what you've got. Maybe just talk a little bit about that. and whether we should or should not necessarily continue to expect bolt-ons or whatever you're thinking?

Well, I'm not sure, Michael, that I would acknowledge the premise of the question, but what I would say is our business development focus is very consistent. As we've said for some time, we're looking for opportunities that align well with our 4 therapeutic areas of focus. We're focused on delivering consistent long-term growth, and we feel confident we're on track to do that through time. Obviously, a meaningful portion of our revenues come from molecules that we license or acquired, and I think they'll continue to be true through time. So it would like to think that we're disciplined, Michael, in the way that we allocate capital, both internally and externally. And I'd like to think when -- particularly when we go externally that we see a path for our shareholders to earn a return and not just for the selling shareholders are to return.

Our next question comes from Yaron Werber from TD Cowen.

So maybe a quick question on the upcoming orange data. The efficacy looks very good on a monthly and Q3 months. DASPRI is sort of a new endpoint that you're validating from the Phase II. Is that going to support the U.S. filing while ESSPRI is going to support the European filing for the symptomatic study? And then if you don't mind, can you file for both Q4 and Q3 months, given they both hit on the primary, but only 2 months hit in the secondary in the first study on joining this?

One, thank you, especially in between the readouts of these 2 Phase IIIs, we're probably not going to go deep today on our full regulatory strategy. But you are correct that there are different preferences around end points in the U.S. and rest of world. and we've taken this very much to the heart in the design of these 2 studies in the primary and secondary endpoints.

Our next question comes from Chris Schott from JPMorgan.

Just had a question on IMDELLTRA. Can you just elaborate a little bit more about how you're thinking about the opportunity unlocked with the 305 data. And maybe as part of that, how quickly you believe the product can ramp following the ESMO data. as part of that, Andrew, can you just talk about the reduced monitoring requirements for the drug as well. I'm trying to get a sense of how much of a hurdle monitoring had been for uptake in the later line settings, that obviously seems to be addressed in this earlier line setting as well.

Thanks, Chris. It's Murdo here. So on the monitoring, we've got an improvement already just approved by the FDA that's now in our label in the second-line setting, with monitoring of less than 6 hours now. So that improves from the 22 to 24 hours that were in the original label, and now we're in a much shorter monitoring period. So that's already helping the ability for primarily community oncology clinics to be able to initiate second-line patients within Delta. When -- as Jay mentioned, in the 305 study, the monitoring actually goes down to 1 to 2 hours. And so there will be, hopefully, a further improvement in the label as we extend that to the frontline maintenance indication. And then IMDELLTRA becomes a very straightforward, very simple product to initiate in our frontline maintenance setting with, obviously, a profound survival benefit to be had. So I think -- this is a medicine given how normal it is that we've been very careful to ensure patient safety.

We're now evolving in our understanding of it. And as with BLINCYTO, as we've moved into earlier disease settings we see that this is a much, much better tolerated medicine. We really only have 1 patient in Delphi 305 with cytokine release syndrome grade all the other patients that experienced cytokine syndrome experienced grades 1 and 2. So what does that mean for the opportunity? Well, it means that we believe we've established a new cornerstone therapy. We believe that nothing else thus far in the category has been able to demonstrate the kind of profound overall survival effect that we have. And I would expect that with things like updated NCCN guidelines with additional awareness of these data, the behavior change in the clinic will be rapid. Obviously, we're moving as quick as we can to ensure regulatory filings and approvals and all the rest of it. But we are ready to support the rate of change that clinicians will affect. I'll just say, I've been talking to our field medical teams who have been out there this week and last week post the presentation of the data at ESMO. And I'm not alone in my enthusiasm for these data, our practicing oncologists are blown away by just the magnitude of effect and the safety profile that we're seeing in an earlier disease setting.

Our next question comes from Umer Raffat from Evercore ISI.

I just wanted to echo the sentiment from ESMO on the groundbreaking data. Murdo, maybe just to end on Chris' question and just to make it easier for investors to understand the magnitude of what we're dealing with here. Is it possible or is it realistic for us to assume something approaching 20,000-plus patients in U.S. being on tarlatamab? And do you envision the maintenance opportunity in first-line alone being $5 billion plus with induction trial next year adding additional upside?

Well, Umer, I think you know me by now and you know the Amgen team by now that we don't issue product-specific guidance. But you can tell the answer to Chris' question, that we're extremely excited about the data set that have been generated here. The opportunity is definitely an interesting one given how rapidly patients progress on in this disease area. And so in second line, you're quite limited as to the addressable patient population. Because, unfortunately, not many patients make it to second line, their disease progresses too rapidly, and they end up in hospice and they end up dying. And so as you move into the earlier lines, the small cell lung cancer addressable population in the U.S. is 35,000. So it's a decent size patient population. The question is, how big is it in each setting and frontline maintenance. But as I said to Chris, this is going to be a very rapid adoption, and we're going to see, hopefully, many patients on delta for a long period of time. And so the duration of treatment here might be quite long as well. And I would like to turn it over to Jay on other clinical development work that we're doing on the molecule.

Yes. Thanks, Umer. The development of IMDELLTRA remains a source of real activity here at Amgen. We're working hard to complete the limited stage small cell lung cancer study that is an event-driven study. as well now having seen the benefit of IMDELLTRA used in the maintenance setting of frontline induction and maintenance use of IMDELLTRA. We've completed, as you may know, a study of IMDELLTRA establishes an alternate dosing capability. And this is very helpful as we start to imagine combinations of Delta with emerging agents such as antibody drug conjugates. IMDELLTRA is showing dramatic data when with chemotherapy, and there's every expectation then that ADC is delivering chemotherapy should be comparably active. And we have undertaken studies with B3 and DLL3 and we'll have more to share there in the future. But just as Murdo said, not only do these combinations and advances in the use of IMDELLTRA as a cornerstone of small cell lung cancer therapy lead to increased response rates, but durability. And we're very hopeful that as the data from the DeLLphi study presented in the presidential at ESMO and published in the New England Journal recently that as these data mature, that patients will reveal to us the full benefit of the medicine. The Phase Ib frontline maintenance study DeLLphi-303 that was also presented at ESMO has matured. And with a median follow-up of 30.8 months, we saw a median overall survival of 37.9 months, which is just unheard of. in this disease setting. So we're very pleased with the development so far, but we have a lot of wood to chop for these patients going forward.

Our next question comes from David Amsellem from Piper Sandler.

Have a daxdilimab question. On the Phase III, are you going to explore a broader cutaneous lupus population? Or will it be specific to discoid lupus, that's number one. And then just thinking about this market, can you talk about sizing in terms of how you think about cutaneous lupus in that population relative to the population and how these are 2 distinct populations and how that informs your physician targeting? Is this a dermatology call point or a rheumatology whole point or a bit of both?

Thanks for the question. I'll start, Murdo maybe you can weigh in on the outlook for the medicine. Thanks for asking about Daxdilimab. We're very pleased with the activity observed so far in discoid lupus prevalent disease, 20 to 50 humans per 100,000 and 5% to 10%, they progress to SLE usually appreciate that there have been innumerable mechanisms of action that have failed patients with lupus in its various manifestations. And in our Phase II study, the effect on Class A, where an improvement from 7 points from baseline is considered clinically meaningful broadly in this population of those greater than equal to 8 at baseline. Improvements that we saw were negative 10% and negative 9.9% for the lower and the higher doses at week 24. And so we're very taken with this medicine in the cutaneous manifestations of lupus. We have not as yet described completely our Phase III design, and we will do that in the future. But it's not lost on us that we've stumbled upon a very exciting and hopeful mechanism targeting these plasmacytoid dendritic cells in this disease. Murdo?

No, I would just add that the prescribing population of physicians here, primarily dermatologists, which obviously, we have good Amgen capabilities and experience there. And for the few rheumatologists that we'll pick it up again, we have strong medical and field commercial teams covering those customers.

Our next question comes from Evan Seigerman from BMO Capital Markets.

I think, Jay, when we met in the small group meeting back in September, you suggested that although MariTide's administered monthly or even less frequently, the side effect duration is comparable in line to what you get with weekly incretins. I would love it if you expand more on how you can measure that in kind of a Phase 1 of any of your trials? And more broadly, just given how much the space and obesity is rapidly evolved even to then. Remind us how MariTide fits within kind of this evolving landscape.

Why don't I start to talk Murdo, about the interesting and reassuring if not exciting, dissociation between the pharmacokinetics of MariTide and the duration of symptomatology, if you could pick up the back half of the question about segmentation. First, I would just say, irrespective of why I think it is true, it is true that this medicine that has a very long half-life designed for tonic activation of GLP-1 receptors as well as inhibition of GIP receptors, that has conferred activity for weight loss in type 2 diabetes with monthly dosing every 8-week dosing and as we described, every 12-week dosing. It is a fact borne out of prospective clinical investigation that though the durable disease activity of the medicine is quite long lived like the molecule. The symptoms aren't -- this is true also for a weekly injectable GLP-1 peptides. And so we're not surprised to see it. Now how do we measure it? You ask here. We've done very exhaustive diaries in early phase clinical investigation to understand the onset, frequency, severity and duration of symptoms. We've shared some of these early plots that we call Manhattan plots that reveal the duration of symptoms should they arise. To date, MariTide has proven very well tolerated. Its target doses and like all GLP-1s benefits from dose escalation. But the durable activity of the medicine does not come with a durable side effect profile, where side effects to date are were observed mostly mild, sometimes moderate and rather short lived for a few days. Murdo?

Yes, it's an interesting observation, Evan, on the amount of activity in this category. There are certainly a lot of daily orals being developed. There's a lot of weekly injectable being developed, some even trying to stretch to monthly. But what we've not seen is a bonafide monthly drug in development that could be dosed as infrequently as 6x or 4x a year. And we continue to believe that MariTide is unique and differentiated in that aspect. It's a simple 3-step dose escalation, 2 months, you're up to your first maintenance dose and then you can find the most convenient dose for your weight loss journey thereafter. So I feel like we've got a compelling offering we're obviously looking forward to seeing the Phase III data when they read out. And we're excited about coming into the market and helping many, many patients reach their weight loss goals. We've also got a broad clinical program, as you know, and that means that we'll also be able to help patients with type 2 diabetes and ASCVD and sleep apnea among others.

Our next question comes from Geoff Meacham from Citi.

I had a similar one for Jay or for Murdo. So ahead of the maritime data next year, I wanted to ask how you guys are thinking about the commercial approach. So mostly thinking about the dynamics of the new Medicare bridge program, payer receptivity, how you're thinking about the OUS markets in advance of data?

Thanks for the question, Geoff. Look, I think I would start first with we're very focused on making sure that consumers and patients are very much in the focus of our go-to-market strategy. I think what we've seen in this category is that patients have a much more important role to play in activating and advocating for their own care and their own weight loss journey. So first and foremost, that is absolutely the priority we will scale and size accordingly. We obviously have a great cardiometabolic team here at Amgen, and we'll be ready to go to market with MariTide. I think on the access and reimbursement front, we expect our unique differentiated profile to help secure access and coverage. And obviously, we're interested in seeing what other government access programs evolve to over time. I think it's good that we've got Medicare access in this category. I think it should be expanded. Ex U.S., I think is going to be tougher. I think it's going to continue to be very much a consumer-driven market ex U.S. but we are hopeful with outcomes data in ASCVD and with type 2 diabetes data and other hard endpoint clinical programs then that we will be able to secure reimbursement in many markets, as I said in the U.S. as well.

Okay. Let's take 2 more questions, and then we'll, as I said earlier, be available some of you who didn't get a chance to ask questions on the call. Let's go 2 more.

Our next question comes from Matt Phipps from William Blair.

With both the OPDIVO and KEYTRUDA BLA filed, just curious what your assumptions are around being able to -- when you can commercially launch those? And how do you think about penetrating the market that is kind of being moved a subcutaneous formulation?

Yes. Obviously, this is a competitive space here. So we're not going to have a whole lot to share with you at this point, Matt. But as you heard from Murdo's remarks, our focus is on developing these medicines, having them available for patients. And again, we've established a pretty good track record here a leader in biosimilars. But Murdo, feel free to jump in if you want to add any further color?

Well, as we always say about our focus on how similar will be a first or first wave with those launches, which is really important to establish a decent competitive position, and we believe that we're there.

All right. Let's go to the last question, please.

Our last question comes from Alex Hammond from Wolfe Research.

So unlike small cell lung cancer, a large share of prostate cancer care occurs in the neural groups and community practices that have low experience managing CRS. So I guess, how are you planning to bring value to make those sites? And how much could the fully outpatient cohort or subcu version change that? And I guess, also how important is it to not need a biomarker to help adoption compared to other treatments that require them?

Terrific. Thanks for the question. Jay, why don't you are your thoughts?

Yes. I'll share on the back side, then Murdo, perhaps you could talk about implementing T cell engagers, where we just have so much experience, truly the leading company in the sector. So for sure, helping the adoption of this medicine is experienced with it and building a comfort with T cell engagers as a therapeutic isn't as much about the or is about the care environment, I can say as a doctor, the reduced monitoring will go a long way to helping as well as a fully outpatient cohort, which we have presented at ESMO in Phase Ib, which demonstrated for Xaluritamig, our STEAP1 CD3 specific that you referenced, the feasibility for a more convenient administration setting. I will say this is not trivial, but those same centers approach many other nontrivial medicines, and so we have every expectation that through clinical investigation as well as evidence generation, we will establish confidence and comfort for prescribing urologists as needed. You sort of threw me the basketball right under the hoop with your question around biomarkers, it helps a lot to not need a biomarker in order to enroll patients and bring access to a medicine. We have some medicines that, of course, require it. But here, the quite high, if not characteristic, expression of STEAP1 in prostate cancer affords a chance to bring this medicine to patients without need for stratification or qualification by a confirmatory biomarker Murdo?

Yes. We've got obviously extensive experience, as Jay mentioned, in bringing bispecific T-cell engagers into different therapeutic context. We've learned a lot from our work in hematology with now in solid tumor with IMDELLTRA. And we have established an actual field organization, we call our bispecific operations team who help with the operationalization in Linx on how to make sure that patients get the appropriate monitoring the appropriate information at point of care. So that team is up and running. We've had it since before the launch of IMDELLTRA. We're now running at scale for IMDELLTRA, and we would apply that to the GU oncology space as well. We've established a field medical presence with these customers and these clinicians. And we also partner very closely with patient advocacy organizations. This was a key success factor in small cell, where the patient advocates are very good, making patients aware of how to self-monitor and how to identify any type of side effect profile that could be side effect profile related to cytokine release syndrome. So really a lot of experience being applied to the GU space that I think will be very helpful in ensuring patient safety and ease of adoption.

All right. Well, thank you all for joining our call. I think I can speak for the group here that we're heartened by your focus on sources of long-term growth that have emerged with clinical data over the last few weeks. As again, I hope you can appreciate business is performing well, the leadership, executing well, and we're looking forward to finishing the year strong, and we'll I look forward also to gathering with all of you next year to review the fourth quarter and to get launched into 2027. So thanks for your support. We'll talk to you soon.

This concludes our Amgen Q3 2026 Earnings Conference Call. You may now disconnect.

Hello. My name is Christa, and I will be your conference facilitator today for Amgen's Investor Call from the European Society for Medical Oncology Congress 2026. [Operator Instructions]

I would now like to introduce Casey Capparelli, Vice President, Investor Relations. Mr. Capparelli, you may begin.

Thank you, Christa, and thank you all for joining our call from ESMO here in Madrid. The slides that we'll be reviewing are now available on our Amgen IR website. Please see again the slides that accompany this presentation for our safe harbor statement.

I'll now turn it to Murdo Gordon to get us started.

Casey, thank you, and thanks, everybody, for being on the call this evening, or this afternoon if you're on the West Coast of the United States. It's our pleasure here at Amgen to host this discussion, which will recapitulate some really exciting and important data that were presented, as Casey mentioned, here in Madrid at the '26 edition of the ESMO medical congress.

So joining me this evening is our Head of Oncology and Development, Jean-Charles Soria, our Senior Vice President of Oncology, Global Development. Also joining me is Kave Niksefat, our Senior Vice President of Global Markets and Access.

And we're privileged to be joined by Dr. Charles Rudin, Director of the Memorial Sloan Kettering Cancer Center, who's one of the world's preeminent small cell lung cancer physician researchers, who joins us to lend us his perspective. Dr. Rudin led the pivotal second-line Phase III DeLLphi-304 study that established IMDELLTRA as a standard of care for relapsed small cell lung cancer, and is here today to provide his perspective on the first-line maintenance Phase III study, the DeLLphi-305, results that were presented just a few hours ago here in Madrid. And of course, Casey will be here to answer questions as well, who you are all familiar with.

Today is one of those days where, at Amgen, we are able to live the company mission. And our mission at Amgen is very simple. It's to serve patients. And as my experience, I've been to many congresses and many ESMO meetings over the last few decades, but this meeting has been a special one, an extremely special one. And today was the kind of day that, here at Amgen, we all appreciate, because it allows us to fulfill that company mission. It allows us to work on a devastating type of cancer, and that's small cell lung cancer, and transform survival expectations.

Our BiTE platform has demonstrated transformative survival benefit in hematologic malignancies, and now in solid tumors. IMDELLTRA clearly demonstrates durable survival benefit in small cell lung cancer. IMDELLTRA is becoming the cornerstone therapy for extensive-stage small cell lung cancer, regardless of the combination choice, including PD-L1s. We have a broad global development program that has the potential to further expand the impact that IMDELLTRA can have on patients. And our innovative oncology portfolio is well positioned as one of our core 6 key growth drivers. And so it is our pleasure to be able to delve into these data with a bit more detail.

Now before we do that, just a reminder of the strength of Amgen's portfolio of first-in-class and best-in-class medicines, with Repatha in cardiovascular disease, EVENITY in osteoporosis, TEZSPIRE in severe asthma and nasal polyps and, soon, esophagitis. UPLIZNA for rare autoimmune diseases, BLINCYTO in ALL, and IMDELLTRA in small cell lung cancer.

We're committed to delivering these first-in-class and best-in-class medicines. We have a broad innovative pipeline across these therapeutic areas. And these differentiated medicines are in leadership positions in populations with strong opportunities where we address significant unmet need. In oncology, of course, BLINCYTO and IMDELLTRA illustrate our ability to translate biology and deep biological insight into differentiated medicines.

And just as a reminder, as we reported our second quarter results, we have a very strong portfolio with these medicines, delivering over 26% year-over-year in Q2 and comprises now 70% of our second quarter sales. So we are definitely building strong commercial momentum with these growth drivers. We are enthusiastic about the outlook given the momentum for these patients -- for these products, with patients that still continue to be underserved across these diseases.

So without further ado, I do want to transition to Jean-Charles so that we can delve deeper into the meat of our program.

Thank you. Amgen oncology R&D strategy is focused on delivering differentiated and transformative therapies for patients with hard-to-treat solid tumors and hematological malignancies. Our strategy is anchored in 2 core pillars: the T-cell engagers and precision therapies, which include small molecules directed at difficult-to-drug targets and antibody drug conjugates. Today we will focus on the T-cell engager platform called BiTE.

T-cell engagers are bispecific antibodies that physically connect the patient's T cell directly to cancer cells, forcing an artificial synapse that allows the immune system to recognize and destroy the tumor. One arm of the T-cell engager, which is an antibody, latches onto a specific protein, which is a tumor-associated antigen, on the cancer cell, while the other arm of this bispecific antibody binds to the CD3 receptor on the T cell. This close physical link activates the T cell to release cytotoxic molecules that will kill the cancer cell or aim at least at killing the cancer cell.

At Amgen, we are pioneers of BiTE medicines. The column on the left is where we started this story of bispecific T-cell engagers or BiTEs, when the technology was new and the impact was uncertain. We have learned and built up on the innovation that brought us BLINCYTO, which was the first ever T-cell engager approved.

And we have expanded the impact of BiTE medicines into solid tumors. We have engineered second-generation BiTEs with convenient IV infusions and are exploring the potential for subcutaneous administration. We have navigated treatment concerns and have achieved mostly outpatient administration and reduced monitoring for our BiTE medicines, improving the overall patient experience. And we have also improved the tolerability of our medicines through effective management strategies.

These were not trivial undertakings, and we have generated a high degree of institutional knowledge and expertise along the way for how to develop, manufacture and commercialize BiTE medicines. This is clearly a strong platform for the company.

The evolution of our BiTE platform is what brought us BLINCYTO, a CD19-targeting BiTE that has revolutionized survival in B cell acute lymphoblastic leukemia. BLINCYTO was our first approved BiTE medicine and has dramatically changed the treatment on B-ALL.

IMDELLTRA, a DLL3-targeting BiTE, has revolutionized survival in small cell lung cancer. Xaluritamig is an investigational STEAP1-targeting BiTE that is rapidly advancing through Phase III in prostate cancer. Xaluritamig, as you can see, is designed to bind STEAP1 on tumor cells and CD3 on T cells, directing T cell activity towards STEAP1-expressing prostate cancers. Xaluritamig is being developed for allcomers with no biomarker testing needed as STEAP1 is highly expressed in prostate cancer.

Xaluritamig development is significant and encompasses broad different stages of prostate cancer. With xaluritamig, we're covering the waterfront of prostate cancer by pursuing a parallel development path across various prostate cancer disease stages, with the remaining large patient populations with significant unmet need.

The Phase III mCRPC, metastatic castration-resistant prostate cancer program, is testing 2 chemo-free regimens: xaluritamig as monotherapy and xaluritamig in combination with abiraterone in existing late-stage treatment settings. We are also quickly moving to the earlier stage of prostate cancer, following the approach we pioneered first with BLINCYTO and now with IMDELLTRA. Our conviction in xaluritamig potential has led us also to this parallel investment approach.

We have introduced the BiTE strategy and platform, and now let's return to IMDELLTRA, a medicine that is transforming the standard for survival in small cell lung cancer. Now small cell lung cancer is a devastating and rapidly progressing disease with survival often counted in months. There has been limited innovation in the field and recent advancements have generated modest improvements in overall survival in the first-line setting.

The question for us when designing the DeLLphi-305 study was whether adding IMDELLTRA to continued durvalumab treatment could improve outcomes in patients whose disease had not progressed after induction therapy. We gained initial insight into this approach from a Phase Ib first-line maintenance study, DeLLphi-303. Some of you may recall that data from this study were presented last year and provided us insights into IMDELLTRA's ability to improve survival. Today we are pleased to share updated survival that are available in an e-poster and will be presented on Monday here at ESMO.

With an additional year of data, we have now observed in the first-line maintenance setting a median overall survival of 37.9 months. This is remarkable data in this difficult-to-treat disease.

It is now my pleasure to introduce Dr. Charles Rudin, a world expert physician-scientist in small cell lung cancer, to walk you through the transformative data from DeLLphi-305 first-line maintenance Phase III trial that was just presented a few hours ago during the Presidential Symposium here in Madrid at ESMO.

Well, thank you, Jean-Charles. It's a pleasure to be able to review these data, which I think are really quite spectacular. This data was presented by Jacob Sands in the meeting today. I was not part of the study directly, but I am quite familiar with the data and happy to go through it.

The DeLLphi-305 trial was designed as a randomized Phase III trial comparing a backbone, which is current standard of care, in the maintenance setting, that is Imfinzi, versus the combination of adding IMDELLTRA to Imfinzi. The trial was one-to-one randomization, quite straightforward, with the primary endpoint of overall survival. Patients were randomized after completing 4 cycles of induction chemotherapy, with immunotherapy, and patients had to at least have stable disease at that point to be eligible for enrollment.

Key eligibility criteria are listed here. I'll just point out that patients with brain metastases, both untreated and treated, asymptomatic brain metastases, were allowed on study. The protocol was randomized and stratified for the presence or absence of brain and liver metastases, the response to first-line chemo IO and the type of platinum used in that regimen.

The secondary endpoints were progression-free survival and then, subsequently, overall survival. And the trial was designed to first analyze OS, overall survival. If meeting that endpoint, progression-free survival was analyzed, and subsequently, response rate and safety were considered.

Next slide. This slide shows the baseline characteristics of patients enrolled in this trial. And you can see that in general, these are well-balanced arms. I'll point out that about 20% of the patients had brain metastases going into the study and about 1/3 of the patients had liver metastases on both arms.

Next slide. This is the data on the primary outcome of overall survival. And you can see a clear separation of the curves here. Hazard ratio of 0.42 with a P value of less than 0.001. The curves separate early, and that separation looks like it will be maintained, essentially consistent in the shape of the curve with the Phase Ib data that Jean-Charles showed earlier. Dramatic results and a clear improvement.

Next slide. Subsequent analysis looking at prespecified subgroups suggested benefit really across the board in all relevant subsets, including those patients with or without brain metastases, with or without liver metastases. So really a clear benefit across the board.

Next slide. This slide shows the data for progression-free survival, which I think is also quite striking. In the maintenance setting on small cell lung cancer, patients began to progress pretty quickly, you can see on the Imfinzi curve, the control curve. In contrast, the combination really extends things out. A median of 7.4 months versus 1.9 months in the control arm. Here the hazard ratio is 0.34, with a P value of less than 0.001. Again, clear benefits.

And I would point a little bit to the tail of the curve. This is still early data with median follow-up for progression-free survival in the order of 14 months, but clearly, it looks like these curves are holding up.

Next slide. Again, if we look at prespecified subgroups, clear benefit across the board, brain metastases, liver metastases, et cetera.

Next slide. In the maintenance setting, we rarely see responses. Patients have had their major cytotoxic therapy as induction maintenance is really a time when patients are continuing on immunotherapy, and the goal there is really to avoid progression. But here we can see that on the Imfinzi control arm, responses were seen in only 4% of patients. I think that's what we would sort of expect. In contrast, the addition of IMDELLTRA here leads to an overall response rate, in the maintenance setting, which is quite remarkable, 26%.

On the right, the durability of their response is also, I think, striking, with over half of the patients who are responders still in response 1 year later. Quite an important result, I think, for patients.

At the time of data cutoff, about 44% of the patients on the combination arm are still on drug. In contrast, only 11% on drug on Imfinzi alone.

Safety is a clear concern here, and of course, adding 2 drugs, you do see more adverse events. But I would point out that those adverse events were quite manageable really across the board. If we look at treatment-related adverse events that led to discontinuation or holding of the drug, it's really a small minority, 3% for each of the 2 drugs. No fatal events on the combination arm attributable to drug.

Next slide. Two of the key toxicities that we think about with BiTE molecules like IMDELLTRA are cytokine release syndrome and ICANS. And you can see here that those were observed on the combination arm, but really at strikingly low rates. And again this was, to me, a very striking data. Only a single patient on the combination had Grade 3 CRS. And none of the patients had Grade 3 or above ICANS. This is actually better safety data than what we've seen previously in patients who had recurrent disease treated with IMDELLTRA.

I think the reason for that, if I can speculate, is that we're really treating minimal residual disease at this point as maintenance, rather than progressive disease which is quite aggressive in patients with small cell lung cancer when it occurs. The events that did occur were quite manageable, as noted here, with very low rates with use of drugs like tocilizumab.

Next slide. So in conclusion, this combination strikingly and significantly improves overall survival and progression-free survival, and leads to objective response in maintenance in contrast to Imfinzi alone for patients with extensive-stage small cell lung cancer who have not had progression on first-line chemotherapy.

58% reduction in the risk of death, 66% reduction in the risk of disease progression or death, and an overall response rate in the maintenance setting of 26%. The survival benefit really extends to all subgroups analyzed, including those patients with brain metastases, liver metastases, and irrespective of the chemotherapy combination used in induction.

I think these are practice-changing data. This clearly defines a positive benefit-risk profile for patients with this otherwise very lethal disease. And I'll stop there.

The patients -- the study was published concurrently with the presentation today in the New England Journal of Medicine. Additional details can be found in that manuscript. We, of course, would like to thank the patients, the families, the investigators and clinical site support. This was a big effort involving many people around the world, and was supported by Amgen and AstraZeneca.

Thank you, Dr. Rudin, for a great presentation. And now let's look at our overall IMDELLTRA clinical development program.

As you can see, we are pursuing a broad global clinical program with IMDELLTRA, establish it as the cornerstone therapy in small cell lung cancer. Our ongoing Phase III studies are intended to move earlier in the treatment paradigm. And we are optimistic that these studies will demonstrate transformative first-line survival.

In addition to the original registration-enabled study in second-line or later small cell lung cancer and the data we have presented today, we are also investigating IMDELLTRA in 2 frontline settings: as first-line induction and maintenance with IMDELLTRA combined with chemo immunotherapy, in the randomized Phase III trial, DeLLphi-312. And in the limited stage, we are studying IMDELLTRA following concurrent chemo-radiotherapy in the randomized Phase III trial, DeLLphi-306.

We are also pursuing flexible dosing to align IMDELLTRA with other treatment regimens and to further improve the patient experience. We've expanded IV dosing regimens as presented at World Lung Cancer in DeLLphi-309 and with subcutaneous dosing as being explored in DeLLphi-315.

We are establishing IMDELLTRA as the cornerstone therapy in small cell lung cancer. It is already a standard of care based on the Phase III second-line data, DeLLphi-304. But we are also evaluating novel combinations of IMDELLTRA with the B7-H3 ADC, DeLLphi-310, and with DLL3 ADC, DeLLphi-313, with the DLL3 ADC.

Additionally, we are exploring IMDELLTRA's impact beyond small cell lung cancer. IMDELLTRA's profound data in small cell lung cancer provides us confidence to explore IMDELLTRA in neuroendocrine carcinomas as we seek to extend IMDELLTRA's impact into other DLL3-expressing malignancies. We plan to evaluate IMDELLTRA both as a monotherapy and in combination in neuroendocrine malignancies beyond small cell lung cancer and in other DLL3-expressing malignancies.

There is clearly more to the IMDELLTRA story, but let's look at the progress we have made today in IMDELLTRA's currently approved indications. IMDELLTRA is an established standard of care in second-line or later extensive-stage small cell lung cancer. IMDELLTRA has revolutionized survival in second-line-plus extensive-stage small cell lung cancer, extending the median overall survival by more than 5 months.

IMDELLTRA is currently approved in over 50 markets globally, with over 18,000 patients treated since launch. In the U.S. IMDELLTRA is available in more than 2,000 U.S. sites of care, with over 65% of sites that have used IMDELLTRA that are in the community setting.

Recent reductions in monitoring time will hopefully allow us to reach additional patients in this approved indication. Significant opportunity remains in the second-line setting as chemotherapy continues to be a common treatment option.

Moving IMDELLTRA earlier in the small cell continuum is important. In the currently approved indication, there are 14,000 eligible patients in the U.S. Moving IMDELLTRA earlier will potentially allow us to reach a significantly larger population, and given IMDELLTRA's observed durability to also treat patients for longer periods of time.

As you can see in this slide, IMDELLTRA has redefined survival for small cell lung cancer. The evidence is clear and compelling, and we hope all of you are as excited about what this means for patients with small cell lung cancer as we are today. Given the transformative benefit observed, we are working to rapidly file with the Phase III data we have shared today with regulatory authorities around the world.

In summary, IMDELLTRA is revolutionizing the treatment of small cell lung cancer across multiple dimensions of care. We have observed unprecedented durable survival, with additional Phase III studies underway. We are working on reduced monitoring times and exploring alternative dosing regimens and subcutaneous delivery. We are rapidly advancing a broad global clinical development program to firmly establish IMDELLTRA as the cornerstone therapy for small cell lung cancer.

And we really would like to take the time to thank all the patients, the investigators and the staff that have made all of this possible. With that, I will turn it back to Murdo for Q&A.

Thank you, Jean-Charles. Thank you, Dr. Rudin. And I'd like to thank one more group of people, Jean-Charles, and that's you and your development organization. Thank you for working so hard to deliver a profound data set and for conducting an exceptional clinical trial. Much appreciated.

So with that, let's turn it over to Christa for our first question. Christa?

[Operator Instructions] Our first question comes from Salveen Richter with Goldman Sachs.

Congratulations on the data. It's Tommie on for Salveen. Maybe if you could help frame the average duration of therapy under the expected first-line maintenance label compared to what you are currently seeing in the approved second-line setting?

And how does this level of efficacy here in 305 help to derisk the ongoing Phase III induction study? Or do you think that this type of high bar may be specific to maintenance alone?

Okay. Kave, why don't you start with the first question on duration of therapy, and then we'll have Jean-Charles comment on, is there a read-through from 305 to the ongoing limited-stage trial?

Yes, Salveen, thanks for the question and thanks for calling on a Saturday, we appreciate it. To give some comparison from the trial setting, in DeLLphi-305, we saw that the average -- or the median duration of treatment was 46 weeks. To put that in comparison, in DeLLphi-304, in the second-line, we saw a median duration of therapy of 18 weeks.

Now obviously, in 305, we're still continuing to follow those patients. And then as you saw in 303, we saw an extended use from those patients, going out all the way to 38 months. So we think there's going to be a meaningful step-up in overall duration of therapy as we move into the earlier-line -- the earlier lines and extend survival even longer than we were in the second-line.

Jean-Charles?

Yes. Well, it's rare to have a medicine that hits 2 consecutive Phase III trials achieving all primary and secondary endpoints in heavily pretreated patients and then in patients who are in the first-line setting who have been debulked by the induction chemo immunotherapy. So I don't know the future and would not predict it, but I feel very confident and sleep very well about what the induction maintenance Phase III trial will bring to the patients.

Jean-Charles, well, if you sleep well, I sleep well. Christa, next question, please.

Your next question comes from the line of Evan Seigerman with BMO Capital Markets.

Congrats on the data. Kind of a follow-up to the prior question. So clearly, we know that there's a great impact of the drug in the kind of maintenance study. But as you move towards the Phase III induction that you've been talking about, how do you think about the importance of the cytotoxic chemotherapy kind of reducing tumor burden and then use of the BiTE to kind of continue the immune effect versus having it all done at once kind of in the front line, first induction-type therapy? Do you think that kind of the effect changes as you move forward in treatment?

Yes. I would take that, and thank you for the question. We started with the maintenance setting because it was very rational to bring tarlatamab after debulking the tumor because we knew we were very likely to have higher efficacy and better tolerability. And that's exactly what we saw, in a very profound manner and consistent across every single subgroup analyzed.

In the induction and maintenance setting, we would like to reach all the patients, as you know. Around 20% of the patients that start induction don't make it to maintenance. It can vary across trials, but is in that range, 20%, 25%. So there is a desire to make sure every patient with metastatic small cell lung cancer has access to the drug. And the reason to combine the 3 of them is that they are highly complementary and might act in ways that allow a broader number of cancer cells to be addressed.

The chemotherapy is debulking, the PD-L1 is calling the immune system by making it visible and trying to recruit T cells from the broad systemic nature of immune system. But IMDELLTRA per se is bringing T cells into the tumor to directly fight against the cancer cells. So you are adding a way to tackle the disease by 3 complementary angles that makes a lot of sense and might allow us to treat, therefore, the global number of patients with small cell lung cancer.

Your next question comes from Matt Phipps with William Blair.

This is Madeleine on for Matt. In the presentation at the conference, the ability to treat beyond progression was discussed. Does Amgen plan to generate data to support that with IMDELLTRA? And with that in mind, how could that impact the average duration of treatment in maintenance setting?

Yes, interesting question. Maybe I can ask Dr. Rudin to comment on treatment beyond progression.

Yes. I think the trajectory of disease when patients are on IMDELLTRA seems a little bit different than what we're used to with patients with small cell lung cancer. We are seeing evidence of what we call oligoprogression, meaning progression at a few sites, 1, 2 sites, without global progression. And we've begun treating those patients with things like stereotactic radiation to control sites of disease progression, while continuing on the BiTEs to allow the patient to continue to benefit from that. And we have seen patients who continue to benefit for many, many cycles after local therapy.

That's not something we have traditionally used in small cell, but I think the landscape seems to change. And as Dr. Sands pointed out, we're seeing that more and more.

Thank you, Dr. Rudin. I would just add that it's something that is routine in EGFR mutant non-small cell lung cancer, that has teached us that when you have systemic control and just a site of progression, there is no reason to give that up, and you treat locally and continue. And that has allowed in EGFR mutant non-small cell lung cancer to be continuing treatment sometimes for extra years.

Your next question comes from Michael Yee with UBS.

Two-part question for Dr. Rudin. Maybe in thinking about the all-important first-line induction study, which obviously would be great to have, as well as the positive maintenance study you now have, can you just maybe comment about how we should think about the overall safety and AE profile of the triplet combination in first-line? And think about that, obviously, as why the maintenance study you're reading out here today makes a whole lot of sense? So I just wanted to think about the induction safety profile and maybe how relevant induction is if you already have a maintenance label. That's the first question.

And the second is, obviously, Dr. Rudin, you must be aware that there was also ADC PD-1 combo data for DLL3. That seemed quite attractive, safe, very high response rates. Maybe you could just comment about that, because I do think Amgen is doing a combination with ADCs as well. So I just wanted to think about how ADCs fit into the mix.

Yes, 2 great questions. So first, the first-line induction. This -- one of the basic fundamental rules in oncology is you give your best drug first. And this is one of the best drugs, if not the best drug, that we have for this disease. So we really want to push it into the first-line setting. As Jean-Charles said, we want all patients to be able to benefit from this.

The safety data with the IO-IO combination that was used in maintenance in this study really supports that we're not going to see additional toxicity. I think if we were going to see major tox signal, it would be because of the combination of 2, if you will, inflammatory molecules. So of course, the proof is in the pudding, we'll need to see that. But the initial data that we've seen in the first-line setting has been reassuring in that context, and we'll see how that plays out. But I actually think the data we saw today helps to reinforce that this should be a safe combination.

You're right, there's a lot of exciting data with the ADCs and ADCs in combination with PD-1s and PD-L1s in small cell lung cancer and really across the board in oncology. I think that is an exciting area and something to build on. Some of the ADCs do seem to have a higher response rate in recurrent disease than any standard chemotherapy, and there's a lot of interest in pushing those into the first-line regimen. And I think IMDELLTRA can be an important backbone for those studies.

Yes, I would just add to that, that we rejoice when innovation is made available to small cell lung cancer patients. ADCs are a sophisticated and elegant way to deliver chemotherapy at the door of the cancer cells. They debulk. We have demonstrated that debulking with chemo followed by IMDELLTRA-PD-L1 works. But we are also contemplating doing that with chemo induction.

That absolutely can be done also, in our opinion, with ADCs, with IMDELLTRA and PD-L1, that will lead you to a regimen that is pretty innovative. And we are excited and actively enrolling in our DLL3 ADC-IMDELLTRA combo and the B7-H3 ADC-IMDELLTRA combo, and a few more to come.

Your next question comes from the line of Geoff Meacham with Citigroup.

This is Jarwei on for Geoff. Maybe just 2 questions for us. I guess, first of all, on the earlier question on IMDELLTRA's treatment duration, I guess, could there be any evidence, whether it be now or later on, that can support a finite course that preserves benefit while reducing burden in capacity requirements and costs?

And then also maybe just thinking about commercial expansion, I guess, what lessons from the high number of treated patients and existing community footprint are most relevant as IMDELLTRA expands in the first-line maintenance? And where do you still see the greatest access or capacity constraints?

Jarwei, I apologize, but we're having a little trouble picking that question up. If you wouldn't mind just repeating for us. Because we think we're picking up static on the long-distance line here.

Oh, sure. How about now? Can you hear me clearly?

Yes. Just maybe briefly first question and then briefly second question. I think we got some of it.

Okay. Sure, yes. Just first question, basically, any evidence that could support a finite course of treatment while preserving benefit and reducing burden in capacity requirements and costs? And the second question was more on lessons learned so far, IMDELLTRA treatment, that could be helpful as you move IMDELLTRA into first-line maintenance. And where do you still see the greatest access or capacity constraints?

Okay. Thank you for that question. I mean when you have an unforgiving disease that comes with a diagnosis in January when you can tell half of the patients that they won't be there at Christmas, it's hard to imagine withholding continuous treatment which is efficacious and well tolerated for this type of patients.

Great. Kave, do you want to handle the market question?

Yes. So look, in terms of the market, whenever you've got a drug that delivers profound efficacy and improvement in the safety profile in an earlier line of therapy, you're really going to see an acceleration of behavior change across the market. And we're incredibly excited about these data sets in the frontline setting for small cell lung cancer. The best analog I've got from my experience here is 2 years ago at ASH when we released the COG 1731 data on pediatric ALL, and you saw a rapid adoption in the marketplace of that data.

So taking the profound efficacy that we've already done, we've also seen an ease of access coming from that reduced monitoring requirement. So as you know, we started with 22 to 24-hour monitoring. Recently in the U.S., we've gotten down to 6 to 8-hour monitoring. In this study, we worked down to 1 to 2-hour monitoring. That is going to enable additional sites to activate to be able to treat patients with this medicine in the frontline setting. But it's also going to increase the capacity at sites that are already activated being able to handle the increase in patient caseload overall.

So the combination of those factors should really add to the benefit. Of course, we're also adding to the profile with the extended dosing, as Jean-Charles referred to in DeLLphi-309, an ongoing investigation with subcu therapy, which will continue to ease the accessibility of the medicine in the U.S. and across the world.

Your next question comes from the line of Jay Olson with Oppenheimer.

Congrats on these impressive results, and thanks for hosting this event. Any preliminary thoughts on resistance mechanisms to IMDELLTRA? And do you think IMDELLTRA-resistant or refractory patients could still respond to other DLL3 targeted therapies?

And then related to that, according to your analysis, are there any patient subgroups that may achieve better OS benefits with IMDELLTRA? And specifically, would DLL3-positive patients maybe have prolonged survival?

I'll ask Dr. Rudin to address those 2.

Yes. We're still learning about resistance, and there's emerging data. I would say at this point, it's anecdotal. Multiple mechanisms of potential acquired resistance to this class of drugs. One would be down-regulation of target, and that has been seen. Another is actually, on the host side, an alteration in the T cells that are actually being stimulated. There's at least 1 case where a progressing lesion was biopsied and it was shown to be mostly actually suppressor T cells as opposed to cytolytic T cells in that lesion.

I think that actually tells us about the benefit of stereotactic radiation to a progressing lesion. The reason for resistance in oligoprogression may be more on the host side than actually the tumor. We're still learning about this, it's an active area of investigation, is I think the best I can say.

What was the subgroup...

Is there any subgroup that had prolonged [ days ]?

The subgroup analysis that was done in this trial, and you have the slide, there's really no subgroup that shows a lack of benefit. It's really across the board.

Your next question comes from the line of Terence Flynn with Morgan Stanley.

Great. Congrats on all the progress with IMDELLTRA. So a 2-part question. I guess you alluded to this, but maybe just any time frame for moving into some of these other tumor types that you alluded to during your prepared remarks and when we might see some data there beyond small cell lung cancer?

And then the other question is just, obviously, this has proven out the BiTE platform on the solid tumor side. So maybe just remind us the broader scope of your efforts here to keep moving forward with additional BiTEs in solid tumors.

Thanks, Terence. I'll ask Jean-Charles to address those 2 questions.

We have already reported activity of IMDELLTRA in prostate neuroendocrine carcinoma. We have an ongoing Phase II trial with the French collaborative group in Europe actively recruiting in neuroendocrine carcinomas of the lung. We are planning other studies in neuroendocrine carcinomas of the GI, of the lung, but also in other DLL3-expressing tumor types. I think there is more than 50 published case reports. But I might ask Dr. Rudin, who certainly has treated non -- DLL3-positive patients outside small cell lung cancer to maybe comment what has been his experience.

Yes. I mean DLL3-positive tumors tend to be the high-grade neuroendocrine tumors. And there are many of these. In the prostate world, this is certainly a mechanism of acquired resistance that we're seeing increasingly frequently now. We also see high-grade neuroendocrine tumors in the bladder and other sites.

Other tumors that express DLL3 include melanoma, which would be another indication. Some of the gliomas and brain tumors actually expressed a decent level of DLL3. And a rare but important population is pediatric patients with neuroblastoma. This is a real unmet need, and we have seen good expression there and preclinical data really suggesting efficacy in targeting DLL3. So those are some of the diseases we could go after.

Christa, perhaps a penultimate question here as we come up close to the half-hour?

Certainly. Your next question comes from the line of Gregory Renza with Truist Securities.

Congratulations on the compelling data. As alluded to earlier, there are several DLL3 T-cell engagers that are coming online, including trispecifics, several global assets. I just wanted to comment, from apart from being first and certainly having this very meaningful data today, what does make IMDELLTRA just structurally different? What do you highlight as the competitive differentiation more structurally when it comes to your asset versus the others that are coming?

DLL3 is an exquisite target. It's very unique in the sense that it's expressed at the surface of cancer cells and it's intracellular in normal cells. That gives you a very clean and unique target that is universally spread in small cell lung cancer and neuroendocrine tumors.

Our T-cell engager has demonstrated indisputable activity across all endpoints analyzed in 2 consecutive Phase III trials. We are very excited by that. It's not just being first, it's that the magnitude of the benefit that is observed is establishing this as the standard of care in second-line and beyond, and now in first-line maintenance. So other assets will need to benchmark against this DLL3 T-cell engager with survivors that have been significantly [ strengthened ].

And potentially in multiple types of combinations and multiple settings.

Absolutely.

Maybe our last question, Christa, please.

Your next question comes from the line of Gary Nachman with Canaccord Genuity.

This is Arsalan Kamran on for Gary Nachman. Congrats on the data. Our questions are, how does management think about the balance between internal development and external BD in oncology specifically? And given the T-cell engager franchise, which modalities or mechanisms, what they're most likely to bring in, if at all? And what stage of development would be the focus?

Well, it's an exciting question to land on. Obviously, we have a very strong oncology team, both in discovery research and under Jean-Charles' leadership in clinical development. And it's important when you have a world-class team like that, that they remain busy. And so we have a great internal pipeline of exciting assets, and we continue to be active looking at best-in-class or first-in-class potential medicines in the outside of Amgen. We continue to maintain a disciplined approach to capital allocation and business development.

And so at this point in time, when you sit at a meeting like ESMO here in Madrid and you look at the substrate of innovation that is happening in small cell and beyond, it's clear that this is a renaissance, if you will, in cancer drug discovery and research, and it's exciting. And given the capabilities at Amgen, it's a really, really exciting place to be.

So as we look at the future, we're also looking at the present. And it's our job now to take these data that have been presented and shared here at the meeting. Among other data, Dr. Rudin also presented an extension and follow-up on the 304 data. We have the 303 extension. So the full suite of evidence behind tarlatamab really demonstrates that this is a cornerstone therapy, foundational to the treatment of small cell lung cancer now. And I think it's fair to say that the quality and consistency and magnitude of the treatment effect size here even exceeded our very ambitious aspirations for these trials.

So it's our job now to translate that into clinical change. As such, we've mobilized our medical teams and made sure that NCCN guidelines committees have these data and aware of it, making sure that we file rapidly with the FDA, making sure that, as we launch the second-line indication globally, we prepare for the addition of frontline maintenance. So seriously exciting times here, but most importantly, exciting to be able to bring hope to these patients with this very, very difficult diagnosis.

With that, Christa, thank you for the Q&A session. Thank you all for attending. We'll close it out here, and we look forward to engaging with all of you over the next weeks and months. From Madrid, it's good night.

Ladies and gentlemen, this does conclude our investor call from the European Society for Medical Oncology Congress 2026. You may now disconnect.

All right. Thanks for joining us, everybody. I'm Terence Flynn, Morgan Stanley's U.S. biopharma analyst. For important disclosures, please see Morgan Stanley's research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. Very pleased to be hosting Amgen this afternoon.

I'm going to turn it over to the company's new CFO, Thomas Dittrich, who's going to make some opening remarks, and then we'll launch into Q&A with the rest of the team. But thank you, everyone, for being here.

Terence, thank you so much, and it's really good to be here. Before we get into Q&A, I'd like to take some time to share a few -- to introduce myself and share a few thoughts on how we see the business today. As many of you know, this is my second chapter at Amgen. I spent nearly a decade here earlier in my career and worked with Bob and the rest of the Amgen team back then. And since leaving, I've had the opportunity to serve as CFO of 3 publicly listed companies, where my remit expanded beyond finance, traditional finance to strategy, transformation and operations. And I gained experience also in a more consumer oriented health care environment and before that, actually in a rare disease environment.

So I come back to Amgen, knowing the company well, but also looking at through fresh eyes, informed by my experiences over the last 12 years. Also given my recent background with a private equity-led IPO of a fast-growing company in a more consumer-focused health care environment. My focus will be on working together with my fabulous colleague, Amgen, as one team, driving execution and financial discipline to enable growth acceleration commercially as well as of the pipeline. And I'll focus on cash-on-cash returns, which is very consistent with Amgen's long-standing approach to capital allocation.

On to the second quarter, our second quarter results were really driven by the breadth and depth of the portfolio and once again demonstrated our ability to grow through patent expirations and increased competition. Our 6 growth drivers, Repatha, EVENITY, TEZSPIRE, our rare disease portfolio, innovative oncology and biosimilar portfolios really delivered. Together, they grew 26% year-on-year in the quarter, and represented nearly 70% of second quarter product sales. Overall, in the quarter, total revenues exceeded USD 10 billion, up 10% year-on-year and 22 products delivered double-digit sales growth. So these results, including strong margin and earnings performance were achieved while we increased the investment in innovation, reflecting the really solid financial structure that Amgen has.

Many of our -- and here's the point many of our medicines address large, underpenetrated disease areas, and that gives us confidence that there are significant opportunities ahead to reach many more patients as we move forward. And we're adding new indications to some of our products like TEZSPIRE, UPLIZNA and IMDELLTRA, while also broadening our geographic reach for those and other medicines. And we have recently announced exciting Phase III results from 2 of our approved medicines. First, we announced landmark Phase III results from DeLLphi-305, evaluating IMDELLTRA in combination with durvalumab as first-line maintenance treatment for patients with extensive stage small cell lung cancer.

The study demonstrated statistically significant and clinically meaningful improvement in overall survival, progression-free survival and objective response rate compared to durvalumab alone. We view these data as important inflection point for IMDELLTRA. As you know, in the first line setting, IMDELLTRA is already becoming a standard of care supported by strong survival benefit, clear clinical differentiation, NCCN recommendations and rapid adoption across sites of care. These landmark results from DeLLphi-305 suggest IMDELLTRA will further revolutionize the standard of survival earlier in the treatment journey and meaningfully shift the treatment paradigm for people facing this devastating disease. We're -- therefore, we are advancing IMDELLTRA through a broad Phase III program across first-line extensive stage and limited stage SCLC while also pursuing more convenient administration.

Together, these programs represent a combined addressable population of approximately 28,000 U.S. patients. Yesterday, we also announced that the FDA has approved an update to the IMDELLTRA label that substantially reduces the recommended monitoring time for the first 2 doses of treatment in an appropriate health care setting. What does this mean? This means the patients receiving IMDELLTRA should now be monitored for 6 to 8 hours from the start of the first 2 doses compared with the previously recommended 22 to 24 hours, an important step in simplifying care for people living with and treating extensive stage small cell lung cancer.

We believe IMDELLTRA has the potential to become a foundational medicine across the small cell lung cancer continuum and will continue to be an important growth driver for our innovative oncology portfolio. We also recently announced positive top line results from the Phase III study of TEZSPIRE in people living with eosinophilic esophagitis, EoE, and positive Phase III data for TEPEZZA in Japanese patients with chronic thyroid eye disease. So beyond these programs, our late-stage pipeline is progressing well and provides additional opportunities for growth, and we are advancing MariTide, for instance, dazodalibep and xaluritamig in Phase III development.

All of those programs have the potential to address areas of significant unmet medical need and to drive long-term growth. We continue to develop olpasiran targeting Lp(a) for cardiovascular risk reduction. Recently, a competitor announced top line results from their Phase III program targeting Lp(a), raising many questions for the field. We look forward to seeing the detailed presentation of these data to better understand the potential implications for the field and to our ongoing clinical research with olpasiran.

Now moving on to our biosimilar portfolio. We are advancing a third wave of biosimilar candidates to KEYTRUDA, OPDIVO, OCREVUS and EYLEA HD. We recently completed a Phase III study of ABP 234, our biosimilar candidate to KEYTRUDA, which met both primary and secondary endpoints. The full results will support our planned regulatory submissions in the second half of this year. And for ABP 206, that's our biosimilar candidate to OPDIVO, our biologics license application with the FDA has been submitted and accepted for review.

There, we expect an FDA action on this BLA by the end of the year. So as we look ahead, our business continues to perform well. We're excited about the future and our ability to drive durable growth well into the next decade.

And with that, Terence, happy to take your questions.

Great. Looking forward to it. I guess the first place I want to start, I've been asking most companies this is just it seems like we're in a different place from a policy perspective versus last year. And so anything that the company is picking up coming out of D.C. as we head into midterm season that we should have on our radar screen?

Yes, Terence. I'll take that and then ask Jay or Thomas to add. Thus far, it's early days going into the midterms. Obviously, we don't know the outcomes of the midterms yet. There's a lot of conversations going on in D.C. around reimbursement, pricing, 340B is a particularly hot topic at the moment and just generally value of innovation. We're also seeing a pickup in policy work outside the U.S. as countries around the world respond to some of the policies from last year when we were with you. So we stand ready to engage with both sides of the aisles on each of these matters.

Our focus is trying to make sure medicines remain accessible and affordable and that there continues to be a good environment for innovation and as a U.S. domiciled company with a hefty U.S.-domiciled manufacturing network continue to be incentives to manufacture in the U.S. But beyond that, too early to tell given what's coming up in about 60 days now.

Okay. And then the kind of related question is 340B, I know, has been a tailwind for a number of companies in 2Q, and there's this pilot that's going in place in January. So how should we think about that heading into 2027 as a potential tailwind to the business?

Yes. I'm going to take that in 2 parts. So generally, on the macro side of 340B, we still see that program with substantial growth. And if you look at last year, there were $100 billion of purchases in the program, $80 billion of incremental discounts across the board, grew 23%. That's the fourth straight year of 20 -- over 20% year-over-year growth. Program has tripled in size since 2020. That's driven by this, kind of, lack of meaningful safeguards within the program that allow hospitals to buy at very low government prices and then resell to insurers, employers, patients, everyone in this room at a substantial markup. Without reform of the core program, we don't see that incentive really changing or the dynamics changing on that overall growth.

Now within that program, and I've been around it for 20 years, you do see from time to time quarter-to-quarter variability, year-to-year variability along those. There was some buying patterns that we had detected early -- late last year when enforcement looked like it was picking up that hasn't really materialized. So we're not in a position to call it going forward other than to say reform needed and without reform, you could expect that growth rate from a macro standpoint to largely go unchecked.

In terms of the pilot, the pilot, there's a rebate model specific for MFP drugs, drugs "negotiated by Medicare." That will help one of our medicines going forward, potentially Enbrel and in the future, Otezla considering it was negotiated last year. But too early to tell at this point, Terence, on exactly what it means outside of those particular products.

Okay, great. Maybe Thomas, over to you. I guess, whenever you have a new CFO in the role, it's interesting to hear about perspectives on setting guidance. Obviously, one of the more important roles. And so as you think about that, anything you can say at this point about your approach to setting guidance versus maybe past?

Yes. I think our philosophy will remain consistent here. It's basically about giving a realistic view of the business, knowing the headwinds, tailwinds and getting that out there and also the investments we are making to achieve our value creation outcomes over time. And then clearly, from a maybe style standpoint or philosophical standpoint, setting guidance, Terence, is always about promise and deliver, and I think that will stay true to that one as well.

Okay. And I think you addressed this in your prepared remarks, but just capital deployment, what's the, kind of, latest strategy there? And then any insights on, kind of, the current market dynamics?

Yes. On capital deployment, our strategy or hierarchy is very clear. It's about really, number one, funding innovation; and then number two, funding the business to bring that innovation to as many patients as possible. That means commercial investments, that also means investments in manufacturing footprint, all of those things. And then on the innovation side, we are pretty agnostic. It's about best innovation, be it inside the company or outside the company.

And then when it's outside the company, clearly, the priority is, is it on target? Is it part of our therapeutic areas? Is it really the best possible science here. Are we the best owner? And then do we have -- do we see positive cash-on-cash returns over time, risk-adjusted, we'll prosecute that very hard. And then clearly, can we integrate anything we would buy rapidly to go into value creation mode quickly.

Okay. Great. Maybe, Jay, we'll pivot over to you. I want to talk about Lp(a). But before we go there, I think the next upcoming pipeline read on the late-stage side is dazo for Sjögren's. So maybe just talk to us about the -- what success looks like in these 2 trials. And then probably the related question might be more for Casey is just disclosure plans around the data.

Yes. Thank you. dazodalibep is a CD40 ligand targeted complex biotherapeutic that we're developing presently in lead indication of Sjögren's disease. This is an area of huge unmet need. It's actually a relatively common autoimmune condition, and there's been very little innovation in this disease until recently. The CD40 hypothesis is strong biologically, and it's supported further still by very compelling Phase II proof-of-concept data with dazodalibep that included patients both in the systemic as well as in this more symptomatic or local stage of disease.

Building upon these findings, we started 2 Phase III clinical trials that are quite brilliant in their design. They segregate the symptomatic and the systemic disease populations, applying different and more focused scores to each on a regulatory paradigm. These 2 studies will read out in the second half of this year, which we are in. And so we're very much looking forward to seeing these data and then reporting them out. It's a humbling thing to develop in Sjögren's disease. There have been a lot of failures, but the support of proof-of-concept data, both on the receptor side and on the ligand side from our company and a competitor are a good setup for these trials.

And what we're hoping to achieve with these studies is both a statistically significant and clinically meaningful benefit to patients, in particular, around the symptoms that they experience that are keeping them from their activities of daily life. So more to follow on the completion of those studies later this year.

And then, Casey, anything in terms of just like disclosure because the question we get a lot is just do they come together? Do they come separately? Are they close trials close enough to read them out together?

Yes. Terence, in terms of disclosure, we try not to predefine how and when we'll disclose. So as Jay said, the studies are on track to read out second half of this year, and we'll have more to say once we have data in hand.

Okay. And then, Jay, you mentioned it. I mean, there have been a lot of failures, I think high placebo responses have been one issue historically. So just anything that you guys have done here versus maybe some prior trials that maybe had run into that issue?

Yes, placebo responses in autoimmune conditions are challenging, in particular, where they're being scored by endpoints that aren't quite as hard as like RECIST criteria on a CAT scan measured in millimeters. And in these multiparametric questionnaires, ESSPRI, ESSDAI, DASPRI, there is always that chance. And so to mitigate that, we power up the study to success.

We segregate the 2 populations with bespoke scores for each that define the integrated Sjögren's disease experience. And we run the studies out just a little bit longer. These studies will run 48 weeks readouts, and we hope that all 3 of these measures will sharpen up placebo response, giving us an even better chance to quantify a potential benefit of dazodalibep.

And any early read if you think you could file on just one positive study. Obviously, you said you segmented the population. So there's, kind of, 2 different groups here. So let's say, again, pick which one of them, there's one positive one, one negative trial. Would that be enough to file on in just a single study, do you think?

We're not operating against a predefined regulatory strategy. A lot depends, as Casey said, by the -- by what we see in the data. And so we'll have more to share on that when we see the data.

Okay. Got it. Okay. Now I want to go over to olpasiran. And again, Thomas addressed some of this in his opening remarks. So I think I know the answer to some of these, but I figured I'd ask them anyway. So obviously, we need to see more data from Novartis. But before we see that, just remind us of, kind of, the key differences in terms of your asset, but also the trial design and then what you'll be looking for in the Novartis data to either give you more confidence or less confidence in those features of your drug and your trial to -- that we should all look to when we see the data, assuming AHA in November.

Sure. olpasiran is a small interfering RNA that targets Lp(a), which is a genetically defined cardiovascular risk factor. And that risk for cardiovascular disease increases with increased Lp(a) in populations. 1 in 5 of us here today has Lp(a). So get yours checked. It's now part of the lipid guidelines to do so and know your risk and modify your risk around Lp(a) for sure. These are facts that aren't influenced by the Novartis readout of late.

Olpasiran is a very powerful medicine. It has about a 95% reduction of Lp(a), 95% to 99% compared to compared to pelacarsen, which was more like 70% to 80% in various clinical studies. This medicine is also given quarterly, which is a potential advantage of the medicine. Our clinical trials are a little bit different. We targeted a higher index Lp(a) measure, 200 nmol/L versus 150 on that study. And we chose a different endpoint rather than a 4-point MACE endpoint that includes stroke, we focused on the 3-point MACE endpoint as our epidemiology analysis did not see stroke as a strong driver of outcomes mapping to Lp(a).

With that said, the Novartis data caught our attention. We had going into their data readout, a predefined set of actions. And we're not just waiting to see what the data actually are. All that's been communicated to date is missing the primary endpoint in the overall study population. That can mean a lot of things. And so we'll go into AHA, where we presume also these data will be presented. And like many in the community will be interested to dissect several parameters. It's a long list, by the way, and so I don't want to consume the rest of our time together. But these large cardiovascular outcome trials afford a possibility to really go deep into a statistical hierarchy if you hit the primary, which they apparently did not.

So we're going to take directional descriptive guidance from things like response to the medicine, a graded response to the endpoint based on the index Lp(a), the admixture of LDL-C control, which has been improving, thanks to Kave's work in Repatha in the broader community as well as predefined subsets of patient populations. A lot of people are interested in ASOs versus siRNAs as a general theme, and we are as well, intending to be a real contributor to this pharmacology.

I'm interested to know how that medicine was tolerated as an ASO with respect to local active site injection, systemic responses and maybe also how they navigated COVID, which was tricky for cardiovascular outcome trials. So there's just a lot to learn from that study, and we just haven't learned it yet.

Yes. You mentioned one of the things that was a question, I think, going into the trial is just background treatment. Obviously, that has improved significantly, thanks to Repatha, also GLP-1s. Is that an area that you think could have influenced it? And are there any differences in terms of your population versus their population high level that you think could also be another factor we need to think about?

I won't speak too much to the differences in populations. There's a lot we've not shared for competitive reasons about the parameters of the patients that we've enrolled on the study. But I do hope that the reason -- one of the driving reasons that the event rates are a little bit lower is improving background care. I will say that our real-world evidence would suggest that we still have a very long way to go even with the tools that we have like PCSK9 inhibitors like evolocumab or Repatha in order to really read drug efficacy through to broad population drug effectiveness.

But LDL-C will be an interesting and important parameter to look at as these 2 biologies, both inflammatory lipoparticles are converging on the same endothelial and vascular smooth muscle pathways of inflammation and atherogenesis.

Okay. Maybe just one for Kave just on the treatment -- importance of treatment guidelines in cardiovascular disease. So again, let's say, olpasiran has positive data 2028. What does it mean from a guideline perspective? Like what's going to be need for guidelines to really, kind of, move the needle? Jay mentioned increasing testing on Lp(a). But how important are guidelines? What have you guys learned from, kind of, the Repatha situation?

Yes. So I think when it comes to guidelines, especially in cardiology, they're obviously quite important. I'd say specifically more recently for Repatha, not only were the guidelines important for an update, even though they did not yet include VESALIUS, but the adoption by the primary care community of those same guidelines, I think it's been a major driver of better LDL-C control more recently overall. In terms of the guidelines for Lp(a), look, it's really hard to predict the time line of guideline updates in cardiovascular disease. I think it was 7 or 8 years between guideline updates this last time.

We were excited to see that Lp(a) testing was in these guidelines, obviously, pending readout of trial. But after the fact, it may be several years before guidelines are updated. I will say there is a different behavior when a patient gets a high Lp(a) than a high LDL-C. With that high Lp(a), given how infrequently it's tested and just seeing that it's a genetic disease, we do see patients much more open to really managing cholesterol in a major way.

And so we do see an activation pathway through its normal risk going into the LDL pathway. That's different than with a high LDL-C where we see patients obviously often try to diet, exercise, and take minimal statins in order to get their LDL down. So different patient population may ultimately yield something. Again, we have to wait and see what we see from the pelacarsen data to understand what it could mean going forward though.

Okay. Got it. Maybe just going over to another cardiometabolic pipeline asset, which again is, I think, going to increasingly be front and center here as we go into '27, is MariTide. Maybe, Jay, you could just remind us, kind of, the target profile here that you're aiming for with these large Phase III trials that you're rolling out. And it sounds like enrollment has been going pretty good, pretty good.

Enrollment to the MariTide Phase III program has been outstanding. We've recently completed enrollment end of August, I believe, Casey, of our obstructive sleep apnea studies. And this is a sweeping set of, in the fullness of time, a dozen Phase III clinical trials that will establish MariTide, we believe, as an important medicine for the treatment of obesity and its most core morbid conditions. And in studying these diseases in one parallel approach, we are starting to get a shape of the rising target product profile. And in a field that has had a lot of innovation and a lot of, I would say, redundant innovation around weekly injectables, MariTide starts to emerge as a bit of a singularity, a medicine that because of its monoclonal antibody background is by design, built to be monthly or less frequently dosed.

This is very important when we think about persistence. There's now more Americans who've taken a GLP-1 and no longer take it, than are on it right now. Why is that? Why do half of patients stop this medicine, -- these helpful weekly medicines at a calendar year? And we've been working to really understand this out in the community and Kave and other, Susan Sweeney, have led this effort. And a lot of it comes down to challenges associated with weekly injectables, symptoms associated with the week injectable, access and durable access to the medicine. Because of the monoclonal antibody backbone, we expect MariTide to be an optimal medicine to start on, if it's your first GLP-1-based medicine and then stay on for the long haul as well as to switch from a weekly injectable or an oral that can also not be very well tolerated or as efficacious to switch and then stay on MariTide.

And the Phase III program will create these data. We've reported the activity of MariTide on an every 8-week administration basis. And we've also shared the insight that on every 12-week basis, MariTide with more of a maintenance mindset is also quite active. When you couple this with outstanding tolerability at target dosing, the target pilot profile of MariTide starts to be really unique. Now you might know that the GLP-1 injectables grew up as twice-a-day medicines and then chemistry achieved once-a-day medicines and miracles of chemistry achieved ultra-long-acting weekly medicines.

And this medicine, owing to its flexibility and dosing schedule, will be very appealing to patients, very appealing to providers and potentially the payers as well. So it's our work now to focus on the execution of the broad Phase III program and turn in outstanding data, which won't be this calendar year on the Phase III program, but we'll have more to say about that in the new year.

And just remind us on the -- I know you guys have done a lot of work on the titration steps to, kind of, minimize the GI tolerability that you see with the GLP-1 axis. So -- where are we on that journey now? And do you ultimately think you'll end up in a place that the rates look very similar to what you see with Zepbound, for example?

Yes. Thank you. It turns out for MariTide, just like all the GLP-1 medicines, whether they're injectable or oral, that the index dosing, the initiation of therapy benefits from dose escalation over a period of time. And through a series of Phase I and Phase II clinical trials, we prepared the data necessary to establish the right dose and schedule for what's for MariTide, a 3-step dose escalation to target dosing that takes 2 months to complete from 21 to 35 to 70 milligrams. Curiously, once a patient has had 70 milligrams, they are attenuated to the GI or other side effects of MariTide largely such that you can go right to target dosing, even if it's 350 milligrams owing to a need for substantial weight loss.

And then that turned out to be quite unique. So we will see in our Phase III program if these Phase I learnings read through to competitive tolerability, which we expect. Importantly, at target dose, we think MariTide can be quite differentiating. We more and more hear about day of injection, nausea and vomiting and challenges associated with the weekly injectables and the orals even.

And here, MariTide owing to its very smooth pharmacokinetics that the antibody just, kind of, hangs out in the bloodstream, not hitting the area postrema with GLP-1 agonism with every excursion from trough to peak in Cmax, target dosing with MariTide is remarkably well tolerated. So we'll have more to say on that when we see the Phase III data, but we expect a competitive profile.

Great. And maybe just last one is the -- Pfizer is working on a monthly program as well. Again, maybe just talk to us about anything that struck you at ADA about their profile versus what you see for MariTide and differentiation because I think a lot of investors are doing these cross-trial comparisons side-by-side, like who's going to have more share in the monthly market. The time lines are pretty similar. So as you look across that long-acting program, what are some of the key features that you think give MariTide a leg up?

Well, Pfizer and others are performing a lot of the standard -- I'm a discovery chemist, are performing a lot of the standard discovery chemistry moves to make what are really short-lived biomolecules longer lived. Adding a lipid can lead to association with albumin, stays around the bloodstream just a little bit longer. Various formulations and gel formulations, of course, have used in the past. And these may lead to tolerability over 1 month. But I do believe that it will be hard for them to measure up as an efficacy endpoint. We'll see as the data reads out, and it's always hard with cross-trial comparisons.

But I know that some of these companies, including Pfizer, are studying those very medicines with weekly dosing. We have no weekly study of MariTide. In fact, we're moving more towards every 8 and every 12-week dosing through our ongoing maintenance and switching studies. So I do believe that there's just nothing like MariTide from a durable efficacy and durability of effect today in late-stage clinical development.

Yes. Okay. Great. Maybe, Kave, I would just go to you, just high level. This market has been front and center, I think, for the last several years in the biopharma sector. And I think estimates -- our estimate is $190 billion. Just what's the company's, kind of, high-level go-to-market strategy? We've seen the rise of the DTC channel here. You guys have leveraged your own DTC offerings for some of your other products. So maybe just talk to us about how you guys lean into that. And then, Thomas, you mentioned, you had some consumer background as well. So maybe there's something you want to add as well to that conversation, but...

Yes. So no, thanks, Terence. I think last year, we announced our AmgenNow program for Repatha. That was our first direct-to-consumer program. We now have, I believe, 4 or 5 medicines within it. It has served 20,000 patients over the last year, 18,000 of those are Repatha patients, providing us early learnings of how to operate within that channel. Look, it's a huge category. I think there's almost 1 billion people on the planet that could benefit from these medicines. There are offerings -- good offerings today that are starting to penetrate that. Over time, we see that market fragmenting into separate submarkets.

We think MariTide can play both in the induction phase and importantly, in the maintenance phase, where we know, as I said earlier, more patients have started and stopped these medicines than are on them today. We look forward to bringing, kind of, some of the capabilities that we've built around Repatha and EVENITY, these very large markets where we're treating lots of patients to bring MariTide forward, building on those capabilities and going more into the traditional HCP setting, but also into the direct-to-consumer setting once we get there.

A lot of this will depend on the profile we see, and we'll see the totality of that profile will help us define where we play and which markets going forward. But Thomas has really good perspective here from his Galderma days specifically on the consumer side, do you want to add, Thomas?

Yes. As you said, it really depends on the profile. And I think Jay has characterized it really well what we're expecting there. When you then translate that to the more consumeristic side of the market, there is a real shift happening where patients no longer act as patients, but as active consumers and make a choice and maybe in this case, wear an Oura Ring, et cetera, they want to know about what their health status is and involve themselves in the choices. So that starts with how they consume data, how they use AI, that they go to social media in the previous place, we knew exactly before any treatment decisions have 5 visits to social media website.

So therefore, it's important that you're not only showing up branded, but also you drive unbranded awareness to satisfy people's information collection requirements. And then the path to treatment is also a different one, and you have to make it as smooth and simple as possible. And then these patients go and choose the treatment outlet, maybe Hims & Hers or whatever, or even centers, on that basis. And then the final point is these patients are commitment patients.

They make choices about their life, be it on the aesthetic side, but also about their health levels that they want to have for themselves and commit to that and stay on that for a longer term and are happy to pay cash with it. So you have to really treat them in that way, but what you get in return is a lot of stickiness from them. Really exciting area and couldn't be at a better place than Amgen at this point in time.

Great. Well, I think we're up against time. But thank you all so much. Really appreciate it.

Thank you.

Thank you.

Awesome. Thank you very much for joining us again today. My name is Mohit Bansal. I'm one of the biotech and pharma analysts here at Wells Fargo. And I have a pleasure to introduce the Amgen Management team with us today. So we have Thomas Dittrich, Chief Financial Officer of the company. We have Paul Burton, the Chief Medical Officer of the company. We have Kave, he's the SVP Global Marketing and Access. And Casey, you all know, he's the Head of IR at Amgen. Thank you very much team, Amgen, for joining us today. And I'll give the podium to Thomas for prepared remarks.

Thank you, Mohit. It's really good to be here. And before we get into Q&A, I'd like to take some time to introduce myself briefly and share a few thoughts on how we see the business today. As many of you know, it's actually my second chapter at Amgen. I spent nearly a decade here earlier in my career, working very closely with Bob and with the team at Amgen. And I've had the opportunity to serve, in the meanwhile while the way, as the CFO of 3 public listed companies where my responsibilities actually extended beyond finance into things like strategy, transformation, operations. And I gained quite some experience in a more consumer-focused health care environment as well.

So I come back to Amgen, knowing the company well, but at the same time, looking at it through fresh eyes informed by my experiences over the last 12 years. Also given my recent background with a private equity-led IPO of a fast-growing company in a more consumer-focused health care setting, my focus will be on working together with my fabulous colleagues at Amgen as one team, driving execution and financial discipline to enable growth acceleration, both commercially and of the pipeline. And I'll focus on cash-on-cash returns, which is very consistent with Amgen's long-standing approach to capital allocation. Now on Q2, our second quarter results were driven by the breadth and depth of our portfolio and once again demonstrated our ability to grow through patent expirations and increased competition.

Our 6 key growth drivers, Repatha, EVENITY, TEZSPIRE, rare disease in innovative oncology and the biosimilar portfolios continue to deliver. Together, they grew 26% year-on-year and represented nearly 70% of total second quarter product sales. Overall, in the quarter, total revenues exceeded $10 billion, up 10% year-on-year and 22 products delivered double-digit sales growth. And these results, including strong margin and earnings performance were achieved while increasing our investment in innovation, reflecting the sound financial structure that Amgen has as a business. And many of our medicines, and that's what's behind it here is many of our medicines address large, underpenetrated disease areas, giving us confidence that there are significant opportunities ahead of us to serve many more patients.

And we are adding new indications to some of our products like TEZSPIRE, UPLIZNA and IMDELLTRA, while also broadening our geographic reach with these medicines and others. And we have recently announced exciting Phase III results from 2 of our approved medicines. As you have seen earlier this week, we announced landmark Phase III results from DeLLphi-305, evaluating IMDELLTRA in combination with durvalumab as first-line maintenance treatment in patients with extensive stage small cell lung cancer. The study demonstrated statistically significant and clinically meaningful improvement in overall survival, progression-free survival and objective response rate compared with durvalumab alone. We view these data as important inflection point for IMDELTRA. In the second-line setting, IMDELTRA is becoming a standard of care supported by strong survival benefit, clinical differentiation, NCCN recommendations and rapid adoption across sites of treatment.

These landmark results from DeLLphi-305 suggest IMDELLTRA will further revolutionize the standard of survival earlier in the treatment journey and meaningfully shift the treatment paradigm for people facing this devastating disease. And that's why we are advancing IMDELLTRA through a broad Phase III program across first-line extensive stage and limited-stage SCLC while also pursuing more convenient administration. Together, these programs represent a combined addressable population of approximately 28,000 patients in the United States. We believe IMDELLTRA has the potential to become a foundational medicine across the small cell lung cancer continuum and will continue to be an important growth driver for our innovative oncology portfolio. We also recently announced positive top line results from the Phase III study of TEZSPIRE in people living with eosinophilic esophagitis EoE, a very challenging disease, as you know, which affects more than 470,000 people in the U.S.

And today, we are pleased at this point -- at this podium here, we are pleased to announce the Phase III chronic [indiscernible] study of TEPEZZA in Japanese patients with thyroid eye disease met both primary endpoints with no new safety findings observed. These results reinforce our efforts to reach more patients in Japan as we continue to broaden TEPEZZA's reach and footprint outside of the U.S. Beyond these programs, our late-stage pipeline is progressing well and provides additional opportunities for growth. We're advancing MariTide, dazodalibep and xaluritamig in Phase III development, and all of these programs have the potential to address areas of significant unmet medical need. and to drive long-term growth for us. We continue to develop olpasiran targeting Lp(a) for cardiovascular risk reduction.

Recently, as you have seen, a competitor announced top line results from their Phase III program targeting Lp(a), raising many questions for the field. And we look forward to seeing the detailed presentation of these data to better understand the potential implications for the field and for our ongoing clinical research with olpasiran. And now moving on to our biosimilar portfolio. We're advancing a third wave of biosimilar candidates to KEYTRUDA, OPDIVO, OCREVUS and EYLEA HD. We recently completed a Phase III study of ABP 234, our biosimilar candidate to KEYTRUDA, which met both primary and secondary endpoints.

These full results will support our planned regulatory submission in the second half of this year. Additionally, for ABP-206, our biosimilar candidate to Opdivo, our biologics license application with the FDA has been submitted and accepted for review. We expect an FDA action on that BLA by end of the year. So as we look ahead, the business continues to do well, and we're excited about the future and our ability to deliver growth -- durable growth well into the next decade. And with that, Mohit, we're happy to take your questions.

Thank you. Thank you very much for this. I have to ask this question. How is Amgen different in your second act versus the first act?

It's -- yes, Amgen is a very different company in the sense that it has grown significantly. It's more than twice the size. The portfolio has expanded significantly. It has much more depth and breadth, as I said earlier, compared to when I joined 20 years ago for the first time. But I'm also a different executive coming back. As I said earlier, I did other stuff, 3 companies. I was an interim CEO in one, the common thread there was all growth acceleration. So it's really good to come back and bring understanding of what the company is and what its core is, which I always had huge respect for, which is really driving innovation and driving science and then complement that with the experiences I've made elsewhere and bring that back home. It's good to be back.

Awesome. Good to have you back. So let's just start with the Lp(a) I'm sure like let's just get it out because that's a question I'm sure -- right? Even from a failed trial, we learned a lot. So what do you want to learn from the detailed data when they come out, whenever they come out? Like what as investors we should be focusing on when the data come out in terms of endpoints, in terms of patient selection, like what are you focused on.

Yes. So I can just start briefly. Look, as you say, and as Thomas said, we need to have a thorough review of the data. Hopefully, it will be presented, published. We'll get a lot more insight then. I think we need to see how the components of the primary endpoint, which is a 4-point primary endpoint fall out, what were the baseline characteristics, particularly in terms of Lp(a), what was the reduction. I think those are going to be the key things. Obviously, we're somewhat differentiated in our design mechanism of action and impact on Lp(a) lowering with olpasiran. But we'll learn a lot, and hopefully, we'll see the data very soon.

Got it. Very helpful. Now coming to IMDELLTRA, congrats on the data. But I mean, this is like -- this is an access/question of community physicians treating a lot of small cell lung cancer because it was like -- this is the disconnect we saw when you were approved in second line plus. that academic doctors love it, but then community centers -- they found it will be difficult. So how can you bridge that gap? And what can you do to make sure that it gets adopted more widely?

Yes. It's a great question, Mohit. And look, I'm really proud of the work that we've done with IMDELLTRA, again, to Thomas' point, really revolutionizing the standard of survival in small cell lung cancer. I got the opportunity to meet one of our early clinical trial patients when I was in Europe over the summer who's been on a survival curve of greater than 5 years now, which is just absolutely incredible. When we look at the U.S., while there was a lot of talk in advance of the challenge potentially for community, we actually see very good community adoption of IMDELLTRA thus far. We've got over 2,000 sites that are using the product actively today. Now one of the remaining barriers to access in the community setting is the label currently identifies that we've required 22 hours of monitoring on the first 2 doses, which often is dealt with in a partnership with a local hospital to initiate therapy.

We're really proud that in Europe, we've already achieved a 6- to 8-hour monitoring requirement, a significant reduction. And in the U.S., we filed and have a PDUFA date for a similar 6- to 8-hour monitoring reduction, which will continue to help that community physician process more and more patients. But importantly, when we look to DeLLphi-305 and the frontline maintenance data that we just announced, very importantly, in that study in the U.S. setting, monitoring was reduced to 1 to 2 hours overall. And so we are looking to expand on that great basis of overall survival use across all sites, but the reduced monitoring requirement will help that community even more going forward, especially as the patient population significantly expands to the 28,000 a year that Thomas mentioned in the frontline setting.

Got it. Very helpful. The other part I want to really focus on is the rare disease program. So you have found a lot of success with the rare disease assets. I mean some of them you got from Horizon acquisition. The trial that is reading out fairly soon is Sjogren's trial. So talk a little bit about your approach there. It has been a difficult disease, so what should be our expectation? And you have 2 different types of trials there. So just talk a little bit about that.

Yes, I can start and Kave maybe add some color. Sjogren's disease, 350,000 patients in the United States. We know it's an autoimmune B cell-driven disease. cardinal features or attack of the tear glands or lacrimal glands and the salivary glands debilitating features. Now about 30% to 40% of patients outside of the tear and salivary glands have systemic features. So the kidney is involved, the lung is involved. And somewhere between 60% and 85% of patients are symptomatic, okay? So those are the 2 populations, systemic and symptomatic. We have published data on a Phase II trial where we looked at both of those populations, and we saw clinically important statistically significant reductions in both of the endpoints.

For systemic patients, it's the SDAI, DAI. And for the symptomatic patients, it's a reduction in SPRE [indiscernible]. And so we now have these 2 Phase III studies that are ongoing that would test both of those populations. And I think patients and physicians will want to see reduction in those 2 types of endpoints. And we have our Phase II data that we've built this program on. And so we remain optimistic that we'll get a positive clinical outcome.

Is there a reason to believe one trial has a better shot versus other?

We saw -- as I said, we saw benefit in both populations in the Phase II study. Biomarkers were reduced as well. There's a publication in Nature Medicine that talks about that. So as you said at the start, this is a high unmet medical need, very few effective therapies today, debilitating disease. So we're excited about this medicine and the benefit it could; have here.

Got it. And then do you think you have to be successful in both trials here? Or why is it?

No, I think they can probably stand on their own. And so as you say, we'll have the data in the coming months and we'll be able to go from there.

Exciting times.

Exciting times.

Right. So going back to you, Thomas. So the question, like I think -- like a broken record, I ask this question, and like I know the answer already. Amgen takes the margins very seriously. That's the answer. But I mean like you have been sitting at a very good margin profile, like 48% in second quarter of 2026, but then there's a lot of investment coming and then there's a little bit of like LOE period as well with some of the assets. So we would love to understand how do you balance the investments and those things, I mean, investments and pipeline. And the related question is, do you think you have enough in the pipeline? And do you think like -- you want to add more at this point?

Okay. Well, that's 2 questions, but let's take them one by one. There is an umbrella answer across both of them. And that is at a high level, we see significant opportunity across our 6 key growth drivers to drive growth forward and on our pipeline that we already have. So we are busy, and we see a lot of potential to grow. So on the first question is, so how do you now get that growth and that value creation going? And their margins do matter. I mean margins matter to us because they matter to you, our owners, our investors. Now we are committed and have worked really hard before my time to become a top-tier margin company, and we are committed to remaining one. Now at the same time, and that comes to your trade-off question here is we would be prepared to flex margins slightly downwards as we have done from the peaks that it was up in the 50s or so, if we see real opportunities to invest behind drivers that create long-term value. And when we say value, it's cash-on-cash returns, right, really hard value.

So there, we would do that and trade that off against growth and value creation going forward. And look, this year is even a very good example. We're guiding to roughly 45% to 46% non-GAAP operating margin while doing all those investments. And what's the missing link in here or the key thing to focus on is actually productivity. It's productivity through process streamlining. Yes, of course, systems, AI very strongly to free up funds over here, but you can invest them over there to drive growth, to drive value creation and not have an either/or. It's actually an and.

And then on the second part of your question, pipeline, yes, of course, the pipeline can always be full and even fuller. But honestly, here, when you look at it, what we have, we have a lot to work on. If you look at my prepared remarks earlier, I lined up a few for you. So that allows us to maintain a high bar for external innovation, and we have very clear criteria on those. I can walk you through what those are, but they are the same that we had before. And when an asset comes around that we feel meets those criteria, then we would go after it, but it's not something we need to do to fill a gap here, I say.

Got it. I mean this is your chance, Paul, to ask a CFO, do you have enough pipeline or do you need more?

We always need more funding. Yes. Look, we do have an amazing pipeline. We have amazing in-line medicines. We help millions of patients a year around the world. I think we have great sustainable growth for the remainder of this decade and into next decade as well.

Okay. Very helpful. And Paul -- sorry, Thomas, you mentioned that you are willing to flex the margin if you have growth profile -- if you have good opportunities. So at 45%, 46%, do you think you are at the low end of that range that you want to be or...

Yes. As I said, we are committed to remaining a top-tier margin company, and we have so many levers to pull. So I mean, we give guidance annually, 45% to 46% is the guidance we have for this year. And we are very, very careful because margins are a surrogate as close as you get to a cash equivalent. So we are very thoughtful of it. It matters to you. It matters to us. But we are not chasing the percentage per se, which would also be a problem because you know companies that chase margin percentages and then sacrifice growth and value creation stop. So we're doing both. We're conscious around it.

Completely makes sense. Kave, so a question for you. So now that we have really good data, [indiscernible] data with Repatha in hand, what are you seeing in marketplace? Because like are you seeing increased use in primary care or primary prevention plus primary care, 2 separate things here because statins are predominantly used in primary care segment. And that's a market which was a little bit late to adopt the injectables. So what are you seeing in this marketplace? And how do you see Repatha growing from there?

Yes. No, it's a great question. And again, we're super pleased with Repatha overall, if I remember correctly, and Casey, correct me if I'm wrong, 37% year-over-year growth -- last quarter, we announced also over 50% growth in new-to-brand prescriptions for the product. overall. We are seeing an inflection in use following the publication of the [indiscernible] data in the primary prevention setting. And that inflection Mohit is frankly coming from every segment that we're operating in. In the third quarter alone in the last several weeks, we're -- according to the IQVIA data, we've surpassed not only 15,000 new patients per week, but now 16,000 new patients per week at the end of August.

And so we are seeing incredible growth. That growth is coming from both segments. It's coming from the primary care segment and the cardiology segment as the product gains greater and greater use backed by guidelines, which Paul can talk to a little more as well. And importantly, just at the end of August, we also received our approval for primary prevention in the EU. And so we are starting that launch cycle as well, but this is a global brand and this data will help power the growth well into the next decade across that global brand. But Paul, do you want to add anything further on the guidelines and the data?

Yes. No, thanks, Kave. The only thing Mohit, I would add is, clearly, we have the ACC/AHA multi-society lipid guideline that came out. Everybody should be below 100 if you have risk factors below 70 or even 55 if you have more risk factors. And the American Association of Family Practitioners, to Kave's point, is now endorsing that guideline as well, which is new, and I think will be very important as we continue to get further penetration into the primary care setting, very important.

That's very, very helpful. Thank you for that. Kave, one more question for you. Then how do you see oral PCSK9 impact your market? Do you see it as an expander or do you see it as a competitor here?

Yes. I think, Mohit, it's probably good to zoom out and just look at the overall marketplace. And right now, we know that there's at least 100 million individuals out there that are not at guideline-based LDL despite the fact that they're on standard of care small molecule therapy. And despite that incredible growth I've talked about with Repatha, PCSK9 penetration is still in the mid -- low to mid-single digits. So we're seeing, in particular, with the orals coming in and other players that it's growing the market much faster than taking share away from any one molecule or the other. And we think that, that trend will continue going forward, just given the size of the market to still be penetrated is so much larger than the size of the market treated today.

Got it. Very helpful. So MariTide is one topic which comes along a lot. You are definitely excited about this. Investors are still questioning and not so much the clinical profile of the drug, but also it's more because of the competitive market, there are a lot of offerings out there. So the question here is that how do you differentiate the clinical trials in a way where you can actually establish that there is a benefit of MariTide into the marketplace. And this is probably where your sales and marketing team is also helping you. But talk a little bit about that. And then where do you see the room in the market where you can actually place MariTide in this space?

I can start, maybe Kave will add some detail as well. I mean, look, MariTide is a highly differentiated medicine, we believe, the opportunity for every 8-week or even quarterly dosing. We're in multiple Phase III clinical trials now across a whole variety of different indications spanning chronic weight management or through cardiovascular disease and sleep apnea, diabetes as well. Our Phase II study clearly showed that we can get 20% weight loss. We have instituted now in our Phase III program a simple 3-step dose escalation at the time of initiation. We've tested that in a Phase III study as well and looked at rates of nausea and vomiting. Meaningfully improves those rates. So we think that, that will be a very attractive offering. And we know from our Phase II data that once patients get to their target maintenance dose, there's a very acceptable tolerability profile.

So look, we think the opportunity for extended dosing, robust weight loss and management of weight with the potential for all of the other additional cardiovascular benefits. We know again from Phase II reductions in triglycerides, high-sensitivity CRP, reduction of 11 millimeters of mercury in blood pressure. So that surround sound of cardiovascular risk reduction is really important. So we see this as a highly differentiated medicine and a huge population of people out there who are looking for that kind of an offering, should be able to provide it with an easy-to-use injection device. We think it will be very attractive for patients and systems as well.

What are you hearing from payers/market place?

Yes. Look, I think it's a little early for conversations specifically with payers. But what we hear universally is that this is a really big market, Mohit. It's going to -- there's a lot of different needs within that marketplace. And the entirety of the profile of MariTide that we believe is coming is going to fit really well into that marketplace. One of the things that I do think is a very large unmet need that, to Paul's point, MariTide is uniquely positioned to potentially solve is this idea of how do you keep the patients that have started on GLP-1, on GLP-1 for a longer period of time. In the U.S., there's now more patients that have started and stopped taking the medicine than there are on the medicine today. And we think that this unique profile of this antibody drug conjugate that could be used as little as 4 to 6 doses per year could offer an interesting solution in that longer-term maintenance setting after the initial weight loss.

And we're studying as such. We've got 2 long-term extensions, studying this lower dosing in a maintenance setting. We also, of course, have a switch study that shows how someone could switch and then switch to and stay on MariTide over the longer period. And so that entire package, we do think is going to be quite attractive in this very large marketplace that is going to have multiple options available within it. Very helpful.

I want to touch upon UPLIZNA is like -- I mean, like your growth products, like I can probably have a half an hour or 1 hour conversation with you alone. But the question is, so what are you seeing in the marketplace for UPLIZNA now like MG launch is well underway? Is it new patients? Is it like second line? Like how -- what exactly are you seeing there?

Yes. So UPLIZNA is a great product from the Horizon acquisition. I think in case you can correct me, I think 90% year-over-year growth in the second quarter. 3 indications, NMOSD, which is the long-standing indication, new indication in IgG4-related disease, first and only medicine approved there. And so we're building a market in that space. And then obviously, gMG, an existing and large market that we are competing in. Within the gMG space, we continue to see about half of our patient volume coming from naive patients and about half coming from switch overall. Mohit, that fluctuates couple of points every month, but that generality still comes. And we have now seen enough data where it looks like our switch data is coming pretty much evenly from the other markets and other players in the market based off their use. So we're really happy with the broad acceptance of this medicine within the gMG community and how it's seen as a solution irrespective of where the patient starts on therapy.

Got it. Very helpful. And we're, of course, expanding into new indications.

Talk about that.

Autoimmune hepatitis and CIDP. So we see that, as Kave says, a very safe medicine with clear clinical benefit now has many other opportunities to.

CIDP have we started the trial?

We'll be starting that very soon and AIH, of course, enrolling.

Awesome. Exciting times. So maybe you don't need BD, but I have to ask this question. The question is like, I mean, like what would be the priorities if you look into external like your balance sheet is in a good position now. Horizon that is -- I think it's out of the way now, so it's in a good position. What are the priorities if you look externally, like what exactly would you be looking at?

Yes. First off, strategic fit to our clear. And then second, it needs to generate positive cash-on-cash returns. We need to be the best owner, the right buyer, best owner, it really -- we need to convince ourselves of that. And then finally, we look for can we integrate it promptly. And that's a clear ladder of priorities. Where we are open is deal structures, for instance, right? That can be -- take various forms from licensing to M&A that -- there we are very flexible and have proven that also in the past that we can, with that approach, absorb assets that we -- that add to us and that bring us forward in exploring and delivering medicines for situations, huge unmet needs. There we act on those. But 4 criteria, and I think they make complete sense.

Awesome. One last question. This is my fifth year at Wells Fargo. This is your fifth year at Wells Fargo. So thank you very much for that. Hopefully, in my sixth year of Wells Fargo, you're also here. What would make you look back -- in 2027, September, what would make you look back at the year and say it was a great year for us? Whoever wants to start.

Maybe let's start with the commercial person here.

For this year, specifically, Mohit?

Well, next year -- you are sitting here next year and looking back at this year.

Yes. I think, again, what would be great for us is to see our great commercial -- our 6 commercial growth drivers keep growing at the pace that they've been growing, Mohit, and hopefully, to see by the time we're here next year and approval for IMDELLTRA in the first-line maintenance setting and helping those 28,000 patients live longer than they can today.

Look, I agree. I mean, I think we take on some of the world's toughest diseases, and we bring transformational innovation to them. And we bring profound improvement in clinical outcome. We do that across all of these growth drivers that you've heard about. I think we're well positioned to continue that growth throughout this decade and into 2030 and beyond. I would love to see Repatha continue to grow. I think the benefit that, that medicine can bring to patients is huge. We bring transformational benefit to small cell lung cancer patients.

We have xaluritamig that we hopefully will see data in prostate cancer patients. Again, I think that platform, that BiTE platform can bring tremendous benefit to patients. And then, of course, as MariTide continues to grow, we're able to treat not only massive populations of individuals here in the U.S. and around the world, but we can also continue to treat smaller populations, but bring that substantial clinical benefit to both of them. I think that will be an amazing thing to look back on.

You to round it out?

And what I would say is, as you all might appreciate, I looked at the company outside in, and now I'm inside. So I have to say I'm even more excited about the growth potential not only across the 6 growth drivers, but there is so much headroom for growth yet even within those. And then the pipeline, looking outside in, and I had to rely, of course, then on the data you all see -- I would say Amgen is hugely underappreciated, but we're okay with that. We'll execute. And then in a year's time, we'll sit here again, and then we're looking forward to your questions, Mohit.

Awesome. On that high note, thank you very much. And hopefully, you'll be here next year. Thank you.

Thank you.

My name is Julianne, and I will be your conference facilitator today for the Amgen Q2 2026 Earnings Conference Call. [Operator Instructions]

I would now like to introduce Casey Capparelli, Vice President of Investor Relations. Mr. Capparelli, you may now begin.

Thank you, Julianne. Good afternoon, everyone, and welcome to our second quarter of 2026 earnings call. Bob Bradway will lead the call today. can be followed by a broader review of our performance by Murdo Gordon, Jay Bradner and Peter Griffith.

Through the course of our discussion today, we will use non-GAAP financial measures to describe our performance and have provided appropriate reconciliations within the materials that accompany this call. We will also make some forward-looking statements, which are qualified by our safe harbor statement. And please note that actual results can vary materially.

Over to you, Bob.

Good afternoon, and thank you for joining us. Our strong results were driven by the breadth and depth of our portfolio and once again demonstrate our ability to grow through patent expirations and increased competition. We're pleased with the momentum across our business and expect to reach more patients with our innovative medicines and biosimilars in the second half of the year than ever before as volume demand for our products continues to grow strongly. This broad-based performance is exactly what our strategy is intended to deliver and it's why we remain confident in our ability to deliver durable growth well into the next decade. .

Turning to the quarter. Total revenues exceeded $10 billion, a 10% year-over-year increase. Notably, 22 products delivered double-digit sales growth and 17 products annualized at more than $1 billion based on second quarter sales. These results, including strong earnings and margin performance were achieved while we increased our investment in innovation reflecting the sound financial structure of our business. That sound financial structure also gives us the flexibility to invest with discipline in both our internal pipeline and external innovation, while supporting the long-term needs of the business.

As we've discussed for some time, our 6 key growth drivers are propelling the business forward. Together, they grew at an aggregate rate of 26% year-over-year and represented nearly 70% of our second quarter product sales. Importantly, many of our first-in-class and best-in-class medicines address large and underpenetrated disease areas, giving us confidence that significant opportunities remain to reach many more patients and contribute to durable long-term growth. For example, while more than 1 million people in the U.S. are on Repatha, there are tens of millions more who would benefit from the therapy.

As our products continue to grow, we're also investing in expanding their long-term potential. We're adding indications, broadening geographic reach, improving dosage administration and expanding payer access across our medicines. Our late-stage pipeline is progressing well and also provides additional opportunities for growth. MariTide, Olpasiran and Xaluritamig are advancing through Phase III development and have the potential to address areas of significant unmet medical need. We remain focused on disciplined execution and generating high-quality evidence required to bring these meds to patients. Jay will discuss our progress there in a few moments. Underpinning these efforts are our investments in technology, data and artificial intelligence, which are helping us advance promising medicines more efficiently from discovery through development and manufacturing.

In summary, the business continues to perform well, and we're excited about the future and our ability to deliver durable growth well into the next decade.

Let me take a moment to thank my Amgen colleagues around the world for their dedication to our mission to serve patients and for the quality of their work every day.

I'll now turn it over to Murdo.

Thanks, Bob. Our second quarter results reflect not only the breadth of our portfolio, but the strength and consistency of our execution across key brands and geographies. The next phase of Amgen's growth is fueled by 6 key drivers: Repatha, which grew 37% in second quarter, EVENITY at 38%, TEZSPIRE 42%, rare disease at 21%, innovative oncology at 18% and biosimilars at 29%. As Bob mentioned, this combined portfolio of products is now representing approximately 70% of sales. These growth drivers are delivering strong performance, with the majority of these medicines addressing large areas of public health. .

In rare disease and innovative oncology, we're sustaining growth through additional indications, international expansion and disciplined pricing. Together, they're driving durable performance and positioning Amgen for sustained growth well into the next decade.

Starting with General Medicine, Repatha delivered $953 million in second quarter sales growing at 37% year-over-year. Momentum continues to build for Repatha with new-to-brand prescriptions growing more than 50% year-over-year in the U.S., supported by increased urgency to treat both in secondary prevention and high-risk primary prevention patients. The clinical evidence supporting Repatha is unrivaled in its class Repatha is the only PCSK9 inhibitor with Phase III outcomes data in both primary and secondary prevention. Our Landmark Visalia CV trial reinforces that earlier and more intensive LDL-C lowering before cardiovascular events occur can deliver meaningful risk reduction. These data further strengthened the case for

Repatha to be the first therapy considered when intensifying LDL-C treatment beyond statins. Repatha should be central to an aggressive LDL-lowering strategy for the estimated 100 million patients worldwide who are still above their LDL-C goals. Repatha has broad access and is uniquely positioned to close the treatment gap and drive sustained growth into the next decade.

EVENITY sales increased 38% in the second quarter to $714 million, building on 27% growth in the previous quarter. In the U.S., the opportunity remains significant with approximately 2 million women a fracture in only mid-single [indiscernible]. EVENITY continues to lead the U.S. bone builder market and is well positioned to reach even more patients. In Japan, EVENITY holds category leadership with more than 55% volume share. 1 million patients have now been treated in Japan alone, representing a major milestone in clinical adoption.

Moving to inflammation. TEZSPIRE sales grew 42% year-over-year, reaching $486 million, driven by strong demand in severe uncontrolled asthma. In the second quarter, TEZSPIRE was the market leader in new-to-brand prescription share in severe uncontrolled asthma among allergists and continues to grow with pulmonologists. TEZSPIRE reaching more patients today through expanded Medicare access, including coverage for self-administration with additional opportunity ahead as Part D access improves. Uptake in chronic rhinosinusitis with nasal pulps is encouraging and is already extending TEZSPIRE impact beyond severe asthma. We expect additional indications to deliver continued catalysts for growth in the future, and Jay will share heard more about those in a moment.

Prolia and XGEVA combined delivered $1.1 billion in second quarter sales, a decrease of 33% year-over-year. This is in line with our expectations given several biosimilar competitors some now launched. Turning to our rare disease portfolio, which grew 21% year-over-year to $1.6 billion, you can clearly see our strategy coming to life. Growth is driven by additional indications, international expansion and disciplined pricing. And we're highly encouraged by the value these products continue to deliver for patients and for Amgen's long-term growth. UPLIZNA sales increased 90% year-over-year to $335 million in the second quarter, reflecting sustained momentum across all 3 approved indications. The compelling biology of a plasma CD19 targeted mechanism, which is designed to deplete the B-cells, driving autoimmune pathology is resonating with both physicians and patients. the pluses durable efficacy and convenient twice-yearly dosing further reinforce this impact. These attributes, along with broad payer coverage and Amgen's comprehensive patient access services are enabling rapid initiation and continuity of care across indications.

Uptake in GMG continues to build supported by an almost even mix of bio naive and switch patients with a doubling of U.S. prescribers since the previous quarter. We believe UPLIZNA is well positioned to establish market leadership in this category. Growth also continues in IgG4-related disease, where significant underdiagnosis remains an increased disease awareness is helping more physicians identify appropriate patients. Recent long-term follow-up data illustrate the durable efficacy profile for patients with IgG4-related disease. And you'll hear from Jay, we see meaningful opportunity to extend the UPLIZNA's growth trajectory through additional indications. These clinical programs further leverage the advantages of CD19-directed B-cell depletion across a broader range of autoimmune diseases.

TEPEZZA sales grew 14% year-over-year to $576 million in the second quarter. We're seeing strong uptake globally with solid execution in Japan following last year's launch. TEPEZZA has now launched in 13 countries around the world with an additional 6 planned in the coming months. Since approval in the U.S., more than 25,000 patients have been treated with TEPEZZA. We're continuing to build momentum by expanding awareness and broadening the prescriber base, including endocrinologists and ophthalmologists to reach more eligible patients. Looking ahead, the advancement of our subcutaneous on-body injector for TEPEZZA represents a meaningful step forward. the Phase III data demonstrated comparable efficacy to IV TEPEZZA supporting a clear path to subcutaneous administration without compromising clinical benefit. This option enhances convenience enables more sites of care for patients and has the potential to drive long-term growth.

Turning to innovative oncology. The portfolio grew 18% year-over-year, generating approximately $2 billion of sales in the second quarter and IMDELLTRA sales increased 115% year-over-year to $288 million. After years with little meaningful innovation for patients with small cell lung cancer, IMDELLTRA has emerged as the best-in-class treatment option to improve overall survival in the second-line setting. We're seeing strong clinical conviction, rapid adoption across sites of care and clear differentiation from other available therapies and IMDELLTRA is supported by NCCN recommendation.

While we have made important inroads, there's still significant opportunity to further penetrate the second-line patient population. Too many patients are still being treated with chemotherapies that do not offer the survival benefit demonstrated by IMDELLTRA. As we continue to expand in the second-line setting, we look forward to data in the first-line extensive-stage small cell lung cancer, which has the potential to further expand IMDELLTRA's impact and unlock additional growth.

BLINCYTO sales increased 23% year-over-year to $472 million in the second quarter, driven by broad prescribing across both academic and community settings in the U.S. and 64% growth outside the U.S. International performance was led by broader first-line adoption, robust treatment duration and strong demand across Europe and Japan. Our biosimilar portfolio delivered 29% year-over-year growth, generating $855 million in sales in the second quarter. PAVBLU increased sales 121% year-over-year to $287 million in the quarter. Adoption continues to expand among retina specialists who value PAVBLU's ready-to-use prefilled syringe format and Amgen's track record of quality biologics manufacturing and delivering reliable supply.

Since our first biosimilar approvals in 2018, the portfolio has generated more than $15 billion in sales. Amgen's deep biologics expertise, global manufacturing scale and commercial capabilities differentiate us and support reliable supply for patients around the world. Our next wave of biosimilars, candidates for EYLEA HD, OPDIVO, KEYTRUDA, and OCREVUS are in late-stage clinical development and represent large market opportunities with the potential to further expand patient access.

Our second quarter results reflect focused high-quality execution, portfolio strength and continued progress in expanding the impact of our medicines for patients worldwide. Reflecting on these results in the broader set of portfolio opportunities, it's clear that we are delivering a level of consistent, compelling performance that's rarely seen in our industry. This performance is grounded in a portfolio, anchored by first-in-class or best-in-class medicines, a team that executes with urgency and a disciplined approach to access that reduces friction for patients. These efforts position us to unlock future growth and drive durable impact in areas of significant unmet need well into the next decade.

And I'd like to now hand it over to Jay.

Thank you, Murdo, and good afternoon, everyone. In the second quarter, we enjoyed continued progress advancing our late-stage pipeline and expanding the impact of our in-line medicines. Starting with cardiovascular disease, where Amgen is a global leader in developing medicines that target remaining, often genetically defined cardiometabolic risk factors for heart disease. Repatha anchors our cardiovascular efforts as the only PCSK9 targeting therapy with outcomes data in both primary and secondary prevention, supported by 51 clinical trials involving more than 57,000 patients and over 100,000 patient years of exposure.

We continue to generate additional insights from VESALIUS-CV the landmark study of Repatha in pre-event cardiovascular disease. We recently reported that for patients with high-risk diabetes with and without atherosclerosis, Repatha reduced 3-point major adverse cardiovascular events by 29% and produced a nominal 21% reduction in the risk of all-cause death. Also based on the positive VESALIUS-CV study, we recently received a positive CHMP opinion supporting a broader label for Repatha in the EU.

Our cardiovascular leadership further extends to Olpasiran, targeting lipoprotein A or Lp(a). Elevated Lp(a) is an independent genetically defined risk factor for cardiovascular disease, affecting approximately 1 in 5 people, having demonstrated greater than 95% reduction in Lp(a) levels in Phase II Olpasiran advanced into 2 ongoing Phase III outcome studies in both primary and secondary prevention. Deep Lp(a) suppression and quarterly dosing position Olpasiran for a potentially best-in-class profile.

A third widely prevalent and modifiable risk for cardiovascular disease is, of course, obesity. Our lead obesity asset in MariTide is fundamentally different from other GLP-1 therapies. As MariTide is uniquely designed for monthly therapy with the potential for as few as 4 or 6 doses per year. Clinical development of MariTide continues to progress rapidly with 9 ongoing and 3 additional planned Phase III studies across obesity and related serious chronic diseases. Beyond establishing efficacy, these studies will guide how to start and stay on MariTide and how to switch from other GLP-1-based therapies and stay on MariTide.

One, start and stay on MariTide. MariTide Phase III dosing features a simple 3-step dose escalation, allowing patients to start MariTide to reach their target dose in only 2 months, followed by monthly dosing thereafter. MariTide's unique monoclonal antibody backbone with appended GLP-1 peptide is designed for extended dosing. Our Phase III maintenance extension studies will evaluate how patients stay on MariTide to maintain weight loss while transitioning from monthly dosing to as few as 4 or 6 doses per year.

Two, switch and stay on maritime. The next chapter in obesity treatment is not simply greater weight loss but achieving long-term persistent benefit. We are, therefore, evaluating switching for weekly GLP-1 therapies to MariTide in a dedicated Phase III study with the goal of enabling patients to move from weekly injections to a maintenance schedule with again as few as 4 or 6 doses per year. Through the comprehensive program, we aim to establish MariTide as the first monthly or less frequent obesity therapy and make long-term treatment easier for patients to sustain weight loss and enjoy durable health benefits.

Closing out our cardiometabolic pipeline, we have decided to stop development of AMG 513 a Phase I asset. As I said before, the bar is high Amgen for obesity medicines. Our next generation of differentiated preclinical programs continues to progress, featuring both incretin and nonincreasing mechanisms of action.

Let me now turn to rare disease, where we are focused on challenging and rare autoimmune diseases with UPLIZNA, Dazodalibep and blinatumomab. UPLIZNA has established the benefit of CD19-directed B-cell depletion in severe autoimmune diseases, including NMOSD, myasthenia gravis and IgG4-related disease with strong efficacy, durable benefit and twice yearly maintenance dosing. In IgG4-related disease, we recently completed a 1-year open-label extension of the Phase III MITIGATE study. Building on the remarkable 87% reduction in flare risk versus placebo in year 1 of UPLIZNA therapy, 100% of patients who continue to plasma treatment remain flare free at year 2. and 71.4% achieved complete remission without glucocorticoids. Based on the emerging profound clinical impact of UPLIZNA in autoantibody-mediated disease, we have initiated the registrational MERCURY study in autoimmune hepatitis, a disease affecting as many as 150,000 patients in the U.S.

We are also planning a Phase III study in chronic inflammatory demyelinating polyneuropathy, a rare and debilitating autoimmune condition that attacks the myelin sheath on peripheral nerves affecting about 35,000 patients in the U.S. For patients suffering from Sjogren's disease, we are developing as alive. Dazodalibep targets CD40 ligand mediated signaling between activated T cells and B cells and has been artfully designed to avoid the platelet related adverse events observed with first-generation CD40 ligand targeting agents. We are conducting 2 dedicated Phase III studies in symptomatic and in systemic disease results are expected later this year.

Turning to inflammation. TEZSPIRE has validated targeting TSLP and the alarming pathway in severe asthma and chronic rhinosinusitis with nasal polyps. We are now extending its potential to other diseases where epithelial driven inflammation plays a key role. Our Phase III study in eosinophilic esophagitis, or EoE, is expected to complete in the second half of the year. EOE is a chronic progressive inflammatory disorder characterized by epithelial driven inflammation, remodeling and dysfunction of the esophagus, affecting over 400,000 patients in the U.S. Building on the impact of TEZSPIRE, we are developing sunecamet, previously AMG-104 as an inhaled anti-TSLP fragment antigen binding protein or fab. In the Phase II Lavante dose-ranging study of sunacamen, we observed numerical reductions in composite asthma exacerbation events or compact, as the primary endpoint at 12 weeks. Although the primary endpoint was not statistically significant, we are encouraged by the overall profile and are planning a Phase III program with AstraZeneca.

In oncology, we continue to expand our bispecific T cell engager or BiTE platform across tumor types and to earlier lines of treatment. IMDELLTRA or torlatimab, is becoming a standard of care after first-line treatment for small cell lung cancer, supported by a strong survival benefit. We're actively advancing IMDELLTRA into earlier treatment lines where we hope to further impact survival with 3 Phase III studies well underway. Success in these early-stage settings would allow IMDELLTRA to reach as many as 28,000 addressable patients in the U.S.

We are also pursuing more convenient administration. DeLLphi 309 is informing our strategy for extended interval dosing. While the new Phase III DeLLphi 315 study is evaluating subcutaneous lamb. Building on the success of our BiTE platform in solid tumors, Xaluritamig is advancing in 2 Phase III studies of metastatic castration-resistant prostate cancer. While we also evaluate opportunities in earlier stages of this disease.

Shifting gears before closing, I'll briefly comment on artificial intelligence. Amgen has a differentiated foundation in proprietary human data high-performance computing and deep scientific expertise. We are applying AI strategically across discovery, development and manufacturing and access to medicines to improve insight, speed and decision quality. The impact on insight from these investments are already proving valuable. For example, in Engen Research, we recently established a Frontier AI laboratory that combines advanced models with proprietary data and scientific capabilities unique to Amgen.

Bringing agentic workflows to discovery research powerfully augments the insights and ideas of our brilliant research scientists. We look forward to sharing more over time. In closing, I'd like to thank my colleagues across Amgen for their continued focus on patients and their commitment to advancing innovative medicines for serious diseases.

I'll now turn it over to Peter for the financial update.

Thank you, Jay. Our strong second quarter performance reinforces confidence in our 6 key growth drivers and our ability to grow through losses of exclusivity. Together, they demonstrate the breadth and the depth of our business and continue to provide a strong foundation for sustained long-term growth. Our non-GAAP operating margin was 48%. We continue to invest in our portfolio and pipeline while achieving strong operating results with non-GAAP R&D spending increasing 10% year-over-year in the second quarter. This reflects continued investment in the innovation that will drive future growth, including MariTide, Xaluritamig and Olpasiran as well as our marketed medicines, including UPLIZNA, TEZSPIRE and IMDELLTRA.

Our non-GAAP cost of sales as a percentage of sales was 19.6%. The year-over-year increase primarily reflected higher profit sharing and royalty expenses as well as changes in sales mix. These factors reflect the continuing evolution of our product portfolio and momentum from several of our growth drivers. We remain focused on operational efficiency, execution excellence and continue to benefit from our leadership in high-quality world-class biologics manufacturing at scale.

We generated $3.5 billion in free cash flow in the second quarter, reflecting continued momentum across the business and enabling us to continue investing for future growth. We spent $500 million in the second quarter on capital expenditures, driven by investments across our United States manufacturing sites including North Carolina, Ohio and Puerto Rico. We continue to expect capital expenditures of approximately $2.6 billion in 2026, reflecting significant investment in our business to scale manufacturing capacity for volume growth, including for MariTide launch. Our commitment to investing in our business and enabling additional capacity supports our long-term growth well into the next decade. In addition, we returned capital to shareholders through competitive dividend payments of $2.52 per share. representing a 6% increase compared to the second quarter of 2025.

Let's turn to the outlook for the business for the remainder of 2026. We are pleased with our strong execution in the first half of the year, and we are raising our 2026 guidance ranges for both revenue and non-GAAP earnings per share. We now expect 2026 total revenues in the range of $38.2 billion to $39.4 billion and non-GAAP earnings per share between $22.30 and $23.50.

Let me highlight a few updates to our outlook for the remainder of the year. For the full year, we now expect other revenue to be approximately $1.9 billion. We expect full year non-GAAP R&D expense to grow high single digits year-over-year, which includes 9 ongoing global Phase III clinical trials for MariTide. This outlook also includes a business development transaction, resulting in a $100 million upfront payment that will increase our non-GAAP R&D expense in the third quarter. We now have an expense to be in the range of $2.1 billion to $2.2 billion of expense in 2026.

And let me remind you of several additional guidance items. We continue to expect the full year non-GAAP operating margin as a percentage of product sales to be roughly 45% to 46%. Our commercial performance allows us to continue investing behind the next generation of growth drivers while maintaining strong operating margins. In addition to the third quarter business development transaction noted earlier, our strong revenue performance has enabled us to make incremental third quarter investments in the pipeline and our commercial brands to drive continued momentum into 2027. As a result and consistent with 2025, we expect a meaningful sequential increase in operating expenses in the third quarter.

We expect a non-GAAP tax rate in the range of 15.0% to 16.5%. We expect share repurchases not to exceed $3 billion. We remain focused on executing our strategy, staying focused on our growth drivers investing in the best innovation and maintaining our rigorous financial discipline that enables us to deliver sustained long-term growth and create value for patients, staff and shareholders. I'm grateful to work with all of our colleagues worldwide and our mission to serve patients.

And with that, this concludes our financial update. I'll now hand it over to Bob for Q&A.

Okay. Thank you for that strong report, Pete. And before we open up to questions, let me just remind you that this is Pete's Swan song earnings call with -- so I'll take a few minutes at the end of our Q&A to thank him and recognize his contributions to our firm. But now, Julian, let's open the line up for questions. .

[Operator Instructions] Our first question comes from Michael Yee from UBS.

This is Diana on for Mike. Just a quick question on the Lp(a), 2-part question. Just thinking about how you in the protocol, is that -- is that involving an interim? And then maybe just -- I know that you guys are doing a MACE 3 endpoint opposed to Novartis is doing MACE IV just given that, do you see the exclusion of [indiscernible] affecting the time of your study versus having a MACE IV endpoint?

Yes. Thanks for your question. As you know, our development of Olpasiran, which is a potentially best-in-class siRNA for modifying the risk of cardiovascular disease attributable to Lp(a) elevations effect, 1 in 5 patients. It's a serious and profound unmet need, and it's terrific to see so much attention for what is 1 of the last known and well-defined genetically modifiable risk factors. We have a terrific study design with OCEAN(a), this is a double-blind randomized controlled trial, as you asked 97 patients have been enrolled in record time, and they are distinguishing features of our design. One is the requirement for elevations of Lp(a) above 200 as animals per liter with this every 12-week dosing in an event-driven study will read out a primary event as you shared, of 3-point MACE.

We focus on 3-point MACE after extensive human genetics and population science analysis indicated to us that the association of ischemic stroke and Lp(a) elevation was not as compelling as other cardiac specific cardiovascular endpoints. And this is, therefore, a potentially important distinction between this study and others. And you asked, does the stroke -- the lack of inclusion of stroke and the endpoint influenced the event rate now by our modeling.

Our next question comes from Salveen Richter from Goldman Sachs. .

On business development, you have reiterated a focus on securing the best innovation and appear agnostic on site structure as long as the deal meets your criteria Walk us through how your latest thinking here is out currently and the capital allocation strategy more broadly? And how much of the near-term BD strategy depends on outcomes from clinical readouts from MariTide and Lp(a).

Salveen, I think our business development strategy is pretty consistent. We've articulated it. I think in that way now over a number of years. So we're focused on the therapeutic areas where we think we can add value in research and in development. We're focused on the 4 areas that you've heard us discuss on this call, and we're continuing to look at interesting opportunities there. And we frequently repeat that our objective is to find and advance the best innovation, whether it's generated internally or externally, and that's what we're doing. I would just observe that we're seeing some exciting early-stage progress in our industry right now.

So I suspect we're not the only ones that are interested in some of the emerging shoots that look intriguing. So we are looking, but primarily in smaller earlier-stage assets. And -- not the answer to your question about the late Phase III trials is not directly. Obviously, our operational plate is pretty full in the late-stage clinical development right now, for example, in cardiometabolic disease. But we try to be mindful of that as we look for external opportunities, but it's not linked as directly as your question implies.

Our next question comes from Chris Schott from JPMorgan. .

This is Taylor Hanley on for Chris at JPMorgan. We had a follow-up on Lp(a). So there's competitor LP(a) data that's expected shortly. -- what will you be looking for when this data set reads out? And specifically, if we do see a 13% to 15% type benefit from that study, how would you think about the potential read-throughs to Olpasiran around .

Thanks for the interest Taylor. Again, with a huge unmet need affecting so many humans globally in the American Heart Association recommending testing -- it's understandable that there will be so much attention on Lp(a), and we quite like our chances with Olpasiran and its profile. What can we expect from the pelacarsen data? We're following it with interest. We can expect perhaps directional insight, but not decisional perspective, owing to the superior properties of our molecule that delivered 95% Lp(a) reduction compared to, say, 70% with that molecule and also some differences in the study design, which we just described. .

Our next question comes from Umer Raffat from Evercore ISI.

Jay, I have 2, if I may, for you. One, based on everything you know right now on all the titration that's been put into place, how confident are you that the vomiting rates in Phase III trials of MariTide will be mid-20s or better? And secondly, are you tracking malignancies on a blinded basis in the ongoing daselhours getting wrong on the CD40 trial? I'd be very curious.

Dazodalibep, Umer, Dazodalibep, it rolls right off tongue. Yes. First, regarding the MariTide clinical development program. We are noses down delivering a very compelling Phase III data package right now, 2026 is a year of very disciplined data generation. Trial enrollment is strong. I think a clear sign of the remaining unmet need and also an interest in the MariTide profile. We're executing a broad therapeutic program very well, and we are very confident in the profile of this medicine.

Second, around Dazodalibep as appropriate for any medicine in Phase III clinical investigation, especially immunomodulatory medicines. We have a data safety monitoring committee associated with these studies. That is just doing their job perfectly. As we would expect, they're capturing all high and potentially associated as well as really any incident effects of the medicine. And we'll learn more about Dazodalibep in H2 of this year.

Our next question comes from Yaron Werber from TD Cowen.

Quick question on Dazo as well. The -- you're the only company running both systemic and symptomatic studies and a lot of the feedback from KOLs is that that's obviously a huge area of interest for them. A lot of the patients that are systemic naturally obviously have glandular manifestations. And so the symptomatic are really extra manifestations. Can you talk about the difference? And at the end, how much of a differentiated label can you get relative to companies who are only working in systemic disease?

Yes, thank you. This is a terrific question. As you know, Dazodalibep is a potentially first-in-class CD40 ligand Fc chimeric protein that's just beautifully designed in order to maximize inhibition of CD40 ligand signaling from activated T cells to B cells and epithelial cells that are enriched for CD40 in the mile of lymphocytic infiltrated glandular tissue, like the salary glance that you mentioned in your question. We are pursuing the Phase III clinical investigation of Dazodalibep in both the systemic population as well as the symptomatic population because there's tremendous unmet need.

There's 350,000 or more patients with Sjogren's disease. There's few effective therapies. Those therapies that are FDA approved are by and large local and symptomatic management therapies and the signal that we saw in our Phase II clinical study, you'll recall there were 2 populations: population 1 at 74 patients with systemic disease. And at day 169, we saw significant movement of the SDI score of 6.3 versus 4.1 on placebo. Population 2. We had 109 patients with symptomatic disease. At day 169, the [indiscernible] score in that case, appropriate for that constellation of symptoms was also superior to placebo, negative 1.8% versus negative 0.5%.

So a big unmet need and activity in these 2 populations that are rightly studied distinctly because there are different clinically useful scores that physicians use to follow them, it's just a very nice data package to build upon for Phase III. And now we're deep in Phase III. We have 621 patients on the systemic study, 434 in the symptomatic. They need to be studied differently for the reasons I've mentioned, and we'll learn more about the impact of this medicine in that disease in H2 of this year. So we're very hopeful, but humble. It's a very challenging disease.

Next question comes from Courtney Breen from Bernstein.

This is Woody [indiscernible] on for Courtney. I wouldn't ask what you guys are seeing on it's impact in the dermatology market with regards to Otezla. Are you seeing a slowdown in volumes and prescribing Otezla? And how should we think about the future of this drug, especially in light of IRA selection next year?

Murdo, why don't you?

Yes. One of the things to remember about Otezla is given the extensive clinical experience with this medicine, the broad label that we have that includes the milder forms of psoriasis and the really clear coverage from payers -- we generally are used as a first stop systemic agent. And what we're seeing is the new entrants are competing with each other after Otezla has tried end. So we're not really necessarily seeing direct competition from the new entrants, we are seeing definitely some pressure on price with Otezla given some 340B exposure on that product. But overall, the volume in Otezla is actually holding up quite good. .

Our next question comes from Terence Flynn from Morgan Stanley.

Great. This is Chris on for Terence. Just a 2-part question on PCSK9. Merck or PCSK9 recently got approved. Can you compare and contrast the key label language differences from that pace? And also, can you comment on the contract dynamics now that there's an RO option? .

Sure. Murdo, why don't you?

Yes, let me take that one. Obviously, the 2 labels really just don't compare. You have Repatha, as Jay mentioned, over 50,000 patients on clinical trial experience reflected in a broad able that includes primary and secondary prevention Repatha can be used as monotherapy or in combination with statins. 10 years of real-world experience reflected in data that we've presented at recent scientific meetings. So as we say, the data behind Repatha are unrivaled, it is the category leader and indeed, the data are unrivaled. I think, though, what's important to remember is that this is a huge market with a lot of patients that are still not at their LDL-cholesterol goal. And additional therapies, much like when inclisiran entered the market, are treating other patients. They are not necessarily competing for share with Repatha.

And so -- we think there's a lot of education that still needs to be done. And we think that the guidelines are important in this market. And we think that we are able to drive utilization in this market more effectively given the compelling data that we generated on VESALIUS.

The other thing that we've experienced with Repatha as we look at persistency data in the market and the real world analysis, this is an every 2-week injection is a really easy regimen for patients to adhere to -- and we've seen limitations with orals, including with statins, where daily oral therapy does have some compliance and some adherence challenges to it. We're also seeing in the label with the new PCSK9 approval that there are indeed food restrictions that you have to be careful with what you eat in the first 30 minutes after you take that medicine. So I think this oral versus injectable is too simplistic a compare and you really have to look at why do you take an LDL cholesterol medicine in the first place and is to prevent a first or a second heart attack, and we've demonstrated that with very clear evidence for Repatha.

Our next question comes from Akash Tewari from Jefferies.

One for [indiscernible]. One of the concerns around horizonal Lp(a) trial is around the extent of LP effect independent of LDLC in horizon trial, we see the baseline LDLCs around like 65 milligrams per deciliter. What's the baseline LDLC in the OCEAN trial you are planning? Or like is it in the same level? And also, is there a possibility that Lp(a) only in presence of a relatively higher baseline LDLC effect? Just trying to understand that point. .

Well, thank you for the question. As I shared a moment ago, we're enrolling the OCEAN study to target an Lp(a) that's a little bit higher than the Horizon study. by targeting 200 or higher in Ocean A, we biased towards a slightly higher risk group of patients. We believe and have seen data from population studies that Lp(a) elevation, to this extent is firmly independent as a risk factor of LDL-C. And if I add on all aspects of your question, correct me, forgive me if I did not the reduction of LDL-C even with improving standard of cardiovascular care to TEPEZZA contributes meaningfully would not be sufficient to drop Lp(a) meaningfully from this elevation to protect patients adequately. So LP(a) directed therapy, we believe, is urgently needed, and we're conducting the studies to assess that. .

Next question comes from Mohit Bansal from Wells Fargo.

This is Susan on for Mohit. A quick question on Repatha and then a longer one on Dazodalibep. On Repatha, that portion of growth is coming from broader primary care adoption versus existing prescribers? And how do you see that changing over time? And then on Dazo, historically, symptomatic [indiscernible] trials have struggled with endpoint sensitivity and placebo effect. I noticed for the Phase III trial that there's 2 primary endpoints measuring symptom improvement. Can you discuss the rationale for using 2 endpoints here? And what the level of concordance is just based on your trial design?

All right. Thanks for the question. It's Murdo. I'll take the first 1 on Repatha and then hand it over to Jay for the second. We are pleased to see that Repatha is growing very nicely, particularly in new-to-brand prescriptions. So new patient starts we grew about 50% year-over-year in the quarter in new-to-brand prescriptions and it's being driven by 2 dynamics. One, cardiologists who already use Repatha for some patients are broadening their use of Repatha. So they're increasing the number of prescriptions they generate on a per physician basis, treating more patients mostly in secondary prevention or in very high-risk primary prevention. So that's roughly about half of our growth.

And then the other half of our growth is coming for primary care physicians and expansion in the number of primary care physicians, in particular, who are prescribing Repatha for their high-risk primary prevention patients. And there, I would highlight 1 specific patient type and that those patients who have diabetes. The primary care community see that as a patient that they should manage for their cardiovascular risk. And given the Vesalius data and then the subsequent diabetes sub study, the data there for adding Repatha for intensifying LDL cholesterol lowering are pretty compelling, and we're seeing more and more primary care physicians adopt the Repatha for those patients in particular for primary prevention.

And your second question around the endpoint selected for the Phase III clinical investigation of dasodalibat in Sjögren’s disease. As I shared moments ago and as you clearly understand from your question, we have undertaken to do separate Phase III studies in each of 2 populations, the systemic population. And in this case, we use the ESSDAI score, which is position observed score that reports on systemic manifestations of Sjogren's disease, a single endpoint -- and in the second study, we are studying the symptomatic population that can have a more localized disease, but symptomatic and measurable for sure. And there, our interactions with regulators and with trialists in the community as well as our own internal guidance was to collect both the prescore as well as the diary for assessing Sjogren's patient reported for the [indiscernible] score at week 48. In this way, we have 2 measures, both validated and other late-stage clinical studies. -- that report on the subjective or lift experience of the patients on this medicine on this study. Thank you.

Our next question comes from Alex Hammond from Wolfe Research. .

So on Intra, given you have a number of Phase III trials underway to bring it into earlier lines, can you provide a little bit of detail on what Amgen is doing to kind of improve those monitoring requirements -- should we view the reduced monitoring in Europe as a good sign? And as a follow-up, could we potentially see amendments for later line monitoring requirements for IMDELLTRA in the future?

Yes. Alex, thanks for the question. This is Jay. The development of T cell engagers is an area of significant expertise here at Amgen having pioneered the field with BLINCYTO and now bringing IMDELLTRA forward for patients with small cell lung cancer, truly the first T cell engager to address a common solid tumor. And so building on this experience of establishing strong efficacy. It's a survival benefit receiving IMDELLTRA in the second line of small cell lung cancer. We're now doing the work needed to expand the impact of this medicine.

And part of that work is combination studies. And part of that work is bringing the medicine forward into frontline therapy and preparing the medicine for a combination utility. And as you ask for sure, making the experience of receiving IMDELLTRA for the patient easier and less burdensome for health care providers or institutions with regard to monitoring. The second line Phase II used on 16 hours of monitoring at that time, appropriate for that stage of development. We now have real-world experience and ongoing clinical study experience all the way down to 1 to 2 hours of monitoring, say, in the context of our limited stage. And with this medicine, iCAN, the neurologic consequence thankfully, is quite infrequent and predominantly was observed at the 100-milligram dose. And so this really opens the door towards sequential reductions in monitoring through prospective clinical investigation as well as longitudinal engagement with federal regulators, actually global regulators with our accruing safety database.

Murdo, anything to add here?

Yes. Thanks, Jay. We're obviously excited, Alex, about the additional data generation that Jay and his team are leading. In the market right now, we've actually been quite successful in getting more and more accounts operationally ready to treat patients with IMDELLTRA, we've got over 2,000 accounts in the U.S. currently using IMDELLTRA opportunity for growth is to treat even more patients in the second line in the near term -- and of course, we've been able to establish an overall survival benefit there against commonly used chemotherapies. And given the operational complexities we've been able to get quite a large base with those 2,000 accounts and ready to be able to treat more and more of those patients. So with an almost doubling of revenues in the quarter, obviously, we're on a nice pace with this medicine and helping give small cell lung cancer patients a shot at real survival benefit, which they prior to IMDELLTRA the second line we're unable to achieve.

Our next question comes from Dave Risinger from Leerink Partners.

Thanks very much, and thanks for all of the details today and all the commentary on the pipeline. So my question is for Jay, please. Regarding MariTide's construct. So it's GLP-1 peptides conjugated to a GIP-tagonist antibody, of course, -- could you discuss the duration of effect of each mechanism and potential implications for duration of efficacy obviously, since the peptide component will last a lot shorter than the antibody. And then if you could also comment on whether you expect real-world patient-led dosing selection for every 1, 2 or 3 months maintenance dosing based upon individual experience. Is that the right way that we should be thinking about it?

Well, Dave, thank you for the question. I wish we only -- we had more time in a way for to take you through the answer. I'll be succinct. MariTide is truly a singularity. It's the only 1 with kind of antibody peptide conjugate and because of the antibody design, unlike peptides, that's through miracles of chemistry last maybe a week in the bloodstream, the antibody design affords a half-life of approximately 21 days. And that's the half-life of the intact molecule MariTide. MariTide, appending peptides were designed and appended in order to maximize stability to tissue proteinases and to serum esterases and other xenobiotic metabolizing enzymes in tissues and in circulation. And because of this, the duration of effect of the GPR inhibitory variable chains of the antibody and the GLP-1 receptor agonizing peptides on MariTide is preserved through this long period of exposure. And what that means is that with monthly dosing as used with starting maritime and with the transition to less frequent dosing, maybe 4 to 6 doses per year as you start to stay on MariTide you switch from another medicine and then stay on MariTide that the GLP-1 agonism and GIP receptor antagonism is quite persistent as the molecule is quite persistent.

Why is this important? Because we're that to, say, burn off with metabolism or illumination of the drug, then rechallenge with a therapeutic dose of the drug will be very hard. And that's not what we're seeing on our clinical studies, as we've shared with less frequent dosing, MariTide target doses proved very, very well tolerated. And so this design is reading through to a truly differentiating clinical activity and a different experience for patients.

Your second question is a little harder. I can't predict the way in which maritime in the fullness of time will be utilized by prescribing physicians and by patients. But what we're seeing is activity in our Phase II for chronic weight management as for diabetes is observed at multiple different doses. And as we've shared that maintenance maritime can be administered on different schedules. And so this would I can say, the physician, this would seem to imply real flexibility in approaching how best to take MariTide.

Murdo, what would you add?

Well, I think your team is doing a nice job, Jay, of generating data that will inform the clinical practice and, of course, patient optionality with 12 doses, 6 doses and perhaps even 4 doses a year. And I think that is different for MariTide than the current weekly injectables that have to be dosed 52 times a year. And there are scan data describing how you can maintain when you dose stretch on those therapies for various obvious reasons. So I think it's a good thing for patients that we're doing those trials, and I think it will be really interesting when the data are available to see how it changes patient behavior.

Okay, Julian, why don't we take one more question. .

Our last question today will come from Jay Olson from Oppenheimer.

Congrats to Peter for a bit run at Amgen and all the best in retirement. Our question is about your cardiovascular portfolio as you look across Repatha, Olpasiran and MariTide. Amgen is building a comprehensive cardiovascular risk reduction franchise. So how are you thinking about leveraging those 3 assets with a coordinated strategy -- and what are the advantages that creates versus competitors who might be pursuing only 1 or 2 components of cardiovascular risk?

Murdo, why don't you share your thoughts?

Well, Jay, thank you for the acknowledgment of the breadth and depth of the cardiovascular portfolio. I think it's obviously a nice opportunity given the foundational strength we have in the LDL cholesterol lowering market and cardiovascular risk reduction market with the leadership position we've established with Repatha. I think what you've heard even on today's call, and you've heard from us prior to this is the experience that we've gained from Repatha has been applied to the clinical development and the design of the clinical programs behind Olpasiran and behind MariTide. We're not just developing Olpasiran for secondary prevention. We're looking at primary prevention. We're not just developing MariTide for weight loss. We're developing it for diabetes and for heart failure and for ASCVD, we're looking at all of the different independent metabolic risk factors that travel with losing weight.

And so it's our intent to fully explore each of these unique medicines, these best-in-class potentially first-in-class of their kind molecules as well as potential combinations thereof. So this is an exciting time for us. We continue to develop additional molecules in the clinic, and we continue to look outside for additional external innovation that could be brought in. So it's an important part of our long-term growth strategy and 1 that we expect to be durable well into the next decade.

Okay. Thank you, Murdo. Thank you, Jay, for the question. Well, as I said, let me just take a minute to thank all of you for joining our call. I hope you can see that our business is in strong shape, and that is indeed a fitting way for Pete to pass to Tom, Thomas Dittrich who will be in the CFO role for our next call. Recall that Thomas Returns is a veteran of the Amgen Finance team. We're delighted to have him back and grateful to Pete for ensuring another smooth transition of responsibilities at Amgen. .

I know many of you have worked closely with Pete since he joined us at the end of 2019, and we've all had fun working with him in his role here and are grateful to him for his many ways or the many ways in which he has strengthened our financial foundations. His disciplined financial leadership has enabled our largest ever investments in research and development, acquisitions and manufacturing capacity expansion. And he's also helped prepare Amgen for the future through our investments in technology, cybersecurity and data capabilities that will serve us well in the years to come. So Pete, on behalf of all of Amgen, thank you for your many contributions. You've been a great colleague and a good friend and we wish you all the best in your next chapter of life. Thank you all. Bye-bye.

This concludes our Amgen Q2 2026 Earnings Conference Call. You may now disconnect.

Good morning. Thank you for joining us. It's my pleasure to introduce the Amgen team. With us, we have Peter Griffith, Chief Financial Officer; Murdo Gordon, Head of Global Commercial Operations; Andrew Martin, Head of U.S. Business Operations; and Casey Capparelli, Head of Investor Relations. With that, I'm going to turn it over to you, Peter, for some opening remarks.

Great. Thank you, Salveen. Good morning, everyone. And Salveen, congratulations on that Knicks win last night. I understand you're now one of the top Knicks fans around. Good. Well, we will be too today when we're with you. So it's great to be here. We appreciate your interest in Amgen. I wanted to share a few thoughts before we get into the Q&A session.

So I think most importantly, we believe there are lots of ways to win for Amgen, especially for patients. We're pleased with our strong first quarter performance, which reinforces our view that 2026 is a springboard year for Amgen. It's a year in which we expect our rapidly growing products to offset the impact of increased competition for the denosumab franchise, and we saw that dynamic play out in the first quarter.

Revenue increased 6% year-over-year. Non-GAAP earnings per share were up 5% year-over-year, demonstrating the disciplined financial management that has long been a hallmark of Amgen. We had 16 products, delivered double-digit or better sales growth; and 17 products now annualizing at more than $1 billion in product sales based on first quarter results.

Importantly, our six key growth drivers, Repatha, EVENITY, TEZSPIRE, our innovative oncology portfolio, our rare disease portfolio and our biosimilars portfolio represents -- represented about 70% of product sales in the first quarter and grew 24% as a group year-over-year. We expect those growth drivers to continue supporting our performance through the end of the decade.

Within oncology, IMDELLTRA now annualizing at more than $1 billion in sales and continues to establish itself as an important treatment option in small cell lung cancer. Within rare disease, UPLIZNA continues to build momentum across NMOSD, IgG4-related disease and generalized Myasthenia Gravis.

We're very encouraged by the progress we're seeing across these franchises. So let's turn to the pipeline then. Confidence continues to build in MariTide as a potential new paradigm for the treatment of obesity, type 2 diabetes and obesity-related conditions.

We're executing across the enterprise from clinical development to manufacturing as we advance MariTide's broad Phase III program and continue to build and optimize manufacturing capacity ahead of launch.

Our manufacturing preparations continue to progress well, and we believe MariTide has the potential to play a very important role across weight loss inductions, long-term weight maintenance and patients transitioning from weekly GLP-1 injections and therapies, with the potential for as few as 4 to 6 injections per year based on our extended dosing.

Our approach reflects how obesity care may evolve. Patients need effective weight loss, but they also need practical and durable maintenance options. And again, that extended dosing should help meet patients with those unmet needs.

Beyond MariTide, we have a robust Phase III pipeline, including olpasiran for the reduction of cardiovascular risk in patients with elevated Lp(a), dazodalibep in Sjogren's disease and xaluritamig in late-stage prostate cancer also exploring and investigating xaluritamig in earlier-stage prostate cancer.

We're investigating, as I said, xaluritamig in earlier stages of prostate cancer. In addition, we continue to pursue new indications for several approved products, including UPLIZNA in autoimmune hepatitis and chronic inflammatory demyelinating polyneuropathy, TEZSPIRE COPD in eosinophilic esophagitis and IMDELLTRA in early-stage small cell lung cancer.

So Salveen, let me just take a couple of moments to provide some additional context around the tax dispute and litigation. We believe some of the framing since our first quarter call overstates the potential cash impact. First, we firmly believe the IRS' proposed adjustments are without merit and our tax reserves are appropriate. We haven't changed that position in the last 4 years.

We will continue to vigorously defend our position as we have throughout this dispute with the Internal Revenue Service. Our position has been consistent, as I said, for many years and reflects the substantial value capabilities, investments, risks and contributions of our Puerto Rico operations.

Puerto Rico is 220 acres or so, 1.7 million square feet and 2,500 colleagues, many of them have technical degrees. It's a very, very important flagship operation manufacturing for us.

So then moving on to 2010 through 2015, a headline numbers from the IRS, they don't translate directly into cash exposure. As we've said before, the proposed amounts include $2 billion in penalties that we believe are wholly unwarranted. We believe the IRS calculations contain approximately $2 billion in errors.

And in addition, any potential payment would be reduced by up to $3.1 billion in repatriation taxes that have been previously accrued and paid. The last payment was actually last year of about $1.85 billion on repatriation taxes and also reduced by $1.9 billion in cash deposits that we've already made with the IRS.

So even if [Audio Gap] the 2010 through 2015, which we don't believe [Audio Gap] proposed adjustment from the IRS and the potential incremental cash impact to Amgen.

For 2016 through '22, those years involve a different tax framework following U.S. tax reform, different tax rates beginning January 1, 2018 forward, lower differences. And in particular, any extrapolation that starts with the 2010 through 2015 year would need to account for the calculation areas that I previously mentioned as well as that different -- those different tax rates and the repatriation tax payments already made.

So having -- let's get all that out of the way. Overall, we're executing against the plan we laid out for 2026. First quarter demonstrates that progress. Key growth drivers performing really well. We've got Murdo and Andrew with us today. I hope you'll explore that.

And that Phase III pipeline continues to advance 3 new Phase III programs with MariTide, a couple of extension or maintenance studies plus the SWITCH study that we've announced, and we're maintaining that rigorous financial discipline that we always do. Lots of ways to win with Amgen. We're very excited about the opportunities ahead for patients and for shareholders.

With that, over to you. Thank you for allowing me to share a few thoughts.

Thanks, Peter. One of the key investor debates for Amgen continues to center around the degree to which the company can offset the losses of exclusivity over the coming years. So walk us through at a high level, the degree to which you believe that Amgen can execute on this front and continue to drive top line growth with the current portfolio and pipeline.

Well, listen, let me flip it to Murdo and Andrew here real quickly. I'd just say somebody asked us earlier this morning about what we said a number of years ago about the long-term growth prospects. And boy, we've hit those hard.

And Repatha continues to be a fantastic franchise. I'm sure you'll [Audio Gap] that exist in primary and secondary prevention with Repatha, with EVENITY and the bone franchise and how well that's doing, with our BiTE portfolio. Thank goodness for the bike portfolio in small cell lung cancer patients in [ IMDELLTRA ]. We're going to go earlier on the IMDELLTRA.

We think lower tumor burden early lends itself exceptionally well to the bispecific T-cell engagers. So that's why we're promptly getting into xaluritamig and investigating that. and investing behind that. So there's lots of ways to win with Amgen. It's growing really, really well.

And look, the first quarter it's the evidence. And look, we've got to continue to execute at Amgen, and we talk about execution excellence all the time, Salveen, up 6% on the top, up 5% non-GAAP earnings per share in the first quarter. We expect to -- and we will work really, really hard to earn that throughout 2026 and going forward.

But let me turn it over to Murdo and Andrew because we're fortunate to have them with us today. I would just add that Andrew mentioned he's headed down to Puerto Rico because he hasn't had a chance to see those operations yet.

And I forgot to mention on Puerto Rico. I think we announced another $300 million going in there this year in investments. Last year, I think we announced about $650 million more going in down there. And so Andrew and I had a chance to catch up, and I was just sharing with them. I've been down there a number of times. It's just a great experience to go down and see the commitment of our colleagues down there, 2,500 plus to creating medicines for people around the world. So Murdo, Andrew, please.

I think you framed it well, Peter. We've got a nice story brewing at Amgen, given that we have a set of prioritized growth drivers, 3 large products with Repatha, EVENITY, TEZSPIRE by our innovative oncology portfolio, our rare disease portfolio and of course, our biosimilars.

So that story of breadth and that focus on those durable growth drivers gives us a real opportunity to sustain the loss of exclusivities that we will face currently with denosumab and Otezla in Europe, which a lot of people forget, we lost exclusivity there.

That business of growth drivers accounts for about 70% of our revenues in Q1 and is growing at 24% year-over-year. So that durable portfolio of growth drivers will allow us to continue to grow through losses of exclusivity through our long range. So that's a nice place to be. And given the number of catalysts for additional growth in that set of growth drivers, we're in good shape.

But Andrew, as you see your business, what are you excited about there?

I'm excited about Repatha, IMDELLTRA, PAVBLU and TEZSPIRE for me or the principal areas of excitement and largely is a byproduct of the enormity of headroom available to us in each of those categories.

If you start with Repatha, there's 100 million or more people globally with elevated LDL, about 50 million of those sit here in the U.S. Approximately 1/5 of those have their LDL today at levels expected as a result of the new ACC and AH guidelines.

PCSK9 have only penetrated about 10% or slightly less than that of that population. So it makes clear the enormity of the opportunity in front of us. And in fact, the momentum that we've created, we are confident, is durable and will sustain through the end of the decade for Repatha.

Same story for IMDELLTRA. We've clearly solidified ourselves as the standard of care in second-line treatment for small cell lung cancer. We frequently hear from oncologists that the durability of response and overall survival rate demonstrated in DeLLphi-304 have completely transformed the way oncologists think about the treatment of small cell lung cancer.

The NCCN guidelines and excellence in execution in the fields have allowed us to open up more than 1,800 sites of care across the country. Notably, half of those or more than half of those are in the community setting, which means we're bringing access to IMDELLTRA closer to the patients and where they sit.

And last, I'll touch on EVENITY. EVENITY is an incredible growth story in a massively undertreated and underpenetrated category of osteoporosis. More than 2 million women in this country have been diagnosed with postmenopausal osteoporosis that are either at very high risk of fracture or high risk of fracture and penetration of the anabolics into that cohort is less than 10%.

So again, another reflection of the significant headroom we have and why we're so confident in our ability to grow through the loss of exclusivity for denosumab.

Peter, you just spoke to the tax situation that's playing out with the IRS here. But you've also noted that the 2010 to 2015 tax [ court ] decision is expected no earlier than the second half of this year. Walk us through the scenarios that could play out when that outcome does come?

Well, I think, Salveen, on that, I would just say we've consistently said that we have confidence in our reserves. We have -- and we have all along. We have confidence in our position, especially after the tax court case itself, which ran from November of '24 to January '25.

By the way, it's not unusual that tax court, it's a different court system that it takes a long time to get a decision because if we do the math, it might be around 2 years before we get a decision, give or take. Think it's important to think about that.

But all along, we've said we continue to have strong confidence where we're at, both in our reserves and all the merit of what we have litigated with the IRS. So we're going to stay right there. We look at our reserves every quarter, we think about those. Our reserves include everything in them. We calculate both.

And the reserves are for everything in the company, not just for the tax case with the IRS. They're for all jurisdictions, all tax issues and so forth. We're very, very thoughtful about that. We're very confident in the tax leadership of the company and spent a lot of time on that. So that's really where we sit on it.

And people ask, "Well, gee, does it perhaps preclude you from thinking about transactions as it somehow affect what we might call our dry powder, so to speak?" I would just remind all our colleagues that in December 22, when we announced Horizon, that case was underway. And we've worked through it with the bondholders.

We had a $24 billion issuance of investment-grade debt, which at the time, I believe, was about the ninth largest issuance ever. And so we had no issues there. We don't expect any. We've got plenty of powder to do what we need to do. So we're going to vigorously defend this.

On the capital allocation strategy here, so how are you prioritizing internal investments such as R&D and manufacturing scale up versus business development opportunities and return to shareholders?

Thank you. So the #1 capital allocation priority to Amgen is to get to the best innovation, whether it's internal or external. And so we're agnostic. We understand we don't have a monopoly on the greatest innovation in the world. We also understand that our shareholders expect us to go out and find it.

And if we do find it, we're looking for, are we the best buyer? Are we the best license? Are we the best collaborator? Are we are the best partner? In other words, when we model that up, what does Amgen specifically bring to that, that's accretive and additive.

And number two, cash-on-cash returns in excess of what we're going to in excess of our hurdle rate. And number three, do we have research in there? Do we have science in the area that's proven? We've found over the years that when we compare where we have science and where we have research to where we execute on transactions broadly defined, we actually perform better and we get better returns.

And then finally, is it something we can integrate quickly? Because being a student of M&A in the capital markets, there's no question the data says faster the integration, the higher the return. And look at Horizon, that's what happened. We got after that quickly. That was a world-class integration by the entire enterprise at Amgen, and the results speak for themselves. And we are so happy to be in rare disease today when we went into it in a big way in December '22.

So I would just say, internal is fantastic. I mean we are working hard on the BiTEs. They're going really, really well. We'll continue to invest in MariTide. That is an internal asset. It's -- we're backing that up. We've got -- we'll have 9 Phase IIIs on that coming up here as we -- I guess we're underway.

3 more after that.

With 3 more after that. So we're going to get to a dozen. I said to Jay Bradner, I said, "Jay, you need 1 more. We'll have a Baker's dozen, but we're going to invest behind that." So capital allocation.

Let me tell you, this company is doing a great job. Rigorous financial discipline, 45% to 46% operating margin guide this year, and we'll be up to 12 Phase IIIs on MariTide. We've got Phase III going on Olpasiran. I think we got about 7,200 patients in there. And then we got [ xaluritamig ] going full speed in Phase III for pre-taxane and post-taxane.

So we've got a lot going on companies exhibiting strong rigorous financial discipline to reallocate back up and innovation. And after that, in our capital allocation hierarchy, if I go down one more notch, we're investing in the business, $2.6 billion guide in CapEx this year. And that's -- we need the capacity to hit the volume requirements that Murdo and Andrew are creating through the opportunities they're getting as they get medicines to these patients.

So we'll continue to vigorously fund that. Last year, we put some money behind UPLIZNA to the -- a couple of those new launches. So we're excited. We've got capital to allocate. We're going to do it prudently, thoughtfully and in a disciplined manner. But the capital allocation hierarchy is not going to change.

And just given that you are at pre-Horizon debt levels here, how willing or interested are you in doing a similar size transaction? And what are the therapeutic areas of focus right now for the company?

Well, let me -- I'll comment on size, but I think it's a great question for me to tend over to Murdo. He and I and Jay and [ Raj ] and I'll work really closely together with BD, but he's got -- he's more articulate than I am on the specific areas and he's deep into them.

In terms of size, look, we our aperture is always open. It was open when Horizon showed up. We had thought about rare and Horizon well over a year before it showed up. We didn't know that it would become actionable, it became actionable, and we were ready to go. And we were able to execute and get it done.

So we're always ready to do whatever we need to do. But again, we go to that capital allocation hierarchy, is that a company with innovation that we're excited about. It might be really small, we won't go out and spend the time and invest in that, might turn into a great opportunity. If it's of a different size and small, medium, large; we're agnostic on size, agnostic on structure.

And we'll do what we need to do to -- if it's going to hit those 4 criteria I talked about for BD, we'll take a good look at it. And if it benefits our patients and our shareholders, we'll get after it. So -- but Murdo should talk a little bit about where we're thinking in terms of the therapeutic areas and different opportunities there, too.

Yes. I think Peter has covered it really well. We look at areas of complementarity, whether that be in our research and development capabilities or in our commercial capabilities.

So if you look at the presence that we had in autoimmune from larger disease areas, translated really well into rare disease when we looked at the Horizon transaction. And as Peter said, we have a really well honed process to integrate new organizations into Amgen and retain the talent as best we can when we do that.

[Audio Gap] As you look forward, [Audio Gap] strength here, we have a very nice growth plan now with the integration of a rare disease business with the products that Andrew mentioned and with our biosimilars portfolio, we can look at a long horizon at earlier opportunities, we can look at mid-stage or even late-stage development assets.

But we're not looking to plug a big hole in revenues anywhere. We've got a nice growth story from the in-line portfolio and the mature late-phase pipeline that we have.

So we're looking in all therapeutic areas. We continue to see oncology, obesity, cardiovascular metabolic, rare disease, rare autoimmune; all as really exciting areas for us. And we do look at everything. I mean we have a large aperture when we look outside the company. So we have an opinion on whatever may transact and whether or not we want to jump in.

Great. Murdo, jumping into the commercial portfolio here. UPLIZNA significantly outperformed in 1Q, driven by the launches in IgG4-mediated diseases in Myasthenia Gravis. Can you highlight how you're thinking about the key launch dynamics to date and the trajectory in both of these indications on the forward?

Yes. No, I'm glad you think it's outperforming. It's always interesting that's in the eye of the beholder. But no, internally, we were excited about this asset when we did the acquisition. And obviously, with positive data in IgG4, I mean, overwhelmingly positive data in IgG4-related disease and then very strong data in the MINT trial in gMG. We see we have a differentiated product in both of those indications.

So strong foundation NMOSD, that continues to provide growth. IgG4-related disease, we're creating the market as we're satisfying it with the only FDA-approved agent there. That's hard when you're doing both, when there's no kind of existing big market where you have a relatively new ICD-10 diagnostic code and you're creating awareness and you're fulfilling that awareness. So that's harder than going into gMG, where there's an established market with incumbent products.

Now the growth outlook for IgG4 is very strong. There's large headroom there. The numbers on [ epidemiology ] are a little fuzzy, but let's say, between 30,000 and 40,000 patients that are eligible for treatment with UPLIZNA. And it's a horrible disease. It goes undiagnosed, physicians often are unaware as to what it is they're looking at. So we're helping with diagnosis and awareness. We're helping patients activate, and that will be a good source of durable growth for the product.

gMG, a little quicker, right? So we're seeing a good source of business coming in from bio-naive patients as well as SWITCH patients. And the SWITCH patients are coming from multiple places, not just one specific product or product category. So very good launch so far.

We did, as Peter mentioned, expand the field resources in both medical and commercial to be ready in advance of the gMG approval. And that's helped, I think, as well being ready. And we're looking at further investments to help activate more patients who are looking for improvements in their activities of daily living despite being on treatment. And we're helping build awareness of the convenience of UPLIZNA and its durable efficacy. But really exciting and a lot of headroom for growth still there.

How do you think the competitive dynamics will evolve with the entry of Regeneron C5?

Yes. I think the experience in complement inhibition in general has been mixed. We are sourcing business from the existing complement inhibitors, and we'll see what the Regeneron profile brings.

But I think given that we're highly differentiated in our mechanism and very convenient in how we [Audio Gap] I really don't see that as a direct competitive threat for us. I think there's so much bio naive and SWITCH patient sourcing that we're doing that we should be able to grow through that.

I should say, we're also in the clinic into additional indications with AIH and CIDP. Peter mentioned in his opening remarks. So we're excited about how that profile, that highly differentiated and convenient profile of UPLIZNA can help patients with those conditions as well.

2027 looks to be a big year for Amgen with regard to cardiometabolic and MariTide, and obesity being one of them. Given the Phase III program, the broad Phase III program is underway, including SWITCH and [ maintenance ] studies, how is your team preparing to launch in this highly dynamic and competitive market? And what do you see as the most important aspects of the commercial strategy?

Yes. Look, we are planning on going to market to establish ourselves as a leader in that category. We have continued to expand, and I'll ask Andrew to comment in a moment here, but we've continued to expand our cardiology and primary care presence for Repatha. We will grow that even further, given the momentum that we're seeing with Repatha in primary care.

We also just presented some data at the ADA on a subgroup analysis from Vesalius-CV for diabetes patients and being able to reduce their risk of an event. So we've got very nice overlap there. That helps, but we'll expand even beyond that for MariTide. So we're already expanding our medical effort. And we will be ready well in advance of those Phase III data coming out for the medical team and then obviously in advance of the FDA approval.

I think it serves us well to have people in territory ready to go well in advance of when the approvals occur. So we're planning on being very competitive in that market with a highly differentiated profile. That's really the thing that we started this journey with, was anticipating in the time frame for when we would launch, there would be a very busy, very competitive market, and that's played out. We've seen that just with a number of new original data presentations at the ADA.

But nothing seems to compare to the differentiated profile that we've got. And so what we said years ago when we started the early Phase I and Phase II clinical trials on MariTide, that differentiation has held up. And so we're in really good shape there.

Differentiated product, the scale of Amgen to be able to go to market, the foundation of Repatha and cardiovascular, I think we've got a really good approach to the opportunity that MariTide represents.

And as we look to all past around data next year as well, Novartis has pointed to about a 13% to 15% MACE benefit from pelacarsen is meaningful for LP(a) control. In the context of just that commercial outlook here, how do you think about what would ultimately drive uptake for a drug of that profile, but also your drug as you look to -- we've seen deeper knockdown?

Yes. Look, I like what we've done in our clinical program. We showed in Phase II that we've got a very potent reducer of Lp(a), 95% to 100% reduction in Lp(a). So if the hypothesis can be validated, olpasiran is the drug that can validate it, given its ability to lower Lp(a). Our patient inclusion criteria, we chose a slightly higher cut point than others did in their clinical trials. So again, slightly higher risk population if the Lp(a) hypothesis bears fruit.

And I like our chances to be able to deliver a strong hazard ratio at the end of that trial. So if pelacarsen reads out favorable, I like that we'll be able to positively differentiate beyond what they show.

And that -- you have to look at the cluster of cardiovascular risk factors here. Physicians are looking to do more and more for their patients. And Lp(a) gets a mention that in the guidelines, it is moderately lowered by Repatha and PCSK9s, but not really.

And so if we are trying to further reduce cardiovascular risk, this genetically defined biomarker needs a specific [Audio Gap] again, no faster [Audio Gap] looks like potentially.

You also have Phase III data in Sjogren's coming by year-end. How are you thinking about the likelihood of success here and the size of the opportunity?

Sjogren's has been a difficult disease area, kind of intractable for a lot of different mechanisms. So I like the purposeful design of dazodalibep. Obviously, the Phase II data look interesting. Horrible disease. Hopefully, in Phase III, we're able to demonstrate efficacy and safety in that category.

But it's a large underserved area where a lot of off-label medicines are used with nominal efficacy and some safety baggage. So very attractive for us. And we've got this -- we were talking about before, we've got the rheumatology capabilities, both in the research, medical and commercial arena. So it fits very well with our portfolio.

And a last question for you, Peter. You raised 2026 guidance on the 1Q call. How would you -- what would you highlight here as potential upside or downside drivers for the 2026 range that we should monitor?

Well, let's go back to those six key growth drivers. So things are going really, really well. with those. So I always like to start with those Repatha, TEZSPIRE, innovative onc, rare disease portfolios, biosimilar portfolio.

But I would say, as we think about the company and what happens in 2026, Salveen, the breadth of the company in the market is strong, 17 products annualizing at $1 billion or more. There's 16 products with double-digit growth or greater, both of those over the prior year's quarter.

And I would just say there's a lot of ways to win there. And our commercial group is working with our operations to make sure we get those to patients in every possible way we can. And so that's strong.

But I would also say we've got this -- in '26, it's important [Audio Gap] we want to win in the pipeline. So it's this disciplined data generation that Dr. Bradner has been talking about for this year. We're working really hard on that. We're going to demonstrate execution excellence in that and make sure we're after that and make the progress we want to make this year in that pipeline also.

So the breadth of the end-market portfolio and how well that's doing the depth of the pipeline and what's going on over there, I think it makes 2026 a year that will be great for patients and strong for our shareholders. And then going out towards the end of the decade and beyond, that strong end-market portfolio, those six key growth drivers, 70% of product sales in the first quarter 24% growth as a group and then going forward, the pipeline will continue to deliver on that.

And we've talked about that, and you've covered Maridebart cafraglutide also known as AMG 133 or as all of you know it, MariTide. And so we're excited about the opportunities that, that will bring and we'll continue to invest behind that.

But Amgen is a great story of rigorous financial discipline, coupled with a very clear capital allocation hierarchy. And at the end of that hierarchy, every time we talk about it, we're going to talk about innovation, the best innovation, whether it's internal or external, and we're working hard at that. And we think we'll continue to be in a position to create value for patients, shareholders and also for our staff.

Just one other question I wanted to touch on. So you've guided to relatively stable operating margins of about 45% to 46% this year as you invest in the late-stage pipeline. How should we think about the evolution of margins as you look to the end of the decade? Could you see expansion back to prior levels?

Well, we don't give long-term operating margin guidance. But in terms of how do we think about the discipline around that, that rigorous financial this one, remember for many years, and that's what you're referring to, beginning in 2013, '14 or '15, I wasn't around then, but we upped our game and took the operating margin up around 50%.

I always said when I came into the seat late '19, I said, if there are opportunities to achieve cash-on-cash returns in excess of our hurdle rates for our shareholders that made sense, we would flex that margin.

And in the last couple of years, thank goodness, we've had the opportunity to do that because that results in -- as Casey mentioned, we're going to have 12 Phase II trials in MariTide at the end of the year. We've got a pass around and moving along with 7,200 patients. We've got value Xaluritamig in Phase [ III ]. We've got the ability to invest behind that.

And we think those are fantastic opportunities. And when we have an opportunity to invest behind what's out in the market right now behind UPLIZNA and make sure that's getting delivered to the patients that should and EVENITY and invest behind that and make sure that's getting to the underpenetrated market that Andrew and Murdo referred to and same with Repatha. I mean, boy, we had an old saying years ago, "Boy, back your winners". And that is such a great medicine for patients with such a great data set.

So that's really how we think about op margin, Salveen, but it's important to us. We understand there's expectations of Amgen to be a top performer in the operating margin percentage, and we're going to continue that. And we're using all the tech and data and AI we possibly can, just like everybody else is.

We have high expectations of ourselves. And we've got a CEO that has high expectations of us and what's going to happen there. And we're excited about that and the challenge that represents.

So we'll continue to be efficient, we'll continue to be effective, and we'll continue to make sure that we produce an operating margin that our shareholders think makes sense in light of the opportunities to invest and in light of the opportunities to exhibit strong financial discipline.

With that, thank you so much. Really appreciate the time.

Thank you, Salveen. Thank you, Goldman Sachs.

Good morning, everyone. I hope you're doing well. Really pleased to see a packed room and really that goes for right now and also just the entire conference. My name is Akash Tewari. I head our pharma and biotech efforts here at Jefferies on the research side. And we have Amgen on the panel today. So really excited to have a discussion.

I'll hand it off, maybe, to Peter for opening remarks, and we'll get going.

Great. Thank you, Akash. Good morning, everyone. Great to see you. We are glad to be here. I'm not used to holding the mic. All right. So we're just -- we're really glad to be here with you. We appreciate your interest in Amgen and a couple of thoughts for you here before we get going into the Q&A.

We believe there are lots of ways to win for Amgen, especially for patients. We're pleased with the strong first quarter performance, which reinforces 2026 as a springboard year for Amgen. This is a year which we expect our rapidly growing products to offset the impact of the loss of expirations on our denosumab franchise and the increased competition there that will occur throughout this year. In the first quarter, we did exactly that. Revenue was up 6% year-over-year and non-GAAP earnings per share was up 5% year-over-year, demonstrating the disciplined financial management that is historic for Amgen. 16 products delivering double-digit or better sales growth. 17 products annualizing at $1 billion or more based on those first quarter product sales.

So as we've been saying for quite a long time, breadth and depth across our portfolio. Importantly, our 6 key growth drivers, Repatha, EVENITY, TEZSPIRE, the innovative oncology portfolio, the rare disease portfolio and the biosimilars portfolio made up 70% of the product sales in the first quarter, and that group grew 24% year-over-year. We expect those to continue to drive us through the end of the decade.

I would suggest in that, that inside the innovative oncology portfolio, we have IMDELLTRA now annualizing at over $1 billion, a medicine for treating small cell lung cancer, and I'm sure we'll talk about that a little bit. Inside of the rare disease portfolio, we have UPLIZNA, which is treating NMOSD, neuromyelitis optica spectrum disorder. It's good for the CFO, isn't it? Not bad. And also IgG4, which it was approved to treat, I believe, last May and then a year ago, May, and then also GMG, generalized myasthenia gravis approved in December, I believe. And so we're very excited about UPLIZNA. So the growth drivers are doing very, very well.

Turning to the pipeline. Confidence continues to build in MariTide as a new paradigm for the treatment of obesity, type II diabetes and obesity-related conditions. We're executing effectively across the enterprise in the pipeline from clinical development to manufacturing. And as part of that, we're advancing MariTide's broad Phase III program and build and optimizing our manufacturing capacity ahead of that launch. And I've had an opportunity to visit all of the sites a number of times and our great manufacturing capacity, our world-class manufacturing capacity is coming along really well. We expect MariTide to be really important for weight loss induction, long-term weight maintenance, patients switching from weekly GLP-1 therapies to MariTide with the potential for as few as 4 to 6 injections per year. Our approach reflects how obesity care may evolve. Patients need effective initial weight loss, but they need practical, durable maintenance options.

And beyond MariTide, we have a robust Phase III pipeline, including olpasiran, which is for the reduction -- being investigated for the reduction of CV risk in patients with elevated Lp(a). I would note Narimon is a cardiologist in charge of our development. So I'm sure we'll want to visit olpasiran here as important as that will be. Dazodalibep being investigated for Sjogren's disease, xaluritamig being investigated for late-stage prostate cancer, another bispecific T cell engager. We're also investigating xaluritamig in earlier stages of prostate cancer.

In addition, we're pursuing new indications for several of our approved products, including UPLIZNA, which I mentioned previously, in autoimmune hepatitis and chronic inflammatory demyelinating polyneuropathy or CIPD, TEZSPIRE in COPD and eosinophilic esophagitis and IMDELLTRA, again, in early-stage small cell lung cancer.

Now Akash, I know you have a KOL or key opinion leader call, I think scheduled tomorrow on the...

On the tax case, yes, that's right.

And so I just wanted to mention on the tax front since there have been some questions around that since our first quarter call. Two related matters with the same core issue, value attribution. The IRS is arguing that our Puerto Rico operation should be treated as if it were essentially a limited-value contract manufacturer. We strongly disagree with that position, and we have since they've adopted it. We've got 2,500-plus colleagues who are United States citizens at our flagship facility there in Puerto Rico, the majority with technical degrees. It's a very complex operations.

Remember, there are 2 tax periods in question now, 2010 through 2015 and then 2016 through 2018. 2010 through 2015, that tax court matter is not new. It's been around for a number of years. There have been no changes in our position on the status of that case. It's been fully tried and litigated. The tax court stopped hearing that case in January '25. We don't expect a decision from the judge any earlier than the second half of 2026.

Now as fully expected in the ordinary course of the IRS audit process, we received a notice of proposed adjustment, or NOPA, as I call it, for similar transfer pricing issues for that 2016 to 2018 period. It's just an early step in what we would expect to be a multiyear process. It's not a final determination. And importantly, our commitment to Puerto Rico continues to grow. Since our first quarter call, we announced -- you may have seen an additional $300 million investment into Puerto Rico on top of the $650 million that we've announced also in the past year or so. Puerto Rico is a core part of our operations, our manufacturing network, flagship facility, advanced manufacturing capabilities for biologics, deep expertise all the way around. So we disagree strongly with any characterization of those as our operations there is limited value contract manufacturing. So we continue to believe the IRS claims are without merit and our reserves are appropriate as we have all along.

Just closing, we are executing against the plan we laid out for 2026. The first quarter demonstrated the strength, the breadth, the depth of the business, 6 key growth drivers are performing, Phase III pipeline moving along, and we're maintaining our rigorous financial discipline on behalf of our shareholders as we're investing for the long term. Lots of ways to win, Akash. I just wanted to share those comments. Thank you.

No, I appreciate that. That's excellent. And the last panel I just hosted was an AI panel. So I'll give a brief question on this, Peter, to you. And it's -- I think we often hear about AI for drug discovery but we had Albert from Pfizer and he's saying, look, right now, for large organizations, it's about how we operate our cost basis much more efficiently, and that's going to be the first wave of changes.

So really, here's the question. China is making drug discovery cheaper. The cost of making drugs has gone down. Commercial organizations are becoming more efficient. And yet, when I look at my model, I'll criticize myself or really the Street widely, we are not modeling these businesses, including yours, being a step order more efficient when we think about the margin structure, right? We still have the 20% to 25% on R&D. We still have the 20% to 25% on SG&A. And then we have the corporate costs, which can often be very substantial. Are we making a fundamental mistake here? And we are going to see enormous improvements in operating structure with companies like yours in the not-too-distant future.

Thank you. It's a very important question. We are fully committed to technology, artificial intelligence, data. And I would suggest we're fully committed to it across the enterprise. And I will invite Narimon in a moment to discuss ways in which we are using it and applying it in our research and our development functions. But I have said all along, Akash, that in research and development, becoming very, very proficient if you're one of the leading biopharmaceutical companies, which we are, we better be good at it, and we better be on it and working it as effectively, efficiently as we can.

As you go across the enterprise, if I -- if you would allow me before I turn over to Narimon, manufacturing, we opened Amgen, Ohio, which is a finished drug plant a couple of years ago, finished drug processing plant. And that is our most technologically advanced plant. So roughly speaking, we have maybe 50% or 60% of the headcount we would have had in a plant before that. And by the way, the labor is fabulous in Ohio. We're super pleased with it. We're actually opening another plant there. It's under construction, AOH 2 right next door.

We call it a Butterfly plant, just to open the wing up. The technology, the AI there is fantastic. We have -- it's either 7 or 8 automated ground vehicles. Nobody drives forklifts anymore. They're automated, no injuries. They don't go on break. They haven't been getting sick. They get recharged and plug themselves in when they've got time to do it. We then move over to the commercial operations, and we're using it very effectively there. We use it -- Kave, I'd invite Kave after Narimon speaks to talk briefly about it. I know we're taking some time, but this is important.

And Akash, I would suggest we're -- I've guided to on behalf of Amgen, a 45% to 46% operating margin this year. Look, as part of that, we have to start and are incorporating some AI to become more efficient. We -- I would suggest AI is going from the individual and functional use cases across companies, including ours, to enterprise use cases. And we're after that. We are pursuing it vigorously. We think it's really important. And we realize, too, that it's going to cost more. When Google does an $80 billion equity offering, somebody is going to be paying for the cost of all this compute at some point. We're all beginning to, and we're going to be thoughtful about that. So we feel it's incumbent upon us to get those returns for our shareholders and most importantly, to use it to get innovative medicines to patients better, cheaper and faster.

So with that, Narimon, maybe a sentence or 2. I know we're taking some time, but this is so important.

Yes. No, thank you, Peter. And thank you, Akash, for the question. As Peter mentioned a moment ago, we're using artificial intelligence, starting with the very beginning of the R and all the way through the end of the D in R&D. This gets into helping us develop new insights, improving our speed, cost and quality of the work that we do in R&D, all of which are very important.

To give you a sense of some examples of that in terms of insights, think about the data that we have had through our work at Amgen deCode and looking at multi-omic data. We're looking at human genomic data, proteomic data, pulling all that information together and coming up with new targets to interdict upon developing new medications. That is now going to be accelerated and assisted with AI, new insights. We also use this technology to help speed up our late antibody optimization efforts in developing the therapeutics, right? We've seen improvements in speed of up to 50% on that angle in developing the therapeutics to then take into the clinic for clinical testing. Once we make our way into clinical studies, we've applied artificial intelligence in helping us select the sites tailored to the population of patients that we're recruiting.

And at times, we've seen a threefold increase in the speed of recruitment on the basis of picking the right sites that are tailored again to the right drug for the right trial. And once you're finished with the clinical studies, there's, of course, another R, and that is regulatory and filing, and we found that artificial intelligence has enormous potential in ingesting all of this data that we've generated over the life cycle of a medicine and putting it in the form of a draft document that will be ready to submit to a regulatory authority for review. So you can see through all of those steps, you get new insights. It helps with the speed, obviously, the quality of the work that we do goes up, and that will ultimately help us reduce cost.

Kave?

Yes. From the commercial standpoint, to build on what Narimon and Peter shared, we're really focused on the use of the technology to speed up the access and use of our medicines around the world. So we've got 3 big areas where we're focused on AI right now. First, remove the friction from getting access to our medicines, both in the U.S. and abroad, going along with the regulatory comment that Narimon made, it's great if we can get the medicine approved faster. We also need to get it paid for faster. And so using the AI to speed up the filing of our reimbursement applications, the quality of those reimbursement applications. But in the U.S., access to medicine in terms of understanding where you are in the insurance scheme, co-pay, prior authorization, patient support. So that's one big pillar, and that's going to show up in the revenue side more than the cost side overall.

Second area is in patient identification, which is really important in rare disease. We've built some really great capabilities of identifying where patients are so that we can interact with the physician around the time that patient is seen. We're using the AI to speed up and enhance those capabilities, which allows the effectiveness of our promotion to go even higher in those areas.

And then third, we know that physicians are using AI to change their own behavior. So making sure that our content and messages are showing up in those workflows in the AI of their choice is helping us identify and get patients on to therapy faster. So Akash, when you think from the commercial perspective, we're going after the efficiencies, but those efficiencies are being reinvested to drive the top line faster more than the cost line down at a differential rate.

I think that's an important point to note. And I think you'll hear that pretty consistently. It's more about top line growth rather than just outright cost cuts. Maybe going into the clinical side, and we'll start with Lp(a). And it's -- to me, you look at the genetic data, it's clearly a predictive marker. But LDL-C is such a rare kind of biomarker in cardiovascular disease because seemingly, the more that it goes down, it continues to have a benefit I always worry for Lp(a), there might be more of a threshold dynamic where you get to a certain range and you can kind of get into a range where it's not really impacting your cardiovascular risk. So there's more threshold dynamic rather than a marginal dynamic. We've seen headlines from Novartis and others in the field that these trials all tend to go longer and longer.

I'd love to get your take about these trials going longer than expected, the difficulties in terms of modeling kind of event rates in a modern cardiovascular population. And should we interpret the fact that these studies are going longer negatively or not?

Thank you for the question. It's a really good question. Let me start by reminding us that we've had over 50 to 60 years of the benefit of looking at LDL, understanding LDL biology and the science. And thank goodness, we're finally getting to the point and concept that lower is better, lowest is best, right? And with Repatha, I think we have developed a very compelling evidence base, a mountain of evidence, if you will, that shows that, that is, in fact, the case.

Now one of the important lessons from that half century of understanding LDL science and LDL biology is that it is the totality of LDL cholesterol burden reduction that is important for patients. So think of it this way. If you have a patient who has had a very high LDL cholesterol, carrying a large load for a very long period of time, that person is at high risk for having atherosclerotic cardiovascular disease, a heart attack, right? And what you want to do for that patient and the science has borne this out and reduce it to a very simple equation from the CTTC data is you want to remove as much aggregate LDL cholesterol burden from that patient for as long as possible, right?

If you look at the math, the equation is for every 38 milligram per deciliter reduced LDL cholesterol, you have a 22% reduction in relative risk for major adverse cardiovascular events. That's the reduction of LDL cholesterol. And it's what makes a PCSK9 therapy like Repatha so powerful, right? Start earlier, take it longer, reduce the LDL to as low as possible. That's where the puck is headed for LDL biology.

How do we apply that to Lp(a)? Your question, all right? Well, Lp(a) and LDL have a lot in common. If you look at the particle structure, they look quite similar for the exception of a covalently bounded more atherogenic and thrombotic protein, the L(a) of Lp(a), okay? And the way that we've approached studying Lp(a) is we want to start with the patients that have the highest burden of disease, highest burden of Lp(a) that are at risk and have shown that they have had untoward cardiovascular events, specifically coronary events, and we want to be able to follow those patients for a longer period of time. And that is exactly how our study has been designed, high Lp(a) threshold, more than 200. We have an incredibly effective medicine with Olpasiran that can reduce that Lp(a) by more than 95%. In some cohorts from our Phase II, we reduced it by 100%, right? And you want to have this type of therapy for those patients that carry such an enormous Lp(a) burden for a long period of time and have already suffered the consequences of poorly controlled cardiovascular risk. So that is the basis of the outcome study that we have designed.

And as you said, Akash, the human genetic data, Mother Nature's experiment, the human epidemiology, all the anecdotes that we're seeing in the field, all point towards this being a very important dimension of residual cardiovascular risk. Once you address LDL cholesterol, you absolutely have to address your Lp(a) and 20% of us in this room, unfortunately, have a high Lp(a). And I really hope that all of us have at least taken efforts to measure it because we have taken so long to understand what LDL values are for ourselves, and that is simply not acceptable, simply not acceptable in today's age with the technology that we have.

So what do we make of the slower event rates? Should we be discouraged? Absolutely not. In fact, what we've seen over time is if you go back to the '80s to the '90s to the 2000s, the event rates for accruing cardiovascular events have slowly gone down in the population, right, of clinical studies. Why is that? Well, we demand them to be on better medicines for one, right? You want to see patients on PCSK9 inhibitors in a cardiovascular outcome study, so you can understand what value your therapy brings forward on top of LDL reduction.

And so that's one reason for it, all right? There are a number of other reasons that could include highly efficacious mechanism with Lp(a) reduction because when you're looking at event rates in a study, you don't know which arm is having the event rate reduced. You're looking at an aggregate value. And so if you have a very effective therapeutic, the aggregate value of the event rate accrual is going to be lower. That is just going to be the simple math out of that.

So I don't really take any negative signs or concern out of the event rate that's coming out of these studies. I think it's a natural outcome that we expect to see from better care and potentially very effective medications being brought into the clinical trial arena. And I remain very enthusiastic about the mechanism, and I'm looking forward to see what the Novartis study will tell us.

It's a very clear answer, and I really do appreciate it. Hitting on MariTide, and really, I think there's an interesting scientific question because your team has talked about an antibody is different than a peptide in terms of how you can sensitize the receptor. I think Jay talked about it marinating the receptor in an interesting way. I wanted to think about that phenomenon versus like you look at Novo, you look at Lilly. I mean these are companies that are more sophisticated than anyone in terms of running these trials because they have the experience.

And I remember going to ADA 2 years ago when the Amycretin data came out, and it's like 50% vomiting on all their amcretin arms. And they're moving forward to Phase III. And even with orfoglipron, the issue of geographic variability came up pretty predominantly because your diet can really impact your nausea rates. So when I look at for your drug and MariTide, really provocative data that you showed with a different kind of titration regimen, but that was 140 patients in sites in Texas. Now we have to extrapolate that phenomenon to a worldwide perspective. And that's really -- I think the question a lot of investors have is, when you think about geographic variability and just the complexities of running these obesity studies, which is seemingly getting harder, not easier because the adoption has gone up, how do you think about that phenomenon relative to also that really provocative data you've shown that perhaps an antibody has a different type of, I guess, desensitization that maybe a peptide won't, right? How should we think about that?

Yes. Thank you. Again, a great and insightful question on your part, Akash. Let's start with some basics. There are over 1 billion people in the world that suffer from this disease that we call obesity, well over 1 billion, right? And that number is not coming down. And we look at the tremendous success we've seen from the newest therapeutics entering the field, and we see that the usage is about point or 2% or less of the addressable population, okay? So there are a lot of people that have yet to even be touched by a medicine that can treat their obesity, and they really need this medicine. So as we think about the whole space of opportunity, there is still almost all of the opportunity that still resides out in the market for patients that need a treatment for obesity.

So the opportunity is remaining very large. It's true that the scientific bar has gotten up, right, has raised from 5 years ago. But the opportunity remains very large, and there absolutely are going to be segments of the population, which I think you're getting to that are going to benefit more or choose one therapy over the other. MariTide has a very competitive and compelling profile from all the data that we have accrued thus far, Phase I, Phase II and our very encouraging experience in Phase III, right?

We have what we believe is a very compelling and competitive efficacy as well as tolerability profile. And more and more people need to understand that these medicines for chronic long-term conditions need to be taken for a long period of time, right? You benefit from medicines, including medicines that reduce LDL cholesterol by taking them for a long period of time. It reduces your burden of disease over your lifetime. That's how you appreciate the benefit, not just on weight, but all the comorbidities that are chronic comorbidities like heart disease, liver disease, diabetes from them. So why is this important? It's important because you have to think about what are the attributes of your medicine and intervention that enable a patient to take it for a longer period of time, right?

So when you talk about a medicine going from being administered daily, which was back in the day of the first GLP-1s daily to then weekly, that was a big innovation. That was helpful. It's going to be very helpful for people to go from weekly to monthly, potentially every 2 months and potentially every 3 months, right? And these are the questions that we are interrogating with MariTide. We start with monthly. We've recently announced 2 studies that are going to look at maintenance beyond the initial phase of treatment that will look at every 8-week and every quarter administration. You mentioned the SWITCH study, where we're taking patients that are starting on their weekly medications.

And again, we're going to help them understand and the world understand what happens for patients when they take those weeklies and decide, you know what, I want to go to every 2-month or every 3-month administration. This will help with a large segment of the population, irrespective of the geography in which they reside. These are compelling basic needs of patients around the globe. And obesity, like many other diseases that we may end up talking about over the course of the day, is a condition where patients will need more options, not less options.

By the way, I will interpret your answer this way, and I think it's quite important. The sense I get, and I think it's a fair point, which is we're so obsessed with these kind of contrived 68-week studies with titration profiles that no one actually adopts in the real world. And your point is when you look at maintenance data, when you look at switch data when patients are already on a background GLP-1, there's tons of data that can show the drug is very tolerable to switch.

So that in and of itself is an opportunity. So it sounds like we don't know the answer to this question, we'll get in the clinical trial, but we're thinking about this the wrong way is maybe the right way...

Absolutely. You're absolutely right. And think about this. Half the people today of those 2% that have access to these medicines stop taking the medicine before a year is up. That's not great for those patients. And so we absolutely have to address the need of those people.

Understood. Kave, this is a transition to maybe when you think about launching MariTide and the commercial opportunity, it's interesting. There's just seemingly this obsession with this race to the bottom on price. And I always feel like whether you're Novo, Lilly or Amgen, you're thinking about a portfolio approach, you're thinking about sequencing patients on multiple therapies, but also the entry point might be $150 at a low dose. But by the time MariTide is getting on the market, you have potentially millions of patients who are GLP-1 experienced who are now in the insurance market, right? And one of the things that I think stands out about your development program is you're running the outcome studies. You're running -- you're getting clinical data as well.

So when you think about MariTide in the U.S., should we think about it not we're thinking about coming in at direct-to-consumer $150 to compete with oral Wegovy. But no, it's going to be patients who have already failed a GLP-1 often an oral or Wegovy. And now they are going to be in the traditional insurance system. Is that the right approach to think about in the United States? And then when you think about ex-U.S. launching an injectable medication, but it's a huge market, how do you launch an injectable product well in the rest-of-the-world market, forget even just EU-5?

You covered a lot of ground there, Akash. So let me just say, I think that, first, having a great partner like Narimon to really work through these issues in advance in development really helps us from a launch perspective. We think we've got the data that's going to, over time, show that it's easy to start on MariTide. It's easy to stay on MariTide. It's easy to sustain that weight loss on MariTide. And we're going to be ready for a number of different kind of segments of that market, whether that's patient-directed market, and insured market, to your point, throughout.

So one of Amgen's strengths has always been the tight intersection with access through our development plans and our commercialization plans. And so understanding the data and the economic drivers of a payer versus a patient is something that we are building that evidence base of so that depending on how the market evolves over the next few years, and it will evolve quite a bit, we're ready for that market. I would say thus far, what we've seen from a pricing standpoint is in line with our expectations of what we thought would happen.

And we are seeing in this market, which is different than a lot of pharmaceutical markets that the price reductions are coming with demand lifts overall, and that's directed primarily by that patient-driven segment. But irrespective of where the patient is, we want to have a solution for them and the development plan is helping us do that for the United States, but also for outside the United States, where some markets will be more patient-driven and some will be more reimbursement.

And just to hit on that, in line with your expectations, actually, that isn't totally dissimilar to, I think, how Lilly would describe it. But there is this sense, I think, with the established players now that we are maybe out until the end of the decade to, at least in the United States, a level of pricing stability. We'll have mid-single-digit declines but they seem quite confident that price of a cup of coffee, you've kind of reached that price point that there is a ton of inherent demand just to have. And really, the work is going to be on insurance access and just negotiating those contracts. Is that maybe the view Amgen has Because, again, MariTide is -- you're going to be thinking about that commercial market pretty shortly.

Yes. I think that's a scenario that's out there, Akash. We're ready for a lot of different scenarios, and we're really looking to see how they play out in the market in advance of our launch. But I think we're going to be ready for those scenarios once we get to market.

Understood. I'm going to sneak in one more question on IMDELLTRA. And it's really about the opportunity in maintenance. And it's funny, a lot of people focus on KEYTRUDA and lung, but I think a lot of the money they make is in a maintenance setting. I don't think that's well appreciated. Would it surprise investors if the maintenance opportunity in IMDELLTRA could actually be bigger than the frontline traditional opportunity there?

Yes. I'm just back from ASCO. I can tell you that the physician community is extremely excited about IMDELLTRA in both the frontline and in the maintenance setting overall, and we're excited to be releasing additional data over time that shows that durability of response getting to long-term survival overall, Akash. I would say that data will still mature to inform the field, but I can tell you my interactions, the field is quite excited about the maintenance use of IMDELLTRA.

Understood. Thank you so much. I really do appreciate it.

It's wonderful. Thank you, Akash.

Thank you, Jefferies. Thank you all.

I'm Tazeen Ahmad. I'm one of the senior biotech analysts here at the bank. It's my pleasure to have our next presenting company, Amgen. Sitting up on stage, our several members from the Amgen team. Thanks in advance for making the trip over from California. We really appreciate it.

So we have Peter Griffith, who is Executive Vice President and CFO; we have Jay Bradner, who's Executive President of Research and Development; and then we, of course, have Casey Capparelli, who is Vice President, Investor Relations. Gentlemen, thank you for making the trip again.

Thank you for having us.

Okay. So maybe we could do a quick overview of the company and some important comments that you -- or statements that you need to make before we go into more detail. So I'll turn it over to Peter for that.

Great. Tazeen, thank you. Good morning, everyone. I would just add, coming over to Las Vegas is there's traffic coming over. But in today's world, there's a lot less going back. So we'll take advantage of that. So thank you for having us. We are glad to be here.

I've got a few prepared remarks I just want to run through and cover before we go to Q&A. We believe, first of all, there are a lot of ways for us to win. And look forward to the discussion around that, and especially winning for patients. We're pleased with the strong first quarter performance, which reinforces 2026 as a springboard year for Amgen. This is a year in which we expect the rapidly growing products we have to offset the impact of the patent expirations and increased competition.

In the first quarter, we did exactly that. Revenue was up 6% year-over-year. Product sales were up 4% year-over-year. Non-GAAP earnings per share was up 5% year-over-year, strong financial discipline exercised by the company. We've got significant breadth and depth across the portfolio. 16 products delivered double-digit or better sales growth in the first quarter year-over-year. 17 products annualizing at $1 billion or more in the first quarter based on first quarter sales. Importantly, our six key growth drivers, Repatha, EVENITY, TEZSPIRE, an then our innovative oncology, rare disease and biosimilar portfolios accounted for nearly 70% of our product sales in the first quarter, and they grew at 24%. An aggregate rate of 24% growth on those six growth driver categories in the first quarter.

Repatha, EVENITY, TEZSPIRE, each hold leadership positions in underpenetrated disease areas where there are millions of patients yet to be treated. These medicines all grew at 20% or more in the quarter and are well positioned for continued growth this year and through the decade. Our rare disease portfolio grew 25% year-over-year, and we see significant opportunities ahead as we scale those therapies in this category by reaching additional patients, expanding into new indications and launching into new geographies. UPLIZNA exemplifies this opportunity. It's experiencing continued growth across multiple B cell-mediated autoimmune diseases. Pretty good for CFO, Jay.

Pretty good.

Pretty good. In innovative Oncology, our portfolio grew 2% year-over-year, driven by our bispecific T-cell engager portfolio or BiTE medicines which are expanding what is possible for patients across multiple cancers. We remain particularly encouraged by IMDELLTRA, which is rapidly becoming a standard of care in late line small cell lung cancer.

Our biosimilars portfolio remains strong, driven by sales of PAVBLU this year. It's generated sales in excess of $14 billion cumulatively since we launched them in 2018. The portfolio is an important contributor to our growth is well positioned as the next wave of biosimilar candidates advances through Phase III development.

Let's turn to the pipeline. Our confidence continues to build in Meritide as a differentiated treatment for obesity type-2 diabetes and obesity-related conditions. We're executing effectively across the enterprise from clinical development to manufacturing as we advance Meritide's broad Phase III program and build and optimize our manufacturing capacity ahead of launch. We expect Meritide to be important for weight loss induction, long-term weight maintenance and for patients switching from weekly GLP-1 therapies to Meritide with the potential for as few as four or six injections per year. Our approach reflects how obesity care may evolve. Patients need effective initial weight loss and practical durable maintenance options.

Beyond Meritide, we see strong potential across a number of other programs in late-stage development, including Oplisiran, our Lp(a) lowering medicine in Phase III development, Dazodalibep in Phase III for Sjögren’s disease and Zaludirimig, which is in Phase III for late-stage prostate cancer. On the tax front, there are two related matters with the same core issue. Value attribution. The IRS is arguing that our Puerto Rico operation should be treated as if they were essentially a limited value contract manufacturer. We strongly disagree with that position.

We've got 2,500-plus colleagues who are United States citizens there, the majority with technical degrees. It's a very complex operation. There are two tax periods in question. 2010 through 2015 and 2016 through 2018. The 2010 through 2015 tax court matter is not new. There have been no changes in our position on the status of that case. It's been fully tried and litigated. We remain highly confident in the case we presented at trial, and we continue to expect a decision no earlier than the second half of 2026.

As expected in the ordinary course of the IRS audit process, we received a draft notice of proposed adjustment, what I call a NOPA in April for similar transfer pricing issues for the 2016 to 2018 period. It's just an early step in what we would expect to be a multiyear process. It's not a final determination. And importantly, our comment to Puerto Rico continues to grow. Since our first quarter call, we announced an additional $300 million in investment building on the previously announced $650 million in our Puerto Rico facility, Puerto Rico is a core part of Amgen's United States manufacturing network with advanced manufacturing capabilities for biologics, deep expertise all the way around. We strongly disagree with any characterization of these operations as limited value contract manufacturing, and we continue to believe the IRS claims are without merit and our reserves are appropriate.

So now let me close. We're executing against the plan we laid out for 2026. The first quarter demonstrated the strength and breadth of the business, the growth drivers are performing. The pipeline is advancing, and we're maintaining financial discipline while investing for the long term. We believe there are a lot of ways to win for patients at Amgen and for shareholders and staff.

Over to you, Tazeen, for Q&A.

Okay. Perfect. Peter. I think you just discussed everything that I wanted to say.

We're so glad about that.

No, there's plenty to talk about. You're a big company with many exciting things going on. So one of the things that I wanted to spend a couple of minutes on was Repatha, which has been outperforming now, and it looks like the pace of outperformance is increasing. So I wanted to get your thoughts about where the demand is coming from? And why do you think like the interest in this particular asset at this time has increased with physicians and patients.

Well, I think -- first of all, I'll invite Casey and Jay to jump in. Repatha is, first of all, it's such an important medicine and what we hope is a developing cardiometabolic armamentarium for patients that Amgen is working on when we look at the rest of the pipeline. But Repatha itself increased 34% year-over-year to over $900 million in the first quarter, about $900 million.

Strong volume growth, increasing urgency to treat patients across both secondary prevention and high-risk primary prevention. Strong prescribing momentum, new brand -- new to brand prescriptions. This is the one that I wanted to make sure I shared with you, Tazeen, increasing roughly 45% year-over-year in the first quarter. Supported by both cardiology in the primary care setting.

So VESALIUS-CV, the recent guideline updates, they're simply reinforcing earlier identification and treatment of high-risk patients. particularly in primary prevention, where the majority of patients are treated. Access and affordability, they are no longer gating factors. Repatha is on virtually every major U.S. formulary. Most patients are paying less than $50 a month. Amgen now provides another avenue for patients to access Repatha and then the underpenetrated thesis is so important, approximately 100 million patients globally still not -- still not at an LDL-C goal and PCSK9 inhibitors are still way underpenetrated. So we see a long runway for growth. We expect Repatha to continue to grow through the end of the decade, as I mentioned, and we put it as our number one growth driver for the company.

Where do you think peak sales could be just based on the pace that it's at?

We don't give peak sales, but I would just refer you to that underpenetrated population. When we think about 100 million patients out there, and there'll be heterogeneous treatments. I know there's potential oral treatments and so forth. But we're so confident in Repatha. We're confident in the data. The data is so strong for Repatha and so compelling. And so we're going to continue to work as hard as we possibly can to help all those patients in those underpenetrated areas get their LDL-C down to the recommended levels.

And is your sales force rightsized for the expectations that you have for growth over the next several years? Or do you think that you could make tweaks to that?

Our commercial group, they -- is my colleague who plays hockey says. Our commercial group skate to where the puck is going to be. Because the head of commercial, Murdo, also a massive hockey fan too. So we love that saying from Wayne Gretzky. And so they're skating to where the puck is. They're always dynamically reallocating our resources to make sure they meet the needs of the prescribers and the patients to make sure we deliver that medicine around the world at the right time to the right patients.

The group has overcome so many barriers. And I think that it's an incredible and special group of people that care a lot about market access, which is so vital to a medicine and secondary now primary prevention to really reach patients around the world. There are very few barriers now to receiving Repatha. I still sit with cardiologists, they don't understand that. It has been 8 years since we had guidelines. Now we have solid guidelines. They may not go far enough, but they're solid and improving and call out PCSK9 monoclonal antibodies by name.

There's a radical decrease in the number of step-through requirements virtually no prior authorizations to reach the majority of patients. And now with Amgen now, patients can access Repatha quite independently and with a very favorable access price. And so this group has done an incredible amount of work in the journey of Repatha to be prepared for this moment where with primary prevention data and the string of manuscripts that will come from that VESALIUS-CV study awareness and the demand for Repatha is rising.

Okay. Maybe one more question on commercial and then we'll go to pipeline. You guys have had a good early launch to UPLIZNA and gMG. You entered a crowded space, one that's expected to become more crowded. So maybe for Jay, as you think about FcRns, as you think about the potential of Regeneron to launch its C5 into the space late this year into early next and other mechanisms that are earlier stage, -- what's giving you the confidence that the UPLIZNA approach is the right one for gMG? And you've talked now many times on calls about how you expect this could become the first-line drug of choice among patients over time.

I would say that the short answer is efficacy, which is very, very strong, and though it's hard to do cross-trial comparisons, the efficacy is better. Second is durability that we observed engendered response rates really improving through the course of the first calendar year therapy. I'd say third is convenience. Patients don't want to experienced their disease, they also don't want to be reminded of their disease treating themselves.

This medicine is given every 6 months after the loading dose, which is quite remarkable. And then fourth is it targets the actual causal biology. Myasthenia gravis is fundamentally driven by autoreactive antibodies produced by a group of cells, B-cells and pre B-cells. And UPLIZNA targeting CD19 works to deplete exactly those cells, a broader group of cells than, say, a CD20 monoclonal antibody that has a limited utility here. And so I think that these four really important features. I mean, any one of them could be strong enough to compel a physician to prescribe.

But all four of these, including the fact that to date, the medicine has been rather well tolerated. That's big for these patients. And so I think we're not surprised, but we're delighted to see the increased uptake and interest in utility of UPLIZNA. And after neuromyelitis optica spectrum disorder after IgG4-related disease, after generalized myasthenia gravis, the pattern that we're observing is that diseases driven by autoreactive antibodies should respond to UPLIZNA. And if you look at that list in chatGPT or your favorite medical textbook like Harrison's, that's a long list of diseases that we're prioritizing and sequentially, just line them up and knock them down. And the next two for UPLIZNA will be autoimmune hepatitis in CIDP.

Okay. So let's stick to gMG for 1 more minute. Where are you seeing the early patient pickups coming from? Are they switch patients? And what are they switching from? And what percent of the usage right now is in treatment-naive.

Thanks. I'll leave it to Casey to discuss the specifics, but we are seeing uptake in both biologically experienced and biologically naive patients.

Yes. And it's roughly a 50-50 split between those two groups at this point. Tazeen, it's a little bit early to be characterizing exactly what therapies individuals are switching to. But as you can imagine, with other therapies that are on a more treated on a more frequent basis, every time they're in the physician's office, there's an opportunity to switch to UPLIZNA as well. And patients are looking for exactly the attributes that Jay described.

Okay. And then on the one that you're pursuing, one of the two that you're pursuing next CIDP, one that's been dominated by FcRn. You also have IVIG as an indicated usage drug. How are you thinking about the dynamics of that market versus what you're seeing so far with gMG?

I'd say more similar than different. I mean the medicine has to work there, but it targets, again, the underlying biology. It meets the patient where they're at with a convenient dosing schema. I should hope that if active, the durability would be another strong feature given the pharmacodynamic suppression of CD19 positive B cells is so durable with this afucosylated monoclonal antibody. So I would say provided strong efficacy, which is really the anchor of why this medicine is so desirable in myasthenia gravis, generalized myasthenia gravis. I think in CIDP, it stands to be very much the same story.

When should we expect to see data on that?

We haven't as yet indicated when that study will read out..

Yes, we'll be starting those two Phase III studies later this year.

Okay. And are those the extent of indications that you want to pursue for UPLIZNA? Or are there others behind it?

No, there are additional indications for UPLIZNA. And I would also share that because we've been in CD19 for so long, and you must know we have an FDA-approved and broadly utilized standard of care frontline acute lymphoblastic leukemia, CD19 called blinatumomab, BLINCYTO for its leukemia use case and intravenous continuous infusion that in our fridges and in our labs, we have a number of molecules targeting this target and this pathway and have built a whole program around B-cell depletion, leveraging CD19. Some of those diseases will track very nicely to an UPLIZNA use case and others will use a pipeline agent. But I would expect to see proof of concept, if not additional data in lupus with and without nephritis and other disease states.

Okay. All right. So now let's move on to some of your pipeline assets. Let's start with Meritide. So there seems to be a bifurcated reaction to this drug. It's either this is great. It's going to be a market share leader in the obesity space or there's not enough data right now for us to kind of know where it's going to land. What is the real differentiation? You've got a mechanism GLP, but it's going to be dosed less frequently. How is that going to compare to a multitude of other companies that might hope to launch around the same time as you guys would. So maybe help the market better understand this drug. Mechanistically, why do you think it could have some advantages over just being another GLP on the market?

Thank you. Well, I would start by saying that Meritide is a very special molecule, and it's not that complicated. It's a GLP antagonist antibody with GLP-1 agonist peptides that has dramatic efficacy on weight loss is extremely well tolerated at target doses that benefits from dose escalation just like all the other ones and it's given less frequently. So I don't think we should overcomplicate it. It's very simple. If GLP-1 peptides were twice a day, they'd be less exciting than every week. And if a mechanism that if a medicine that exploits this mechanism can be given monthly or as Peter shared, maybe every 8 weeks, where we've already shown and presented data demonstrating real efficacy, maybe every 12 weeks, as we've indicated, we've some maintenance data that gives us conviction there, and we continue to study every 8 and every 12 weeks in prospective and now Phase III trials.

I wouldn't overcomplicate it. It's a very active increasing based weight loss medicine that is just given less frequently. And that's very special. The antibody core affords an opportunity for patients not to inject themselves every single week. And as we continue to see in real-world evidence, weekly injectables are challenging for patients to stay on. And if half of patients are stopping the use of these medicines at 6 months or 12 months, are the patients getting what they need, the protection for these serious diseases are the payers getting what they deserve for providing access to these medicines. And so the features of Meritide could improve patient persistence and for chronic diseases, that really, really matters. But I wouldn't overcomplicate it, an incretin-based medicine that is given less frequently.

As said by CFO.

Simple as it gets.

Tazeen, think 52, 12, 6, 4, which one of those do you want if you're getting poked?

Yes, it's a fair point. When I got my flu shot, I didn't ask if it could be weekly. And so let's see how the data appears when we read out these Phase III studies, but we are very confident in the profile of this medicine, the design of these trials. Their execution has gone very, very well. And I wouldn't overcomplicate it.

Okay. Now what about the tolerability profile? I think there's been some questions about it. You're looking at various titrations [ cavada ] anything you could share on that front?

Yes. I'd break tolerability into two conversations. One is tolerability at target dose. It's extremely well tolerated at target dose. You could be on 350 milligrams of this, you could get it every single month. And as we've shown with the Manhattan plots from Phase II, the drug is just innocuous, just very well tolerated by patients. And the reason for this is it's an antibody core. So you're just kind of marinating in it. It's just smooth exposure.

When you do a pill or a weekly injectable, there's a spike, a medicine is absorbed and then it's metabolized, absorbed and then it's metabolized. And the part of the brain that experiences nausea and vomiting is called the area postrema and the hypothalamus and it responds to these jolts. And so if we see, let's say, the data from oral GLP-1s as presented to date and you look at their Manhattan plots, which is how symptoms are tracked over time, there's just a scattering persistence of nausea and vomiting. I think some data was even disclosed today about switching from injectables to orals. And there was real associated almost 19% nausea, significant vomiting moving to more frequent dosing.

Meritide a target dose is just smooth exposure and a smooth experience. upfront treatment. Here, Meritide is more similar than different to other injectables, that to get a GLP-1 medicine on board you need to start low and go slow with dose titration. And we've learned, as every other company has prosecuting this mechanism, that no dose escalation is worse at 1 step, that 2-step is better than 1 step -- and as we shared on our earnings call that 3-step is unsurprisingly better than 2 steps ploy 3-step dose escalation in our Phase III studies and have real confidence that the upfront experience with Meritide will be competitive and on treatment experience will be extraordinary.

Okay. And let's talk about the opportunity for it to be used in the maintenance setting.

Yes. None of these diseases go away after 52 or 72 weeks, which is how we're studying these medicines in clinical investigation. And in this room in rooms like it, those numbers matter, and we're going to deliver great numbers. But in clinical practice, these physicians are seeing patients, and these patients are experiencing these diseases for a whole lifetime. And so how patients can remain on therapy and derive durable benefit for their whole lifetime because we're not curing obesity with these medicines. But we are effectively treating it.

We are effectively treating associated diabetes and many other related conditions. We and others have become very interested for what happens after the primary endpoint. And through long-term extensions and now dedicated Phase III clinical investigation, we intend to characterize the benefits of Meritide when used for an additional year after a year of treatment or beyond.

And there, we believe that one might even require less Meritide than the acute and treatment phase because the long-lasting antibody has long-lasting effects. And so we've seen data in Phase II clinical investigation in our Part 2 extension that every 8-week and even every 12-week dosing can maintain lost weight. And the field of obesity is not surprised by this because they've talked about this metabolic set point for a long, long time, and these medicines are reducing that set point and then keeping the weight off.

We now want to follow up on this strong signal in two ways. One is could maintenance Meritide be less frequent than treatment Meritide. And second, if we can switch from Meritide to a less frequent Meritide, could we get people off weekly injectables to a much more convenient maintenance Meritide? And so we announced in our earnings call that we are initiating clinical investigation on a maintenance as well as on a switching to Meritide experience that will feature less frequent dosing. This is very important to translate efficacy which is what you see on a clinical trial to effectiveness, how well medicines can work in the real world.

Okay. How long do you expect this maintenance study that you announced to last?

Well, we have, I think, reported on clinicaltrials.gov, the length of the maintenance studies, and they'll be about a calendar year.

Okay. And in terms of pace of enrollment, do you think that this is going to be quickly enrolled?

The long-term extensions are invitations to patients who've been on the Phase III clinical trial to continue. And there, we expect real followership, really strong participation because when we did our Phase II clinical study and we offered patients to complete on to a maintenance, I think we had more than 90% conversion. Is that right, Casey?

That's correct.

Yes, more than 90% participation. So you get an e-mail or your doctor or clinician asks you, could you be interested to keep taking this medicine for a year and more than 90% signed up for that, which is people voting with their feet and their thumbs. So we're expecting very strong participation. And in fact, all of our clinical studies of Meritide have enrolled ahead of expectations. These are a strong set of clinical trials.

Okay. So we'll stay tuned on updates from these studies as we go forward. Let's maybe take a minute to talk about a couple of other pipeline assets and indications. I wanted to maybe spend a little bit of time on Lp(a) because you've got a competitor that's going to have data coming, I think, later this year, for which nearly everyone expects there to be a read-through for Amgen. So rather than me talking to investors about what the right read-through should be, I thought I would ask you, Jay, what is the right read-through to be thinking about when we see the Novartis data released for Lp(a) later this year?

No, I know that medicine well, and I'm following that research very closely as our -- as is this community. I would say that the read-through from the Novartis readout midyear will be sort of directional, but not absolute as to what to expect from our OCEAN(a) study that is forecast to read out later. It's a event-driven study. And the reason for that is that, number one, we're both testing a really strong hypothesis with very effective medicines.

Lp(a), a genetically defined risk factor for atherosclerotic cardiovascular disease. Each Lp(a) particle is 6x more atherogenic pound for pound, than an LDL-C particle. And look at all that we know about LDL-C and its reduction in its management. experiments of nature have shown that a gradient that as Lp(a) ramps up in our blood streams, a risk for heart disease ramps up in parallel. And so both of these companies are testing the same hypothesis. I like our chances.

Our medicine is quite a bit more potent than the Novartis medicine. If that medicine, pelacarsen reduces Lp(a) 70% to 75%, our medicine olpasiran flatlines Lp(a) more than 95% could matter. Second is our study has a slightly different endpoint. Novartis uses a 4-point MACE endpoint, major adverse cardiovascular events. We're using a 3-point endpoint. We didn't see from an epidemiologic standpoint, quite as much weight around stroke. And so we've thought to consolidate all of our alpha around the endpoints that we think will really move the needle for patients. And in that regard, Novartis is a good company with a good molecule, asking a good question. And so we're very interested to see the outcome, but the guidance, we think, would be -- for us would be directional.

Okay. And when the data does come out, does that allow you to make any changes if you need to? Would you think you would want to?

I think a late-stage protocol amendment would not be our preferred path forward. We are very confident in the design of this trial.

It's an event-driven study. So I think some folks had expected maybe it could come out later this year, but now you think expectations are sometime into next year. When would you have a better sense of guiding towards a data readout?

We -- there's a monitoring committee that's tracking these events. We're performing this study in collaboration with the leading global cardiovascular group. We and they have executed through the development of Repatha cardiovascular outcome trials in a very expert way. We are forecasting the event rate is not going to read out this year, and we'll have more to say about the readout as the aperture narrows on the target date, which is a certain number of events.

Okay. And maybe last question really quickly. How big do you think this opportunity is?

One in five humans is born with an elevated Lp(a). And we are studying secondary prevention first. But should that be positive, as for LDL-C, I would have a hard time explaining scientifically why that mechanism wouldn't work in primary prevention, which is a much bigger number of people. So it's a big opportunity.

Would you put it on the same level as LDL like statins and those types of drugs are bigger?

It feels like that. It feels like that. But Casey, what would you say?

I'd say it will be dependent upon the Phase III data.

Of course. And I guess if you needed to build a sales force for that, what kind of investment would you need?

I would say, and it's a good point. If you think about Repatha and what Peter described in terms of our cardiometabolic foundation that we built, very strong cardiology presence, very strong primary care presence. You can layer in olpasiran on top of that. And then also think about Meritide and the various metabolic diseases that we're studying with Meritide, but also fit right in. So we feel like we have the potential to have a very strong cardiometabolic presence in general, especially if you -- if we're successful with Meritide and with olpasiran on top of what we built with Repatha.

You actually bring up a good point. What type of overlap would there be in physicians prescribing Repatha and those who might prescribe it for Lp(a)?

It would be a high degree of overlap. Lipid management clinics are now measuring Lp(a) and the current guidelines from the AHA, one thing they got just absolutely right was recommending that patients know their Lp(a) number as all of us in this room should because even without effective medicines that we hope to have in the near term, knowing you have an elevated genetically defined risk that you can't eat better and it goes away, stop smoking it goes and go away, even Repatha doesn't make it go away, you approach your life a little bit differently perhaps.

Maybe you do an extra 15 minutes on the treadmill every morning. And so I think knowing about Lp(a) is very important. And in that way, the community is activated. Lp(a) measurement is in the guidelines, and that leads to the question, okay, so what can we do about it?

Okay. With that, we're out of time. Thanks, gentlemen, for joining me today. Thanks, everyone, for listening..

Thank you, Tazeen, and thank you, BofA.

My name is Julianne, and I will be your conference facilitator today for the Amgen Q1 2026 Earnings Conference Call. [Operator Instructions]

I would now like to introduce Casey Capparelli, Vice President of Investor Relations. Mr. Capparelli, you may now begin.

Thank you, Julianne. Good afternoon, everyone, and welcome to our first quarter of 2026 earnings call. Bob Bradway will lead the call today and be followed by a broader review of our performance by Murdo Gordon, Jay Bradner and Peter Griffith.

Through the course of our discussion today, we will use non-GAAP financial measures to describe our performance and have provided appropriate reconciliations within the materials that accompany this call. We will also make some forward-looking statements, which are qualified by our safe harbor statement. And please note that actual results can vary materially.

Over to you, Bob.

Okay. Good afternoon, and thank you for joining us. We had a strong first quarter and are well positioned to achieve our objectives for the year. Recall, we previously described 2026 as a springboard year for Amgen, a year in which we expect our rapidly growing products to offset the financial impact of patent expirations and increased competition while our next generation of molecules progress through the R&D pipeline, setting the stage for sustained long-term growth.

As you can see from our progress thus far, we're on track to achieve these objectives. With steady execution through the rest of the year, we expect, once again, to demonstrate that we can grow through a period of patent expiration and deliver attractive performance for our shareholders with a strong portfolio of innovative medicines and biosimilars that meet the needs of patients with serious diseases.

As you listen to Murdo's presentation in a moment, the momentum of our 6 key growth drivers. Together, they generated 70% of our sales in the quarter and grew in aggregate by 24%. That strong performance sets us up well for the year and well beyond.

Turning to the pipeline. Our focus this year is on disciplined data generation and execution across a number of important Phase III programs, which again, we expect will drive attractive long-term growth for Amgen. Our confidence in MariTide as a differentiated treatment for obesity, type 2 diabetes and obesity related conditions, continues to build. We're executing effectively across the company, building the capabilities we need to bring this medicine to market.

As Jay will discuss in a moment, we're disclosing additional Phase III studies of MariTide, one of which will evaluate switching from the weekly injectables to MariTide on an every 8 or 12 week schedule. In other words, we'll evaluate switching from medicines which are injected 52 times a year to one which can be injected as few as 4 or 6 times a year. In addition, we'll evaluate weight maintenance for MariTide on a schedule of 4 or 6 injections a year as well. We expect there will be a great deal of interest in these data.

Beyond MariTide, we see strong potential across a number of other programs in late-stage development, including Olpasiran and other innovative programs in Phase III. We've talked about the excitement we feel about the convergence of technology and biology including the application of artificial intelligence across the company. Here, too, we're making great progress. And there's no question we're in a period of tremendous change, and we're encouraged by the progress we're making in embedding new capabilities.

We're doing this across the company, and we took steps early on to have Dave lead these efforts, and we're grateful to -- accomplishments leading activities across the company. I'll have more to say about Dave at the end of the call, but before we turn to Murdo, let me just thank my Amgen colleagues around the world for their dedication to our mission to serve patients and the quality of their work again this year.

Murdo, over to you.

Thanks, Bob. As mentioned in the first quarter of 2026, 16 products achieved double-digit or better sales growth and 17 products are now annualizing at sales of $1 billion or more. Overall, we delivered 4% growth in product sales, driven by a diversified portfolio of fast-growing products that continues to outpace the impact of losses of exclusivity. The evolution of our business is now well underway with our 6 key growth drivers, which include Repatha, EVENITY and TEZSPIRE, 3 innovative medicines, delivering significant clinical benefit for large populations of undertreated patients, also included our rare disease, innovative oncology and biosimilars portfolios. Collectively, these growth drivers delivered 24% year-over-year sales growth and generated $5.6 billion in sales in the first quarter, representing almost 70% of total product sales.

Starting with General Medicine. Repatha delivered $876 million of first quarter sales, up 34% year-over-year. Growth was driven by increased urgency to treat patients in both secondary prevention and high-risk primary prevention, where intensive LDL-C lowering with Repatha significantly reduces major cardiovascular events. The ACCHA updated their dyslipidemia guidelines now reinforcing earlier risk identification, lower LDL-C level and targets and earlier uses of therapy like Repatha. These guidelines do not yet reflect the practice-changing Vesalius CV data, leaving a clear opportunity to further evolve clinical guidelines and quality measures. We expect these additional changes will further encourage cardiologists and primary care physicians to manage LDL-C levels below 50 milligrams per deciliter alongside lifestyle modification to reduce cardiovascular risk in both primary and secondary prevention.

Position to our landmark VESALIUS-CV study has been strong with sustained increases in new-to-brand prescribing across cardiology and primary care, particularly in support of high-risk primary prevention patients with diabetes. At the recent ACC meeting, the VESALIUS-CV subgroup analysis in patients with diabetes and without known significant atherosclerosis was presented and simultaneously published in Jan. These data further reinforce the consistent and significant benefit of Repatha, delivering a 31% reduction in cardiovascular events.

A trend in lowering mortality rates was also observed. The body of evidence is now very clear, treating patients earlier with Repatha can lower cardiovascular events. In the U.S., Amgen now is further strengthening access to Repatha by offering a simplified cash pay option to patients. We're seeing encouraging patient interest in this direct access model, which now also includes Enbrel, Otezla, and AMJEVITA.

Repatha is now the only PCSK9 inhibitor with positive outcomes data in both high-risk primary and secondary prevention patients. These data, along with Repatha's broad access, create an imperative to close the treatment gap for millions of patients for whom Repatha can help reduce heart attacks and strokes and potentially save lives.

EVENITY sales increased 27% in the first quarter to $562 million. U.S. sales grew 35% year-on-year, and EVENITY maintains leadership of the U.S. bond builder market with a 65% market share. To date, approximately 320,000 U.S. patients have been treated with EVENITY, supported by increased investment and an expanded field force. However, the unmet need remains significant, with more than 90% of the 2 million women have very high fracture risk remaining untreated, presenting a clear opportunity to expand the market and drive additional EVENITY growth and impact. In Japan, EVENITY has been prescribed to more than 900,000 patients since launch. And it leads the bone builder category with over 55% market share. We see a positive reaction to the treatment guideline updates by the Japan Osteoporosis Society, which further improves EVENITY's positioning and potential.

Moving to inflammation. Test buyer sales grew 20% year-over-year, reaching $343 million in the first quarter, driven by robust patient demand and solid execution across both pulmonology and allergy specialties, partially offset by a burn in channel inventory. TEZSPIRE remains well positioned to reach more patients in the U.S., given its differentiated TSLP that targets multiple inflammatory pathways driving severe uncontrolled asthma, including in those patients with coexisting chronic rhinosinusitis with nasal polyps. This new indication is gaining traction and helping expand TEZSPIRE's reach across a broader patient population.

PROLIA and XGEVA combined delivered $1.1 billion in sales in the first quarter, a decrease of 32% year-over-year. Erosion of exclusivity remains in line with our expectations, and we anticipate accelerated sales erosion over the remainder of 2026 driven by increased competition from multiple biosimilars.

Our rare disease portfolio grew 25% year-over-year to $1.2 billion. The plasma sales increased 188% year-over-year to $262 million in the first quarter, reflecting growing demand across all 3 approved indications. We're encouraged by the pace of growth and the potential that it plasma has to help patients living with rare autoimmune conditions with significant unmet need. uptake in gMG has been strong across both by naive and switch patients, supported by broad access for most covered patients without requiring a step through another approved biologic. Given this momentum, we see a meaningful opportunity for to become the first-line and first switch choice for appropriate patients living with gMG.

Momentum in IgG4-related disease continues with UPLIZNA adoption led by rheumatologists and increased prescribing by GI specialists and neurologists. In NMOSD, UPLIZNA continues to maintain its leadership as the most prescribed FDA-approved therapy in the U.S.

TEPEZZA sales grew 29% in the first quarter to $490 million. In the U.S., more than 25,000 patients have been treated since launch, with growing interest from both new and returning prescribers, increased prescribing from endocrinologists and a broadening specialist base. We see rising awareness of moderate thyroid eye disease in the U.S. This positions TEPEZZA for growth, supported by its best-in-class efficacy, well-established safety profile, industry-leading patient services and broad payer coverage.

We're also encouraged by the positive Phase III data for the on-body injector, which demonstrated comparable efficacy to IV TEPEZZA and supports a clear path to subcutaneous administration without compromising clinical benefit. This convenient dosing option will enable TEPEZZA administration at additional sites of care and expand access for more patients in the future. Following our launch in Japan in 2025, we expect additional global launches of TEPEZZA in 2026 and beyond.

TAVNEOS sales were $119 million in the first quarter, up 32% year-over-year driven by strong volume growth. Since its launch in 2021, more than 8,000 patients have been treated with TAVNEOS, and Jay will comment on recent regulatory events in just a few months.

Our innovative oncology portfolio, which consists of BLINCYTO, IMDELLTRA, Vectibix, KYPROLIS, LUMAKRAS and Nplate grew 25% year-over-year, generating $1.8 billion of sales in the first quarter. IMDELLTRA delivered $258 million in first quarter sales, driven by deep clinical conviction and continued adoption across care settings. More than 1,800 U.S. sites now administered IMDELLTRA with a majority of doses delivered in the community setting. This progress has been supported by the combined efforts of our commercial, medical and access teams to remove operational barriers that physicians encounter in practice, helping expand patient access to treatment.

IMDELLTRA has become the standard of care in second-line small cell -- an aggressive disease with poor survival outcomes and few effective options to extend life.

BLINCYTO sales were $415 million in the quarter, increasing 12% year-over-year, driven by broad prescribing across both academic and community settings. BLINCYTO is widely recognized as the standard of care in combination with multi-agent chemotherapy for patients with Philadelphia chromosome-negative B-cell ALL.

Our biosimilar portfolio delivered 14% year-over-year growth, generating $835 million in sales in the first quarter. PAVBLU, our biosimilar delivered $280 million in first quarter sales. Adoption continues to expand among retina specialists who appreciate PAVBLU's ready-to-use prefilled syringe, and Amgen's track record of manufacturing biologics and delivering reliable supply.

Since our first product approvals in 2018, our biosimilars have generated more than $14 billion in cumulative sales, contributing meaningful growth while expanding patient access to high-quality, lower-cost biologics.

Our first quarter results reflect both the strength of our key growth drivers and the commitment of our commercial, medical and policy colleagues globally to improving the lives of patients facing serious diseases, and we remain focused on extending the reach of our medicines to even more patients in 2026.

And now I'll hand it over to Jay.

Thank you, Murdo, and good afternoon, everyone. Let me begin with MariTide, a new paradigm in the management of obesity, obesity-related conditions in type 2 diabetes. The unique antibody peptide conjugate design of MariTide delivers a potential for strong efficacy with monthly or less frequent dosing and favorable tolerability to improve long-term treatment. With existing obesity medicines, treatment burden and dosing frequency remain barriers to long-term persistence on therapy. For individuals with chronic conditions, sustained treatment is often required to realize the full health benefit of therapy. MariTide's unique properties, particularly its potential for monthly or less frequent dosing may help reduce treatment burden and improve persistence on treatment over time.

Towards this objective, we are excited to announce two new Phase III studies that focus on longer-term maintenance therapy with MariTide. We have initiated 2 long-term extensions of our ongoing Phase III chronic management studies to evaluate MariTide maintenance for durable weight loss. Participants who completed 72 weeks of treatment in the parent trial will enter a 48-week extension treatment period, where they will receive a monthly every 8-week or quarterly dose of MariTide. To date, our clinical trials have studied MariTide in the initial management of obesity and overweight. We recognize that many patients may wish to switch to MariTide from weekly injectables. Today, we announced the initiation of another new Phase III study that will evaluate switching from weekly injectable GLP-1 therapies to MariTide, following dose escalating to a convenient every 8-week or quarterly dosing schedule. Combined with our ongoing pivotal chronic weight management Phase III trials, the MariTide program will inform physicians on how to start a new patient on MariTide and how to switch to a more convenient, less frequent dosing.

Previously, we described the benefit of dose escalation for improving initial tolerability with MariTide. We observed marked improvements in GI symptoms progressing from 1-step to 2-step dose escalation. Our accumulating experience with 3-step dose escalation is quite positive. For example, we recently completed one of our standard Phase I physiology study preparation for potential regulatory filings that utilize 3-step dose escalation. As anticipated, 3-step dose escalation further decrease the rates of nausea and vomiting as compared to prior experience with 2-step dose escalation.

We believe that 3-step dose escalation and less frequent dosing are effective and well tolerated because of the unique antibody backbone of MariTide. The long-lived stability of an antibody creates a gentle and smooth step-wise increase in sustained drug exposure. Stable drug levels avoid the frequent peaks and troughs of daily orals and weekly injectables that may contribute to intolerability.

We remain confident and excited by MariTide and are focused on delivering high-quality clinical data to support future regulatory filings. The studies are enrolling well, indicating strong physician and patient interest in MariTide. MariTide is emerging as a new paradigm for patients with obesity, diabetes and related conditions as a well-tolerated first monthly or less frequently administered medicine.

Turning from one major public health challenge to another. We continue to build on the landmark findings from Repatha in the prevention of neovascular events. In March, a new prespecified subgroup analysis from the Phase III VESALIUS-CV trial was presented at the American College of Cardiology and simultaneously published in the Journal of the American Medical Association. In this subset of high-risk patients with diabetes and without known significant atherosclerosis, Repatha demonstrated a significant 31% reduction in major adverse cardiovascular events, including heart attack.

Repatha also demonstrated a nominal 32% reduction in the risk of cardiovascular death and a nominal 24% reduction in all-cause death. Taken together with the VESALIUS-CV data presented last fall, these findings reinforce the breadth and magnitude of benefit from Repatha in the primary prevention of cardiovascular disease. We look forward to sharing additional insights and analysis from VESALIUS with the scientific community, notably at the upcoming American Diabetes Association Annual Meeting.

Olpasiran, our potentially best-in-class small interfering RNA medicine that delivers greater than 95% reduction in Lp(a) with a quarterly dosing schedule continues to progress in Phase III clinical investigation for secondary prevention of cardiovascular events. We have recently initiated the Oceana CCDA study that evaluates the effective Olpasiran on the burden of non-calcified plaque in coronary arteries as measured by coronary CTN geography.

Attention to Lp(a) in medical practice is rising, reflected by the recently updated ACC/AHA lipid guidelines that now recommend broader Lp(a) testing.

Moving to rare disease, we continue to build strong momentum across our portfolio. For UPLIZNA, we recently received European Commission approval for generalized myasthenia gravis. Supported by a strong biological rationale, we expect to initiate 2 pivotal Phase III studies of UPLIZNA in autoimmune hepatitis and chronic inflammatory demyelinating polyneuropathy by the second half of this year. We are also advancing TEPEZZA, where we recently reported positive Phase III top line data for subcutaneous administration via an on-body injector. These data demonstrated robust efficacy in patients with thyroid eye disease consistent with intravenous administration alongside a favorable safety profile.

Subcutaneous administration of TEPEZZA represents an important step forward in improving convenience and expanding treatment options for patients with thyroid eye disease. Dazodalibep, our first-in-class CD40 ligand targeting fusion protein continues to progress with 2 Phase III studies in Sjögren's disease now fully enrolled. These studies address both systemic and symptomatic disease, and both are expected to complete later this year.

As publicly disclosed, the FDA proposed to withdraw the approval of TAVNEOS. We continue to believe that TAVNEOS is an important medicine for patients with ANCA-associated vasculitis, a rare and life-threatening disease with limited treatment options. We are confident in the benefit risk profile of this medicine and expect to engage further with the FDA on this topic.

Turning to oncology. Our bispecific T cell engager or BiTE platform continues to deliver meaningful impact for patients with advanced cancer. IMDELLTRA is emerging as a standard of care in line extensive stage small cell lung cancer, delivering an unprecedented survival benefit in a disease that has seen very little innovation for decades.

As we work to advance IMDELLTRA into earlier lines of therapy, we are encouraged by the apparent improvement in median overall survival in the first-line maintenance setting to 25.3 months observed in the Phase Ib DeLLphi-303 study. Frontline maintenance with IMDELLTRA is now being evaluated in the ongoing Phase III DeLLphi-305 study.

Xaluritamig, our first-in-class STEAP1 targeting bispecific T cell engager is advancing rapidly with two ongoing Phase III studies in metastatic, castration-resistant prostate cancer. Multiple ongoing Phase Ib studies are underway, where we've taken a deliberate and differentiated approach towards earlier stages of disease to maximize long-term patient benefit.

First, in biochemical recurrence, where patients experience a rising PSA without clinically evident disease, we are evaluating xaluritamig's monotherapy without androgen-deprivation therapy. Second, we are advancing into metastatic hormone-sensitive prostate cancer, where we are evaluating xaluritamig on top of standard of care hormonal therapy with the goal of developing a more effective regimen without chemotherapy.

One last but important note about our oncology portfolio. Following a comprehensive review, we've taken the decision to discontinue development of AMG 193, our MTA cooperative PRMT5 inhibitor.

Over the last several years, amidst the rapid advances in artificial intelligence, we've taken a principled approach to reconsidering and augmenting drug discovery and therapeutic development at the intersection of powerful AI models develop both externally and internally with Amgen Research and insight-rich proprietary data sets, we are beginning to see meaningful tangible advances across Amgen R&D. Integrated multi-omics data resources at Amgen to Code Genetics identify new targets for therapeutic consideration, in particular with the noncoding regions of the human genome study to population scale.

Anti-body lead optimization has accelerated by 50% from contributions, both to lead discovery and lead optimization. In clinical development, we have designed and implemented a proprietary site selection model that improves clinical trial enrollment with a significant and in some cases, up to threefold improvement in enrollment rates. Leveraging large language models and agentic AI for regulatory filing preparation, we are seeing early promising results in data ingestion, integration and document drafting. These are early innings. But we are captivated by the potential for AI and data science to deliver measurable impact in value in R&D and across the enterprise, as Peter will highlight in a few moments.

With the retirement of our and beloved colleague, David Reese, I'm excited to lead the AI and data transformation across our business at the enterprise level, working in partnership with our leadership, staff and collaborators. Let me close by saying that we are encouraged by the progress we've made in the first quarter with a continued focus on disciplined data generation across the portfolio with a robust pipeline and meaningful breadth and depth across 4 therapeutic areas, we are well positioned to deliver continued innovation for patients with long sustained value.

I want to thank my colleagues across Amgen for their continued focus on patients and their commitment to advancing innovative medicines for serious diseases.

I'll now turn it over to Peter for the financial update.

Thank you, Jay. We are pleased with our strongest quarter performance, executing through a full quarter of the patent expirations and losses of exclusivity. Our non-GAAP operating margin was 45%. We continue to invest in advancing our pipeline with non-GAAP R&D spending increasing 16% year-over-year in the first quarter. This reflects increased spending on our late-stage pipeline, including continued investments in MariTide, IMDELLTRA and Olpasiran. Our non-GAAP cost of sales as a percentage of product sales was 19.5%, driven by higher profit share and royalty expenses and changes in our sales mix. We expect these factors will continue to negatively impact the cost of sales in future quarters. We further expect second quarter operating margin to be in line with the first quarter operating margin.

Our non-GAAP OI&E resulted in $480 million of expense for the quarter including a gain of about $90 million from retiring debt through open market repurchases. Our non-GAAP tax rate decreased 1 percentage point year-over-year to 13.6%, primarily due to net favorable items in the current year period, partially offset by the change in earnings mix. We generated $1.5 billion in free cash flow in the first quarter, reflecting continued momentum across the business.

We spent $700 million in the first quarter on capital expenditures, driven by investments across our U.S. manufacturing sites, including Ohio, North Carolina and Puerto Rico. We continue to expect capital expenditures of approximately $2.6 billion in 2026, reflecting significant investment in our business to scale manufacturing capacity for volume growth. including for MariTide launch. We see technology and artificial intelligence and increasingly important tools to help Amgen operate with greater speed, productivity and scale across the enterprise.

Beyond what Jay described, we are also seeing tangible benefits in other parts of the business. In AI-enabled automation, it has reduced production line clearance time at one of our manufacturing sites, from approximately 30 minutes to about 2 minutes per batch run. We are also seeing promising results as our colleagues across Amgen use AI to enhance productivity.

In addition, we returned capital to shareholders through competitive dividend payments of $2.52 per share, representing a 6% increase compared to the first quarter of 2025. Let's turn to the outlook for the business for the remainder of 2026. As we said last quarter, we expect 2026 to be a springboard year for future growth. Our strong first quarter performance reinforces that outlook, and we're raising our 2026 guidance ranges for both revenue and non-GAAP earnings per share.

We expect 2026 total revenues in the range of $37.1 billion to $38.5 billion and non-GAAP earnings per share to be between $21.70 and $23.10. These ranges reflect our confidence that the emerging growth drivers will more than offset the outgoing legacy brands. Note, our guidance does not include any potential business development transactions that may occur throughout the remainder of the year.

Let me highlight a few updates to our outlook for the remainder of the year. For the full year, we now expect other revenue to be in the range of $1.7 billion, $1.8 billion, we now anticipate non-GAAP OI&E to be in the range of $2.2 billion to $2.3 billion of expense in 2026. We now expect a non-GAAP tax rate in the range of 15.0% to 16.5%. And let me remind you of prior items that have not changed. We continue to expect -- the full year non-GAAP operating margin as a percentage of product sales to be roughly 45% to 46%. This reflects our commitment to investing in the best innovation as we continue to rapidly advance the MariTide Phase III program and additional key late-stage assets. We expect share repurchases not to exceed $3 billion.

Finally, in regard to our ongoing tax litigation, the tax court litigation covering tax years 2010 and through 2015 remains ongoing. And while we expect a decision no earlier than the second half of 2026, we remain confident in the case we presented at trial. We are currently under audit by the IRS for the 2016 to 2018 tax years. In April 2026, we received a draft notice of proposed adjustment, or NOPA, from the IRS for 2016 to 2018, asserting significant adjustments primarily related to the allocation of profits between the United States and Puerto Rico.

The approach taken by the IRS is similar in nature to our 2010 to 2015 dispute with the IRS currently pending in tax court. If sustained in full, the adjustments set forth in the draft, NOVA could have a material impact on our financial statements. We disagree with the draft NOPA and have informed the IRS audit team that its draft calculation methodology is inconsistent with the positions asserted by the IRS and the tax court, which positions were more favorable to Amgen than the draft calculation methodology taken by the IRS audit team.

We firmly believe that the IRS positions are without merit, and we also believe that our tax reserves are appropriate. We intend to continue to vigorously defend our position just as we have throughout our entire dispute with the IRS. We remain focused on delivering sustained long-term growth and creating value for patients, staff and shareholders by doing what we said we would do, executing on our growth drivers, advancing innovation in areas of high unmet medical need and maintaining rigorous financial discipline. I'm grateful to work with all of our colleagues worldwide in our mission to serve patients.

This concludes our financial update. I will now hand it over to Bob for Q&A.

Thank you, Peter. Julianne, why don't we open up the lines for questions. I know it's been a long day for many of our callers. So let's jump straight in and try to get to everybody. So as many questions as we can. Try to limit you to 1 question each, please. But let's get started, Julianne. .

[Operator Instructions] Our first question comes from Yaron Werber from TD Cowen.

Great. Maybe, Jay, unsurprisingly first question on the MariTide switch studies. Can you give us a little bit of a sense? Are you switching sort of one-to-one-to-one to monthly, every 2 months and every 3 months? And are you looking at superiority or noninferiority and sort of what's the noninferiority sort of margin?

Yes, Yaron. Thank you for the interest. As I just shared, people naturally very interested to know what will it take to switch from a weekly injectable to a medicine potentially quite a bit more convenient and quite active. And so the SWITCH study is designed to provide that experience. There will be 300 subjects on study with obesity or overweight. There will be a run-in on weekly semaglutide or tuzepatide, and then they'll switch to MariTide. As I said, every 8 week or a quarterly basis. The primary endpoint of this trial will be a change from baseline body weight after 52 weeks of MariTide treatment. We look forward to these results.

Our next question comes from Salveen Richter from Goldman Sachs.

Could you just comment on the MariTide switching study and why it only evaluates the every 2 months and 3 months or not every 1 month? And then as you think about the profile today and how significant do you expect the maintenance opportunity to be for MariTide?

Why don't I start with the question around the design of the SWITCH study, Murdo, and then you can talk about the opportunity thereafter. We have a lot of experience with monthly MariTide in this program, which is featured in to date, all of the enrolling Phase III programs. And we've had a really good experience in the maintenance setting in our Phase II Part II. In that regard, the long-term extensions that we've just described where we switched from MariTide to MariTide give us a chance to explore less frequent dosing after effective dosing and comparably in the SWITCH study, we're focusing that trial on the learnings of going from weekly to in every 8 weeks and every 12 week treatment regimen, which can make MariTide quite attractive to patients is successful. Murdo?

Yes. Thanks, Jay. Thanks, Salveen. Obviously, the goal here for weight loss is to lose weight and then sustain it over multiple years, so that you can get the full medical benefit of the treatment. And given that we are coming later into this market, and there will be many, many patients already on other weekly treatments, we thought it would be helpful to prescribers to clinicians and patients to understand how to convert, how to switch from those weekly agents to, as Jay mentioned, a more convenient regimen like MariTide.

Importantly, it will also be necessary to describe once you reach your weight loss goal on monthly MariTide, how you would want to modified that dose interval either to QA week or to Q12 week for even more convenience. And so -- we've taken the opportunity, given the timing of our launch and order of entry to fully describe how to start patients on MariTide then how to switch from other treatments that patients may be on and they may be dissatisfied with.

Our next question comes from Luca Issi from RBC Capital Markets.

This is on for Luca. I have a question for IMDELLTRA. IMDELLTRA clearly done very well so far in second-line setting. Can you tell us more about what for IMDELLTRA, not only in terms of the opportunity you get when you move to the fronter lines, but also now with IMDELLTRA part of the real-time clinical trial pilot program. Could you help us understand the process? Is the idea basically FDA will look at your data scientists together as the is going and for indications with no healthy volunteers, you essentially can go straight from first in human to approval without posing for safety or end of phase reviews? And curious what made FDA take IMDELLTRA as the pilot program?

Well, let me please start, Luca. Thank you for the question. IMDELLTRA is really emerged as the standard of care for patients with second-line small cell lung cancer because as I mentioned moments ago, the unprecedented efficacy afforded by IMDELLTRA just the most important endpoint, overall survival. As for so many medicines in advanced cancer, medicines that work in later stages of the disease, tend to confer even more clinical benefit when they've moved to earlier lines of therapy and earlier stages of lower disease burden, especially when they're used in combination. And so we are advancing IMDELLTRA quite actively and aggressively into frontline induction as well as frontline induction and maintenance. The maintenance experience with IMDELLTRA and the frontline experience will be an extensive stage small cell lung cancer, and these studies are rapidly progressing. Further, we have the DeLLphi-306 study, which studies tarlatinab versus placebo after chemotherapy and radiation in frontline limited-stage small cell lung cancer. We're so hopeful for these trials and just cannot wait to read them out.

As you've described, we have had a chance to collaborate with Commissioner McCary and members of the FDA on imagining what a clinical study might look like in the real-world prospective practice. And we have a very fine design coming together with the FDA that will give us a chance to characterize IMDELLTRA in a clinical trial setting, but in the real world, leveraging things like electronic health records and real-time data capture as opposed to the way the clinical trials are conducted today. This could be a very important experiment for us and for others because so many clinical trials initiated don't complete. Enrollment is very challenging, managing data and packaging it and submitting it to regulators is quite a bit big book of work. And if there's a way to do this in more real time, we would all benefit from having this learning. So we're looking forward to working with them on that.

Yes. Thanks, Jay. The other thing that I would add here is we've seen very good progress in where patients are treated for their small cell lung cancer with IMDELLTRA. And we've seen really good uptake in the U.S. in community oncology. We've seen a very good launch in Japan. We expect to be launching in the second line indication across multiple markets this year. And then as Jay said, we have a nice randomized clinical program reading out through the balance of this year into next to further expand the use of this product. IMDELLTRA seems to have very durable survival as we've seen in our Phase I data. And importantly, in these innovative trial designs that the FDA is in discussion on, this will further help physicians, primarily those in community settings and regional hospitals or in community oncology practices, better care for their patients closer to their homes, which is a really exciting opportunity.

Our next question comes from Michael Yee from UBS.

Maybe a question on Olpasiran. Obviously, you guys have a well-designed study and potentially superior drug. I'm wondering if you think that background therapies such as GLP-1 or PCSK9, either would impact your trial design or your competitor trial design, and how you think about that impacting the overall results of what we might see from a competitor.

Jay, why don't you answer that?

Yes. Thank you for the question. And we see it the same way. The OCEAN(a) study is a very well-designed study, a randomized controlled trial of almost 7,300 patients with over 200 and the medicine Olpasiran with best-in-class performance characteristics as you cite, 95% reduction in Lp(a) with every 12-week dosing. So we're really looking forward to reading out this event-driven trial.

We have built this study around a very high-risk group of patients. Elevations in LP(a) are genetically defined. And as such, 1 in 5 individuals will have elevated Lp(a). Unfortunately, to your question, you can't take a GLP-1 medicine or a statin or even Repatha and meaningfully reduce levels of Lp(a). This independent risk factor maps to a very atherogenic and inflammatory characteristic of the LPA containing particle, which is actually 6x more inflammatory atherogenic than the LDL-C containing particle, which, of course, we and others have shown to be a dramatically an importantly modifiable risk factor.

And though we observed improvements in the standard of care for patients with cardiovascular disease, and we contribute to that with Repatha. We're very confident in the study as defined, which focuses on a high risk, high leverage elevated LP(a) population treated with direct and targeted therapy to Lp(a) itself.

Our next question comes from Terence Flynn from Morgan Stanley.

Great. Bob, I was just wondering, we've seen pretty active M&A year thus far in the sector. just as you think about Amgen's needs, potential size of opportunity, how are you thinking about the BD and M&A landscape right now, given your current needs, but also your stronger balance sheet?

Yes. I think, Terence, I would not sure I'd use the word needs the way you have in your question, but we're very active in business development, as we always have been looking for innovation that we think we can add value to. So that remains the case. I think the areas where we're interested are very clear to you and to our investors. And we'll continue to see if there are things that again, that line up in a way that we can take over programs and still add value to our shareholders.

Our next question comes from Geoff Meacham from Citi.

Great. Murdo, Repatha has been consistently strong, but I want to get some perspective from you on penetration into primary prevention? And where could it go? And as you look to the Olpasiran data, how do you think primary prevention looks as a key market within the LP(a) segment?

Thanks for the question, Geoff. We're really excited about what's happening in primary care. As you'll recall, we expanded promotion and coverage of our primary care sales team at the beginning of last year. We expanded our medical teams in anticipation, of course, of some of the news flow that we've seen new data from the VESALIUS-CV trial that we presented last November at the AHA meeting. And then as Jay mentioned, the subsequent sub-study in diabetes patients without atherosclerosis, also showing significant benefit with a 31% reduction in 3-point -- 31% reduction in 4-point So we have a clear opportunity to help these patients who are in the care of the primary care physician. The average diabetes patient without documented atherosclerosis is someone who's not being referred to a cardiologist. And so since the change in our label, which occurred actually just prior to the VESALIUS trial being presented. We've been out there talking to primary care physicians. We've seen really, really good uptake.

In the quarter, we had strong overall growth in Repatha globally. But if you look at new-to-brand prescription evolution in the U.S., we were up 44% in the quarter, and that's being driven by increased depth of prescribing by cardiologists, and increased breadth of prescribing by primary care physicians. So very strong foundation, very pleased with the momentum, but we still have a huge opportunity ahead of us in primary prevention promotion of Repatha, the only PCSK9 with that data generation now.

So real opportunity for us. Now when we look at Lp(a), the one thing I will say that helps us is the new treatment guidelines that came out from the They have recommended that everyone who is at risk of cardiovascular disease be tested. As you know, this is a genetically determined level. So you really only need to do the test once. It's affordable. It's accessible. And so that bodes well for having some population of patients who will know their Lp(a) level. And I do think that primary care physicians will play a significant role in treating those patients in lowering their Lp(a) levels with hopefully a product like Olpasiran should the data bear out.

Our next question comes from David Risinger from Leerink Partners.

So my question is for Murdo, please. So congrats on the launch of Amgen Now, I think that occurred last fall. Could you provide some quantification on the uptake of Repatha by cash pay patients? And I don't know if it's meaningful enough yet, but possibly the current mix of sales between cash pay and covered given the strong ramp of Amgen Now? And then is Amgen considering leaning into offering Repatha as a cash pay product ex U.S.?

Thanks for the question, David. We've been pleased with the overall response to the Amgen Now offering. As you'll recall, Repatha is offered at a $239 a month price point. And we are seeing cash paying patients interested in pursuing Repatha. Now at the same time, however, it's important to note, we've opened up access substantially for Repatha. And so many patients now can access Repatha without much friction and their physician can simply attest that the patient meets the criteria for the indication of the product. So I wouldn't expect the cash paying component of patients going through Amgen Now to be substantial.

We are in the kind of the 8,000, 9,000 patient range of patients moving through the Amgen Now program, and we continue to see more and more interest there. So it's been a success. But as a percentage of total Repatha, as you'll know, it's relatively small.

Our next question comes from Matt Phipps from William Blair.

I was wondering on some of the blinatumomab updates. First off, you noted in the press release that enrollment has stopped in the SLE trial. Can you give us any updates on that status. And it also looks like you're pausing enrollment of the subcu administration and ALL, any additional reasoning for that pause?

Sure. Thanks, Matt, and happy to take the question. Blinatumomab is proving to be an important component of standard of care for adults and children with relapse and refractory B-cell leukemia. And its current instantiation is delivered by intravenous continuous infusion. We have studied and characterized subcutaneous, we administered blinatumomab in the past. And there is a chance with this medicine for even higher remission rates, as we have previously shown at the EHA presentation, we observed 89%, 92% remission rates with manageable safety in adults with relapsed and refractory BALL. And so we're very encouraged by the efficacy seen with subcutaneous blend and are moving subcutaneous blend or earlier lines as you shared. We have a potential registration-enabling Phase II initiated in adults and adolescents. We have a Phase Ib/II study of subcu as well initiated in pediatric patients there with relapsed and refractory and MRD-positive B-cell ALL.

As you noted, we have paused some of these studies for enrollment. BiTEs are known to have inflammatory side effects. We prioritize patient safety, especially in the conduct of clinical investigation and observing a handful of inflammatory reactions were -- at this moment, collecting some patient data and having a dialogue with the FDA, we expect to be able to open these studies back for enrollment shortly.

Our next question comes from Chris Schott from JPMorgan.

I just want to come back to MariTide, sounds like some encouraging earlier stage data on the titration. Are you able to provide any more color on what levels of vomiting and duration of vomiting you're seeing with the 3-step titration from some of these earlier studies, if you can't provide specific numbers, just maybe directionally where that's shaking out versus Olavi or is outbound?

Yes, Chris, thanks. The level of nausea and vomiting observed with 3-step dose escalation is lower than we've seen before. Dose escalation works for GLP-1 agonism based therapy that is known. In our experience, 1-step improved GI tolerability significantly. 2-step, improved it further. And today, we share the unsurprising by accumulating data that provide clinical confirmation that 3-step dose escalation further improves GI tolerability. Now we await efficacy and tolerability data from the ongoing Phase III studies, but we're quite encouraged by what we've seen.

Jay, on the question on duration, you may help him understand what we see -- help Chris understand what we see and how it's different from what we're observing from the weekly and dailies -- in terms of the side effect...

Side effect profile. Yes. Before we started this research, we didn't know with a long-acting medicine like Maritime that can be delivered monthly or every 8 weeks or every 12 weeks, enjoy durable efficacy owing to high time on target. This antibody backbone leads to very smooth and stable exposure over long period of time engaging GLP-1 receptors and gift receptors in the brain and peripheral tissues. With that durable efficacy be associated when there was a side effect with a long-term side effect and that we don't see. When we do observe nausea and vomiting, it tends to be quite short in its duration over the course of one or several days, no different than the weekly GLP-1s. But different than the weekly GLP-1 and different than oral GLP-1s that are short half-life medicines, this trough-to-peak spike that's experienced every time these medicines are taken, we believe can be associated with intolerable side effects in the GI and otherwise. And this can be avoided with a steady, stable, long-acting medicine like MariTide. We see this target dosing of MariTide by Manhattan plot, versus what's reported in the field with more frequent dosing. And so in the fullness of time, this could prove to be a very important attribute, keeping patients on the medicine for the length of time that they have these diseases, which is for many of them, a lifetime.

Our next question comes from Akash Tewari from Jefferies.

For DAZO Phase III Sjögren's program, you're making interesting bets splitting it up into systemic and symptomatic patients. What kind of drove that decision? And which one of those trials are you even more confident will work? And can you go over any of the biological difference between DAZO and then the Novartis CD40, but also Sanofi CD40L which both ended up discontinuing their programs?

Akash, I love your questions because they invite a mechanistic characterization of these molecules, but I'll try to keep this brief, though it will be hard for me. We observed in Phase II very strong activity of dasodalibeb, which as you comment, is a CD40 ligand FC fusion protein, targeting protein. And the performance against the STI score in Sjögren Syndrome is quite a unique situation. It has proven very hard to develop effective medicines in Sjögren's disease. But seeing movement in the STI score that made us very motivated to follow this up in Phase III clinical investigation. The presentation of this heterogeneous disease can be quite different clinically. And so we thought to segregate in order to have clear clinical outcomes in these clinical trials into 2 Phase III studies, patients with what we'll call systemic disease but then also very sick, a separate study of moderate to high symptomatic disease, but they are with low systemic disease activity. In the case of these 2 populations might be considered differently to observe meaningful differences attributable to those biological, those clinical presentations. These studies have completed enrollment and completion of both studies is expected in the second half of this year.

Dazodalibep is a product of a long sought after drug discovery campaign, honestly in the field of immunology. cD40, CD40-ligand signaling is fundamental to T cell B-cell co-stimulation, CD40 ligands on T cells, CD40 on many, many different kinds of cells. And that makes this molecule very different than CFC 533 from Novartis. What is true of Sjögren's disease, whether or not it's systemic or symptomatic is that T and B cell activation is the primary driver. This isn't a dry gland disease. It's enriched with inflammatory cells. And so we believe the CD40 ligand is the right lever to press on as it will impact all downstream signaling by targeting the upstream CD40 ligand on T cells. So we look forward to reading out these studies. One with the SDI score, another with the DAS score appropriate for a symptomatic study in the second half of this year.

Julianne, let's take one last question, and then I'll have a couple of remarks and we'll be finished.

Our last question today will come from Louise Chen from Scotiabank.

I just wanted to ask you, if you get MariTide approved, what are you playing for here? Do you want to be the #3 player behind Noble Lilly? Or are you assuming a higher position than that with your product?

Louise, that's a tempting question to consider a softball pitch over the middle of the plate here at the end of the day. But Murdo, do you want to offer any quick thoughts for Louise, and then we'll wrap up.

Well, I think we're going to be the best monthly or less frequently prescribed agent, Louise. But no, no sincerity. This is a highly differentiated product. I think the opportunity is substantial to come into a market with something -- there really is a new paradigm-changing opportunity for a massive category. And our focus is going to be on helping as many patients as possible in that category, whether they are de novo patients who have yet to attempt a weight loss treatment and they'll be new to MariTide or whether they're on another therapy and they're not achieving the results they like or they're not enjoying the frequency of injections or they're having side effects and they want to try another treatment. And we will, across the business -- across the company, we will be ready to go into that market and compete effectively with all of the other companies that are already there.

I know some of our competitors have risen to the beta of that question, Louise, but we'll resist and wait instead until we have the data in hand. And as you know, we're working diligently to try to generate the necessary data to register this molecule. And as Murdo said, help as many patients as possible. There are very many who need differentiated therapy like this, and we're looking forward to having the data so that we can appropriately talk to them.

But before we wrap up, I just wanted to -- as I mentioned earlier in my remarks, I just wanted to take a moment. And acknowledge that Dave Reese will be retiring from Amgen at the end of the second quarter, and I wanted to thank him publicly for his contributions to Amgen over the past 20 years. As a long-standing leader and former Head of R&D, Dave's legacy here, as you all know, includes a generation of innovative medicines.

What you may not be as familiar with is that Dave has been a persuasive champion for change and new technologies at Amgen. And recognizing long ahead of many others, the growing importance of AI and what he called the Hinge moment, Dave both raised his hand to be Amgen's first Chief Technology Officer, and helped attract Jay Bradner to be his successor as Head of R&D. So we're thrilled, excited about the progress that we made in artificial intelligence and data under Dave's leadership as well as the other businesses that Dave has had responsibility for. And again, we're grateful that Jay will build on what is a very solid foundation following Dave's retirement at the end of the second quarter.

Dave is both a close colleague and friend to many of us, and we will all miss him and wish him well and what we're sure will be a very active retirement. So Dave, on behalf of all of Amgen, thank you. And let me thank all of you for joining our call as well. Thank you.

This concludes our Amgen Q1 2026 Earnings Conference Call. You may now disconnect.

We're ready to get started. On behalf of Leerink Partners, I wanted to welcome you all to the session with Amgen. So very much my pleasure to welcome Peter Griffith, the company's CFO. And actually, in between Jasper and Peter is Casey, who runs IR. Jasper Van Grunsven, is that how you pronounce your last name?

It's very good.

My apologies. I got Jasper right, at least. So he runs rare disease for Amgen. So I thought we'd have Peter kick it off with some opening comments.

Dave, thank you, and good morning, everyone. We're so glad to be here as we always are here in South Beach. I have a few prepared thoughts that I'd like to share. So we exited 2025 with strong momentum across the portfolio. 13 products delivered double-digit growth, 14 exceeded $1 billion in annual sales and 18 delivered record performance. That breadth supported double-digit growth in both revenue and earnings per share in 2025.

The momentum is underpinned by our 6 key growth drivers: Repatha, EVENITY, TEZSPIRE and rare disease, innovative oncology and the biosimilars portfolios. Repatha, EVENITY and TEZSPIRE all grew over 30% year-over-year in 2025 and delivered record sales with each representing a multibillion-dollar global franchise. These medicines address large unmet needs where there are millions of patients yet to be treated and represent growth drivers not just for 2026, but for the rest of the decade.

Our rare disease portfolio delivered $5 billion in 2025 sales, up 14% year-over-year, driven by reaching new patients, geographic expansion and launching new indications. UPLIZNA is a great example of this, growing 73% in 2025, supported by the IgG4-related disease launch. We expect continued growth in 2026 as that launch progresses and we build on the recent generalized myasthenia gravis approval and launch. We also plan to initiate additional Phase III studies of UPLIZNA in autoimmune hepatitis and chronic inflammatory demyelinating polyneuropathy later this year.

Our innovative oncology growth is being driven by our bispecific T-cell engager or our BiTE platform. IMDELLTRA, our DLL3 targeting BiTE has rapidly become the standard of care in second-line or later small cell lung cancer. With 3 Phase III studies in its early-stage small cell lung cancer underway, IMDELLTRA has the potential to reach many additional patients. We're also progressing xaluritamig, our first-in-class STEAP1 bispecific T-cell engager, with 2 ongoing Phase III studies in metastatic castrate-resistant prostate cancer. And we're also actively evaluating opportunities to expand xaluritamig into earlier lines of prostate cancer.

Our biosimilars portfolio generated $13 billion -- excuse me, it's accumulated cumulatively about $13 billion in sales. And in 2025, it generated $3 billion of product sales, growing 37% year-over-year. The momentum here is in part due to the strong uptake of PAVBLU, our biosimilar to EYLEA. Future growth is going to be driven by our biosimilar candidates to OPDIVO, KEYTRUDA and OCREVUS, which are all currently in Phase III development.

Let's turn to the pipeline. 2026 is going to be a year of disciplined data generation across multiple Phase II and Phase III programs that support long-term growth. We remain confident in MariTide's potential as a differentiated treatment for obesity, type 2 diabetes and obesity-related conditions. In a field featuring dozens of potential daily oral and weekly injectable medicines, MariTide stands alone as the only therapy in late-stage development to offer the paradigm-changing prospect of strong efficacy and favorable tolerability at monthly, every other month or even quarterly dosing.

The fully enrolled OCEAN(a)-Outcomes study of olpasiran, our potentially best-in-class small interfering RNA medicine targeting Lp(a) continues to progress. This is an event-driven study, and the aggregate endpoint accrual rate remains lower than initial predictions. While we recently pushed out our estimated completion date, our conviction in olpasiran remains very strong based on the genetic and epidemiologic evidence that has established elevated Lp(a) as an independent risk factor to heart disease.

Finally, we're advancing dazodalibep, our CD40 ligand targeting biotherapeutic with 2 Phase III studies in Sjogren's disease now fully enrolled and study completion expected in the second half of 2026.

Turning to a few financial updates. We see strong momentum in the business for the full year. However, in terms of quarterly phasing, historically, Q1 is lighter for us relative to subsequent quarters, and we expect that to be the case this year as well.

Let me remind everyone of a few points from our recent earnings call on the outlook for the first quarter. As we typically see with the United States insurance cycle, we expect a seasonal Q1 headwind from benefit plan changes, reverifications and higher patient co-pays. We also expect Otezla and Enbrel to follow their historical pattern of lower sales in the first quarter relative to subsequent quarters. I'd also add that as of January, Otezla now faces European generic entry. And for reference, European sales of Otezla were USD 282 million in 2025.

We continue to expect accelerated erosion in 2026 for Prolia and XGEVA, including in the first quarter because of a full year of biosimilar competition. Additionally, we saw approximately $250 million of inventory build in the fourth quarter of 2025 that could potentially impact first quarter sales. And consistent with lower Q1 product sales, we expect first quarter non-GAAP operating margin to be the lowest of the year and roughly consistent with the fourth quarter of 2025, which was approximately 43%. I also provided some commentary on the full year outlook on our recent earnings call, and I'd encourage you to reference the Q4 transcript for my full remarks.

And in closing, as we enter 2026 with strong commercial momentum across our diversified set of 6 key growth drivers and a Phase III pipeline that spans 4 therapeutic areas with meaningful depth and breadth, we're well positioned to deliver sustained long-term growth.

And with that, Dave, I'll turn it over to you.

Excellent. Well, thank you very much for that, Peter. Would love to have you talk a little bit about opportunities for growth beyond 2026 and what you think the investment community may be underappreciating?

Thanks. Great question, Dave, and I'll invite Casey and Jasper to hop in when they'd like to. They certainly have plenty to add here.

I would recap those 6 key growth drivers. I always think about those, and they're doing so well. So Repatha, we can talk about the VESALIUS study and the Outcomes data there. We can get deep into that. Jasper actually worked Repatha for a number of years and did a great job getting it going, about -- starting about 5 years ago, he was involved in that. EVENITY, what a great medicine, went through $2 billion last year, and there's so many -- that's such an underpenetrated market. postmenopausal women. This is a great medicine for that. And certainly, TEZSPIRE, getting through $1 billion last year, severe uncontrolled asthma. I would also add on that, I can't resist mentioning the chronic obstructive pulmonary disease study underway, Phase III. And that's, I think, the third leading killer of humans on the planet. So that's super important.

I think about the rare disease portfolio, too, Dave. And I just think about those medicines. I look at UPLIZNA and it's just doing so well, and Casey and Jasper can talk about even some of the additional studies beyond the successful gMG approval into the autoimmune area that we're thinking about with inebilizumab, that's close enough, which is the molecule itself for UPLIZNA. And so a lot going on there. We like to think about that.

I would say when you get to innovative oncology, I just have to pause for a moment and IMDELLTRA. This is a bispecific T-cell engager addressing a horrible disease, small cell lung cancer, where survival rates have been very challenging. This medicine has had a very rapid uptake. It's on our -- it's the first medicine to address a common solid tumor, and it's done it really well. I think we launched that in about May of '24, and it's been very successful. And that one, I certainly would hope over the long run, really continues to do well for patients with this very, very serious disease.

And then biosimilars. So through $3 billion last year, a strong year, certainly, PAVBLU was a contributor to that. But going forward, thinking about our molecules relative to KEYTRUDA and OPDIVO and OCREVUS that I talked about, that's strong, too.

So we've got the 6 key growth drivers. We've got a strong Phase III pipeline. So we're busy. We're investing. And of course, we'll talk about MariTide. We know we'll do that. As CFO, I'd just remind you, we've got 6 Phase III studies underway, and I'm glad we do, and they're important. But that certainly is a significant investment our shareholders are making in that -- what we expect to be a really, really important medicine in the battle against obesity disease and all the related indications and type 2 diabetes.

So I think there's a lot. It's the breadth and depth. It's the 18, the 14, the 13. So certainly, the 14 products that generated greater than $1 billion last year. And so we're just really 18 record, 13 double digits. Did I get that right? So it's kind of -- that's how I think about it, Dave, breadth and depth, driving innovation at speed and scale. That's what the company is doing. And we're busy. And we see this year as a super important year of execution excellence. We've got a great portfolio. We're fortunate to have a great pipeline and myself and our colleagues are focused on sustainability of that growth rate over the long term. Do you fellows have anything you want to add?

I'd love for maybe Casey to talk a little bit about MariTide. So you had mentioned monthly, every other month or quarterly dosing. But could you just provide a little bit more color, Casey, on how you get there? I think the first Phase IIIs just have monthly dosing that are reporting out early next year. So maybe if you could share some insights on how we should think about the potential for different dosing in the future.

Yes, sure. Happy to do so. Yes. So to set the context, Dave MariTide, as Peter said, has 6 global Phase III studies underway. We anticipate additional Phase III studies coming online this year in type 2 diabetes. The 2 that are most advanced are our 2 chronic weight management studies. That's where we're looking at monthly dosing over the course of 72 weeks. There's a short 3-step dose escalation period to initiate those studies. But think about that as driving patients towards their weight loss goal over the first 72 weeks with monthly dosing. Then with MariTide, and we established this through Part 2 of our Phase II chronic weight management study, we observed that with lower monthly dosing or with quarterly dosing, we were able to maintain weight loss that was achieved over the first 52 weeks for a subsequent 52 weeks.

And so we feel like there's many options once the patient is at their weight loss goal with MariTide to stay on lower monthly dose to potentially move to every 8-week dosing to potentially move to quarterly dosing to maintain the weight that they lost. And interestingly, particularly with the quarterly dosing in that second 52-week period, we saw MariTide was very well tolerated in the quarterly dosing. That was a question that we thought was important to answer since it was such a long time between doses, you could imagine tolerability kind of coming back to almost a treatment-naive situation, and that wasn't the case. We saw a very well-tolerated molecule. And that's been consistent with MariTide where it is once you're at target dose of MariTide, it's a very well-tolerated medicine. And obviously, we're quite encouraged by the data we've seen thus far and are investing heavily behind it, as Peter had indicated.

Excellent. That's great. So maybe we could pivot to UPLIZNA, Jasper. Would love to hear you talk about the long-term potential, including which indication is your favorite, i.e., might be the biggest percentage of the pie longer term?

That's an interesting question. Let me start with where Peter left off. Like if you think about Amgen's growth portfolio, like look at those numbers, I'm very excited about that. If you look at 18 products with record sales, 13 products with double-digit growth, that breadth is very exciting. If you bring that to the rare disease portfolio, we see similar numbers across all our franchises in rare disease. And UPLIZNA is a unique example in that. And UPLIZNA in last year grew 73%. And I always have to remember -- remind people of that 73% is driven by our base indication, which is NMOSD, which where we saw very good new patient growth, very strong adherence, which is important. And so it's driven by NMO and, let's say, 8 months of the IgG4-RD launch, which is a very exciting new indication, a very big unmet need, like we're the first FDA-approved therapy in that indication. And UPLIZNA has a fantastic profile there. I can talk about that a little later.

But what we see is very good strong uptake there. So we have over 500 active prescribers there in that indication, and that's breadth of prescribing. You expect rheumatologists to prescribe. We see GI specialists prescribe. But even beyond that, we start to see prescribing. So we feel very good about that. So that's our 73% growth last year is NMO full year, 8 months of IgG4. And then as Peter said, we have the gMG approval December last year, which basically means a launch this year. And that uptake has been very exciting as well.

gMG, of course, it's a busy area. But I always say it's a busy area with competition, but there's still a very big unmet need. And people don't often see that. But if you look at the existing therapies, patients cycle through them relatively quickly. Like I think more than 50% of patients only stays on a therapy less than 12 months. So that tells you there's still a significant unmet need. And when we talk to physicians and patients, they talk about unmet need in a way, hey, we need a durable therapy that doesn't have additional flash between dosing. And that's exactly what UPLIZNA offers in our opinion. And we see since launch, and it's very early, we see very good uptake, and we're particularly excited by the breadth of uptake. So we see both bio-naive patients, probably 50% of our new patients are bio-naive and 50% come from switch.

So if you put that together, we expect continued strong growth. It's honestly very difficult to say which of those indications would be biggest. I think all of them will significantly contribute to UPLIZNA and the rare disease portfolio. And then, of course, as we deeply believe in upstream CD19-directed B-cell depletion has a very good mode of action in autoimmune disease, we also have these other indications that Peter mentioned. So we think UPLIZNA is set for a very, very strong future growth.

Excellent. That's great. And so in gMG, obviously, it is crowded and will become more crowded. Could you talk about UPLIZNA's competitive positioning and just how you see its adoption?

Yes. So I just explained already that we still see that as a big unmet need. I explained that. And I just also explained what our insights were around what physicians and patients want. And what UPLIZNA offers, if you think about CD19-directed B-cell depletion, what we offer is we offer that very strong durable efficacy. That's one. Second, we have a very known and well-tolerated safety profile. And three, we have, in maintenance, twice-a-year dosing. And then we have a pretty broad set of sub indications in gMG as well.

So if you put that together, I think we have an extremely competitive profile. If you compare it with existing competition as well as future competition, I think we are very competitive if you just put that together. And that's what we see because we get patients uptake in bio-naive and we get patients uptake in switch.

Excellent. Excellent. So why don't we turn to TEPEZZA. So the company has a forthcoming subcutaneous version. Could you just discuss that product profile and how quickly you might be able to convert the market from IV?

Yes. So If you look at thyroid eye disease, it's good to know that we also feel there -- and again, it's the story that Peter said as well for many of our indications, but the penetration, so the unmet need is big. So the penetration is still only single digit. And that's mostly in the area of the chronic or low clinical activities score disease patients. So that's important to know. If you then think about the subcu formulation, we feel that subcu is a more patient-friendly sort of convenient formulation that specifically will help unlock in that chronic patient population, so we think it will significantly help. Of course, we have to wait until our Phase III read out before we can comment more on what the actual profile will be and how we will launch that subcu formulation. But we feel it will significantly help in unlocking that chronic patient population.

Excellent.

And Jasper, is it also fair to say that, Dave, we envision IV continuing, IV TEPEZZA continuing, but also bringing online a subcutaneous administration, which will help us, as Jasper was saying, to reach additional patients, particularly in that low clinical activity score setting.

Excellent. So why don't we turn to dazodalibep, if I'm pronouncing that correctly? So...

The CFO way to describe it is daz. You're beyond that, Dave. I just say daz.

Yes, that makes a lot of sense. Keep it simple. So it's clearly an important pipeline opportunity. If you could just share your thoughts on it and news flow ahead.

Yes. So dazodalibep, let's call it daz, indeed, is absolutely a very exciting asset for Amgen. And it starts like in rare disease, it starts with the unmet need. And we know in Sjogren's disease, there is very significant unmet need. We currently have around 350,000 patients diagnosed in the U.S. And if you look at the subset of patients or the subset of patients in that 350,000 diagnosed, we basically have 2 big groups. One is the 30% to 40% systemic disease groups, 30%, 40% of those patients has systemic disease. But another 60% to 80% of patients have some overlap between those groups, obviously, 60% to 80% of patients has only symptomatic disease.

But if you talk to physicians and patients, the unmet need there when it comes to dryness, fatigue, pain is very, very significant. And we've seen in our Phase II data that we show initial efficacy in both of those indications. So we feel we feel that looking forward to our Phase III trial that we have potentially a good profile there. And we're very excited about the unmet need is significant there.

Excellent. Excellent. And so you said the timing was second half.

Mm-hmm.

Excellent. Okay. Great. And just so that we understand sort of based upon your prior data, regarding adverse events, what are your expectations for antidrug antibodies and the risk of thromboembolic events?

Yes. Let me jump in on that one, Dave. So daz is a CD40 ligand targeting fusion protein. And it's specifically designed and engineered to avoid some of what we saw previously with other monoclonal antibodies that were targeting the CD40 ligand or CD40 pathway where there was platelet aggregation, thromboembolic events. And so in our Phase II study, we saw a favorable safety profile. It provided us the confidence to advance into Phase III. Obviously, in larger number of patients, we'll continue to watch the full safety profile of daz. But the way that we've engineered the molecule hopefully will allow us to avoid some of what others have seen with monoclonal antibodies targeting the same pathway, and we're optimistic for what Phase III can bring. But obviously, the data will inform us in terms of the potential of the molecule and its safety profile.

Excellent. That's great. And then why don't we just pivot back to MariTide, just given how important that product can be for the company. There's been a lot of changes in the market recently, obviously, greater pricing pressure. Lilly has had declared earlier this year that it's much more of a consumer market than they originally expected. And I guess would love to hear about -- if we think about the market being in 2 segments, commercial coverage and consumer. I would love to hear your plans for the consumer market. And then on the commercial side, we get questions about how Amgen will compete with the rebate wall from Lilly and Novo given their current dominance in obesity.

Yes. So let me start and then Peter and Jasper, feel to add on. So it starts with the evidence base that we're generating with MariTide. So 6 global Phase III studies underway, 2 in chronic weight management, 2 in obstructive sleep apnea, 1 in heart failure, 1 in ASCVD, both Outcomes studies and then obviously in type 2 diabetes as well. So we are working to establish a very comprehensive evidence base for MariTide. And we feel that's important both to characterize the molecule, but also to characterize the potential of reaching a number of different patients with obesity or obesity-related conditions.

That plays into how you think about entering the market. I would say, details to be determined in terms of our exact approach to the market, but we're watching carefully. We're well aware of the consumer element of this and thinking through how we can best position MariTide with respect to all of the different aspects of the obesity market and which, as you know, Dave, are rapidly evolving, and we feel a little bit advantaged to be watching how things play out as we think strategically about how to ultimately bring MariTide to market.

Maybe just for a minute. Casey, talk a little bit about the adherence because we think MariTide is characterized and the data turns out the way that we hope it does, that perhaps it's able to help patients and their adherence, given the adherence on the weeklies is not as strong probably as we would hope.

Yes, it's a good point. It's really why does monthly dosing matter in a way. And we see that there is -- that currently treatment burden and dosing frequency continue to be barriers to long-term persistence on therapy. I mean we feel like with a monthly or to maintain weight, a less frequently dosed molecule, we have a real opportunity to improve adherence, improve the patient experience.

And why does that matter? To your point, Peter, that matters because in order for patients individuals living with obesity-related conditions to experience the long-term benefit of that medicine, they have to remain on the medicine to achieve those health benefits, to improve their diabetes, to improve their cardiovascular outcomes, to improve their sleep apnea. These are chronic conditions need to be treated chronically. And we feel like a medicine with MariTide with its dosing frequency and long-term tolerability at favorable tolerability at target dose really helps to fit what we see is an emerging unmet need in the space.

Maybe just one add on and Jasper, I'll turn it to you then, is when you think about Amgen's history, Dave, with Repatha, with Prolia, the ability to generate delivery of important medicines to areas with significant unmet medical need, millions of patients. We have that history. It's not a perfect analog, but it's our commitment to trying to get these medicines that have huge impact where there is a significant unmet need to get them to those patients.

So we've built our capacity for that. We're building our capacity for that. We've got to guide out this year, $2.6 billion in CapEx. We're working hard on yield management. We're working hard on the science and manufacturing. We're working hard on making sure the devices are just right for doing this. So we're focused on that. The company has been focused on it for a long time. So Jasper, you've been trying to say something?

No, no, but it's like your question was on the commercial launch. And I think, Casey, Peter, you said it very nicely. If the profile of MariTide shapes up the way it does in Phase III, I think we have a very competitive profile. I just want to reiterate what you said, Peter, is like the commercial capability that we built in cardiovascular and cardiometabolic where we have like a track record over 10 years, getting Repatha to a very successful brand, I think, it's a very important base that we launched MariTide of, which is pretty unique if you look at all the competitors developing in obesity. Of course, we have formidable competitors with Lilly and Novo, but I think Amgen with this cardiometabolic franchise and footprint is really -- will be very competitive commercially as well.

Excellent. Well, we are actually about to run out of time, but I had one more question for Peter. So obviously, you have a strong balance sheet, a lot of flexibility. But how do you see the current M&A environment, meaning there are a lot of companies that are looking for attractive targets. And so it'd just be helpful for -- it would be helpful to get your perspective on that current environment and opportunities or challenges for Amgen in executing in that environment.

Sure. Just to level set and calibrate, we were able last year by the end of the third quarter to get back to the balance sheet that we committed to when we announced the Horizon deal in December of 2022. And Jasper and the team in rare disease did a great job integrating that and making it all work so well.

So let's just start with that and then just say as we take that -- the strong balance sheet and we think about M&A, in terms of inorganic activity, mergers and acquisitions, licensing, collaborations, partnerships, Dave, which we're structurally agnostic. We're always in the market. We're always looking, but we always stick to our principles. So our capital allocation hierarchy, number one is the best innovation, either internally or externally. And so we're committed to finding the best innovation.

Now let's get to your point, which is, can you get it at somewhat of an effective value for shareholders? Well, our first principle is are we the best buyer, collaborator, licensor, partner, which simply means when it's in our hands, can we add to it? Are we accretive to that? Can we model it a little bit better than everybody else in a realistic way. Number two, cash-on-cash returns. We always stick to that. Number three, do we have research in the area. If we've got research in an area, we think we do a lot better with any one of those structural inorganic opportunities. And fourth, can we integrate promptly? We think returns are generated by promptly integrating acquisitions and these other types of partnerships and licensing and collaborations.

But acquisitions in particular, and we showed that with Horizon. We were able to achieve accretion in the first full year. We achieved our pretax cost synergies of more than $500 million a little bit early. And as I said, we were able to strengthen that balance sheet early. So moving quickly, that fourth thought in our minds. So we always prosecute these. We want to have an opinion on everything, too. We think it's super important at Amgen that we see what's out there and what's available. And if it becomes transactable and it makes sense, we'll certainly participate, but we'll stick to our rigorous discipline in terms of how we look at these opportunities.

Excellent. Well, that's great. Right. To wrap up, thanks so much for being here. Appreciate it.

Thank you, Dave. Thanks for the invite.

Thanks for having us.

Thank you.

Good afternoon, everybody, and thank you once again for joining us for the 46th Annual TD Cowen Healthcare Conference. I'm Yaron Werber from the biotech team, and it's a great pleasure to moderate the next fireside chat with Amgen. With us today, returning from a hiatus from IR in an expanded role is Justin Claeys, Senior Vice President of Finance. To his right, really for the first time with us is Kave Niksefat, who is SVP of Global Marketing and Access. And to his right, needs no introduction, Casey Capparelli the new Head of IR and our guru on everything, Amgen. So gentlemen, thanks so much. Let me turn it over to you maybe for some opening remarks, and then we'll go into Q&A.

Yes. Thank you, and thank you, Yaron, again, for having us back at Cowen. We're glad to be here. So a few prepared remarks for us to open, and we'd like to share before moving over to Q&A. We exited 2025 with strong momentum across the portfolio, 13 products delivered double-digit growth, 14 exceeded $1 billion in annual sales and 18 delivered record performance. That breadth supported double-digit growth in both revenue and earnings per share in 2025. The momentum is underpinned by our 6 key growth drivers, Repatha, EVENITY, TEZSPIRE and our rare disease, innovative oncology and biosimilars portfolios. Repatha, EVENITY and TEZSPIRE all grew at over 30% year-over-year in 2025 and delivered record sales with each representing a multibillion-dollar global franchise. These medicines address large unmet needs where there are millions of patients yet to be treated and represent growth drivers not just for 2026, but for the rest of the decade.

Our rare disease portfolio delivered $5 billion in 2025 sales, up 14% year-over-year, driven by reaching new patients, geographic expansion and launching new indications. UPLIZNA is a great example of this, growing 73% in 2025, supported by the IgG4-related disease launch. We expect continued growth in 2026 as the launch progresses and we build on the recent generalized Myasthenia Gravis approval and launch. We also plan to initiate additional Phase III studies of UPLIZNA in autoimmune hepatitis and chronic inflammatory demyelinating polyneuropathy later this year.

Our innovative oncology growth is being driven by our bispecific T-cell engager platform or BiTE. IMDELLTRA, our DLL3 targeting BiTE has rapidly become the standard of care in second-line or later small cell lung cancer with 3 Phase III studies in early stage small cell lung cancer underway. IMDELLTRA has the potential to reach many additional patients. We are also progressing xaluritamig, our first-in-class STEAP1 bispecific T cell engager with 2 ongoing Phase III studies in metastatic castrate-resistant prostate cancer, and we are actively evaluating opportunities to expand xaluritamig into earlier lines of prostate cancer.

Our biosimilars portfolio generated $3 billion in 2025 sales, growing 37% year-over-year. Momentum here is in part due to strong uptake of [indiscernible] our biosimilar to EYLEA. Future growth will be driven by our biosimilar candidates to OPDIVO, KEYTRUDA and OCREVUS, which are all currently in Phase III development. Turning to the pipeline. 2026 will be a year of disciplined data generation across multiple Phase II and Phase III programs that support long-term growth. We remain confident in MariTide's potential as a differentiated treatment for obesity, type 2 diabetes and obesity-related conditions. In a field featuring dozens of potential daily oral and weekly injectable medicines, MariTide stands alone as the only therapy in late-stage development to offer the paradigm-changing prospect of strong efficacy and favorable tolerability at monthly, every other month or even quarterly dosing.

The fully enrolled OCEAN(a)-Outcome study of olpasiran, our potentially best-in-class small interfering RNA medicine targeting Lp(a) continues to progress. This is an event-driven study and the aggregate endpoint accrual rate remains lower than initial predictions. While we recently pushed out our estimated completion date, our conviction in olpasiran remains strong based on the genetic and epidemiologic evidence that has established elevated Lp(a) as an independent risk factor for heart disease. Finally, we are also advancing dazodalibep, our CD40 ligand targeting biotherapeutic with 2 Phase III studies in Sjogren's disease now fully enrolled and study completion expected in the second half of 2026. I'll now turn it over to Justin for a few financial updates.

Great. Thank you, Kave. And Yaron, it's great to see you again. Great to be back and join the conference. As Kave mentioned, we see strong momentum in the business in 2026. Given that we're now into March, I did want to remind everyone of some points on our quarterly phasing. Historically, Q1 is lighter for us relative to subsequent quarters. I'll highlight a few points on this from our recent earnings call where we gave some commentary on the outlook for the first quarter. As we typically see with the U.S. insurance cycle, we expect a seasonal first quarter headwind from benefit plan changes, reverifications and higher patient co-pays.

We also expect Otezla and Enbrel to follow their historical pattern of lower sales in the first quarter relative to subsequent quarters. I would also add that as of January, Otezla now faces European generic entry. For reference, European sales of Otezla were $282 million in 2025. We continue to expect accelerated erosion in 2026 for Prolia and XGEVA, including the first quarter because of a full year of biosimilar competition. Additionally, we saw approximately $250 million of inventory build in the fourth quarter of 2025 that could potentially impact first quarter sales.

And consistent with lower Q1 sales, we expect first quarter non-GAAP operating margin to be the lowest of the year and roughly consistent with the fourth quarter of 2025, which, as a reminder, was approximately 43%. Peter provided commentary on the full year outlook on our recent earnings call, and I'd encourage you to reference the fourth quarter transcript for his full remarks on that. In closing, we entered 2026 with strong commercial momentum across our diversified set of 6 key growth drivers and a Phase III pipeline that spans 4 therapeutic areas with meaningful breadth and depth. We're well positioned to deliver sustained long-term growth. Yaron, over to you for Q&A.

Great. Thank you so much. That was good to know. I think news about the Otezla generic as well. Okay, maybe, Kave, to you, first question since we have you on market access, which is critical. So Amgen has done very well financially and continue to -- pricing has been variable across assets, and you obviously have both rare, to oncology, to mass market. What's the secret sauce? What's Amgen's secret sauce on Access and negotiations and formulary placement?

Yes. I think from my perspective, Amgen has experience and access across a wide number of therapeutic areas. We're in 4 therapeutic areas now. We've got experience and access in over 100 markets around the world. We build in access as part of our strategies from early on in our pipeline to make sure we're generating the evidence that we believe makes our products competitive not just from a physician choice standpoint, but from a payer choice standpoint and evidence that helps us justify the economic value that our medicines bring going forward. I think that integrated approach from molecule inception all the way to on market and LOE has allowed us to perform very well from an access perspective, making sure that our medicines that we invent are accessible to patients at prices that are affordable to the health care system.

And is it -- it's how you negotiate access on an annual basis or how you negotiate access even on a portfolio basis? What sets you apart?

Yes. So again, I think access negotiations in general happen at a product level within a category versus the other therapeutic options that are there. And again, I think that body of evidence that we create either through clinical trials, the real world that we're able to bring the fact that we're forthright in thinking about access allows us to navigate those potential headwinds as a forethought rather than afterthought, Yaron?

Repatha, I think, is really -- has been one of the examples, right? I think Access was tough. There was 2 different SKUs. One of them was pulled and then Access has really improved dramatically plus the data continues to get enhanced. Obviously, the latest data is primary prevention. Technically, that was on the label already. But now you have Amgen 1 (sic) [AmgenNow ] at a monthly price of $239. How important is Amgen 1 (sic) [ AmgenNow ] ? Or is it just another vehicle, but overall, it's really the rest of the channels are going to be really the most important?

Yes. Thanks, Yaron. And we've named our program AmgenNow, not Amgen 1, but that's okay. We know there's a lot of these that are coming up. Let me talk a little bit about Repatha, and I'll build in the AmgenNow answer there, if you don't mind. I think Repatha is a great example of how Amgen's Access skills have come to really unlock a really critical medicine in the U.S. and around the world. There's over 100 million individuals around the world with elevated LDL despite the fact that they're on standard of care therapy.

Only about 5% of them today are on a PCSK9. As the market leader, most of those 5% are on Repatha. By opening up Access, we think we can continue to penetrate that very large population that is underserved today. And by bringing the changes that we've done in the U.S., for example, Repatha is now listed as a preferred therapy on virtually every formulary regardless of whether it's Medicare or commercial. Average co-pay is down to less than $50 a month. The over half of Medicare patients no longer need a prior authorization to get the medicine. And we've now got great data with primary prevention, 36% reduction in first heart attack, 25% reduction in MACE, 20% reduction in all-cause mortality that with that good access environment is allowing us to scale.

Now despite that great Access environment, we know that some patients remain uninsured or are in high deductible health plans or are on one of the limited number of plans that are still making it challenging to get Repatha. And that's where Amgen now comes in. It's a direct-to-patient offering, $239 a month, in line with the lowest price around the world for Repatha. And we introduced that program in October. So we've been on the market now for about 5 months. We've been very pleased with the uptake thus far. We've got over 5,000 patients in the U.S. using Amgen now to get their Repatha. And we see that as an additional channel, Yaron, that goes beyond the very well-covered insurance channel to make sure that any patient who wants Repatha, whose physician wants them to have Repatha is able to get and afford Repatha in the U.S.

There is increased competition. Leqvio is now waiting for its outcomes. It's Q6 months. I think the access there has been improving. And there's going to be a couple of orals, one a little bit more differentiated from the other, one is from Merck, the other one is from Astra. Any thoughts about how does that work in a competitive dynamic? And again, we're aware that the other 3 don't have outcomes yet.

Yes. So let's just start. If we look back at cardiometabolic markets, the history of them, we would say that, first and foremost, the goal here of us, and we think the goal of the field is to improve penetration into that 95% that is not yet on therapy rather than just fight over the relatively small patient population that has access to therapy today -- is on therapy today. When we look overall -- these additional entrants, we expect will grow the overall penetration of the market at a rate that's faster than share is consumed by them.

And so we think that, that increased share of voice will increase focus on LDL and increase treatment rates overall. In terms of the competitive dynamic, as you've said, we're really proud to have 2 outcome studies, both primary prevention and secondary prevention. These add to the mountain of data that's been created on Repatha. We've done over 30 clinical trials ourselves. There's hundreds of clinical trials that have been run with Repatha. We think that, that primary prevention data, which is unique to Repatha is a huge differentiator and allows us to continue to hold our competitive position as new competitors enter.

Can we maybe move to Tezi? So Tezi posted $1.5 billion to Amgen. The accounting is a little complicated, as everybody knows, because of the AstraZeneca relationship. It obviously sold more than that globally. That was up 52% year-over-year. And now CRS with nasal polyps was approved in October. For Dupi, CRS is now more than $1 billion in that brand. Where -- do you have any sense what percentage of new patients is Tezi getting and maybe overall share in asthma right now?

Yes. Yaron, I don't have those numbers off the top of my head. What I would say is that Tezi is the one molecule in the severe asthma class that can be used irrespective of eosinophilic or allergic status overall. It's the one medicine that can be used for all patients with severe asthma. That's been a differentiating factor for us.

It's been very competitive across the different phenotypes of patients that the other competitors are targeting overall. When we look at polyps, polyps is a really important indication. One, it's highly comorbid with severe asthma. And so it helps us continue to penetrate and win additional share of the asthma patients that also happen to have nasal polyps. It's also representative of a highly eosinophilic disease. And so with the great data that we showed with its high efficacy to prevent surgery, we think it helps us in both of those populations and further penetrate the market.

Okay. And then UPLIZNA launch, I think since its launch, more than 500 unique prescribers have written it for IgG4. The market right now based on claims is thought to be around 35,000, so not small at all. The feedback from clinicians, data looks really good. There was one question about what does it sequence relative to Rituxan because Rituxan is obviously a lot cheaper. And now you just got gMG approval, too. So maybe we'll start with IgG4. Do you have a sense how is it being used? And is there a large patient population that is now getting tapped? Or is it mostly for new patients?

Yes. So as you said, Yaron, we see the market the same way. We see about 35,000 patients diagnosed with IgG4 disease as of right now. This designation of IgG4-related disease is only about 10 to 15 years old, coding for it in the U.S. is only 2 years. So we do expect that, that could -- that number could evolve over time as additional treatments are used in the field.

As you've said, to date, we've had about 500 unique prescribers prescribe UPLIZNA. This is a very diverse disease that is viewed by a diverse set of physicians. And we see this as a patient finding and physician activating game -- ground game, which we've done quite well with TAVNEOS, for example. In terms of where it's being used, we see it used at all lines of therapy right now. We're seeing it as a first-line therapy. We're seeing Rituxan-experienced patients come in. This is an area where UPLIZNA is the first and only approved medicine for IgG4 with an 83% reduction, if I'm remembering my number correct, reduction in overall flares. And so we are seeing the community respond very positively to the disease, and we think uptake will continue across activating additional prescribers and finding additional patients.

And then for myasthenia gravis, any sense where the drug is going to get used?

Yes. So we got approved for myasthenia gravis in December. And so we've been now on the market for about 2.5 months overall. MG has about 80,000 to 100,000 patients. Competitive field, obviously, other biologics in the market already. Launch to date, about 50% of our prescriptions are coming from bio-naive patients, about 50% are coming from bio-experienced patients. We think the market is reacting to what we saw in ADVANCE, which was this was a market that was interested in a reliable therapy that had durability, efficacy and convenient extended dosing. And with UPLIZNA being twice a year after an initial induction dose of -- induction 2 doses, we think we've met that bar.

And so we're seeing uptake across the board, Yaron. I'd highlight as well that specifically in the bioexperienced market, given the frequency by which other therapies are offered, it's offering us a number of opportunities to play for switch. And that frequency is giving us additional shots on goal as patients progress and need to come back for reevaluation and retreatment.

Does it make sense to run a SWITCH study to help inform how to use the drug?

Yes. I think we remain interested in a number of things on UPLIZNA, Yaron. We're not going to announce a SWITCH study today, but we do know that, that is an area of interest. And like I said, the community is already appears to be switching without that study.

We've done a fair amount of work with physicians, and they are interested in using it broadly. 6 out of 10 right now are going on Vyvgart right away. And so the feedback -- the one challenge with UPLIZNA and their fans of the durability is that it's slower action. And so not all patients would qualify. Does -- how do you think that's going to ultimately fit into where you really get stable in terms of traction?

Yes. I think time will tell on the market exactly how that plays out. Look, physicians right now are excited to be getting experience with this medicine. We're excited to bring another option overall to patients around. And in due course, we'll see exactly how it plays out across the marketplace.

Let me actually zoom out. And when we talked about access overall, I neglected to ask about Europe because sadly, Europe is not as big a part of the market these days. Is -- are things stable in Europe now? Are they getting -- continuing to get more challenging? And are they -- are you beginning to see that they are willing to pay a little bit more for medicines?

Yes. I think last year was a bit of a wake-up call across the ex-U.S. markets around where the U.S. sits within the drug innovation ecosystem and how some of their systems have progressed. I'd say we're in constant discussions with governments around the world, making sure that they understand what the world looks like in a post most favored nation setting overall and advocating just like we've been advocating before that Europe, in particular, should recognize the value of medicines that we bring. We're seeing some governments start to react and start to think differently. We're seeing some that are not. But there's definitely -- the challenges remain in terms of access across Europe, and we're looking forward to engaging on those.

With PAVBLU was off to a really strong launch, but it's probably not going to remain the only biosimilar. It's a question of when the next ones will come, whether it's starting next year. As much as the launch has gone well, I think it's got less than a 10% share right now, roughly in the U.S. What is it going to take to really expand it further?

Yes. So we're really pleased with PAVBLU thus far. We -- last year, we think we did $700 million of total sales as the only biosimilar on the market.

I was thinking, by the way, of all anti-VEGF and bispecifics, not just EYLEA.

Yes. And overall, Yaron, I think the way we see this market continuing to evolve primarily based off new biosimilars entering, which, as you've said, we're expecting from what we've seen externally to occur at some point this year. Until that comes, we continue to be the only biosimilar on the market and compete with the innovator.

And is that this year in the U.S. or mostly ex U.S.?

I think time will tell you, Yaron. There's a lot of factors that affect how and when biosimilars enter, and I think we'll just have to watch how that landscape evolves.

Yes. Any -- maybe from a payer perspective also or a marketing perspective for MariTide, pricing in general has continued to come down. The Access has gotten more resolved, and now it's really about differentiation. As you think about MariTide maybe for maintenance, what do you think you need to show in any sense, how do you weave that into a clinical program?

Yes. So maybe I'll just start by saying that we're obviously aware of the pricing changes that have been underway. The price has evolved in line with our expectations. We continue to be very excited about MariTide. We think we have a differentiated asset, especially whether it's monthly or less frequent dosing. And as you got to see in Ohio, we're proud of the manufacturing capabilities that we have and think that those will give us the ability to continue to compete as price evolves.

In terms of the maintenance setting, it's obviously something that we're quite excited about. We provided some update earlier this year on our phase -- our Phase II, Part 2 data, which tested less frequent dosing. It's obviously a competitive market. In due course, we'll have an update with how we plan on using that data and how we plan on approaching the market from a maintenance standpoint in light of pricing and competitive dynamics.

As it relates to MariTide, I had 2 questions. One is by the time you get on the market, which I'm assuming is 3 to 4 years from now, how do you see the competitive dynamics having changed, assuming the only 2 other products on the -- other 2 companies are Lilly and Novo with expanded product lines? And how important do you think it is to be able to have approvals not for obesity or weight loss, but from an insurance standpoint to have approvals for the 7 chronic conditions that obesity is related to that result in a reduction of morbidity, mortality and cost.

Maybe we'll just restate the question for those on; the webcast.

Please go ahead.

Yes. I mean just to summarize. So I think the first question was how would we plan on competing given that there are folks on the market today, and we would be coming later. Just to clarify, we haven't commented on launch time lines. So we'll let you make your own assertions there. And I think the second part of the question we caught.

Yes. So -- and the second part of the question was, how do you plan on competing against other companies that have multiple offerings. So...

And do you think that it's important to have approvals not for obesity or weight. I don't personally don't care about the 16% or 19% weight loss or 22%. I think that the insurers are more interested in the docs in the 7 chronic conditions that obesity is related to where you can have a significant reduction in morbidity, mortality and cost.

Yes. So let me address that then in 2 parts. One, we're excited to be bringing a differentiated molecule to the marketplace. And we think that differentiation earns us a seat at the competitive table with what we're bringing, really focusing on efficacy that is in the mid-20s on weight loss and big impact on cardiometabolic parameters, including HbA1c, a tolerable medicine that we're looking to improve the initiation protocol with 3-step dose escalation and then finally, monthly or less frequent dosing.

In terms of the obesity-related conditions, that's an area we're very interested in. As we shared earlier, we are on 6 Phase III clinical trials, and then we were also looking to add type 2 diabetes. But our clinical trials for the related conditions are ASCVD, heart failure and sleep apnea. And then we believe that the whole suite of evidence will be important, not just for payers, but to compete in the class.

Maybe a question again, Kave, while we have you on Sjogren's. It's an area we've done a lot of work on. Technically, it's not an orphan market. But once you look at the patient population being RFRO positive, moderate to severe, naturally becomes an orphan market. Can a market like that, and you're looking at both systemic and symptomatic and you're the only company right now, and that's critical because 60%, 70% of patients are actually symptomatic. So everybody else is going for the smaller segment, albeit obviously important. Can it support premium pricing?

Yes. So Yaron, let me give you how we see the market, which I think might be just slightly different than as you see it, but we see about 350,000 patients that are RO or RF positive diagnosed. And we see this as a serious but also highly heterogeneous disease. Given that heterogeneity, we see room for multiple therapies in this market. And we think some will go in the first line, some will go in second or later line, some will go for the whole population, some will go for smaller populations.

And obviously, we'll have different value propositions depending on exactly where they sequence overall. So we see a lot of different routes to make this a viable marketplace. As you shared, we are studying in both the systemic and symptomatic populations separately. The systemic population, we see that as roughly 30% to 40% of the market. And then the symptomatic population, we see that as 60% to 85% of the market. Now that doesn't add to 100%. That's because some of these patients are both systemic and highly symptomatic overall. But we decided to run 2 different Phase III trials to cover the waterfront to understand the effect this medicine can have on both those populations.

The reality is when we talk to physicians, for the most part, they tell me, first, it's a Sjogren's patient. And you kind of have to really dig under to see how they're subclassifying between those 2 population types. We thought -- given the data we saw in Phase II, we'd study the entire population. So when they see a moderate to severe Sjogren's patient, they can hopefully, depending on the data, pull for dazodalibep. So it's an opportunity we're excited about. We've been excited about since the time of the Horizon acquisition, where we got this molecule. And both of those studies read out at the end of the year. And based off the readouts of those studies, we'll understand exactly what our path to market is. And really, are we positioning for a broad population or a smaller orphan subset population?

To your point, the symptomatology is fairly variable, anything from dry eye to fatigue to some arthralgia, -- it could be a lot more systemic and has a real tissue involvement. So that's why I'm trying to -- for me, it's a little hard to try to figure out the price -- if you look at some of the other companies working in this space, Sjogren's is probably going to be an add-on indication, and they're deep, deep in orphan pricing. I guess Novartis will be first, and we'll have to see how they price. But by virtue of the competition, it looks like they're going orphan, and that's maybe that's the opportunity. But the question is it severe enough?

Yes. I think, again, time will tell based off that Phase III data exactly where this product gets positioned and the size of the population that addresses to the opening point you made, I think this is an area where we will wait for the data and follow the data before making any commercial decisions.

Yes. Maybe finally, just a broad question. In general, pricing for biologics is going down. I'm talking about mass market and volumes are going up a lot. So to your point, Repatha $239 x 12, it's about $,3000 -- just under $3,000 a year. MariTide and obesity drugs now are anywhere between $300 and $400, $500 a month. And they require a lot of injections and a lot of injectors. So I guess my question with Amgen, I mean, you're making drugs that are costing $150, $200, $300 and making drugs that cost $3,000. How do you work on the margins?

Yes. Thanks, Yaron. I would start by saying that this evolution is exactly what we've expected. We certainly, I think, for years now, have seen that U.S. prices -- prices in the U.S. and around the world would face pressure over time. And our strategy has been volume-driven growth. So you're right to kind of square that circle, what you need is a manufacturing footprint and a capability where you can keep your cost structure under control and manage that. So that's something we've been doing for years.

If you look at Prolia and denosumab, I mean, that's a primary care medicine where we've been able to earn a very nice return. And I think credit to the manufacturing and the operations team, what they're very focused on year after year is driving more productivity and efficiency gains. And so that's definitely part of the game plan.

When Amgen launched the new sort of high-yield perfusion and high-yield manufacturing, does it normally go into all products or certain products get that and some of the other ones don't.

It's really product by product, kind of case by case.

But is it -- maybe final question, fair to assume that Amgen is making money in every drug?

I don't -- I mean we don't disclose the gross margin by product, but I think if you look at our overall results, I think they speak for themselves.

Well, team, thank you so much. Good to see you. We appreciate it.

All right. Welcome to the afternoon sessions of Citi's Virtual Oncology Leadership Summit. My name is Geoff Meacham. I'm the Senior Biopharma Analyst here at Citi and Jarwei Fang from my team with me as well. We're thrilled today to have Jean-Charles Soria from Amgen, who is the Senior VP, Global Development in Oncology. We did this session last year, a lot of really good meat on the bone. We also have Casey Capparelli from the IR team. So guys, welcome. Thanks for joining us.

Thank you so much for the invitation

Yes. So I guess, Jean-Charles, we'll just kick it off with kind of the high-level questions on Amgen's kind of oncology approach. Maybe just talk through kind of as you see then the top priorities within oncology for Amgen on the R&D side, maybe what are the bigger opportunities? Are you guys good with the technologies you have in place. And now it's just a matter of moving the products through clinical development at a high level? Just wanted to get some perspective from you.

Yes. Thank you for that question, Geoffrey. Well, we have a framework that allow us to see how oncology or investments we'll be delivering. We believe that we are committing to bringing differentiated and transformative therapies. We don't want marginal benefit. That's one of the big rules. So there's one rule that we want to steal, to play both in hard-to-treat solid tumors as well as selected hematological malignancies. The third one is that we have at least two clear pillars in our modalities, one being the T-cell engagers and the other one being the precision therapies with our small molecules.

I would say on the T-cell engager front, we have invested for decades, and we are the only company with T-cell engager approved, both in hematological malignancy and solid tumor, and there is more to come there. The frontier of bringing T-cell engagers in frequent solid tumors is a very important one for us. On the small molecule front, we are strong chemistry -- teams have been able to get to very tough targets such as KRAS or PRMT5. That being said, we are also looking at diversifying our modalities, among which we believe ADCs as can play a role.

But we're very selective in where do we choose to play because it needs to be leveraging our own strengths and we're a biologics company with good chemistry understanding that makes, for instance, choosing other modalities, not the ideal fit for us. So that's the global framework.

Yes. Yes. And it's interesting, Amgen is one of the companies that can really add value along the entire way of the value chain. I think going back to the deCODE data, right, on the discovery side straight through to technology using BiTE and other platforms, I think that's somewhat unique. I mean, there's not necessarily a need to to do a deal to bring in new technologies, nothing that you guys don't already have, in-house, in a dramatic way, right?

Yes. Thank you for that comment, Geoffrey. I think resilience is an underrated virtue in pharma, like we have stick with T-cell engagers for a very, very long time. It's a little bit North Face or the Annapurna to bring them to solid tumors without HLA restriction and in frequent ones. We are very glad for the patients that are on IMDELLTRA is bringing transformative benefits in small cell lung cancer. And we are very hopeful to see xaluritamig potentially doing that in prostate cancer, a tumor type where immunotherapy is basically totally inactive. But we monitor the external environment, and we are convinced we don't have the monopoly of the best science, but we will do selective investments where we see it's complementary to our priorities, to our own pipeline, and it's truly transformational.

Yes. Well, you mentioned IMDELLTRA. So let's get into the market of product portfolio, and that's a good place to start. So full approval, extensive stage small cell lung cancer, but many other tumor types that it could go into. Maybe just help us with kind of the commercial backdrop here. How do you see kind of the next 12 to 18 months roll out on a geographic basis? And maybe help us with -- remind us of the other data sets to come that could further expand the label for this exciting medicine.

Yes, Geoff, why don't I jump in on the -- just the commercial aspects and then Jean-Charles, I'll turn it to you to highlight maybe just reflections that you've heard clinically from the approved indication, which is second line or later small cell lung cancer, but also maybe a few words on the development program.

So as I mentioned, Geoff, approved in second line or later small cell lung cancer that's full approval received last year in 2025. And in addition, NCCN guidelines have been updated to reflect IMDELLTRA's benefit in that setting. And so we feel like we have a lot of momentum commercially in reaching patients with IMDELLTRA, in fact, over 1,600 sites in the U.S. now administer IMDELLTRA, and the majority of our doses are provided in the community setting. That was an open question that we had, our ability to really reach patients that are treated with small cell lung cancer in the community setting.

And based upon what we've learned from BLINCYTO, we've really been able to do that in a fairly rapid fashion with IMDELLTRA. We have approval in Japan, pending approvals in other geographies based upon the Phase III study that generated full approval in the U.S. I mean, we're excited about the potential to continue to reach patients with this second line or later setting in the currently approved indication. But there's a lot more going on with IMDELLTRA even beyond the current approved settings. And Jean-Charles, maybe I'll turn it to you to talk a little bit more about that.

Yes. Thank you, Casey, for that context setting. We fit IMDELLTRA, we saw such a compelling activity on the basis of the Phase I, II that we launched multiple Phase III trials. And we have, on top of the already disclosed positive second-line Phase III trial, three other ongoing Phase III trials. One in the first-line metastatic setting in the maintenance setting, that's Trial 305, which is fully enrolled. We have another first-line metastatic trial, which is Trial 312 that is enrolling. And we -- that gives IMDELLTRA combination with chemo and PD-L1 upfront.

And then we have another Phase III trial ongoing in limited stage small cell lung cancer. So we really want to bring the value of this modality to the whole spectrum of the disease.

Just given the modality of this with being a DLL3. Jean-Charles, maybe help us with kind of the -- any other tumor types that you think could be suited here? I know obviously, the -- mostly the focus is on small cell lung cancer, but are there reasonable opportunities looking broadly across the lung or other tumor types?

Yes, certainly, Geoff. Thank you for that. Beyond I expand on other tumor types, we are also doing a lot of efforts to make this more convenient and friendly for the patients and health care providers. We are testing BLINCYTO subcutaneously that will alleviate a lot of the pressure on the beds. We are doing alternative testing, so not only Q2 weeks, but also Q3, Q4 weeks, those trials are ongoing, we are prospectively testing whether the monitoring can be reduced to shorter timeframes like 6 to 8 hours or even shorter. All of these will facilitate the uptake of this therapy in community-based hospitals and beyond.

But your question more specifically is, are there other tumor types in which these DLL3 T-cell engager could potentially play. And the answer is yes, we have reported data on the activity of our T-cell engager in neuroendocrine prostate cancer and that's a different type of neuroendocrine tumor versus small cell lung cancer. That's neuroendocrine differentiation on the therapeutic pressure. It happens when you have people with prostate cancer that had multiple lines of therapies and then you have a transformations to a standard endocrine form at the same way you can have EGFR mutant adenocarcinoma, the lung that develops small cell lung cancer transformation on the therapeutic pressure. Those are areas where potentially this asset could be developed.

Right. Okay. That makes sense. And then moving down the pipeline to, I would say, more recently marketed products like LUMAKRAS. Same thing there in terms of expanding the opportunity beyond lung into colon cancer. I know you guys have done some work on this over the past couple of years. Maybe give us a status update of where the Phase IIIs are going? I know you are still enrolling first-line lung in colorectal, but are there any other kind of line extensions that make you more excited as you look at LUMAKRAS as a brand that's still growing and impactful to Amgen.

Thank you for the question. LUMAKRAS is currently available in both second-line non-small lung cancer and third-line colorectal cancer in combination with our on Vectibix. Longer-term growth of LUMAKRAS will probably be driven by -- it's moving into earlier lines. So let's discuss lung and then colorectal. In non-small cell lung cancer, we have seen that the combination of LUMAKRAS with chemotherapy did led to durable responses with a very good manageable safety profile. And this was notably in treatment-naive patients with KRAS G12C mutation. So this is why we launched the CodeBreaK 202 Phase III trial that is testing the combination of chemotherapy with LUMAKRAS versus chemotherapy and pembrolizumab, that in KRAS G12C patients who are PD-L1 negative.

For the colorectal tumor types, the triple combination of LUMAKRAS, Vectibix and FOLFIRI, show very compelling objective response rate of around 55% with the disease control rate north of the 90%. And the responses were observed, regardless of the number of prior lines of therapy including progression [indiscernible]. And this is why we launched a first-line colorectal cancer that is currently enrolling and hopefully, will bring this therapy into that earlier line setting.

Okay. That's helpful. I think Jarwei from the team had a couple, we wanted to stick with marketed products with BLINCYTO, but then obviously, that has a pretty deep pipeline behind it. Jarwei, go ahead.

Yes, definitely, on BLINCYTO, you have a number of Phase III studies that are currently enrolling. One of which is, I believe, it's the Golden Gate Study for older patients with leukemia. I guess just thinking about the opportunity and also just the bar for efficacy that you need to see there, how do you think that represents the -- another leg of growth for BLINCYTO going forward?

Thanks for that question, Jarwei. I would say what we have come to realize with BLINCYTO is that as we move this asset to earlier lines of therapy, we see higher efficacy, better tolerability, and that's an important trend. And in fact, it's a blueprint that we are using for the development of IMDELLTRA, referring specifically to the Golden Gate Phase III study. This is in older adult patients, mostly 55 years and above with newly diagnostic B-ALL. And that is an indication where we have chemotherapy sparing regimens that are very important for those patients who have less tolerability. So that will bring a new perspective for BLINCYTO. We're also advancing subcutaneous blinatumomab who has the potential to improve convenience tolerability and efficacy.

And we believe this is going to be very important also for this asset. We have had Phase Ib data suggesting better efficacy at CIV. And we have other trials that are going to be -- we exploring this in a more registrational manner.

And so for the subcutaneous formulation of BLINCYTO, do you expect certain indications or certain age groups to see faster uptake? Or could you see a scenario where subcutaneous formulation kind of supplants the current route of administration, fully?

Well, we will be driven by the data, correct? And what the data told us in a very limited Phase Ib setting was that this potentially will bring more convenience and even higher activity. But you imagine the efferent number of trials, it took for BLINCYTO to be validated in later lines relapsed/refractory earlier. Now the first-line setting, you will need to do that movement for subcu at the same time. So let's see how the initial readouts pan out. But yes, that could be potentially a framework, Casey, anything to add on that?

No, I think you covered it. I would just quickly mention, Jarwei, I know we're focused on oncology, but we're also exploring blinatumomab in the space of autoimmune disease where B-cell depletion has been shown to be important in a variety of autoimmune settings. We have a couple of Phase II studies underway exploring blinatumomab, both in the SLE with and without nephritis setting as well as in refractory rheumatoid arthritis. And so potential to even move beyond oncology with the B-cell depleter like BLINCYTO.

I would like to add, Jarwei, that it makes complete sense mechanistically, correct? Because CD19 is B-cell antigen and B-cells produce antibodies. And if you suffer an autoimmune disease because you have auto antibodies, depleting the B-cells that produce those autoantibodies is rationalisticy very logical those -- the pad that Casey has highlighted for our own BLINCYTO in that setting. .

Got you. Makes sense. And maybe just one more, shifting back to IMDELLTRA real quick since we talked about BLINCYTO and the subcu formulation. Ease of access for patients and also reducing bed burden is definitely top of mind for community centers. Could we see later on as IMDELLTRA becomes more mature in its product cycle, that subcu might one day be explored as well? Or do you have to see BLINCYTO data first as a gating factor for the BiTE program, for BiTE platform rather?

Yes. Thank you. Well, in fact, we are exploring IMDELLTRA in a subcu Phase Ib trial that is ongoing because we are completely cognition of the barriers of patients being treated in community base hospital need to overcome and not competing for the beds, being able to provide subcu, being able to do Q4 dosing versus Q2 dosing or being able to have less of a follow-up after administration are some of the levers. We are very actively trying to pull through with prospective data and therefore, making IMDELLTRA more available.

Makes sense. And I think, Geoff, I think you have a few questions on prostate. Maybe we can move to that.

Yes, yes. Let's switch gears, Jean-Charles to xaluritamig, which is a super exciting product in prostate and Ewing Sarcoma, but there's a lot of investments you guys have made in prostate. Maybe just at a high level, talk through how you think the differentiation could play out. That's obviously a pretty crowded market, but so far, you've had some pretty compelling kind of mid-stage data. Maybe what makes you exciting as you turn the card -- prepare to turn the card over on larger-scale Phase IIIs and then move to market. .

Yes. Thank you for that question. What is really exciting for us with xaluritamig in prostate cancer is that it levers a mechanism of action that has currently no approval. There are no PD-1s, PD-L1 or CTLA-4s approved in prostate cancer. Patients with that disease are very well aware of that and really would like to see an immune-related asset that could bring sustained responses, that's number one.

And the second one is that we have seen very clear signs of efficacy, both in PSA 19 and PSA 50 but more importantly, in objective response rate for this asset. And therefore, we are going to do many things -- we are doing many things in our Phase III trials to differentiate ourselves in a very competitive landscape, as you rightly highlighted. First, we want to lead with the gold standard of survival evidence, especially versus highly active chemotherapy comparators.

We are designing our pivotal programs to generate overall survival in both the post-taxane and the pre-taxane setting, that's a bold bar in prospect cancer, but we are confident and we really want to make sure that we are having the right comparators with the right endpoint.

The second element is for us to speak to market. We have prioritized monotherapy development in the post-taxane setting because that's an area with very high unmet medical need, and we want to reach the patients very, very quickly. The third element I would say is we want to be differentiated in terms of practicability, meaning we don't need a biomarker gate and our breadth of addressable patients is extremely broad in the prostate cancer space. We don't need enrichment through PSMA or through PET or through a mutation or anything else. That's another element.

And finally, the chemo-free regimen for the pre-taxane setting is another pillar of differentiation. We are positioning ourselves as a potential non-chemotherapy option with survival advantage versus chemotherapy that's both twice because you're putting OS as an endpoint because you want to show that you can beat chemo without being combined with chemo. So those elements are very, very clear. And we believe in this combination, in that setting.

Finally, we want to remove a lot of the friction that comes from implementing a new modality with a new mechanism exception and new tolerability challenges for the clinicians. So as we are enrolling on our Phase II trials, we are working very much hand in hand with investigators to clarify the type of adverse events and how do we learn and moderate them and what is the optimal management of this therapy. Prostate cancer is a world where you have multiple players, whether it is Urology, the Nuclear Medicine doctors or Medical Oncologies. Those would be the key differentiator drivers.

Yes. Yes. I wanted to ask you on a couple of the comments as a follow-on to your response. When you think about prostate overall, it's a lot of different markets. And so I was wondering if there is a way to maybe take advantage of some of the differentiation. Would there be a regulatory incentive, for example, to maybe pursue accelerated approval for post-taxane just given the unmet need or chemo or hormone-free doing a head-to-head. Could you take advantage of faster regulatory pathways through that. I'm just trying to think of ways to maximize the novelty from a clinical development perspective with regard to the mechanism.

Thank you for that. We haven't shared any details of any of our statistical analysis. So I'm not going to reveal anything here. But I would reply to your question by saying that we are so convinced of the importance of this therapy that we are bringing in and this is completely under -- regarded by many investors to earlier lines. We are -- we have 3 ongoing Phase Ibs, one in the neoadjuvant setting. So before surgery. We have one in biochemical recurrence. And we have one in hormone-sensitive prostate cancer.

So we already changed the narrative. We are now waiting for our Phase IIIs to read out positive in castration-resistant prostate cancer, post-hormonal therapy, post-taxane. We are already testing it in the Phase Ib sitting in the earlier sites of prostate cancer. So we hope that we'll generate data that will help us then move to that setting in a registrational trial.

I mean, Geoff, I want -- just to build on what Jean-Charles is saying. One of the things that provides us confidence to do, as Jean-Charles described, is what we've observed with both BLINCYTO as well as IMDELLTRA. And that is when you move the T-cell engager earlier in the treatment paradigm into settings of lower tumor burden you really see impressive inflections in survival. And we saw that with BLINCYTO, we're seeing evidence of that with IMDELLTRA and that furthers our hypothesis and the rationale to pursue xaluritamig in the early stages of prostate cancer as well. We'll have to see what the data teach us, but that underpins some of the thinking that Jean-Charles just described.

Okay. That's helpful. Thanks, Casey.

Makes sense. And maybe just sticking on xaluritamig for a little bit longer. We often get questions on prostate cancer, but Ewing sarcoma is certainly one that isn't really brought up very often. And given you have a Phase Ib study and a pretty broad population going on in relapsed/refractory. Maybe tell us a little bit more about xaluritamig's opportunity there and why STEAP1 would be a good target for that type of indication. Jean-Charles, I think you're on mute.

I am on mute, thank you for letting me know. So in drug development, we always navigate this tension of what can we do for rare indications, but when you have an asset like xaluritamig, where the development plan in a common indication is there and its clearing is compelling. Going to Ewing sarcoma is something that was justified by the biology of the disease, the extremely high levels of expression of the target. And the true unmet need because if you fail the frontline therapy in Ewing sarcoma, and this is both for young adults and pediatric cases. It's not a good prognosis.

So we are very excited to bring this innovation in that setting and the trial is open and we are eager to see what it will bring. But the biology makes sense, the unmet need is there, and it's a rare disease, but we can justify doing it because we have already made an investment in the common tumor type.

Jean-Charles, let's switch gears to maybe the earlier to mid-stage pipeline. So AMG 193 in development for mTAT solid tumors. Talk a little bit about kind of what insights at Amgen has gained here given this -- the mechanism. I think it does showcase kind of Amgen's more discovery kind of angle here to bring a unique asset like this. But talk about the next -- what tumor types do you think is -- could this work for the best, based on the data that you have today, I know you have Phase Is in lung, but maybe lead us down to the path of where the science could go in terms of other tumor types.

Yes. Thank you. Thank you for that. We presented our data at ESMO presidential session and show activity across multiple tumor types, that we have focused the development more on long and gastrointestinal solid tumors. In lung cancer, we have a Phase Ib combining AMG 193 with different standards of care to see the combinability, that's an important one. In lung, we also are doing the randomized dose optimization to define what will be the recommended dose for registrational trials. And that one is ongoing. And it makes sense because it's a very big tumor type where the prevalence is significant. I mean, not significant at least good enough that you have enough patients.

And we are also combining AMG 193 with other standards of care in the setting of gastrointestinal tumors. And we -- I would just refer also to a trial in which we are combining AMG 193. We did the revolution medicine RAS inhibitor in pancreatic cancer. This is to tell you, we are following the science and the biology and combining with what makes sense as the standards of care in different tumor types or standards of care to be common in the case of tarlatamab.

Jean-Charles, are there lessons to be learned in the case of the mechanism here from resistance. In other words, can you find other dual mechanisms as you try to think about a combination sphere that could help mitigate the risk of that and maybe maximize the antigen activity.

That's a very good question. In fact, the biology of PRMT5 inhibition in the setting of the pent-up deletion is a new one, is a new frontier. We had the first generation inhibitors that were not really active, that had a lot of hemtoxicity, but squeezed inhibitors that are MTA-comparative are a new reality. And -- what we are discovering is that the biology of how the tumor response to that therapeutic pressure is pretty unique. We have not only objective response rates, but we have stable disease that become, with time, objective responses. That's not common in oncology to have that transformation. So it's an area where further investment in our understanding of science is yet needed and more to come as we unfold the results.

Yes. Yes. And I guess just as a follow-on to that, when you look at the tools that Amgen has in place, I mentioned the deCODE. Also the utilization of more AI driven. Talk a little bit about how that -- how technology has played a bigger role in maybe discovery, but also just trying to maximize the earlier Phase I data that you get that can maybe derisk a drug or give you a window into maybe other tumor types?

Yes, that's a very good question. We completely recognize how important the pace of change through technology and AI and machine learning is changing the world, the world of biology, the word of drug development, the world as a whole. And at Amgen, we are literally leveraging these tools from targeting identification and molecule design and generation of target antibodies to translational insights and better understanding our own clinical data. The tools will help us enhance our ability to analyze complex data sets.

You need to understand the complexity of putting those data sets in X5 is beyond human understanding, when you have very rich omics and radiomics and clinical data points. That's an area where patent recognition will be expedited through AI. Our goal is not just speed, it's also precision in improving the quality of our hypothesis and how we prioritize things and how we execute. You can imagine, for instance, how important it is to have an AI protocol uttering tool that will help you get protocols that are sharper with zero consistencies where we'll integrate amendments in an easier manner. Those are obvious ways.

With you AI has an amplifier of human expertise. These technologies really augment with our science and our drug developers, can generate in terms of creativity, in terms of experience, in terms of analysis. But we need to maintain extremely high standards. We are a regulated environment. So this needs to be done within defined guardrails. We are embedding AI and advanced analytics in most of our research engines, we are already seeing a shortening of the timelines as well as enhanced decision-making. And I'm very optimistic of what this will bring. It's accelerating quarter-by-quarter. It's getting better and better.

So maybe sticking onto the AI theme. Given the potential of your BiTE platform, how are you leveraging AI and maybe looking at other targets that you could look at, maybe your research into what other solid or liquid tumors that you maybe could target. Maybe give us a sense of the types of work you're doing to expand that platform and just make it even more fulsome than what we've already seen.

Yes. Thank you for the question. Obviously, creating new white space for T-cell engagers, but other modalities too, is extremely important, correct. We suffer in our industry from sometimes all going against the same targets. We were quite unique with DLL3 T-cell engager. There are many other modalities. So creative white space is very important. And it comes frequently through the very unique conversions of biology, technology and compute power. And I will give you a very clear example. We announced a deal with a company called DISCO Pharmaceuticals because they were ahead of us on understanding the surfaceome.

So the surfaceome is the reality of expression at the surface of a cancer cell of the different proteins, but people have a very simplistic view of how they are expressed. In fact, they create communities, they cluster together in certain ways. They have different densities. There are many new technological tools and AI tools that have helped tremendously accelerate the understanding of who is clustering with who and in which proportions that all of a sudden gives you a white space for new targets that would be dependent on the coexpression of an existing target. You can choose to say, what I want to know, who's the best and closest partner of DLL3 in proximity in a surface cancer cell.

Well, we announced a deal with DISCO Pharmaceuticals because they found a very interesting target in small-cell lung cancer. And that's an example of bringing in a very concrete way what the advancement of biology computing and technology can't.

Just as a follow-up to that, Jean-Charles, I know on bema, you guys aren't pursuing the gastric indication, but is FGF still an interesting target to you guys? Is there -- are there ways to go back to the drawing board using something like AI to maybe find some lessons learned here to try to redeploy into other tumor types. Just want to get your perspective on that.

Yes, sure. Casey, you want to start?

Happy to start. So for bemarituzumab, Geoff, as you mentioned, we've decided not to pursue regulatory submission in frontline gastric cancer. We're currently determining what the best next steps are for that program, and I think we'll have more to say beyond that. Jean-Charles, anything that you would add there in terms of...

Yes. We follow the science. So we need to understand what happened in the Phase III trials. So we are looking at elements from the biology that will explain some of the results, and we will share more down the line. But we follow the science train, not only for developing of assets, but also for analyzing some of the outcomes.

Okay. That's helpful. I guess in conjunction with use of AI and biomarkers. Just help us with kind of how much emphasis does Amgen have on things like novel biomarkers, diagnostics, things of that nature. I wasn't sure if there is an approach to embed more kind of discovery or bells and whistles, if you will, in a Phase I on more novel mechanism drugs like IMDELLTRA, like xaluritamig, that could help you down the road, right, more maximize treatment effect and minimize tolerability?

It's a great question. Thank you. We have a precision medicine department that serves all the therapeutic areas that is trying to bring that value. The value of better predicting what's the best biomarker package of an asset that will enter Phase I. Do we have molecular predictors of efficacy, but also the reverse translation of when you see an extreme responder or you see emergence of resistance, what is driving that? So we really believe in the value of that and we are investing. There are many frontiers, correct, in oncology, one of them being the availability of some of these markers in the blood versus the tissue.

The tissue is the issue very frequently in oncology. Everyone wants the tissue and people get very small biopsies. So that's a frontier where we have interest, and we hope to advance radiomics and combining radiomics with our old omics from deCODE and combining that with additional single cell analysis or clinical data to create if you want a more comprehensive multidimensional data set of clinical points is another one where we are investing.

Yes. And just the last question, just along those lines Jean-Charles. With regard to, say, cell and gene therapy, are you -- that hasn't historically been a major focus from Amgen, but is that a sort of modality or technology that I think, overtime, Amgen could develop? Or are you pretty comfortable with the bispecific and T-cell engager and pDC. You have a lot of tools right now in the tool chest. So I guess that's the question. Do you add more? Or do you maximize kind of working out?

Thank you for that question. Our pillars on T-cell engagers and small molecules are not meant to be exclusive. So we will invest where it makes sense and leverage our strengths. I mean ADCs is one area which could make sense because we are a very strong biologics company and have good chemistry. But on the cell therapy front, that's a completely different modality and quite competitive. I mean, it's around T-cel engagers, correct. We are happy to see our T-cell engagers bringing benefit for solid tumor patients. We have not seen cell therapy deliver that in solid tumor patients. So cell therapy with other complexities in terms of the production, the availability, the cost. So we are very pragmatic. We follow the data points. And that is the answer I will give it to you. We will follow the science, but be very selective. Amgen is very disciplined in what it does. So we are not spreading and making beds everywhere. We are selectively making certain beds.

Makes sense. Okay. With that, we're out of time. So Jean-Charles, thank you so much, Casey, as well. I appreciate the input guys. Super helpful conversation.

Thank you for inviting us.

Yes. Thank you for having us today. Good to see both of you.

You too.

All right, everyone. Good afternoon. This is David Amsellem from the Piper Sandler Biopharma Research team and a happy almost Friday to everyone listening in. So in the next 25 minutes, we're going to be speaking with Amgen and lots to talk about when it comes to immunology and inflammation. We're delighted to have CMO, Paul Burton. We also have from the IR team or the Head of the IR team Casey Capparelli as well. Thanks, gentlemen, for joining us.

So I know there's a lot to talk about. And last week, there were some new developments in terms of new clinical trial initiations and also new data. So I'm admittedly going to bounce around. But one product I wanted to start with, Paul, if you don't mind, is UPLIZNA. So obviously, you had the label expansions last year. But you did discuss last week plans to initiate Phase III studies in autoimmune hepatitis and also chronic inflammatory demyelinating polyneuropathy later this year. So I guess a high-level question here. You got a B-cell depleter in UPLIZNA. So maybe talk about your rationale here for moving ahead with these 2 clinical settings and help us better understand the rationale for B-cell depletion in both of these clinical settings.

Great. David, look, thanks for having us. I think as a company, we have strong experience in B-cell depletion. We have BLINCYTO which has had data from a number of centers, looking at patients with RA as well as systemic sclerosis, showing clinical improvement there. And we also have a master Phase II protocol actually enrolling patients both with SLE or rheumatoid arthritis, looking at both UPLIZNA and BLINCYTO. And so UPLIZNA is a remarkable medicine, 6-monthly dosing, excellent safety profile. And both autoimmune hepatitis, AIH and CIDP are conditions where pathogenic B cells seem to play a central role, probably through autoantibody production, but immune disregulation as well. And so UPLIZNA being a B-cell depleter targeting CD19 is interesting because it's able to really target a broad spectrum of B-cells, pre B-cells, mature B cells and then plasmablasts.

And we think it's this breadth of its activity that is able to bring about diverse range of improvement in disease driving autoantibody conditions. So AIH is characterized by liver inflammation and that can cause progressive scarring and loss of liver function, CIDP, disabling immune-driven neuropathy that damages peripheral nerves, myelin. And both of these diseases have quite a lot of similarities with IgG4-related disease as well as generalized myasthenia gravis, where UPLIZNA because of its B-cell depletion activity has been able to show durable and really quite profound clinical benefit. So it's really this scientific basis where we've had proven effectiveness of UPLIZNA that makes us think that AIH and CIDP are really important unmet medical needs where UPLIZNA could play very strongly. And so that's why we're interested now in tackling those diseases.

And then one more quick question before I kind of move on to other parts of the I&I portfolio in terms of just how you think about the sizing of these to populations? Just help us better understand how you think about that, particularly relative to gMG and IgG4-related disease. And I mentioned IgG4-related disease because our understanding of the population is it looks to be a good bit bigger than what we thought it might be. So I'm kind of asking a similar question about these 2 populations and how are you thinking about that?

Yes. I think IgG4-related disease is interesting. When you have an impact for medicine, I think physicians are more likely to diagnose and to treat. And so that's important. For CIDP, we think the pool in the U.S. is around 35,000 patients. So that would be the prevalent pool with maybe about 7,000 to 10,000 incident new cases diagnosed a year. AIH is probably larger than that, but it's difficult to get an absolute number on it. But that just gives you a kind of a ballpark sense of where we are.

Okay. All right. That's helpful. So let's talk about Daxdilimab. So you announced -- or the team announced last week, positive results in -- Phase II discoid lupus, so just wanted to take a step back here. So Daxdilimab, I think it was acquired by the Horizon transaction, if I'm not mistaken. It did fail a Phase II study in SLE. Obviously, it worked in particularly challenging cutaneous manifestation with lupus. So I guess with that in mind are -- as you think about a product like this a plasmacytoid dendritic cell depleter, are these kind of cells more prominent in cutaneous manifestation of lupus? Or maybe put differently, can you talk to the mechanistic rationale behind the success in discoid/cutaneous lupus, but the failure in SLE.

Yes. So as you very rightly say, David, Daxdilimab is a first-in-class molecule that targets something called immunoglobulin like transcript 7 protein or ILT7. And it seems that, that is involved in driving plasmacytoid dendritic cell function and in turn interferon production. So Daxdilimab is essentially a plasmacytoid dendritic cell depleting agent, just like we've talked a little bit about in a different setting with UPLIZNA, which obviously goes after B sales. So SLE is an autoimmune disease. It tends to affect the skin, joints, kidney, the nervous system as well with autoantibody production and often you get complement depletion.

Discoid lupus is a skin manifestation. So it's similar to lupus, but it has SLE, but it has a different underlying pathology. It's driven, as I said and you said as well by plasmacytoid dendritic cells, interferon production in the skin, which leads to this dermatitis. And so we think because of that biology and the pathology that Daxdilimab would be a good potential therapy for discoid lupus. And in fact, as you say, we did do a Phase II study of Daxdilimab in those patients with discoid lupus. It met the primary endpoint, which was really a reduction in disease severity index at week 24. And it also met the key secondary endpoint, which was looking at investigator-assessed global assessment of disease activity.

We also have a smaller study, a Phase II study in just 12 patients with dermatomyositis where it also showed clinical benefit. So while, it didn't show the efficacy that we were hoping for, as you say, in SLE, we think that this positive Phase II in discoid lupus, coupled with the biology, coupled with the pathophysiology in that disease makes us feel confident that we can take this molecule into that setting and hopefully provide some clinical benefit there in these patients with discoid lupus. So we're excited about that.

Is the plan to move right to Phase III? And do you evaluate discoid lupus specifically? Or do you look at a broader population with cutaneous manifestations of lupus?

It's a great question. And I would say we're still thinking about exactly that we want to be very thoughtful. This is a difficult disease with few treatment options. We think we have a very attractive asset here. So I think we probably need a little bit more time just to continue to look at the data and plan the Phase III and then we'll share those plans in due course.

Okay. And then looking at Daxdilimab more broadly, can you just talk generally about other autoimmune disease settings where you think a product with this mechanism could play a role? And maybe just I'll ask bluntly, are you thinking about other potential indications for Daxdilimab regarding its development?

Yes, certainly, we'll be very methodical and very thoughtful in that anywhere where plasmacytoid dendritic cells, interferon production may have a role. We'll obviously think about but we're going through that whole process now. So I think we need just a little bit more time, and I will be able to comment more on that.

Okay. And then I wanted to spend a little bit of time on dazodalibep, which your CD40-directed treatment. So I believe the enrollment in your pivotal is wrapped up. Before we talk about Sjogren's, which I think is a really interesting space, can you talk to the underlying mechanistic rationale here?

Yes, absolutely. So for dazodalibep, the CD40, CD40 ligand axis, there's a common theme here, I think, David, in many of the diseases we've talked about, the CD40, CD40 ligand axis really drives B-cell activation cytokine production. And there is good evidence that it's active in Sjogren's syndrome. And so dazodalibep is a fusion protein that inhibits CD40 ligand. And by blocking this pathway, we think that we can interrupt the upstream immune activation that contributes not only to autoantibody production, but then in turn as well the downstream inflammatory cascade that you see in Sjogren's disease or Sjogren's syndrome. We think that mechanistically, dazodalibep is well suited to Sjogren's disease because it's heterogeneous and there's frequently immune activation across all of these different disease manifestations in that syndrome.

Okay. So I know you're running the 2 Phase IIIs, one is moderate-to-severe systemic disease activity. The other is a different population...

High symptomatic burden.

High symptomatic burden, it's low systemic disease activity. They're very different populations. So I guess what -- there's 2 questions I have here. One is how are these 2 different groups managed? And I guess, secondly, how could the drug be beneficial in both of these groups given its mechanism of action.

I think the answer to the first part, today, Sjogren syndrome is really managed symptomatically. So you have good oral care, tear replacement, analgesia for the pain. And sometimes, you can use glucocorticoids and steroids. So there's really not a good definitive treatment for it. We did publish the results in 2024 of our Phase II study, which also looked at these 2 groups independently within that study. And we were able to see an improvement in disease activity index as well as patient-reported outcome. And so that gives us confidence that going in now to this Phase III study that enrolls those 2 groups of patients.

But if the medicine behaves as it did in Phase II, we would hope to see a successful clinical outcome there. I think what we know about the disease is that CD40, CD40 ligand axis is active across both of those types of manifestations of Sjogren's. So I think you can have one therapy that is able to attack that underlying pathophysiological mechanism and bring about clinical improvement, albeit in 2 different subsets of the disease.

Is there a path to approval in 1 of the 2 subgroups or maybe put differently, do you have to have success in both studies to be in a position to file?

I think we would have to wait and see -- wait and look at the data and see how compelling it is. Again, we were successful in the Phase II in both groups and so we'll be hopeful that we'll be there as well.

Okay. And then on the competitive landscape or potential competitive landscape because there's a lot of white space here. But what are your thoughts on the FcRn directed treatment nipocalimab in Sjogren's and how you think as dazo stacks up versus that agent?

Just to remind everyone, we're hoping to have results from our Phase III study in the second half of this year. And I think, honestly David, we'll have to wait, it's just around the corner, really to see that and then how it compares. I would say that we are the first therapy to demonstrate efficacy in Phase II in both of those groups that you mentioned and that we're now studying them definitively in Phase III.

Okay. Okay. So let's -- let's talk about TEZSPIRE and all things, TSLP, lots going on. So I wanted to start with the label expansion for TEZSPIRE in chronic rhinosinusitis with nasal polyps. So this is a little bit of a commercial question and a little bit of a science question, which is how you see the product fitting into a treatment landscape relative to IL-4, IL-13 directed treatment and also the IL-5, I mean, I guess -- or maybe asked differently from a mechanistic perspective, how do you see the fit and also how TEZSPIRE could have an advantage in the nasal polyp indication?

Yes. Okay. So CRS with nasal polyps is a heterogeneous inflammatory disease. It often coexists with asthma, other respiratory conditions as well. And as you say, most therapies target the single or double downstream Th2 cytokines, IL-4, 5, 13. But those therapies do not address the upstream drivers like TSLP, which is involved in epithelial dysfunction and immune activation. And I think we've talked about this in the past. What's so exciting about TEZSPIRE is that it attacks TSLP right at the top of the inflammatory cascade. And so that gives it a differential profile. So upstream therapy can take out multiple inflammatory pathway. It's not only cytokine production downstream but also these diseases are often mediated through inflammatory cells, particularly eosinophils being recruited and activated.

So if you can control TSLP, you really can control both of those different pathways. And I think that mechanism we've seen has given strong adoption and confidence in some of the prescribers. In the -- just to remind everybody as well in that Phase III WAYPOINT study that underpinned the approval of TEZSPIRE in CRS with nasal polyps were able to show statistically significant clinically meaningful reduction in nasal polyp severity. Almost complete elimination of the need for surgery and a big reduction in the use of steroids versus placebo. So I'd say in summary, we think we're well positioned to reach more patients due to the differentiated mechanism, upstream mechanism of action. It's broadly applicable across multiple different patient phenotypes and that's widely appreciated by prescribers today rather than a single downstream pathway.

And one thing we hear a lot about is the extent to which is coexisting, a lot of coexisting asthma and nasal polyps. So -- is it your view that having nasal polyps in the label is something that actually can enable you to reach more asthma patients with TEZSPIRE?

Yes, it is. I mean we think that about the coexistence of chronic rhinositis and severe asthma is probably about 20%. So the overlap is large and really highlights a significant overlap between the 2 diseases, underlying pathophysiology that is both cytokine as well as [ eosinophilically ] driven and really supports the clinical value of TEZSPIRE in these 2 indications.

And then just touching a little bit more on asthma. What are your thoughts on the implications of the availability of an ultra long-acting biologic? I mean we have the -- we have now once or twice a year, depemokimab, that product recently is approved. I know it's mechanically different, but how do you see that impacting TEZSPIRE, if at all?