Hutchmed China Stock

Good morning, good afternoon and good evening, everyone. Welcome to HUTCHMED's special webcast following our announcement earlier today of the BD transaction with GSK. I'm Frederick Cheng from HUTCHMED Investor Relations, and I'm pleased to moderate today's discussion. [Operator Instructions] Please note our safe harbor statement and disclaimer. The performance and results of operation of the HUTCHMED Group contained within this organization -- within this presentation are historical in nature, and past performance is not a guarantee of future results.

Joining us today from HUTCHMED's management team are Dr. Dan Eldar, Chairman and Non-Executive Director; Mr. Johnny Cheng, Acting Chief Executive Officer and Chief Financial Officer; and Dr. Guangxiu Dai, Executive Vice President, Head of Discovery and Global Portfolio Management. Without further ado, it's my pleasure to invite Dr. Eldar to deliver opening remarks. Mr. Eldar, please. Chairman, I think you are on mute.

Thank you, Fred. Today's agreement with GSK clearly embodied HUTCHMED's strategic vision to build a globally competitive oncology portfolio anchored by differentiated innovation centered around the first-in-class novel ATTC payload platform assets with meaningful combination potential with standard of care for earlier line treatments.

GSK is a leading biopharma company, world-class multinational partner with a global development reach and expertise to maximize the potential of HMPL-A830. The strategy of HUTCHMED is to generate a platform, which can produce a number of drug candidates using AI and the experience accumulated by many years of drug discovery development and production.

We understand that we cannot bring all our candidates to global markets by using internal resources only. And therefore, we choose the best strategy to maximize the value of each ATTC drug candidate. At times, we shall maintain all rights. At other times, we intend to license ex-China rights, knowing that an excellent partner like GSK has the ability to accelerate development.

Sometimes, you would see us embarking on joint development and sometimes licensing global rights. This partnership we announced today is another validation and acceleration of international access that is central to our strategy. It also demonstrates how we can create the most significant shareholders' value as well as the greatest impact on the lives of patients globally. Thank you. Fred, please proceed.

Thank you, Chairman. The next, Johnny, please.

Okay. Thank you, Fred, and thank you, Chairman, for sharing your vision and view of this platform and also the direction of the company. So now we just have a quick highlights of the key terms of this transaction. Our A830 is a first-in-class preclinical asset, which is a KRAS EGFR antibody conjugate. We are licensing A830 ex-China rights to GSK.

This is a co-development deal in which HUTCHMED will be responsible for the global Phase I development and GSK will take over the ex-China development post Phase I. The total deal size is around USD 1.3 billion, including upfront of $110 million. And once commercialized, HUTCHMED will receive tiered royalties. The benefit of HUTCHMED in doing this deal is that we can accelerate the global development of A830 and unlock multiple indication opportunities.

As mentioned by our Chairman, this also serves to validate our ATTC platform by reputable multinational company. As for GSK, this transaction will expand the global oncology reach as well as extend the expertise in this area. It also enriches and advances their next-generation R&D portfolio from ADC to ATTC. I will now pass to Dr. Dai to share with you all the details of A830.

Thank you, Johnny, and thank you, everyone, for your time today. While KRAS is a key protein that drives cell growth when mutated, it causes cells to divide uncontrollably, leading to tumor development. In fact, KRAS mutations are found in about 30% of all human cancers, particularly in hard-to-treat solid tumors like CRC, pancreatic and lung cancers.

These tumor types also frequently overexpress EGFR. While first-generation KRAS inhibitors have been a major breakthrough, patients often face 2 big issues. Number one, the on-target off-tumor toxicity limits how much drug we can safely give to patients and for how long. And secondly, the cancer quickly adapts and find ways to bypass the treatment frequently by turning up the upstream tyrosine kinase receptors such as EGFR.

Then this brings us to our ATTC HMPL-A830. 830 consists of an EGFR antibody attached to a novel small molecule KRAS payload via a cleavable linker. 830 is a novel therapeutic designed to hit cancer cells from 2 directions at once using targeted delivery. The EGFR antibody acts as a homing system. It specifically targets EGFR, which is heavily overexpressed on the surface of tumor cells.

Once found, the drug enters the cancer cell, release the KRAS payload and shuts down the intracellular signaling driving tumor growth inside. And importantly, the cancer -- the antibody is more than just a delivery vector. It functions as an active drug on its own by directly blocking EGFR signaling pathway.

By combining dual EGFR and KRAS inhibition in one drug, we aim to achieve simultaneous pathway blockade right where it is needed the most. So why is this strategy so powerful for patients? First, it overcomes drug resistance. Upregulation of EGFR is a well-established mechanism that cancers use to escape stand-alone KRAS inhibitors. By targeting both EGFR and KRAS at the exact same time, 830 blocks the bypass pathway before the tumor can escape. And secondly, 830 offers an improved safety profile.

By delivering the payload directly into EGFR expressing cancer cells, we reduce systemic toxicity in normal tissues. This means we can potentially achieve better efficacy at doses that patients can tolerate. And thirdly, 830 expands our combination potential. Because of the improved safety, 830 can be combined with frontline standard of care treatments like chemotherapy, opening up broader clinical applications early in treatment.

And finally, 830 is not just a single asset. It validates our broader ATTC platform technology. By pairing novel target payloads with antibodies, we are building a pipeline of precision medicines. Beyond 830, which targets KRAS and EGFR, we are also advancing programs targeting PIKK pathways across HER2 and EGFR targets, including A251 and A580. So with global Phase I trials underway, we are well positioned to deliver a powerful new class of targeted cancer therapies. Now back to Johnny.

Thank you, Dr. Dai. So just to recap our recent announcements of 2 positive Phase III readouts. HUTCHMED and AstraZeneca are very happy with the results of both of these trials. The excellent results in terms of PFS and OS and the relevant data of these trials will be presented at the forthcoming academic conference.

More importantly, in addition to milestones income, HUTCHMED will receive royalty income once all these indications are commercialized, including for the SAFFRON trial, a tiered royalty of 9% to 13% on global sales. We estimate around 1/3 of MET amplified overexpressed patients that still resistance to EGFR treatment will benefit from this combination therapy.

On the China side, as you can see, we have 3 indications already commercialized. Together with SANOVO, once approved, Savolitinib will expand its benefits to first-line MET overexpression and EGFR mutation patients. For all these indications in China, HUTCHMED will receive 30% royalties from AstraZeneca. I will now pass it to Frederick to coordinate the Q&A session. Fred?

Thank you, Johnny. So we're going to take some questions from the attendees. First of all, let's have Paul Choi from Goldman. Paul, please.

Can you hear me now?

Yes, we can hear you.

Okay. Great. Congratulations on the deal. I had 2 questions. First, in terms of clinical development time lines, currently, the trial on clinicaltrials.gov is indicating relatively limited information. Can you maybe comment on how you're thinking about prioritizing lines of therapy, whether treatment experience or not across the three tumor types you've disclosed, lung, pancreatic, and colorectal?

And then my second question is, given the recent approval of [ RASONQUE (daraxonrasib) ], can you maybe comment on how you're thinking about where the clinical bar is, maybe starting with pancreatic cancer and other solid tumor types?

Thank you for your question. Well, in terms of the clinical development plan for Phase I, we are enrolling -- we are going to enroll patients with KRAS mutations within -- across also all tumor types, not just the CRC, pancreatic lung. But I guess in reality, these are going to be the three major tumor types included in the Phase I.

So for Phase I, we are going to definitely start from the [ late line ]. And then in the near future, we intend to initiate the combo study and to move into the first line with -- in combination with chemo or IO. So this is the initial clinical development plan.

And for the KRAS inhibitors, that's the one you mentioned, the Revolution compound definitely is a breakthrough therapy in -- especially in pancreatic. But we think that our molecule ATTC A830, it not just targets the KRAS, but also targets upstream EGFR, which has been clinically confirmed to be one of the resistant mechanisms.

So we believe that the ATTC would offer a more favorable benefit in the solid tumors. So there's a good chance that we can either get confirmed as a monotherapy and/or moving to the front line. I hope that address your questions.

Okay. Thank you, Paul. And then we're going to invite Adam McCarter for your [ fill ] question. Adam, please.

So we had great news today on the announcement. First question is really whether you could provide any details of when GSK first expressed interest in A830. And could you give us a sense of how the discussions and the diligence process developed from that initial interaction through to today's agreement?

Yes. Thank you, Adam. So as you also noted that this is a preclinical asset. So certainly, I think throughout our deep platform with multiple different targets. I think as we mentioned in the previous results meetings that many multinational companies have constantly engaged with HUTCHMED for discussions of potential collaboration. So in terms of GSK, I think this particular A830 actually fits into their interest, especially when they have already got ATTC platform, which they have one already in the market, and they have 2 in the clinics right now.

So ATTC serves as an advancement to the next-generation R&D work. So in terms of our engagement, I think we have a constant dialogue with multiple multinational company. So in addition to this particular transaction, we do not eliminate future opportunity and possibility that we will collaborate with other projects of our ATTC platform also.

That's brilliant. And if I could just follow up with a second question. So yes, just building on that GSK relationship, you said in the news this morning that this GSK secured a right of first negotiation over another earlier-stage ATTC candidate. Could you provide any information on this candidate, development stage of it or expected time line for that asset? And what do you think would need to happen before a more substantive licensing discussion could begin with GSK on that?

Well, all I can say is GSK have expressed another interest on one of the early development of ours within this ATTC platform. And of course, as we progress with our development, the level of interest may evolve further. And when the time comes, I think we will have to disclose in terms of if there is further transactions with GSK.

But otherwise, this is a right of negotiation -- first right of negotiation because they have also identified expressed the further interest on one other asset of our platform. So the remaining other platform, of course, we have engaged with other multinational companies that we continue to progress with our discussion.

Thank you very much, Adam. As we're approaching the end time, we're now going to conclude today's webcast. Thank you very much for your time and continued attention to HUTCHMED. And the IR team of HUTCHMED will remain available to address any follow-up questions or provide further clarifications. So please do not hesitate to reach out to us. Thank you again, and we wish you a good day, afternoon or evening. Thank you.

Welcome, everyone. Thank you for joining HUTCHMED 2026 Interim Results Announcement and Presentation.

Before we start, I would just like to go over the safe harbor statement and disclaimer on Page 2. The performance and results of operation of HUTCHMED Group contained within this presentation are historical in nature, and past performance is no guarantee of future results.

Next, I would like to invite our acting CEO and CFO, Johnny Cheng, to start the opening. Johnny?

Okay. Thank you, David, and welcome, everyone, again, joining our interim results webcast tonight. Together with me, we have our Deputy CFO, Lorenso Chiu; also our George Yuan, Head of Commercial; and also our Dr. Dai, Head of Discovery and Global Portfolio Management. All of us will be sharing with you our first half results and outlook.

So on Page 4, as you can all see, we have achieved a lot in the first half. China product sales have very strong results, especially ELUNATE and SULANDA, which grew by over 40%. FRUZAQLA global in-market sales were strong. Ex-U.S. markets were up 70% after rapid geographic expansion.

On the bottom left, we have received 2 approved label expansions, fruquintinib for RCC and savolitinib for GC. In addition, we have 3 NDAs in China under priority review.

On the top right, our next wave of innovation focuses on ATTCs. We have 2 first-in-class assets which have entered the Phase I clinical trials. A third asset, HMPL-A830, has cleared its IND and will be entering the clinic in the second half. At the same time, the global SAFFRON study and the China SANOVO study will have their data readouts in the second half.

I will now hand it over to Lorenso Chiu, our Deputy CFO, to discuss our financial results.

Thank you, Johnny. On Slide #6, I'd like to give more details of our financials for the first half of 2026. First of all, our oncology revenue was $162 million, including $121 million products revenue. This represent an about 23% growth over the first half of 2025. Johnny already mentioned our China product sales have shown a very good performance in the first half. I'd like to highlight that ex-China demand for FRUZAQLA continues to grow as well, achieving an overall 40% growth in in-market sales. With this first half result, our full year guidance remains in the range of $330 million to $450 million. Altogether with other ventures revenue, the total group revenue amounted to $278 million.

Next, please. On R&D expenses, which amounted to $79 million for the first half, compared to $72 million for the first half of 2025. The increase reflects on one thing, we initiate the global Phase I trials of our ATTC assets, including 251 and 580. In addition, we increased our investments in our discovery capabilities, including our talents and AI.

On the bottom line, we continue to be profitable with net income of $16 million. It is important to note in last years, we have included a $416 million SHPL divestment gain, and also the share of the post divestments, about $21 million. With this strong operating results and cash flows, we continue to have a very good cash reserve of $1.4 billion.

Now I'd like to hand over to Mr. George, our Head of Commercials, to give an update of our China commercial.

Thanks, Lorenso. As Johnny mentioned, global geographic expansion continue to drive our FRUZAQLA growth. If we look at the first half, we see a 70% growth in the geography outside the U.S., which is very strong. And also, if you look at the Q2, the growth rate actually accelerate to 27%. And also, we still believe that there still has opportunity to get more country get launched and also go into the reimbursement. Takeda already confirmed the fiscal year guidance of a 25% growth.

Next slides. If we look at China, our -- we have a very robust growth for ELUNATE. We are in a highly competitive market. If we look at the first half, we are growth at 41%, and the current NRDL renewal bring us a continuous growth opportunity with the second-line EMC included. And also, we synchronized our mCRC reimbursement scope with our label. The NRDL renewal actually provide us a unique opportunity for future growth, and also, we keep our price flat.

Second-line RCC get approval in May '26, and also, this provides us another opportunity to apply for NRDL this year. And in -- from based on IQVIA hospital audit and our ATU study, ELUNATE continue to be a market leader in third-line mCRC.

Next slides. Beyond FRUZAQLA and ELUNATE, we also have a strong performance on ORPATHYS and SULANDA. ORPATHYS, we have -- we are target to include such indication in this year NRDL, renew by end of this year, and also, we get approval third-line MET-amplified GC. In the coming months, we are looking at SAFFRON and SANOVO readout. For SULANDA, we have strong growth in first half based on the highly recommend by CSCO guideline for the NET. And also, the CSCO guideline change the recommendation about the SSA. The SSA, dose escalation will not be recommend after progression-free -- after the disease progression. And also, this growth is a result our focused strategy -- focus on top-tier city and the top hospitals.

Next slides. Looking to the future, sovleplenib, our Syk inhibitor, will bring us into the hematology immunology fields. This is the first-in-class medicine, and it can help patients to transform their treatment in both ITP and wAIHA. If we look at the ITP in China, we have 360,000 patients, and the current treatment, TPO, steroids, still cannot meet the medical needs of those patients. And with this product, we provide a very unique value for those patients for long-term, stable, predictable disease control. Also for wAIHA, which is a relatively small indication, but it's under critical needs for new medicine. We will be the first target therapy after 30 years in the field. And we will significantly reduce blood infusion for those patients.

Now, I will hand over to our R&D, Dr. Dai.

Thank you, George. Now, let's transition into our R&D updates. Over the next few slides, I'll share how our late-stage clinical programs are progressing toward key commercial approvals and how our innovative platform is unlocking brand-new opportunities to address major unmet medical needs.

Next slide, please. Looking at our recent achievements, we've hit several critical milestones across both solid tumors and hematology. Our novel ATTC platforms represent a huge strategic growth driver for us globally. The early biological profiles of ATTCs gives us high confidence in their ability to target major solid tumors and differentiate from other ATTC products. We've officially taken the first 2 ATTCs into the clinic, A251 and A580, initiating global Phase I trials. The third ATTC, A830, recently cleared the IND in both the U.S. and in China.

We secured approval for fruquintinib in renal cell carcinoma in June 2026. This is another important approval for fruquintinib after CRC and in EMC.

With surufatinib, we have kept momentum strong with our Phase III trial in first-line PDAC fully on track, addressing an aggressive cancer type with very few viable options.

Savolitinib, our second inhibitor, is making rapid progress on lung cancer autoimmune indications. The NDAs for ITP and wAIHA are currently under priority review. These mark huge steps towards establishing a new, highly effective standard of care in these conditions. The pivotal Phase III data of ESLIM-02 was recently presented at EHA this year. Savolitinib expanded its commercial footprint with the third-line gastric cancer approval. This is the fourth regulatory approval for savolitinib after previous lung cancer approvals. And 760, our potent PI3K/BTK inhibitor, successfully initiated its Phase III trial in second-line DLBCL.

And fanregratinib reached a pivotal moment with its NDA acceptance for FGFR positive intrahepatic cholangiocarcinoma. The data was featured at ESMO GI this year. Together, these achievements reflect a highly efficient R&D engine, strengthening our commercial presence today while laying the foundation for our global ATTC platform tomorrow.

Next slide. Let's dive a bit deeper into our individual core assets, starting with savolitinib, our second potential global commercial product. Savolitinib targets lung cancer driven by MET alterations, which remains an area of significant unmet medical need. We are fast approaching several important milestones. In the second half of this year, we expect data readouts from 2 key studies, SAFFRON on a global scale and SANOVO in China. SAFFRON is our global registration Phase III trial. It targets second-line patients with EGFR mutant nonsmall cell lung cancer who developed MET amplification or overexpression after progressing on TAGRISSO. Currently, these patients are on heavy chemotherapy. SAFFRON directly compares our oral combination of savolitinib plus TAGRISSO against double chemotherapy. When approved, this trial will replace chemotherapy with an oral target option and opening access to major markets like the U.S. and Europe.

SANOVO targets the first-line setting. We know that a significant subset of lung cancer patients present with coexisting EGFR mutations and MET overexpression right at initial diagnosis. SANOVO evaluates combining savolitinib with TAGRISSO directly upfront versus TAGRISSO alone. By attacking both targets from day 1, our goal is to deliver deeper response and prevent resistance from emerging. And together with our proven Phase III SACHI data, which showed a dramatic hazard ratio of 0.32 in PFS over chemotherapy, these upcoming readouts from SAFFRON and SANOVO position savolitinib to capture leadership across the entire treatment paradigm in MET-driven lung cancer.

Next slide. This slide highlights sovleplenib, which is spearheading our next wave of hematology and autoimmune products. wAIHA is a deliberating disease where red blood cells are destroyed prematurely, leaving patients severely anemic and often they rely on high-dose steroids and frequent blood transfusions. In our Phase III ESLIM-02 study presented at EHA, sovleplenib achieved a 66% durable response rate compared to 15% in the placebo group. Patients on sovleplenib reached target hemoglobin levels in a median of 3.1 weeks, twice as fast as the placebo. Substantial drop in rescue therapy and transfusion, only 16% of sovleplenib patients require rescue therapy, compared to 54% on the placebo. And furthermore, red blood cells transfusions were significantly reduced to just 11% versus 43% in the control group, allowing the patients to taper or completely discontinue their baseline steroids.

When you compare this to the emerging peer options like nipocalimab, sovleplenib shows a clear competitive efficacy advantage, delivering a much higher durable response rate, without forcing patients to stay on a chronic high risk immunosuppressants. We are eager to bring sovleplenib to a patient population that hasn't seen a new target therapy option in 30 years, and currently, the NDA is under priority review.

In ITP, what sets sovleplenib apart from standard of care agents like TPOs and TPO-RAs is exceptional efficacy without associated thrombotic complication warnings found on their peer labels. In ITP, sovleplenib achieved a striking durable response rate compared to placebo, even though 75% of the enrolled patients had failed prior TPO therapies. ESLIM-01 study is also under priority review in China.

Next slide. Turning to Slide 17, let's look at 760, our highly potent selective and reversible BTK inhibitor characterized by long target engagement. Currently, this is the only BTK inhibitor in late-stage clinical development targeting the second-line DLBCL all comers. Our Phase II study showed encouraging response rate, PFS, and safety profile. Our Phase III registration study in China is actively ongoing, comparing 760 in combination with R-GemOx against the placebo plus R-GemOx, with primary endpoints of PFS and OS. And we expect to complete enrollment by the end of 2027.

Next slide, please. Here, I want to highlight our novel ATTC platform, starting with A251. ADCs, like in HER2, have transformed HER2-positive cancer treatment, generating billions in revenue. However, acquired resistance to DXd, the cytotoxic payload used in HER2, remains a major clinical hurdle as patients inevitably progress. The DXd induced in resistant model on the bottom show that in HER2 loses potency almost completely, shifting the curve far to the right.

In the same resistant cell model, because A251 utilizes completely distinct mechanisms targeting the PI3K and PIKK signaling pathways rather than DNA-damaging toxins. Its killing activity in DXd-resistant cells, shown in the green curve, remains identical to DXd-sensitive parent cells, shown in the blue curve.

Next slide. And beyond treating drug-resistant tumors, A251 has strong potential as a frontline treatment, as shown in this gynecological cancer and GI cancer xenograft models. Combining A251 with the first-line standard of care yields significant tumor volume reduction compared to either therapy alone. And crucially, this synergistic effect does not come at the cost of added toxicity, proving A251 can safely be combined, which is what we aim to achieve with ATTCs in the first place, which is better efficacy and better safety.

Our clinical strategy is twofold. A monotherapy track for a fast-to-market approach in late-line setting, and a combination track targeting frontline indications. And our extensive pre-clinical data supports the A251 development strategy. The clinical trial is on track at dose escalation stage.

Next slide. Our second ATTC asset is 580, which pairs the same payload with an EGFR targeting antibody. Blockbuster drugs like TAGRISSO treat EGFR mutant nonsmall cell lung cancer, but resistance eventually develops. In a nonsmall cell lung cancer model carrying the challenging EGFR exon 19 deletion and the resistant mutation, third generation TKIs like TAGRISSO completely lose control of tumor growth, as shown by the red curve. 580, represented by the blue curve, achieved profound and sustained tumor regression as a single agent. This highlights its enormous potential for lung cancer patients.

Next slide. Then by combining 580 with an EGFR inhibitor, we can simultaneously shut down primary receptor signaling and the downstream escape pathways. The pre-clinical data reflects a highly significant synergistic anti-tumor efficacy, supporting our long-term plan to move this asset into frontline cancer regimens. This global asset entered Phase I trial earlier this year. The trial is going very well, recruiting patients from China sites and the U.S. sites in parallel.

Next slide. What makes our ATTC platform so unique is the payload itself. Historically, the industry has struggled with PAM pathways, pan-PI3K or dual PI3K [ employs ] small molecules were simply too toxic to be delivered systemically, resulting in severe side effects like hyperglycemia or mucositis. Single node inhibitors were safer, but their efficacy was limited. Our innovation was to design a highly selective payload that harvests multiple key nodes along both the PI3K and PIKK pathways with very high affinity, and then tether it to an antibody. This ensures the payload is delivered inside the tumor cells, maximizing intracellular kinase inhibition while sparing healthy tissues from systemic toxicities. The kinase tree on the right illustrates this high selectivity of the payload.

Next slide. The ATTC approach opens up massive opportunities. The PAM pathway is the single most frequently altered pathway across all solid tumors. It plays a dominant role in breast cancer, lung cancer, gastric and ovarian cancers. By effectively targeting this pathway with our ATTC technology, we can potentially reach millions of patients across a wide range of cancer types.

Next slide. With A251 and 580 currently in global trials, 830 entering the clinic soon, and more candidates behind them, our pipeline is well-positioned to deliver a sustained growth for years to come.

Thank you. And I'll give it back to Johnny.

Thank you, Dr. Dai. A quick highlight on our outlook. So on the innovation side, as mentioned by Dr. Dai, multiple ATTC programs are progressing well, and we believe around this time next year, there should be a total of 5 programs already in clinics. More importantly, our efforts in AI will be transforming and accelerating further discovery and development in our innovation platform.

On the commercial side, we expect FRUZAQLA's sales growth to continue. We anticipate it will reach its next sales milestone in the near-term.

Regarding our hematology portfolio, our commercial team is preparing for the launch of our immunology assets, which is anticipated to commence next year.

And finally, we are continuing to engage many multinational companies on collaboration discussion regarding our ATTC program.

I will now pass it back to David to begin our Q&A session.

[Operator Instructions] The first question comes from Matthew of CLSA.

This is Matthew from CLSA. I have 3 questions. First is regarding the collaboration opportunities for the ATTC programs, 2 in clinic and 1 about to be in clinic. So could you elaborate more on the kind of progress, because I think that there's been some expectation of the maybe early-stage collaboration before. So, yes, can you comment on that?

And second one is regarding your HMPL-760, the BTK inhibitor. Yes, as you mentioned, you have got initiate the Phase III trial for DLBCL in China. And may I understand how is this drug different from other BTK inhibitors, and why would you choose the DLBCL to proceed for Phase III, as there are no other BTK inhibitors approved for these indications, including the covalent ones and also the noncovalent ones are non-approved?

And the third question is regarding on the financial side. I know that the Other Ventures is a low-margin distribution business, but may I still have some color on why in the first half is on a constant exchange rate basis declined by almost 20%? Okay, those are my questions.

Thank you, Matthew. So I will invite Dr. Dai to answer the second question, and Lorenso to answer the last question. And the first question regarding the collaboration opportunity, basically, we are continuing, and we have active multinational companies engaging in discussion with us on, not just one program, but multiple ATTC program. As you know that our programs are still at the very early stage, so different expectation in terms of timeline and information to be provided from our side to the collaborate potential partners. They have kind of different requirements. So all I can say right now it is we are in active discussions with multiple parties, and the discussions are progressing well. When I think the discussions is coming to a close to mature and is disclosable items, then we will be making an announcement to the public.

Maybe Dr. Dai, you can answer the question number 2 regarding the 760 BTK.

Sure, Johnny. So, yes, we are -- we have actually started Phase III study, with 760. It is a combination of 760 plus R-GemOx versus R-GemOx. We pick DLBCL, obviously, because it's the largest lymphoma subtype, accounting for about 40% of lymphoma. And no other BTK inhibitors has been approved for this particular subtype of lymphoma. So it represents a huge unmet medical need and good market potential.

And with our 760, it's reversible BTK inhibitor, and in earlier clinical study, it demonstrated a very good selectivity and safety profile. And we actually had a Phase II study validating its efficacy in the second-line setting. It is the same study design, and we achieved a very impressive overall response rate and the CR rate, and a very favorable safety profile to encourage us to go into the Phase III study. So it is a very exciting opportunity for 760, and we hope to achieve the enrollment completion as fast as we can.

Johnny, I will answer question 3. As for the Other Ventures, I think you are right to point out that our Other Ventures is a low margin business, which is not our focus. We are putting our focus on our major oncology revenues. As you can see, the growth is there. And that is the reason that there was some decline in the Other Ventures business. But I don't think we need to look into too much about behind this, because, as you said, it is low margin and it is not our core.

Maybe I just supplement that. I think as highlighted by Lorenso, this is not our core business. And it is basically, it is a logistic distribution business. The reason there has been some decline is because of the volume-based procurement list has actually in China have been expanded. So some of the previously -- our customers in the logistic distribution side have actually affected by the volume-based procurement, in terms of their selling price and so forth. So that services business is not what we focus because of the -- basically because of the high working capital requirement for this business. So as a way to manage this business, we try to just maintain this line of business to help to gain insights into the commercial channel in Shanghai. So I think that the drop, it doesn't actually affect the bottom line. It doesn't affect in terms of the entire business operation of HUTCHMED.

So the next question is from Chen Chen of UBS.

So my first question is on sovleplenib. So this candidate is expected to receive approval next year. Could you please elaborate on your commercial preparation strategy in China, including pricing, well, marketing access, and NRDL, and your sales force? In addition, what are your overseas R&D plans and priorities for this asset?

My second question is on ATTC. So what is the expected timeline for clinical data readout from your candidate 1 and 2?

Thank you. So may I ask George to answer the first question and Dr. Dai do the second question?

Yes. Thanks, Chen Chen. For sovleplenib launch preparation, we are focused on few areas. One is -- first thing is market access, value proposition. We need to make sure this product's going to the NRDL, and we expect this product to get approval maybe in the first half this year and -- next year and qualify for the NRDL negotiation. One of the challenges is how can we position us very well to achieve affordable and realistic price in this disease. One of the understanding is, we will do a kind of [ HUR ] data based on our clinical trial.

On the other side, we also would like to work with a patient group, with opinion leaders, to understand the pain points of the current treatment and try to make sure we really leverage those patient insights to make sure the government understand there's a main needs and there's a quality of life, a kind of compromising for those patients who receive other treatments. So this will help us to leverage the future.

On the other side, we definitely will do the guideline, we do the KTL, as well as a physician education program, also a patient advocacy group as well.

And if you look at the current setup for the launch, we have already built up a dedicated hematology team with a lot of experienced people in the hematology side. We are starting to work with our partners to understand the market potential, try to figure out what's our first wave target hospitals, territories, and the resource deployment.

Okay. I'll get the second question. So the first and second ATTC assets are both in the middle of Phase I dose escalation. The trials are moving very fast. Enrollment has been going strong in the U.S. and in China sites. Investigators are very excited about the novel mechanisms and the differentiation. They understand the rationale, and they are enthusiastic about the new mechanism of the ATTCs. So we will find the right time to disclose the clinical data sometime in 2027.

The next question comes from Paul Choi of Goldman Sachs.

Can you hear me?

Yes, we can.

I want to talk a little bit about first ask on sovleplenib as you sort of look at the warm autoimmune hemolytic anemia landscape, and just sort of the other products or candidates that are in that category, how do you think about potential developments and planning for a global trial outside of China? Just sort of any additional thoughts on what aspects or differentiation are needed there? And then I had a follow-up question.

Dr. Dai? Yes.

Of course.

George here.

So 523, now both studies in ITP and wAIHA were completed in China. We are waiting for CDE's feedback on our NDA data. But in ex-China, we are -- our strategy is to develop this asset through partnership.

But any thoughts on, again, sort of what clinical differentiation might be needed versus development strategy?

Right now, the treatment paradigm, for example, for wAIHA, the first-line is mainly the steroids, like George mentioned earlier. And we are targeting the second-line patients, which doesn't have a lot of choices other than the steroids. So the unmet medical need is very high in China as well as in the U.S. And as you can tell from our Phase III data, the overall durable response rate is very -- looks very promising compared to the other competitors, which is FcRn antibody product. So we think this asset has great potential, so we are actively looking for partnership to co-develop this asset outside the China.

Yes, maybe I can add because this wAIHA is regarded as a rare disease, and we also have a plan to apply U.S. orphan drug status.

Okay, great. My second question is on HMPL-453 fanregratinib. You advanced it through the second-line ICC population on the oncology side. But I want to ask what your thoughts on -- are on potential endocrinology applications such as achondroplasia and other bone growth disorders, and if you think this might be a potentially appropriate candidate there.

With 453, our main focus right now is intrahepatic cholangiocarcinoma, second-line. And we are -- we have started the confirmatory trial to get this indication confirmed in the same setting.

The next question comes from Adam McCarter of Cavendish.

And a couple of questions from me just on the commercial portfolio. So, obviously, it was encouraging to see the recovery across ELUNATE and SULANDA. And -- but just on ORPATHYS, you did highlight the opportunity for NRDL inclusion following the SACHI based approval. I'm just wondering how significant do you think that could be commercially. Do you expect that to be a key driver of a recovery in China sales, or is the more meaningful inflection point still this de novo readout and the opportunity to further broaden adoption? That's my first question.

George, you would like to answer that one?

Yes. I think the SACHI inclusion in the NRDL will significantly improve the growth potential for the brand because if we look at the data, if you look at the EGFR-resistant patients, there are quite significant amount of patients with MET amplification. And so far, there is no other choice. And the bispecific monoclonal antibody in China is not included in the NRDL from Johnson & Johnson. So we still have a growth potential. And also, this combination will extend the TAGRISSO treatment duration as well, and as well as kind of levers for AstraZeneca to compete with other TKIs. That's why we believe that this is a strong growth potential. Having said that, also one of the hurdle is that we still need a secondary biopsy, so there is a kind of adoption at practice in the medical side.

That's great. My second question, again, on the commercial side of things is for FRUZAQLA. Just wondering how we should think about the growth trajectory for U.S. sales going forward. And should we now be thinking about a period of steadier growth with ex-U.S. markets becoming an increasingly more important contributor to incremental growth for the brand?

Okay, maybe I'll just comment on this one. I think for FRUZAQLA, for the last year almost, I think there was some Medicare impact in terms of the gross to net. But as you can see, the growth momentum is through the geographic expansion of the ex-U.S. markets in the first half especially. We have looked at 70% growth there. And also, I think one point to note is although the geographic has expanded, but the NRDL in those market is only 50% so far. So we believe there will still be a lot of opportunity for ex-U.S. Earlier, we have also shared with all of you that from our information from Takeda, that they expect U.S. side, basically, the size of U.S. peak sales versus the rest of the world will be kind of a 50/50 ratio. So we believe there's still a lot of growth momentum behind this global sales of FRUZAQLA.

If I could chance maybe a final question, just on, obviously, reiterate the guidance. And could you just help us try and understand the key drivers that determine whether the business lands towards the lower or the upper end of the range? In other words, should we primarily be thinking about the contribution from milestones, continued recovery of the China portfolio, or ongoing growth in ex-China for FRUZAQLA revenues?

Yes, well, I think, as you can note that in the first half, the guidance for this year is actually $330 million to $450 million. So with our base line achievement, it is without any business development contribution in there, we will be at least beating the lower end of the guidance. But with certain potential partnering, which we recognize some upfront income, that we can reach higher or even exceeding the high end of the guidance. So that is the range. But also other factor that can affect the second half is, as we mentioned, FRUZAQLA, that we do anticipate that it will reach another level of sales milestone that would contribute, again, some onetime commercial milestone income that would also help us to meeting or even exceeding our target that we have given out to the market. So we are quite confident that we will be able to achieve this guidance that we have given out to the market earlier.

[Operator Instructions] The next question comes from Julie Simmonds of Panmure.

Julie Simmonds from Panmure Liberum. Just again, on the milestones. There was a milestone in the first half from Takeda. I was just wondering what that related to. And then beyond the sales milestones to which you just referred, are there any other milestones anticipated? I was wondering if there was anything due from Astra on the SAFFRON trial readout.

No. Actually, in the first half, just to clarify, it was from the approval of the RCC, renal cell carcinoma, so it was from Eli Lilly. And yes, so in terms of our second half, besides the sales milestone, so far we do not expect any other milestones from our partners yet. But in terms of if we achieve good results for our sovleplenib, we will be receiving milestones more likely next year, not this year.

And then just as far as sort of the overall margins are concerned, you've done slightly better, I think, probably in terms of sort of balance between sales and spending than maybe I'd thought you might do. Is the aim to continue to remain, to try to continue to be broadly breakeven to slightly profitable going forwards in your sort of thinking of how the business is going and using the cash in potential business development activities?

Yes, definitely. I think it is a strong commitment, requirement by our Board that we will continue to be breakeven. And that's a commitment that we made a couple of years back. And this is a strong commitment from all our management team. So this is not going to be changing. And of course, we will balance with investment in area definitely that would drive growth and creating value for the shareholders. So that's why we're accelerating ATTC program. At the same time, of course, we are exploring business development opportunity with our partners so that we can basically creating, accelerating our ATTC innovation opportunity.

[Operator Instructions] At this moment, I don't see any further question online. Johnny, would you like to make a concluding remarks?

Yes. Thank you, everyone, for joining this interim results. And we look forward to meeting again, I think, in later on. We will be planning for a R&D day sometime later this year. And we will make relevant announcement in due course. Thank you.

Thank you, everyone. And this conclude our interim result presentation. Thank you. Bye-bye.

Bye-bye.

Hello, everyone. Welcome to HUTCHMED 2025 Full Year Results and Business Update. Today, we're going to go through our results in a formal presentation by our senior management, and then it will be followed by Q&A. Before I start, let's turn to Page 2 with our usual safe harbor statement. Basically, the performance and results of our operation contained within this presentation are historical in nature, and the past performance is no guarantee of future results. The information in this presentation is subject to changes and HUTCHMED has no liability for any loss arising from the use of this content. My name is David. I'm the Head of IR of HUTCHMED. We are very happy that we're going to have our senior management to present the results. Let me hand off the time to our acting Chief Executive Officer and Chief Financial Officer, Johnny Cheng. Johnny?

Thank you, David, and thank you, everyone, for attending HUTCHMED's 2025 results webcast. Joining me today is our Deputy CFO, Lorenso Chiu, who will give us an overview of our financial performance. Our Head of Commercial, George Yuan, who will share with you our commercial performance; and our Head of Discovery, Dr. Guangxiu Dai, who will provide an update on our R&D pipeline progress. Next slide, please. A quick highlight of our 2025 achievements. We are pleased with our ex-China FRUZAQLA sales, which had 26% growth versus last year, resulting in $366 million in in-market sales. More importantly, FRUZAQLA has rolled out to over 38 countries already. As for our China sales, it has rebounded in the second half of the year, achieving 21% in-market sales growth versus our first half interim results.

In terms of our cash position, we have about $1.4 billion, which allows us to accelerate our global ATTC development and provide resources to explore potential in-licensing and M&A opportunities. On the right-hand side, we have now advanced 2 of our ATTC programs into the clinic, which we believe will have huge market potential. In addition, we are pursuing potential business development opportunities with multinational companies. In terms of the progress of our pipeline, I will leave it to Dr. Dai to share with you later on. I will now turn it over to Lorenso for the financial review and outlook. Lorenso?

Yes. Thanks, Johnny. And let me give an overview of our key financial highlights for 2025. Total oncology revenue was $286 million. This includes $71 million R&D-related upfront and milestone revenues. For oncology products revenue, as Johnny already mentioned, there was a rebound from our China oncology products, which recorded 21% growth in in-market sales in the second half, while FRUZAQLA continues its global expansion. On net income, we recorded a profit of $457 million for 2025, mainly due to the SHPL divestment gain of $416 million. Excluding this onetime gain, our core operations remain profitable.

Next, please. Our R&D expenses for 2025 was 148 million. Expenses were lower versus 2024 as many of our late-stage trials are in the completion stage with multiple NDAs now awaiting approvals. In addition, we began shifting our investments into our early-stage ATTC assets with 2 candidates already in the clinic. Our cash position has been further strengthened to about $1.4 billion. That positions us well to accelerate both investments and developments of our ATTC programs. Next, looking forward to 2026, our oncology revenue guidance is in the range of $330 million to $450 million. This reflects a solid growth from 2025, driven by strong growth in our China commercial products with contributions from new indications as well as FRUZAQLA continued scope expansions. In addition, let's consider the potential partnership opportunities for our new drug candidates, including ATTC. Now I'd like to hand over to George to give an overview of the China commercial.

Thanks, Lorenso. First, let's look at the FRUZAQLA, our business partner, Takeda's performance. They delivered a very strong 2025 with 26% growth, and if you look at the Q2 -- the second half, the second half, the growth actually is accelerated mainly due to the market expansion we launched some of the new markets like Portugal, Belgium and South Korea. Also, the strong Japanese performance and some of the Europe performance uptake also contribute a second half strong growth. This reflects a market needs for safe and effective medicine in the later-line mCRC treatment. Also the physicians experience enhancement and also the reimbursement progress contributed to those growth. If you look at the U.S., we do see some of the headwind, mainly due to the medical Part D redesign.

Next slide. For China performance under the brand name ELUNATE -- in China, we posted a minus 13% growth, mainly due to a soft performance in the first half as we scale back some of the sales force after our GC second line setback and also some of the productivity improvement programs. But we successfully turned around the business with more efficient approach to focus on the top-tier cities and hospitals. In second half, we delivered 33% growth and successfully renewed our online deal with no price cut and include our EMC second line. Also, we submit NDA for RCC, those are all contribute to our future growth.

Next slide. If you look at the ORPATHYS and SULANDA, which is 11% of our total 2025 in-market sales, they are relatively soft due to the fierce competition. For SULANDA, we also face multiple PRRT those nuclear medicine moving to the clinical stage and fighting with us with limited patient pool. Although we have some kind of headwinds, we do see some progress. First is for ORPATHYS, we have a first-line METex skipping, adding to the NRDL. Also, we have SACHI approval to drive future growth. Our SAFFRON/SANOVO readout what we are expecting in this year. For SULANDA, we maintain our market leader position in NET performance in the TKI markets. Also, we have renewed our NRDL with no price cut. Our Phase III PDAC study is on track.

Next slide. We are building on behalf -- in addition to our solid tumor, we are building our hematology portfolio. We get our first medicine, first-in-class treatment for EZH2 mutation and follicular lymphoma approved. This is our first hematology products launched in China. This also gives us a beachhead in the hematology, and also the TAZVERIK include our China's first commercial insurance drug list. We are one of the 19th medicine including drug list. This gives us a kind of future growth opportunity to explore the commercial insurance.

On the other side, those TAZVERIK provide us a beachhead in the hematology to leverage these products, we can engage our hematology opinion leaders, establish our core team with expertise in the hematology to prepare the future hematology launch. [Sovleplenib] prepared to launch early 2027, and our ITP is already resubmit and wAIHA indicating will potentially submit in the first half of 2026. Also, we have additional pipeline in the hematology, the IDH1 and 2 inhibitor for AML and also the BTK in the DLBCL also start our Phase III study. So in long run, we were aiming to build our very strong hematology portfolio. Now let's turn over to our Dr. Dai.

Thank you, George. I'll provide an update on our R&D pipeline progress. The 2025 proved to be a great year for our pipeline, featured by fast regulatory movement and high-impact clinical data. We have achieved major progresses across our core areas, oncology, hematology and our next-generation technology platforms. In oncology, savolitinib has reached critical regulatory and clinical milestones in both China and global markets. SACHI was approved in China in a speed record for second-line EGFR mutant, MET-amplified non-small cell lung cancer. SANOVO and SAFFRON completed Phase III enrollment and third-line gastric cancer filed NDA in China in late December 2025.

In hematology, savolitinib, our Syk inhibitor has solidified its position with ITP NDA resubmission and robust positive Phase III data readout in wAIHA. Perhaps most excitingly, our antibody target therapy conjugate ATTC platform is now a clinical reality with our lead assets, A251 and 580 moving into global clinical development. A251 has started patient enrollment in China and in the U.S., closely followed by our second ATTC drug candidate, 580, which was first dosed in patients just yesterday. Beyond this, we are seeing broad success with Fruquintinib EMC included in NRDL, Fruquintinib RCC and Fanregratinib, IHCC gaining NDA acceptance and Surufatinib moving into Phase III for first-line PDAC.

Next, I'll dive deep into how this progress is define our growth trajectory. Next slide, please. With savolitinib, we have dual focuses here, maintaining leadership in China and expanding the global footprint. In non-small cell lung cancer savolitinib has been approved in China for first- and second-line METex14 alteration as a single agent. For second line, the combination of savolitinib and osimertinib represents a promising chemo-free oral treatment strategy to address mechanisms of resistance due to MET alteration following EGFR TKI treatment in this advancing setting.

In this setting, SACHI has been approved in China and SAFFRON is expected to have a readout in mid-2026. For first-line SANOVO Phase III study of savolitinib and osimertinib will read out in the first half -- in the second half of 2026 or early 2027. Savolitinib is more than just a lung cancer drug. We also reached an important milestone in gastric cancer with China NDA for third-line MET-amplified gastric cancer being accepted and priority review granted.

Next, please. The data from SACHI is compelling. In 2026 Lancet publication, SACHI study demonstrated a clinically meaningful OS benefit, 22.9 months versus 7.9 months in ITT patients who didn't receive subsequent MET inhibitor treatment. The hazard ratio of 0.32 is a clear indicator of OS benefit. Earlier, we have presented at ASCO that combination of savolitinib and osimertinib shows a clinically meaningful improvement in overall response rate and duration of response versus chemotherapy as second-line treatment. In particular, SACHI demonstrated clinically and statistically meaningful PFS improvement in ITT patients as well as in patients who failed third-generation EGFR TKI treatment.

Next slide, please. Turning to Sovleplenib, a Syk inhibitor. Our focus is on addressing the large unmet medical needs in immune-mediated hematological disorders. In ITP, we have resubmitted our NDA in China. NDA has been accepted and granted with the breakthrough therapy designation and priority review. The clinical profile of Sovleplenib is highly competitive in the 3-year follow-up study, the median duration of exposure is over 86 weeks. The cumulative durable response reaches over 66 weeks. Over 51% of patients achieved durable response. This is highly consistent with 48.4% durable response rate in the double-blind phase of ESLIM-01 study. Sovleplenib shows a superior durable response rate compared to many existing ITP therapies, including Syk inhibitor fostamatinib and BTK inhibitor, Rilzabrutinib as well as Efgartigimod and FcRn drug approved for ITP in Japan.

Sovleplenib's durable response rate is comparable to or better than TPO/TPO -RA drugs. A key differentiation for sovleplenib is its safety, particularly regarding vascular risks. It's well known that TPO/TPO -RA drugs have been associated with thromboembolic and thrombolic complications in ITP patients. Sovleplenib clearly demonstrates a highly competitive clinical profile in the safety and efficacy. Next slide, please. The ITP market potential is significant and growing. In China alone, there are over 250,000 actively treated ITP patients, representing an addressable market of USD 500 million to USD 700.

Next, please. Next is our innovation engine, the ATTC platform. This platform is designed to combine the precise delivery of antibodies with the potency of target inhibitors. A251 is a first-in-class ATTC consisting of a potent PI3K/PIKK inhibitor conjugated to an HER2 antibody with a DAR 4 through a cleavable linker. Next slide. A251 targets a massive global market across several HER2-expressing solid tumors, including breast cancer, gastric, gynecologic cancer and many other HER2-expressing cancer types. Next, please. The scientific and strategic importance of this platform targeting the PAM pathway cannot be overstated. The PAM pathway is the most frequently altered pathway in solid tumors appearing in 38% to 50% of all tumor cases, much higher than the other major drivers like RAS, HER2, EGFR and ALK.

For instance, PAM alterations are often seen in breast cancer, gastric, ovarian and cancers, prostate cancers. This gives A251 and other assets from this platform a massive total addressable market. Next slide. While small molecule inhibitors targeting PAM pathway and PIKK pathway have historically faced issues with high toxicities and poor [indiscernible] PK properties, it is always challenging to balance clinical efficacy and safety. The ATTC platform is designed to reduce these on-target off-tumor toxicities by delivering the payload directly to the tumors. The A251 payload is a potent inhibitor targeting multiple nodes in PAM pathway and PI3K pathway with high affinities in PI3K alpha, other PI3K isoforms and mTOR, ATR and ATM.

Its biochemical profile significantly differentiates from the profiles of the others targeting PAM and PIKK. We believe this is an advantage of the ATTC approach. The payload demonstrates high kinase specificity in a broad kinase panel hitting targets in the 2 families only. Next slide, A251 demonstrates strong HER2-dependent inhibitory activities, meaning IC50 is in the range of 0.2 nanomolar in HER2-positive cells regardless of PAM status in a single-digit nanomolar in HER2 low compared to 36 nanomolar in HER2 non cells. The HER2 expression level really determines how much of the payload is delivered to the tumor cells and how potent A251 can be. And crucially, A251 exhibits a bystander effect that allows it to overcome HER2 heterogeneity by killing neighboring HER2 non cells.

The preclinical data has been published at 2025 EORTC conference. Next slide, please. A251 has started a global Phase I study in the U.S. and in China. The dose escalation and building dose expansion and optimization is essentially one study in China and U.S. following the same protocol. We believe this is the fastest way to define a global dose. The trial targets HER2-expressing solid tumors with PAM status being tested retro respectively. This will inform the biomarker strategy for future development. The strategy includes utilizing A251 as a monotherapy for late-line treatment and exploring combination therapies in frontline setting. Next slide. We are accelerating discovery and development of ATTC and ADCs and this is the next-generation innovation time line. Our second ATTC asset 580 has started the Phase I opening sites and recruiting patients in China and in the U.S.

The third ATTC asset 830 is anticipated to enter global Phase I this year. We are committed to maintain the momentum from the innovative platform in the coming years. Next slide. Looking ahead next 15 months, the upcoming milestones include for savolitinib, we expect readouts for both SAFFRON and SANOVO. We anticipate the label expansion with China NDA approval for the third-line gastric cancer indication. For Sovleplenib, our Phase III trial in wAIHA successfully met its primary endpoint, clearing the path for the next regulatory filing, which will happen in the coming months. Our next major milestone will be the China NDA approval for ITP. For the innovation platform, 3 ATTCs will all be in the clinical development in 2026. Beyond these highlights today, we expect China NDA approvals for Fruquintinib, RCC and Fanregratinib in IHCC as well as Surufatinib PDAC enrollment completion within the next 15 months. We look forward to another great year. And with that, I'll turn back to our acting CEO, Johnny.

Thank you, Dr. Dai. So in summary, we are very excited about our outlook for 2026 and beyond. We have multiple potential NDA filings upcoming, so including from SAFFRON and SANOVO readouts later this year. In addition, our new hematology products are expected to drive future sales growth in China. On the innovation side, our strategic efforts will be focused on accelerating global development of our ATTC programs and at the same time, exploring business development opportunities to further validate and add value to this platform. Finally, our oncology revenue guidance of $330 million to $450 million factors in our FRUZAQLA ex-China commercial growth and the positive impact of adding new indications for Elunate. With that, I will turn it over to David to start our Q&A session.

Thank you, Johnny. Thank you, everyone, for the presentation. We will now do the Q&A session. [Operator Instructions] The first question comes from CLSA, Matthew.

Congrats on the results. I've got a few questions. First is regarding the oncology guidance in '26. In '25, you received multiple, for example, sales team restructuring kind of stuff, the growth is actually a decrease. So the '26 guidance seems to imply something 15% to 16% year-over-year oncology growth. So can you elaborate a little bit more about how I should be modeling the key drug sales for this, yes. This is my first question.

Asking my question in one batch. And second thing is about the kind SAFFRON readout. Do you have any color why the top line readout has been delayed from first half to second half? And third question is -- the last question is about -- can you elaborate more on the indication of the ATTC platform the first 2 candidates into the clinic, for example, the A251 [indiscernible]. And my understanding right that is more like on the post HER2 refractory breast cancer setting what kind of setting we are looking at in the future?

Thank you, Matthew. So for the first question, I will defer to Lorenso and the second and third question is to Dr. Dai. Lorenso?

Yes. About the guidance -- Matthew, thanks for the questions. About the guidance, as you pointed out, for 2025, there was a decline in the product sales. But as you can see, in the second half, we saw a strong momentum of recovery. And we expect that this will continue in the 2026. And together, we'd like to highlight, that we're expecting more growth coming from the new indications. As you can see, we have the [indiscernible] RCC, which is currently under review. And we believe that with that approval, that will bring in more revenue and the growth. And also about the FRUZAQLA, there's a strong growth in '26 expected due to the continued expansions of Takeda. And also, we can see that there are more and more countries are now in the market. And then with that full year penetration in 2026, that will continue the growth. Johnny, do you anything you want to add?

Okay. So second and third question, Guangxiu -- Dr. Dai.

Yes. So the SAFFRON readout is expected to happen in mid-2026. And the third question, A251 now is enrolling HER2 expressing solid tumor patients not restricted to post HER2 patients.

The next question comes from Matthew Guggenbiller. Go ahead, Matthew.

Can you hear me okay?

Yes.

Great. This is Matthew, on for Alec Stranahan from Bank of America. I guess 2 questions from us. On the SAFFRON readout, you said expected May 2026. Can you maybe clarify expected location of that medical meeting versus company event? And then for ATTC readouts, can you just maybe clarify expected patient number sort of follow-up we can expect from those?

Dr. Dai?

Okay. So the SAFFRON readout will be in, like I said, in the mid-2026. We'll share the data as soon as [indiscernible] informs us of the results. What's your second question? Can you repeat your question?

Yes. In terms of initial clinical data for the ATTC assets, sort of size and scope of those in terms of patient number follow-up?

The trial is still at early stage. We don't have a definitive time line for the data readout.

Got you. And then maybe one on commercial dynamics as well. I think first half had some headwinds from off-label sales, increased generic competition and sort of sales force turnover. I guess, can you speak to how those trends are looking in the second half and whether you expect those to stabilize throughout '26?

Okay. Matthew, we invite our Head of Commercial, George, to answer this question.

We -- because we cannot -- for the GC last year, we faced some GC setback. The indication is not yet approved. That's why if you look at the sales force, the original setting is we prepare for the GC. So the field force is a little bit overcapacity when we lost the GC indication. That's why we rationalized the team and also we try to focus more on the top hospitals. And that's why we have some kind of [indiscernible] the team, which lead to some kind of performance issue in the Q1 and the first half -- but everything is moving into the right direction. The turnover is significantly reduced. Also the vacancy is already filled. That's why we have a very strong team now, and those kind of momentum will carry over to the 2026.

No follow-up question, then David.

Next question is from Cavendish, Adam.

So a couple of questions. So yes, just in today's announcement, I noticed that you mentioned that AstraZeneca continues its efforts to increase MET testing as a standard of care in late-stage non-small cell lung cancer. And could you comment on how the pace of MET testing adoption might influence the potential uptake of savolitinib in the [indiscernible] setting in China and then globally, if SAFFRON is successful?

Yes. So Dr. Dai, yes.

We do not have additional information on this question.

Okay. No problem. Just on the second question then. So on the ATTC platform, could you elaborate on your partnering strategy, you are pursuing with the multinational pharmaceutical companies? And more specifically, are you considering out-licensing certain assets earlier in development to accelerate validation of the platform while potentially regaining greater control over other assets to maximize longer-term value?

Well, I think I will answer these question. In terms of our strategy for the partnering with the ATTC program, first of all, I think as you can see, we have a strong pipeline already building up for this ATTC platform. So we now have positive responses from potential partners, and many of which are multinational companies. We have ongoing discussion with all those potential partners.

So with our large portfolio that we anticipate that we will build on, I think we want to advance and accelerate this development. So hence, we have considered to potentially license out some of these programs. So also, in addition, I think we also have this AI capability, which we can further develop some more candidates into our platform. As a result, I think this is why we also consider potential partnering opportunities. Furthermore, I think as this platform is really one of our next wave, we would also like to validate this through this partnering strategy.

That's great. And I guess just if I could try my hand on final question is just sort of maybe a broader one. As we think about the HUTCHMED story going forward, how should investors balance the contribution of the existing commercial portfolio against the emerging opportunity from the ATTC platform? And in particular, do you see the next phase of value creation increasingly driven by the pipeline and the platform assets rather than the marketed product?

Well, we see, as we have our second wave of, as we mentioned, hematology asset that will be going into the commercial side that would add into our existing commercial -- already commercialized portfolio. So that would be increasing our balance of our investment in R&D. So we will continue to ramp up our R&D expenditure. Last year, in 2025, in terms of our investment in R&D was probably the lowest in recent years, mainly due to a lot of programs we're waiting for approval -- pending for approval, and we are also at the early stage of development of this ATTC program. But going forward, we do take this accelerate our global development strategy for ATTC. And at the same time, with the expanded commercial assets, we will be able to generate more income, so we can balance out our ATC investment.

The next question is coming from UBS, Chen Chen.

Well, my first question is on surufatinib. We see that it has started Phase III patient enrollment. So I'm interested in like partner strategy. So are you considering like BD like after data readout? Or you are now in talks with any potential partners right now because the Phase III will enroll like a few hundred people, so it would be very expensive.

Okay. I will answer from a strategic side, and then I will invite Dr. Dai to comment further. We have no -- at the moment, no intention to partner this program out. But Dr. Dai in terms of the status of our development, you can -- perhaps you can comment a little bit.

Sure, Johnny. So the Phase III first patient in has -- was achieved in December 2025, and we hope to finish the Phase III enrollment in the next 15 months. And we hope that surufatinib can provide another therapeutic option for the first-line PDAC patients and agree with Johnny that currently, we don't have our licensing.

I see. That's very clear. Well, so my second question is on your like R&D guidance in this year. So we noticed that you have started like a few Phase III trials such as like surufatinib as we discussed just now and also like BTK, DLBCL and also a few like early-stage trials such as ATTC candidates. So I'm just wondering like what's your guidance for your R&D expense this year?

Okay. Just to clarify, we do not give out any public guidance on R&D expenditure. But as we mentioned that 2025 was the lowest level. We do intend to ramp up, as you also mentioned, a number of programs that we are actually advancing as well as our strategy on accelerating our ATTC program. So going forward in the next few years, we do want to ramp up to a very reasonable kind of higher level of investment on R&D in the range of $250 million to $300 million, I think that would be the ideal level of R&D investment. Of course, we will be -- stick to our commitment to the investors that we will be profitable in a sustainable situation. So therefore, we will be investing as we will be able to generate sufficient commercial income to cover our R&D investment.

Okay. Great. Maybe the last question for me. So I saw that you have a very strong cash position by the end of 2025. And you also mentioned that you are planning to do some like in-license and also some M&A. So can you please elaborate a bit more on that side?

Yes. So yes, $1.4 billion of cash on hand. So our priority is, of course, as we mentioned, accelerating our global development for ATTC program. We are open because with these cash resources, we are open if the opportunity arise for in-licensing late-stage commercial assets or potentially some assets that is complementary to our portfolio. But I think M&A and this in-licensing opportunity, we are open-minded because we are in a good financial position, but we have no fixed target at this stage.

The next question comes from Panmure, Julie Simmonds.

I was just wondering on the move into hematology products, whether this changes what you're investing in sales and marketing and what changes to the sales infrastructure it requires.

Thank you, Julie. So George, would you like to comment on this?

Because hematology is a very specialized team, that's why we already start up a new business unit with dedicated sales, marketing and medical capability to address this kind of market opportunity. And with the future pipeline adding to the business, we will expand the team.

Lovely. And then secondly, just on the impact in the U.S. of the Medicare Part D changes. Just wondering how much impact you expect that to have on sales in 2026, whether you can make any comment?

Sorry, I didn't hear your question. Could you repeat again?

Yes. Just questioning about the changes to Medicare Part D that went on in the states that are obviously impacting your sales there. And if you've got any thoughts on what impact that might have into 2026?

We have received no new changes so far. The impact factors into 2025 has been reflected. Despite that impact for U.S., I mean, we still achieved a 26% growth for our food sector through our partners. So we do anticipate that in -- sorry, 2026, we will be expanding rolling out of all the ex U.S. countries. So far, already 38 countries have been commercialized in terms of this food sector. And we continue to see that the NRDL in those countries will be expanded. So the total impact for ex-China sales, we see that U.S. will continue to grow, but also outside of U.S., that is the key driver also.

Next question coming from Daiwa, Wilfred Yuen.

I want to follow up on the revenue guidance that range from $330 million to $450 million, which is a wide range versus last year anyway. Maybe can you give us more color as to the breakdown between the oncology product sales and the R&D milestones payment? Are you expecting some additional milestone maybe to hit the high end of the guidance $450 million?

Lorenso, would you like to tackle this question? I will add to it.

Yes. Further to what I explained earlier, I think you can look in this way because we do not give any guidance of particular items within this revenue guidance. But for your information, I think it will be worth to note that in 2025, our revenue has included some of the upfront and milestones, which if you exclude those, the base would be lower. And then for the 2026, the guidance reflect a kind of a solid growth from 2025. In addition, I think some of the factors that I mentioned, the growth from our China -- China products with the new label expansions and also the new indications would drive further growth. So I hope that could address the questions. Johnny, do you want to add some more comments on this?

So Wilfred, I think basically, you should take the guidance as the middle of this range, right? So the lower end potentially, if some of the -- at this, I think the low end of the guidance is where we are very confident, and we are also very confident that to achieve high of this guidance. So $330 million has factored in, as Lorenso said, many of the organic growth.

In addition, we also factor in for a base kind of baseline growth for our ex-China sales, which, of course, is run by our partner. So conservatively speaking, we are very conservative to give this low-end guidance, but you can expect the midrange of that is almost like a 36% growth. between $330 million to $450 million is about [indiscernible] that is more like 36% growth versus this year's 2025 performance. So I think this is a guidance that basically can reflect the business growth as well as the potential if we have licensing, of course, we won't take all the upfront income. We will potentially apportion part of the upfront income and factoring into the upside.

Next question coming from Goldman Sachs, Paul Choi.

My question is on savolitinib and assuming clinical success coming up here with SAFFRON, can you maybe comment on how you think Tagrisso, savolitinib combination would be sequenced in the treatment paradigm given the recent launch of J&J's RYBREVANT bispecific? And just how you think about guidelines evolving directing oral options versus bispecific options?

Yes. Thank you. So George, do you have any color to share on this?

Yes. This is -- I think this first thing is this provides an oral -- 2 oral products for those EGFR-resistant MET amplification patients. So this is -- we provide very efficacy and as well as convenience. But we do know the J&J bispecific antibody do provide another option, but all depends on doctors' perception regarding how the treatment paradigm shift is still precision medicine win the game or not. The testing, the secondary testing win the game or not. So it depends on how AstraZeneca is shaping the [indiscernible].

Thank you, Paul. I see a couple of questions in the chat box. Some of that actually has been kind of answered already. There's a question -- Johnny, the question is what is the thought about the need to decide appointment of a permanent CEO? Or are we happy with the current situation?

Okay. I think we have -- the company has made an announcement in August. I think no status change as yet regarding the announcement. So Dr. SU is focusing on his health right now. And yes, so we have this interim arrangement. And as you can see, we have a lot of talents within our management team. Today, we have Dr. Dai and also we have Lorenso Chiu joining this webcast. So the company has been running for 20-odd years, and we have a very loyal and also capable talents within our talent pool. So -- and everything has been running very, very smoothly and also progressing in terms of our pipeline as well as our commercial strategy, everything it is now working as per plan.

Thank you, Johnny. I don't see any outstanding questions right now [Operator Instructions] There's another question talking about SAFFRON readout delay from first half to second half. But as Dr. Dai has mentioned, the most likely scenario will be around mid-'26. If no further questions, Johnny, would you like to do a concluding remark?

Thank you again, everyone, for spending the time to attend this webcast. And if you have further questions, please by all means to feed through our IR colleagues. Thank you.

Thank you, everyone. And this concludes our results presentation. Thank you very much. Thank you very much.

Hello, and Welcome to Deutsche Bank's Virtual Investor Conference, dbVIC. This is Zafar Aziz from the Deutsche Bank team. I'm pleased to welcome our next presentation by HUTCHMED from Hong Kong. Before I introduce our speaker, a few points to note. [Operator Instructions] All of the presentations were recorded and can be accessed by the Deutsche Bank website, adr.db.com. I'm very pleased to welcome HUTCHMED, over to you.

Thank you very much, Zaf. Thank you, everyone, for joining the presentation of HUTCHMED. My name is David Ng. I'm the Head of IR and Capital Strategy for HUTCHMED. Together with me, we also have Matthew Kwong, VP of Finance, joining us today. So for those who are already familiar with HUTCHMED, welcome back again to listen to our latest update. For those who are new to our story, we definitely have a lot of exciting things to share with you about.

And before we formally start the usual safe harbor statement and disclaimer. Basically, the performance and results of operations contained in this presentation are historical in nature, and past performance is no guarantee of future results. So let's start.

We have this summary slide that I think quite succinctly cover our past, our current and most importantly, our future direction. On the left-hand side of this slide, you have the circlesing global commercial success, and we are very happy to have our innovative drug FRUZAQLA doing very well during first half this year with sales up 25%. Again, for those who know this, we have been selling in China for a couple of years, but we got FDA approval in 2023. Our marketing partner, Takeda, has been doing a fantastic job ramping it up in the U.S., in Europe and Japan over the last a little bit more than a year, and it has been doing great.

So of course, this not just validate our science, but it also provides us with a very strong financial foundation, helping us to be profitable since 2023, '24, and we expect to remain self-sufficient in our capital funding in the upcoming years, thanks to this innovative drug finally materializing in global sales.

And we are expecting the second one. This is a drug called ORPATHYS for lung cancer. It has been going through both trials in China, global trials. The trial name is called SAFFRON. We anticipate completion very soon, and then the readout of the data will be first half next year. Our marketing partner, AstraZeneca, when this product potentially get approved in the U.S., we will be commercializing this one. We hope that will be sometime around 2027.

So I think with these 2 products, we hopefully will have 2 commercial global products supporting both our financial as well as validating our science. I probably won't go over into too much details of the near-term catalysts. By the way, this presentation is also on our homepage. So if you miss anything, you can definitely go back to download this presentation on the HUTCHMED homepage. We do have a couple of upcoming catalysts in the next 12 months, definitely very relevant for our stock price performance.

But I definitely want to spend more time today to talk about our future, which we have a new generation technology platform called ATTC, antibody-targeted therapy conjugate. I think many of you have already heard of the term called ADC, ADC, right? I think you can look at our ATTC to be the next generation of ADC and even more improved version of ADC, focusing specifically on improving the safety and the toxicity of this kind of molecules initially target oncology, but maybe down the road, it may also have potential autoimmune application.

The very first drug candidate coming out from our ATTC platform, that one is called A251. We have just presented the preclinical data in the EORTC conference just a little bit 2 weeks ago in Boston. And right last Friday, we also host an R&D Day, both online and offline, explaining even in more details by our Chief Medical Officer on our first molecule. And for those who may have missed that, again, the webcast replay is also on our homepage for our ATTC platform.

The reason why I say this is very important is not -- is that because this is not just one molecule. If this ATTC platform works, it will generate many, many more drug molecules. Of course, it's still at an early stage. We have got some very good preclinical evidence. And then our plan is to get it into patient Phase I trial in December this year. We had already got the IND approval in the U.S., and we are pending to receive the IND approval in China. So expect 2026 next year to be a year full of news and events coming out from this platform.

Apart from the science, which we think we are global first in this so-called ATTC category, the other thing that we bring a lot of attention to this is the potential out-licensing opportunities. We have been attracting a lot of interest from global pharma into this platform, and there are possibility of BD opportunities in the -- when we disclose more clinical data down the road.

So I think on this slide, we do have very solid financial foundation that make us very self-sufficient, not relying on the capital market for further funding. But at the same time, the most -- more important thing is our ATTC platform, which if start to generate good results. It will provide us with an even bigger pipeline of products that we will -- can bring to patients in needs down the road.

Now we do have a very big slide deck here. So apologies for not going through every single slide. But I will just jump to this one right here, which is our first half sales of some of our key products. Again, like FRUZAQLA has been doing quite well, up 25% first half this year. For those who have been following us even more closely, you may have looked at some of our marketing partner third quarter sales. And then we roughly have about quarter-over-quarter growth of around 10% for both the FRUZAQLA, which is overseas fruquintinib. And then also for domestic fruquintinib, we also start to see some quarterly improvement.

Now -- but again, like this is the present. Let me jump a little bit to the slide where we talk about our upcoming future potential. So first of all, our late-stage pipeline is very solid. For our fruquintinib, we had already been selling it for colorectal cancer. But since early this year in China, we also got approval for a second indication called EMC, endometrial cancer. This is a combination therapy with another PD-1 drug that we can address the market.

And I think we also have the third indication called renal cell carcinoma, RCC, which we have already presented very impressive data in ESMO, the ESMO conference just last month or early this month. And we have also submitted or filed the -- to the China NDA, which if everything goes smoothly, the approval probably would land around middle next year potentially. So with that, we will actually have 2 more indications for fruquintinib to support its further sales growth in China.

For the other product, savolitinib, we had got a second indication approved on June 30 this year. This is the second-line lung cancer focusing on the MET amplifier. MET, of course, is a biomarker, roughly in 1/3 of the patient population in the second-line EGFR setting. So it's definitely a very sizable patient population. And we are the only one around the world with such late-stage data focusing on the MET-specific patients.

For the overseas trial, similar to this SACHI trial that you saw there, the overseas counterpart is called SAFFRON. I mentioned briefly just a moment ago that our marketing partner, AstraZeneca is close to completing the recruitment and the data readout will be first half next year according to AstraZeneca guidance. And if, again, everything goes smoothly, potential U.S. approval in 2027, which may bring our second innovative drug to be globally commercialized.

Back in China, we are also working on another even more impressive trial in the first-line setting. This is a trial called SANOVO, fully recruited. Again, this is also a very highly contested market in the first-line lung cancer space for the MET overexpression, it's a very decent market size as well, ranging from 30% to 50% of the first-line lung cancer patients have overexpressed MET proteins. So if the results are satisfactory, this will also address a very sizable market.

The third drug called surufatinib, the thing to look out for is December, we will present the pancreatic Phase II data at a conference. So watch out for that one, and we are planning to -- if the data is satisfactory to roll into Phase III trial. Again, pancreatic cancer is what a lot of people call cold tumors, very tough-to-treat cancers. And we are using our surufatinib in combination with another PD-1 and chemotherapy to target this tough-to-treat cancer.

I'll skip the next one and go straight to the blue one called sovleplenib. This one, if you remember, we presented very impressive data, durable response rate of around 51% and this is compared to most of the new modality just hovering around the 20% to 30% durable response rate. Unfortunately, we had some CMC issues earlier this year, and we have to change to a new formulation. We don't have to redo the Phase III trial, but we do have to resubmit the data. The time line we now anticipate to resubmit the data for the China authorities will be first half next year.

This is for the indication of ITP, which is basically blood platelets being too low in the body and you kind of bleed very easily. It's a chronic disease. It's an autoimmune disease. It's definitely a new area that we are very excited about, and we plan to commercialize it in China when it potentially get approved hopefully in 2027. It is also working on another indication, a little bit rare disease called warm AIHA, second-line setting. The data will be probably around early next year to present the data. So if that is also successful, sovleplenib will have 2 potential indications addressing a very sizable market population.

Now so this is -- this slide and many of the slides that I just went through for those who are familiar with HUTCHMED, you probably have seen it a couple of times before. What I'm going to show you next, I think, is pretty new. So the next slide, we're going to talk about the early-stage pipeline. Focus on the bottom 3 coming out from our ATTC platform. The first one is called A251. And we disclosed just 2 weeks ago basically the composition of this.

Now let me also jump to the next slide here, where we talk about the structure of this ATTC. It's made up of a large molecule and antibodies, right? And we disclosed that this antibody is a trastuzumab biosimilar, a HER2 targeting antibody. And it's going to have a linker, a cleavable linker. So far, it is still quite similar to the ADC that you've seen out there. But what differentiates us from all our peers is for the payload, instead of using a nonspecific chemotoxin, we are using a specific small molecule drug, right? So instead of like a payload, we use a small molecule drug. As the payload, which means that it will be even more selectively targeting certain mutation or certain mutated pathway, which is manifested more strongly in certain oncology indication.

And this concept, I think, is quite easy to understand, but we actually don't have anyone trying this so far as far as we know in the clinical space. So we probably is still the first company pushing this ATTC composition into clinical trial globally first in the upcoming months.

The other thing that is also quite new is this particular small molecule drug, we call PI3K/PIKK. It's basically focused on a pathway called PAM, PAM pathway. there are no commercial drug on the PAM pathway yet. And the reason is that it's a very toxic molecule. So I think the scientific community is already quite well aware and has a good consensus that this particular molecule targeting this pathway is very effective in eliminating tumors. Unfortunately, it's just too toxic. So I think this is a very important point, right? For our ATTC, we are not just limiting to this HER2 with PI3K combination. We're going to have different combination, and a lot of investors ask us what other are we thinking about?

Think along the line of small molecule drug, which may be known to the scientific community, but was just too toxic. So it was not able to be easily commercialized as a drug or approved as a drug. But when this small molecule is loaded onto this ATTC platform, it becomes very selective. It becomes very destined for the tumor tissues. And then this toxic small molecule or this very potent small molecule will be deliberately delivered just to the tumor tissues and take its effect on eliminating the tumor tissues. So this is basically the concept, right?

And as I said, we do have a couple of other combinations that we're working for. We have not disclosed that yet. We kind of disclosed the code name -- the second molecule is called A580. We anticipate entering clinical trial around middle part of next year. And then the third one is A830. We targeted towards the end of next year to end the clinical trial. And as we disclose more data coming out from this #2 and #3, we will also disclose the actual composition, right?

But again, think along the line, small molecule drugs that are very effective, but were just too toxic in the past to be turned into a drug for cancer patients. Now with this platform, we can load it on our ATTC, and it become like really targeted to the tumor tissue.

Now of course, just a caveat here, we have done a lot of very good work in the preclinical stage, in animal stage. We haven't tried on human yet, right? So -- and then that's why as the human trial kicks off in December and when the data start to roll in 2026, it will be very exciting for us as well as our potential licensing partners down the road to look at really how safe this ATTC platform can be, right?

Now just to dig a little bit deeper into this market that we are looking at. In fact, this particular slide that we created just last week even surprised me. I think many of you are much more familiar with some target like EGFR, like HER2, right, or maybe even RAS. Very few people talk about this PAM pathway. And it turns out that it is present in 50% of the solid tumors globally, right? So this is not a small number. And why do we know about this or why we're not more familiar with this is because this pathway or molecules targeting this pathway is just too toxic. It works very well, but it's just too toxic, right?

So -- and then for some of the major cancers, which have this PAM pathway alter, we kind of outlined it here. And again, because we use HER2 as our large molecule, we also present some of the prevalence of different HER2 expression in the breast cancer space. And the clinical trials that we plan to kick off at this stage, this is our plan. And you may notice this is also slightly different from our tradition -- the tradition of HUTCHMED by doing things one at a time, right? We want to go a little bit more aggressive this time. We are working on different tumor in different cohorts at the same time.

And you may notice that we are also working on the later line, like the second line, third line indication as well as the first-line indication at the same time. Why? As you may know, the competitive landscape has dramatically changed in China last 2, 3 years with a lot of these licensing deals providing a lot of funding and a lot of bullet for our competitors to work faster and go into innovative modality earlier and sooner.

So we need to also pick up our speed. We now have a much stronger balance sheet of about $1.4 billion cash, and we want to put this cash into the right use by working on multiple trials. And we also -- actually, if you look at this, we also have a cohort looking at HER2 low, which is also a very sizable market out there. We haven't disclosed the tumor. I'm pretty sure we will disclose it in the near future. But these are all very large addressable market that we are working on. So that's kind of our current plan for ATTC. And then this is another slide just to give you an idea of the precedence of this PAM alter pathway in different type of cancers. And then, of course, we have the HER2 antibody or target preference in different type of tumors.

But definitely watch out for one thing that we are trying to see whether it works for HER2 low. So not just HER2 positive, but also HER2 low, which again is another big market out there.

Now again, like we haven't disclosed what other antibody that we are working on. Someone may say like why HER2, why not something more -- even more crazy or even more innovative than that. I think at this stage, this PAM or this PI3K small molecule is new. It's not new to us, but it's new to the clinical space. We haven't put it into clinical trial yet. So we want to kind of conserve the riskiness to that part, whereas for the large molecule part, the antibody part, we are picking HER2 deliberately, which is a very good, well established, very well-known profile antibody.

And also for the linker, we kind of have not elaborated too much on, but this is also a very well-established linker that we are using. And the most innovative part or the part that the clinical space haven't seen too much data is actually the small molecule part, the small molecule payload.

So the upcoming few months, we are going to see 2 things. Number one, whether this small molecule drug does work well for cancer. Number two, whether putting this large molecule linker and a small molecule together, whether this construct conceptually is stable enough when injected into human body and whether this will have good efficacy and more importantly, safety.

One last point I want to emphasize about ATTC is that we call it a chemo-free conjugate. Again, like this is in contrast to the ADC out in the market or under development, which still rely on the chemotoxin, which is kind of like a nonspecific toxin attacking all the tissues.

With our chemo-free ATTC molecule, many people are asking us, are we going to replace chemotherapy or are we going to replace ADC. I think the path -- at least at this juncture, the path that we want to take is not necessary to replace, but to be potentially used in combination, in combination with chemotherapy, of course, preferably in the earlier line setting and also in combination with ADC out there. We've got very good animal data showing that it does work very well, now is to put the test into human trial.

I noticed that I have roughly 5 minutes left. So I'll just pick one slide, and I will just go into some of the questions that is already on the line. So this is kind of our road map, still mostly focusing on our existing pipeline, not too many ATTC molecules out there, right? But it's still a very busy, very eventful next 2 years even from our own pipeline. But I would have to say that if this ATTC platform starts to deliver, the value or the impact from this ATTC platform may be even bigger than what you see on this particular slide coming out from our established late-stage pipeline. So I will wrap up here, and I will go into a couple of questions here.

So first question, let's see, can you elaborate on China growth driver versus U.S., EU market?

I think China continued to present one of the largest patient population, but then the pricing is a little bit compress, right, whereas the U.S. and EU market definitely have a better pricing for our drug. So we will continue to do both, right? China is our home base. We developed many innovative drugs from our excellent scientists from China, but we will definitely try to bring this drug to all around the world, definitely include U.S. and EU market.

The next question is, can you discuss the clinical time line and upcoming milestone for ATTC program?

Yes. So the 3 that we have disclosed, we expect to kick start the first one December into human trial and then the second one around middle part of next year and then the third one towards the end of next year. So hopefully, by the end of next year, we will have 3 ATTC molecules in clinical trial.

And next question is, how is HUTCHMED leveraging strategic partnership to accelerate?

Very good question. I think we do have a very strong balance sheet, right? But we think that with our many molecules coming out from the ATTC platform, we are definitely very open to out-license some of that even in the early-stage development, right? Because it not just validate -- and we're definitely looking for multinational pharma to be a potential partner, right, because it's not just going to help validate the science, but it's also going to bring in potential upfront payment, which will again help us to be very self-sufficient to support even a bigger pipeline coming out from the ATTC program down the road.

And the next and last question, a little bit similar, how do -- how will we allocate the capital and commercialization of our oncology drugs?

For overseas market, we will look for multinational partners. We've enjoyed a very good partnership with AstraZeneca with Takeda. For China, we plan to use our own sales team to do the commercialization. We have about 700 people. They are very well trained. They are definitely ready for more products to commercialize in China and to support our home base.

With that, I think I have about 30 seconds left, and I want to thank everyone who has been listening to our presentation and everyone who has been supportive on HUTCHMED and definitely looking forward to an even more exciting 2026. So thank you, everyone.

Hello, everyone. Good evening and good morning. Thank you for joining HUTCHMED 2025 R&D Day event. For your reference, you can go to our website to download today's presentation slides.

The performance and results of operations of the HUTCHMED Group contained within this presentation are historical in nature, and the past performance is no guarantee of future results. [Operator Instructions]

So now let me welcome our CMO and Head of R&D, Dr. Michael Shi, to start the today's presentation. Michael?

Thank you, Ng. Good morning, good evening, everyone. Happy Halloween. And so today, I'm going to give you a research update for HUTCHMED pipeline. So today, we're going to talk about the -- our main antibody target therapy conjugate platform and really showcase some of the new next-generation platform. And also recently, last week, we actually presented our first candidate, HMPL-A251 at the EORTC meeting in Boston. So I'm going to highlight some of the progress and show you the results and our overall preliminary development plan strategy. And then I'm going to show the late-stage pipeline progress and with a closing remark and then we're going to start a Q&A session.

Okay. So for the ATTC platform we introduced to the investor early this year is really the new development for the past 3 years at HUTCHMED. We're really looking at some of these progress and the platform. So before we go that and we really talk about the current development in the toxin-based antibody drug conjugate, ADCs. As we know, there are 19 ADC has been approved worldwide. And despite the design and the rationale expanding the therapeutic index, the traditional toxin-based ADC also have a very similar toxin profile. And microtubule and the tubulin isomerase inhibitor and both have some common feature for toxin-based toxicities such as myelosuppression, thrombocytopenia and hepatotoxicity and some of the ocular toxicity or neurotoxicity. So far there's really the limitation. There's certainly room to improve to overcome these challenges. And the HUTCHMED antibody target therapy conjugate really designed to target a protein required to [indiscernible] cancer growth.

And one of the important feature of what we believe it has the synergistic combination activity with antibody because the antibody we chose really have the antibody and the function to really have a potential synergistic effect. And more importantly, we know the ADCs has very difficult profile to combine with the traditional chemotherapy, which is often required for frontline chemotherapy. So we think the ATTC will overcome this chemo-resistant and also have the potential to be dosed long term. And from toxicity perspective, although the -- it have the antibody-based toxicity but we believe the antibody target therapy payload have the low on-target and off-target tumor toxicity. And also, they bypass some of these traditional small molecule systemic toxicity, for example, liver toxicity and QT prolongation, et cetera and low myelosuppression and also support a long-term use. So we think this just will be a unique platform to really enhance some of these and overcome some of the resistance and difficulty for the toxin-based ADCs.

So when we select these development for ATTC, really selecting some of the functional antibody and conjugated with the target therapy, which traditionally a small molecule have poor solubility and very hard to link the antibody. So we're really working on the linker and the payload to have this ATTC platform develop. And with the lower free target therapy in the circulation and also have a wider therapeutic window compared with the oral systemic exposure. And also, it has a great opportunity because they can combine with the other therapies, for example, target therapy, immunotherapy and more importantly, the chemotherapy. So this will potentially have a opportunity to be used in the frontline. So to show some of the -- highlight some of the first target therapy, the -- really the unique invention here is the target therapy payload targeting the PAM, PI3K/mTOR pathway. So the PAM pathway, PI3K/AKT/mTOR pathway is very attractive therapeutic target because it has a very -- cover a very broad range of the tumor type, have a high frequency mutation in some of the most common tumor type.

For example, in breast cancer, the PI3K PAM pathway mutation representing about 70% of the patient -- breast cancer patient. Also in endometrial cancer, for example, has very high mutation rate. Also in the other common tumor type, it also have a very high frequency. So -- and also, this is in the development stage, there are quite some small molecule, pretty much the previous effort focused on the small molecule development but have a very few success. And also talking about the mutation is really play a role in the toxin-based ADC resistance. So this is one of the report last year from ESMO showing that HER2 ADC disitamab vedotin RC48 in breast cancer patient type. And in the clinical study in the overall patient population, the PFS and ORR is better but with patient with PAM-altered pathway really show for poor prognosis activity. For example, the PFS, that's actually lower, response is lower because this driver mutation really leading to the drug resistance for ADC product.

And also in the DESTINY-CRC01, also showing the driver mutation for PIK3CA and also RAS mutation, patients with these mutations also have a lower response rate and shorter PFS compared with the wild-type patients. So really leading to -- there's opportunity to really improve to develop a target therapy as a payload to overcome this resistance. I also mentioned about the traditional development for PI3K/mTOR pathway, really focused on small molecule. There are quite a pipeline of development, including multiple companies invested in this PI3K inhibitor development and -- but with very few success. And the first generation and second generation pretty much halted due to the systemic toxicity. And later on, there are mTOR inhibitor, for example, everolimus, PIK3CA alpha, alpelisib and capivasertib is AKT inhibitor, leading to the approval but they also have a pretty hard to handle tolerability profile and also the overall survival has been hampered.

And there are -- 2 weeks ago, we see the new PI3K inhibitor gedatolisib really showcase some of the activity in the breast cancer but it still has a very high difficulty in toxicity, for example, mucositis and some myelosuppression as a side effect. So targeting PAM pathway alteration really showing as a promising approach for breast cancer. For example, in the slide here, we show in the overall breast cancer patient population, you can see the PAM pathway mutation, including PI3K mutation, AKT mutation and PTEN loss, representing about 70% of the patient with this mutation. In HER2+ patient population, including hormone positive or negative patient population, the PI3K PAM pathway mutation is representing close to 40%. And in the HER2- patient population, triple-negative patient population, these mutation even have a higher presence.

So really presenting a big opportunity for developing PI3K inhibitor targeting breast cancer patient population. In the gedatolisib study, we do see there is a improved PFS and activity in not only in overall patient population, representing inhibiting target in HER2+ patient population also show good activity and -- but adverse events such as stomatitis also pretty high. Okay. So here's the profile for our pan-PI3K pathway inhibitor, PI3K/PIKK inhibitor. And this is HM606 (sic) [ HM609 ], in short, we represent 606 (sic) [ 609 ]. This is our first targeted PI3K inhibitor using as a payload. So the profile for this molecule and showing in the kinome, you can see the major inhibition really showing focus on the PI3K and PIKK activity is very high selectivity and very few -- small off-target activity. And this is the profile compared with the other kind of PI3K or PIKK inhibitor. Gedatolisib and dactolisib and buparlisib, you can really see 609 has a very robust and potent inhibition against all these PI3K and PIKK pathway.

Here's the biochemical characterization of this -- our first ATTC is the A251. And as we can see, using this we look at the payload, you can see this has a pretty potent inhibition of the PAM pathway. When this pathway is activated, it's commonly in the breast cancer cell lines, you can see very robust dose-dependent inhibition of the PAM pathway, including AKT S6 or so. And also in the PIKK pathway, when you enhance the PIKK pathway by treating with bleomycin, you can really activate all this DNA repair process and using the payload 609, you can see also a dose-dependent inhibition of this pathway. And also in the panel of 130 cell lines, we can see in many cell lines with mutation of a PAM pathway, HER2 pathway alteration, RAS/RAF pathway mutation and other cell lines. 606 (sic) [ 609 ] has a very potent activity with IC50 about 1 nanomolar. And also on the right-hand side is the cell growth inhibition of 609 by tumor type. And also show -- demonstrate a nanomolar range and also high potent activity across many different tumor cell lines.

So now let me talk about the antibody part. The first proof-of-concept molecule where we develop is using HER2 as a antibody. We all know HER2 alteration really leading to a poor prognosis in cancer, in many tumor type. For example, HER2 amplification and overexpression has been shown is as a poor prognosis factor and HER2 amplification or overexpression lead to the patient with a shorter half-life -- shorter lifespan. And also HER2 overexpression and amplification really cover many tumor type. So what we also looking at the anti-HER2 therapy is really, for example, developed by trastuzumab is a functional antibody with intact Fc and leading to ADCC activity. So it works by blocking extracellular domain cleavage to prevent the formation of its active form of HER2 and also block the dimerization of the molecule and reduce the signal transduction pathway and also mention the antibody leading to the antibody-dependent cell-mediated cytotoxicity and also the HER2 antibody downregulation through the endocytosis through the lysosome.

So to sum up for our concept and for the development of ATTC, we use HER2 as a therapeutic antibody and PI3K/PIKK pathway inhibitor as the payload. This provide opportunity to really inhibit the most major oncogenic driver and the downstream signaling pathway of HER2. And it has the potential to overcome the resistance for trastuzumab-based therapy and also the antibody and the payload will have a synergistic activity to -- with the enhanced antitumor activity. So this pan-PI3K-based HER2 ATTC is really expected to increase the efficacy and synergism and also improve the safety profile to overcome some of the narrow therapeutic window for the traditional PI3K inhibitor.

So now let me move to the first candidate, A251. We showcased this molecule at the EORTC meeting last week in Boston. So here's the structure for PI3K -- the A251. It has the payload 609 and is a highly potent PI3K/PIKK kinase inhibitor and has the potential synergy with the HER2 antibody. And we also show you some of the data we have the potential for combination with chemotherapy as ATTC and also show the bystander effect. The [indiscernible] portion is the HER trastuzumab biosimilar and with a credible linker and with the antibody -- drug to antibody ratio of 4. Here's the in vitro binding activity. It does show A251 and the HER2 antibody has a very similar binding activity. And also this figure show the internalization of the antibody A251 ATTC and also the naked antibody.

So at 37 degrees, we can see the internalization. On the right-hand side, you can see the intracellular trafficking of the antibody drug conjugate. So here is the blue color is showing the nuclear staining and the red color is really with the HER2 antibody. Green color is showing the lysosome. And when you incubate cells, you can see it has a time-dependent internalization of the antibody, both the naked antibody and also the A251. As you can see, with the time when you merge the signal, the red color and the green color will overlap with the times of incubation, really showing the antibody has been internalized into the lysosome. And also, we show you the activity for payload 609, now for the whole antibody target therapy conjugate has a similar feature as the payload alone when you do the in vitro cell inhibition assay in HER2+ PI3K mutant cell lines. We can see a potent inhibition, dose-dependent inhibition of the, first of all, AKT S6, for example, really showing the target pathway inhibition and leading to clear the pathway PARP inhibition and leading to apoptosis.

And also on the right-hand side is the PI3K -- PIKK pathway inhibition showing this molecule also have a in vitro inhibition of the PIKK pathway and also leading to the DNA damage when you use the A251 has increased the DNA damage. And also next, we show the activity in the panel of cell lines for A251, showing the growth inhibition on the left-hand side. You can see in the 26 cell lines we have tested, HER2+ cell line with PI -- PAM pathway alteration or without alteration, it has very robust potent activity, actually 0.2 nanomolar range to have a very good tumor growth inhibition effect. And in HER2 low PAM-altered pathway, it still demonstrated potent activity, although the potency compared with the HER2 overexpressed positive patient population, it has less potency and also has some less magnitude [indiscernible] in HER2 low, the cell lines.

And here down the right-hand side, we show the bystander effect. In the HER2+ cells, we can see the A251 showing very potent bystander tumor killing effect. And it doesn't work on the HER2 low cell lines but you co-culture the HER2-positive and HER2 low cell lines, you can clearly see the robust tumor killing with the bystander effect. And also, we test this molecule in the -- in HER2 resistant cell lines. So one, on the left-hand side, we can see the comparison of the A251 with the HER2 in cells, in breast cancer cells with using the siRNA silencing of the SLX4, which is one of the key gene to turn on the resistance because it's one of the DNA repair enzyme. And when you're really silencing the SLX4, you can see a right shift of the potency of the payload DXd or DS-8201 in HER2. It has less -- need a higher concentration and also the less -- the inhibitory effect, compared with the A251, the -- compared with the payload itself and A251, you can see there is no right shift and the payload and ATTC maintain the same potency to inhibit this resistant cell line.

And on the right-hand side is the developed cell line resistant to -- in HER2 or the payload. And you can see, again, right, the DXd treated cells and in HER2 treated cell have a right shift and less potent killing effect compared with the parent cell. But in the payload 609 and ATTC A251, you don't see -- you don't observe this right shift and maintain the same tumor killing effect, cell tumor killing effect. And here is the, one of the proof-of-concept study we have done for A251. And here, you can see the black label is the vehicle treatment and the red color is the payload 609 itself at 0.5 milligram per kg IV injection biweekly. And the pink color is the trastuzumab plus 609. You have also increased cell growth inhibition. And A251 at 10 and 30 milligram per kg, really showing robust tumor inhibition activity and causing tumor regression.

So this is very important because this is HER2+ and PTEN loss xenograft model. We can see a single dose injection of A251 can have 2 weeks sustained tumor suppression, unlike the small molecule. So you need multiple dosing to have a modest antitumor effect because this is actually the MTD level of the payload for 609. And also on the safety side, you can see this -- on the left-hand side is the same model. You can see the ATTC A251 and then that does not lead to the body weight change. But the small molecule, 609, the payload and the 609 plus trastuzumab, you actually see when you dose the small molecule, you can see actually a quite significant body weight loss and they recover, when you dose again, it will lead to additional body weight loss. So this is pretty much the -- this is really the maximum tolerated dose for this small molecule payload. And so as you can see, really in the preclinical model, you can see this activity of the A251 has a more safety profile compared with small molecule or small molecule combined with the company -- with the antibody.

Also on the right-hand side is a very classic example because the small molecule 609, when you see the dosing, the [indiscernible], it has a very transient and high glucose increase, same with the 609 plus antibody. On the other hand, A251, the glucose level remain unchanged because the PI3K inhibition leading to hyperglycemia is really a classic hallmark for this class of PI3K inhibitor. So in this preclinical setting -- model, we really demonstrate using the ATTC concept, you can really increase the safety profile for this PI3K inhibitor because it's a targeted delivery of this conjugate into the tumor cells, leading to the release and inhibited the tumor unlike the small molecule, really have a higher systemic exposure and lead to HER2 PI3K pathway inhibition leading to the toxicity. We also test the A251 in multiple xenograft model. And here is the 2 model we have shown is the breast cancer cell line with HER2 overexpression and the PI3K mutation. And also the lower one is the ovarian cancer model with HER2 expression and HER2+ PI3K-mutated model.

On the red line is the 10 milligram per kg in HER2 as a control. I can see in these 2 models, we can see a faster and deeper response for A251 leading to the tumor growth inhibition compared with the DS -- compared with the HER2 itself. Here, we also test the panel of HER2 low PAM-altered cell line, endometrial cancer cell line. And in the -- with the tumor xenograft model. Again, we can see in HER2 low model, we can see a more rapid tumor growth inhibition of A251 compared with -- in HER2 in the [ upper ] model. And in the cervical cancer model, we can see the activity of A251 is similar to -- in HER2. We further test some of the model without PAM pathway alteration. In HER2+ PAM nonaltered xenograft model, we can see in HER2 and A251 has about similar antitumor activity. So in all of the model we have test, we can see the A251 pretty much have a stronger activity or at least comparable to DS-8201 in HER2 at the equivalent dose level.

Here's the pharmacokinetic profile for A251. We can see on the right-hand side, you can see a single dose injection of the A251. We can see the total antibody and the antibody and A251 have the high sustained exposure. And 609, the free payload, which has remained very low concentration compared with the conjugated ATTC. And the right-hand side, we also conduct a stability -- plasma stability study compared with -- in HER2 A251 have a more stable half-life compared with the -- in HER2 in the monkey and the human plasma. Here's the in vivo pharmacodynamic activity for A251. We have the vehicle control and also A251 10 milligram per kilogram IV injection and monitor the time course for the phospho-AKT, phospho-S6. You can see there's a time-dependent inhibition of this PAM pathway. And H2AX [indiscernible] H2AX is a marker for DNA breakage. You can see the increased DNA damage and also leading to increased cleaved caspase which is [indiscernible] representing the apoptosis.

And the CD68 is a marker for macrophage inhibition. You can see the macrophage infiltration into the tumor cell. You can see really leading to the ADCP, antibody-dependent cytotoxicity. And also, we look at the distribution of the payload in the tumor cell. In the tumor cell, we can see a sustained and high exposure of the payload into the tumor cells and the [indiscernible] in the plasma level is actually remained low. And again, they just representation of the inhibition of the pathway leading to the PAM pathway and -- with inhibition leading to apoptosis and DNA damage and ADCP activity. So in summary, A251 is the first-in-class PI3K/PIKK inhibitor conjugated with HER2 antibody, has robust and potent antitumor activity in HER2+ model without or without PAM moderation, also showing quite good activity in HER2 low tumor model with the PAM mutation. And also it has a favorable PK profile and have a much improved safety profile compared with small molecule payload itself.

And so we have completed the GLP tox study and filed a China and U.S. IND. And we already received FDA clearance for this U.S. IND and our Phase I clinical study is starting to enroll patients later this year. Here, I'm going to show you some of the high-level clinical development plan. Of course, the Phase I, we're going to start with the single dose escalation. We are now -- we are enrolling HER2+ or low patient population. And PAM pathway alteration will be tested retrospectively. It's not the requirement for enrolling patients. And further dose expansion will be tested in HER2+, PAM+, HER2+ and PAM nonaltered pathway patients. And also we'll test the HER2 low and PAM mutated patient population. And we will further expand in multiple tumor type with or without the PAM alteration. And also, we will test when we define the dose for a single agent, we also will start the A251 in combination with standard chemotherapy in the earlier line, in the frontline setting.

And also, we're going to test the solid tumor in the HER2 low patient population with the PAM alteration. So here is, as you can see from this molecule with -- we have pretty mature HER2 pathway functional antibody and also the very broad PI3K inhibition. So the PAM pathway is quite common compared with other driver mutation, ALK alteration, EGFR in Western patients and HER2 amplified mutated patients. So PAM pathway alteration really representing a very broad range of tumor type. The new incidence for all these cancer type is very high. And also in the breast cancer, we can see HER2+ patient population represent a 15% to 20% patient by the standard testing. And as we know, HER2 low patient population also have a very robust percentage, representing 40%, 50%. And the HER2- patient population is a smaller percentage. So this will really provide a good opportunity and targeting a larger HER2 expressed patient and also with the PI3K mutation because HER2 is also a one of the downstream -- because PI3K is also downstream of the HER2 activation pathway.

So we think this molecule really can cover very broad range tumor inhibition in the breast cancer area. And so just thinking about the HER2- second-line breast cancer with the gedatolisib, for example, recently demonstrated activity, the market size representing about $5 billion. So we believe even HER2-, part of the significant portion of the patient will have HER2 expression. And these will -- can still potentially be patients benefit from the A251 in addition to HER2+ patient population. So this molecule really representing a good opportunity for the broader tumor type development in the future. So I show you the first molecule, A251, as the -- our leading molecule, which is -- will enter clinic later this year. And also here, you can see the PAM pathway alteration really cover very broad range of tumor type, lung cancer, breast cancer, colorectal cancer, breast cancer, for example.

And the HER2 pathway expression also show pretty -- cover broader range of the tumor type. And here represent our opportunity for our first molecule. And by the same concept, we think other important antigen, right, TROP2, EGFR, for B7-H3, for example, all these have a very broad coverage for different tumor type. By leveraging the payload, not only the PI3K/PIKK inhibitors 609 but also other target therapy, which have -- inhibiting major pathway driver mutation cell lines. We think this ATTC platform can really cover very broad range of tumor type, representing a huge opportunity for the development. So our first molecule has already get a U.S. IND clearance and starting enroll -- will start to enroll patients soon. And the second molecule, A580, which is with a different antibody and will -- we have not yet disclosed but we are targeting to have the Phase I initiation early next year in the China and the U.S. Third molecule, A530 (sic) [ A830 ] and will also enter the clinic in the second half of 2026. So we kind of update you about the ATTC platform and the lead molecule enter the clinical development.

We'll -- I'm going to cover some of the new development in the late-stage pipeline. So HUTCHMED has really developed a deep pipeline covering multiple tumor types. Our first approved product, fruquintinib, we already approved in the colorectal cancer and worldwide ex China has been covered by Takeda. And in China, we also continue to develop additional indication. FRUSICA-1 was reported already in endometrial cancer. So we get NMPA approval for pMMR endometrial cancer December 2024. And also second-line RCC, we have showcased this FRUSICA-2 trial data at ESMO 2 weeks ago in Berlin. I'm going to show you some of the highlight of the data. And the NDA has been submitted and under review in NMPA. Our expectation is that we're getting approval late next year. Also MET inhibitor savolitinib also making tremendous progress. And we show the clinical data of SACHI in second-line EGFR mutated MET amplified patient population in combination with osimertinib, demonstrate the robust clinical improvement and it was approved by NMPA under fast track review in June '25.

And also our partner -- global partner, AstraZeneca has also presented data in SAVANNAH, really demonstrate the high and clinically meaningful in durable response. Also, we are all very much looking forward to SAFFRON, which is the global AZ lead study in second, third-line EGFR mutant -- EGFR mutant MET amplified or overexpression lung cancer has a data readout next year. And SANOVO is the first-line MET overexpression patient population in combination with osimertinib. We have fully enrolled the patients in August. And also, we are anticipating the GC, gastric cancer in MET-amplified patient. We are conducting single-arm registration trial with the patient enrolled in April and the readout with the potential NDA in this year. And SAMETA is in the papillary renal cell carcinoma, is also lead by our global partner, AstraZeneca.

And also the other approved products, surufatinib in China, we're also having a Phase II/III study in first-line pancreatic cancer in combination with PD-1 and chemotherapy. Phase II is fully enrolled and the data readout we're going to showcase later this year. And tazemetostat is the global first-in-class molecule, EZH2 inhibitor. We licensed from Ipsen. We have completed our bridging study and the study -- and the drug was approved earlier, March 2025 by NMPA in the third-line follicular lymphoma. And also, we're making great progress in the second-line lymphoma trial. Also for sovleplenib, our Syk inhibitor through the ESLIM-01study in the second-line immune thrombocytopenia, we have submitted an NDA. As we know, there is a impurity issue we have been addressed. We reached agreement with CDE, really define the intake level and moving forward with the resubmission early next year.

And also our second-line autoimmune disease is warm autoimmune hemolytic anemia study. We already complete the enrollment with the potential readout and NDA next year. Newer pipeline is the second-line FGFR2 inhibitor fanregratinib and also with the potential for NDA this -- later this year. And our dual IDH1 and 2 inhibitor ranosidenib also in the Phase III study in the AML. Here's the fruquintinib with sintilimab combination versus standard of care in China, axitinib or everolimus. The data FRUSICA-2 has been presented at the ESMO Congress through the oral presentation by Professor Zhenhua Liu. Here's the trial design is the fruquintinib plus sintilimab versus the investigator choice of axitinib or everolimus. And the clinical endpoint, primary endpoint is the BIRC review PFS by independent radiology assessment.

And here, it was demonstrated in the primary endpoint by BIRC analysis PFS. fruquintinib plus sintilimab versus comparator really show very robust activity with a median PFS of 22 month versus 6.9 month of the axitinib or everolimus group. And it's highly with a hazard ratio 0.37 and has a very similar results for the investigator assessment. Also in terms of response rate by BIRC review and the investigator review, we can see over doubling of the overall response rate by sintilimab and the fruquintinib combo really showing this activity in this patient group with a very high unmet need. We have seen the 63% reduction in the risk of disease progression by the combo drug, really impressive PFS by central assessment, about 15-month difference. And so it's highly significant, very robust response rate. It's highly clinical meaningful. The NDA is currently under review by CDE. We're expecting approval next year.

Also, we are conducting the Phase II/III first-line pancreatic cancer trial. Surufatinib and the camrelizumab, which is [indiscernible] PD-1 along with the standard of care gemcitabine plus nab-paclitaxel versus gem versus nab-paclitaxel. So the Phase II results will -- has been accepted by the ESMO Asia. So we'll present this top line data in the ESMO Asia meeting in December. On the savolitinib side, the MET -- SAVANNAH study by AZ presented data at ELCC in March in Paris, showing the high response rate of 56% and 55% by the BIRC review. And METex14 skipping patient population, we also presented our confirmatory Phase III study at ELCC and really showing very impressive overall survival for the second-line, 25 months and first-line, 28 months in ELCC. Clearly demonstrate this is one of the longest overall survival has been reported among all the MET inhibitor in METex14 non-small cell lung cancer setting.

SACHI data really provide a future growth. The OSI+SO really showing the clinical robust activity was presented as a oral preliminary presentation at ASCO and the manuscript has been accepted to be published in Lancet. We are looking forward the SAMETA trial in the PRCC, the savolitinib with IMFINZI versus SUTENT. So this trial has been recruited. The readout will be next year. And also AZ lead the SAFFRON study also has reached the enrollment target. And we expect a positive -- we expect the results next year. If positive, this will really be hopeful for our second molecule can go to the global NDA. And in China, for this SANOVO study, first-line OSI+SO MET amplified overexpressed patient enrollment is completed and we are really hoping for the readout later.

On the gastric cancer in MET-amplified patients, we also will have the potential to submit NDA. The next molecule is an EZH2 inhibitor, tazemetostat. It -- we have conducted a bridging study, really showing a very consistent study compared with the global trial, Ipsen trial and really showing a robust complete response rate of about 18% and 63% overall response rate and very high percentage of clinical benefit rate. So the drug has been approved. We are further conducting along with our partner, Ipsen, to conduct a global SYMPHONY-1 trial. And this is the tazemetostat in combination with R square, rituximab and lenalidomide and versus placebo with R square. And we are very happy that China wild-type patient has completed the enrollment. And this global trial will not only move the -- if positive, will not only move the tazemetostat to the second line but also has the potential not only in the mutant patient population but also the wild-type patient. So our partner and Ipsen and HUTCHMED are really working towards the full recruitment for this patient group.

Fanregratinib is the FGFR2 inhibitor. And we have previously agreed with the CDE and using the single-arm registration to -- in order to potentially have their conditional approval in this registration cohort in the 2 week on/1 week off schedule, 87 patients were recruited. And so we are expecting the data readout and if positive, we'll file the NDA this year. Sovleplenib is the Syk inhibitor and we first report our ESLIM-01 result at EHA and really showing a very robust or durable response rate of 48%. And last year, we showed the follow-up long-term study demonstrated overall response of 81% and durable response for 51% and has very fast [ on-site ] to increase the platelet. And also unlike the TPO-RA, which also stimulate the platelet production but also has the opportunity to overshoot.

So TPO-RA has a potential for [indiscernible] thromboembolic events, which in the ESLIM-01 study for sovleplenib, the thrombocytopenia is -- thromboembolic event is not a safety concern. So it has a highly differentiated clinical activity and safety profile. We know we reported earlier this year, right, the -- although the previous NDA was delayed through a impurity issue but we have reached agreement with CDE, really defined the intake level and we are continuing to conduct a stability study, bioequivalence study with this new formulation. Our targeted resubmission is in the first half of next year.

And also, we have completed the enrollment of our Phase III ESLIM-02 trial in wAIHA autoimmune hemolytic anemia and we are potentially with the readout next year and if possible, the submission in China. And the -- here's the Phase I data we have shown in the wAIHA patient population -- in previously treated wAIHA patients, we have demonstrated overall 66% overall response rate and also the 47% the durable response rate and really showing the highly robust activity for the Syk inhibitor, not only in ITP but also in wAIHA patients.

So I gave you an overview of the ATTC platform and also the -- our late-stage pipeline advancement. So to summarize, so for today and beyond, we are really striving for global commercial success. And our partner, Takeda, really showing the fruquintinib global sale first half of this year really increased by 25% to $162 million, showing robust growth. ORPATHYS or savolitinib with our partner, AstraZeneca, we have the potential to really -- if the SAFFRON data is positive, will be our second molecule [indiscernible] potentially registered internationally. And ELUNATE is, fruquintinib is continue to grow with the new indications with the endometrial cancer approval will certainly will help the commercial launch. And also with the new RCC trial, we hope the fruquintinib plus sintilimab in the RCC trial will receive the approval in the next 12 months. And SAFFRON, of course, SAFFRON and SAMETA led by the AZ development will all have Phase III readout next year. And if positive, will potentially strong catalyst for the company.

And surufatinib PDAC in combination with PD-1 and chemotherapy will have the data readout. And again, the FGFR inhibitor, fanregratinib and also the Savo GC in gastric cancer with the MET amplified patient will have -- all have the potential for NDA submission. And more importantly, looking for the future, we are thinking our next-generation technology platform, antibody target therapy conjugate, ATTC profile has a huge potential. And we have multiple selective candidates currently at the -- enter -- will enter the clinic. And the first is already reached the IND clear in the U.S. And also with the company has a strong balance sheet and also relative small market cap, we think our future potential is really have a great opportunity. And along with our robust cash position, certainly, we are continue to looking at in-licensing and out-licensing opportunity. So hopefully, our effort and advancement can be appreciated in the investment road and really leading to long-term growth and generate value for our shareholders.

So with that, I'll just wrap up and opening for questions.

Okay. Thank you, Dr. Shi, for the detailed analysis. [Operator Instructions] The first question comes from Alec Stranahan from Bank of America.

Really great to see progress across the pipeline. I guess first on the ATTC platform, how important is it for you to really drive monotherapy efficacy in your molecular design of your ATTCs versus, I guess, optimizing safety to align it with frontline combo opportunities, especially when we're talking about assets like A251 that go after broadly expressed targets?

Yes. Thank you, Alec. Yes, it's a very good question. So for us, right, of course, the traditional development is really try to see some activity in the late-stage setting. So that's why we enrolled patients with -- previously treated patients. And our belief it is in the target patient population, for example, HER2+ and with the PAM altered or nonaltered patient, we will expect to see the activity. Certainly, we explore multiple cohort in the late-stage setting if we have defined the patient population could have a more robust activity, could certainly lead to the potential accelerated registration approval. But the main difference here for the ATTC, for A251 example, is what we consider is the opportunity to really advance to the frontline. And we have demonstrate multiple model, have synergistic activity with the traditional chemotherapy or standard of care therapy.

And a lot of these toxin-based ADC really have difficulty to combine with other chemotherapy. So that's why we think this is a advantage for us. And also, this is a unique opportunity to really take on this combined U.S.-China trial, right, to really simultaneous development to advance our pipeline because, as you know, the FDA is really encouraged the earlier line development, right, instead of just the frontline setting -- late-line setting because through this project frontrunner activity. So we think even at the -- when we have the dose escalation and even we have this [indiscernible] design with a backfill strategy to expand the dosing. Once we see activity or certain signal, we will have the opportunity to start a combination study and soon to really advance this development because our hope, we have shown this -- the combination, not only with the chemotherapy and some -- even the model with toxin-based ADC also shows synergistic activity.

So the key driver for this ATTC platform is really moving to the early line and to compete with the standard care. In combination with the standard of care versus standard care, we think that will be the future growth driver. And as you know, even the toxin ADC has a lot of efforts to combine with chemo but the data really from the safety profile, discontinuation, combinability really show strong limitation. So we believe that's where we can compete in for the tumor type because this unique profile for this ATTC platform.

Okay. Okay. That makes sense. And I guess one on the frontline PDAC opportunity for surufatinib. I guess, what do you sort of see as the bar for efficacy in the Phase II readout in December in combination? And I guess, how should we be thinking about the activity of surufatinib here versus PD-1 alone, given the control arm only includes gem/nab-paclitaxel?

Yes. So we are looking quite some historical data, right? Because pancreatic cancer is highly fibrotic and is usually considered as a immune desert. So PD-1 plus chemo alone, right, really haven't shown very robust activity. And from our perspective, the surufatinib is not only a VEGF inhibitor, it's also inhibit CSF1R and FGFR, really has a very strong potential through our early study. The initiation is a Professor [indiscernible] trial with the PD-1 and surufatinib combo with different chemo regimen and showing the ORR rate is about -- over 50% and compared with standard of care about 25%. And in particular, the ORR reported at ASCO GI earlier this year, showing the OS benefit is really beyond 12 months, right, about 15 months.

So that's what we think not only for the PS side -- PFS side but OS side, this combination has a unique advantage compared with the chemo alone or chemo plus PD-1 alone. So the bar, we think, right, is if you compare with the gem/paclitaxel and the -- usually the overall survival is very short, like 9 months or so. So I think with over a year OS, with the robust PFS, we think this combination really show pretty impressive opportunity from the early phase data. So again, the data presented will really show how we evaluate the bar. You will see this soon. And that will really define what is the bar we want to overcome to lead to the Phase III.

Next question from Goldman Sachs, Khalil Fenina.

This is Khalil, calling in for Paul Choi. I guess a couple of quick questions from us. One on the earlier-stage ATTC program and one on the later-stage pipeline. I suppose starting with ATTC, you've identified prostate cancer as the second largest commercial opportunity here in the longer term. And just given the emergence of nuclear medicine in the space, I'm just curious like in your view, do you envision perhaps running a study in like Pluvicto experienced patients to see if those types of agents amplify PAM at all? And then the second question is just on ITP. You mentioned looking to further develop it ex China. Just curious what the status was on that.

Yes. Thank you, Khalil. For the prostate cancer, right, because what we think this, the payload targeting PI3K/PIKK has very broad opportunity really against in multiple tumor types. And so we think, at least from a development perspective, we have very many options where to go to. And certainly, we'll probably choose a few tumor type through the company, see what is the late-line setting will -- readout will be and also start a combo study to really get the clinical evidence-driven kind of a development plan, right? Because certainly, in the nuclear medicine, evolving nuclear medicine, certainly, I see the Pluvicto data is quite impressive. And -- but in terms of future development, we probably will have to see how the expansion cohort readout and where the strongest evidence or opportunity will lead us to guide our future development plan.

Certainly, prostate cancer is on the book but we have to look at how the data readout in many tumor types to really make the decision for the early line development in the future. In terms of sovleplenib and so we have quite communication with the CDE because it was submitted and under review because we reported early this year, we certainly have reached the -- mutually agree that the [indiscernible] limit, right, to be acceptable. And in order to accomplish that, we have to kind of change the new formulation. And through this, we're going to work on the BE study and also with the stability testing to really satisfy the requirements. So the targeted resubmission is early next year. And so this is -- we think with this clear agreement guidance, I think we have a path for the sovleplenib in China, not only for the ITP but also with wAIHA when it's readout earlier next year.

So in terms of global development, we believe this newly agreed -- I mean, this agree with the limit actually with the CDE is the most kind of industry standard, including the global FDA, EMA is [ agreedable ] intake limit. So I think that formulation will certainly satisfy the global development for this product for a global potential. So I think that really opened our store. Again, we mentioned we paused the U.S. and EU development just really because of this issue. But now I think we are in a position to really looking at international development. As you can see in the ITP study, at least, for example, the ESLIM-01 data is show -- clearly show a highly durable response rate. And the long-term exposure demonstrate a sustained platelet increase and a durable response compared with all these existing product of -- including a new one, right, the FcRn with the [indiscernible] and all these activity, we think Syk inhibitor really representing a probably best-in-class modality to really in this patient group.

And because ESLIM-01 data is really heavily pretreated patient, they filled all the first line and also the 75% of patients filled the TPO-RA. And so certainly, in the heavily pretreated patient, we can see this most robust ORR really showing this as a opportunity. Certainly, we will reposition and really thinking what is the fast track for the global development. And in parallel, I think we can reengage some of the discussion with the partner and to really leverage this molecule's unique -- because this dual mechanism inhibiting the, engulfing the platelet or red blood cell and also the blocking the B-cell activity. So these are certainly a strong clinical evidence activity. We think this -- with this newly developed formula, it certainly have a pretty good opportunity to be further developed globally and open the door for discussion for future partner. Yes. Also, by the way, we're going to present our long-term, the final ESLIM-01 data at ASH. It has been selected as a oral presentation. So I think it will reignite the interest for sovleplenib.

Next question comes from Jefferies' Clara Dong.

I appreciate putting together this very informative presentation. So 2 from us. So maybe can you broadly just talk about how the programs developed through your ATTC platform will complement your existing commercial and late-stage initiatives and how kind of this integration will support your long-term strategic vision? And how do you prioritize your indication selection for those programs? And then also given the novelty of the ATTC platform, would you be able to share any color in terms of what's the bar for safety you're looking for, for the very first ATTC candidate?

Yes. Thank you, Claire (sic) [ Clara ]. And they -- for ATTC, right, I think just really leverage our traditional HUTCHMED small molecule expertise, right? For target therapy, we really work on the linker and the payload to really have a opportunity to generate this molecule and platform because from antibody selection to the target therapy payload selection really provides some good opportunity. So I think the first wave of development, of course, we are really science-driven, target-driven and thinking where the development will really leading to not only the highest clinical potential proof-of-concept and clinical success but also the development path will synergize with our expertise traditionally, as you can see, is the GI cancer, lung cancer, for example, right? So with the further development and with the antibody, with the target payload selection, really, I think we have many, many opportunity, many different type, which just really cover a very broad range of tumor type.

So the development probably will focus initially in the area we think we have a strong interest to be further developed. And of course, it's data-driven, science-driven but also if it's proven to be successful, right? And so far, you asked about the bar of the safety or so at least from the preclinical data, we really see this platform and overcome some of the traditional limitation for small molecule for systemic exposure because as the example that I show you for A251, right and in the GLP tox study, we don't see this hallmark for the PI3K small molecule inhibitor. And for example, hyperglycemia, myelosuppression or so. So just from preclinical data, we know because this selected target delivery of the ATTC into the tumor cell and the very low exposure of the small molecule payload in the circulation, really demonstrate the safety margin compared with the systemic exposure for small molecule. So we think the safety level really from the preclinical data really show us this is have a substantial increase from the traditional small molecule approach.

And the combination with all the multiple target development, multiple antibody development, we think it really generates a unique platform. So to just give you some color, I think our next wave product, right, after this proof of concept for the first wave molecule, certainly, there are more innovative molecule on the way, including bispecific ATTC and probably more do payload kind of the ATTC also in the research stage. So I think this will represent huge opportunity for our platform. And of course, there are only limited resource. We have to focus on area where we expertise to really develop fast proof of concept. And certainly, with the future potential partnership, we certainly think they can really broaden the indication, broaden the development because these -- all these molecule have potential targeting broader tumor type, high-frequency driver mutation overcome the resistance. So the opportunity is really quite huge from our perspective. So will be the focus of our company's new effort for these globally competitive first-in-class assets.

Our next question from Cavendish, the -- Adam McCarter.

Really interesting. So I guess the first question I have, the safety data for A251 looks really encouraging, as you say, Dr. Shi, particularly the absence of the elevated blood glucose levels. So you mentioned that this may relate to the compounds targeting ability, which is helping to limit systemic toxicity. But could you elaborate on whether you're seeing differential inhibition across AKT isoforms and tumor cells? Some of the tolerability issues seen with earlier pan AKT and PI3K inhibitors have been linked to the AKT2 inhibition. So it would be useful to understand how A251 compares mechanistically in that regard.

Yes. Thank you, Adam. Yes, also very good question. Of course, we're actually looking at these -- all these potential PI3K/AKT pathway inhibition, right? So in short, right, because we do see the free payload release in the plasma is actually quite low. If you calculate from that exposure curve, the free payload itself is actually showing pretty much less than 1,000fold or even higher kind of a differentiation. And pretty much all these free payload concentration we have seen is well below the IC50 level to reach the target inhibition. So that's why we do see the safety profile margin. And also through monitoring, right, is we understand -- is because the dose we select for the tox study, we really monitor the threshold.

So we can see the certain, I would say, on-target kind of the AE profile, it's reversible, it's dose dependent. So that's why we feel this ATTC provide a very safe window for future development. So hopefully, certainly, we hope this will be represented in the human study, right? So really looking for the first-in-human study and how the safety and the activity will pan out. If it is clinically proven, I think they will represent multiple huge opportunity, right, for the next wave of product we are developing.

That's great. And if I could just ask a second question. So you've highlighted that your ATTC platform differs from the standard ADC approaches. Just wondering if you could expand on the competitive landscape here. Are there many others pursuing this targeted therapy payload strategy with similar design principles? Or is your approach relatively unique at this stage?

Yes. I think this -- the field is really evolving very rapidly, right? I think all the scientists really thinking about different way, right? You can -- there are different approach, right? Even you see this -- the most recent example, right, Innovent is linking the immunotherapy with the target -- in the antibody, right? So certainly, I wouldn't say the competitors won't invest or develop in this area. But I think we are also in a very strong position because HUTCHMED is really have a long-standing, right, small molecule expertise. I thought our strength is really in the linker and the payload. And also, we have really working in multiple target therapy development areas. So I think with a deep understanding of biology, coupled with the strong medicinal chemists and new -- newly more innovative novel antibody or bispecific antibody, we think we are in new -- I mean, very strong position to really leading and innovate in this field.

Since there's no more question, this will be the end of this presentation and our R&D Day event. Thank you again for joining us and we wish you a wonderful day. Bye-bye.

Thank you.

[Statements in English on this transcript were spoken by an interpreter present on the live call.]