ARCA biopharma, Inc. Stock

Thank you for standing by. My name is Kate, and I will be your conference operator today. At this time, I would like to welcome everyone to the Oruka Therapeutics presentation of Interim data from EVERLAST-A. [Operator Instructions]

I would now like to turn the call over to Alan Lada. Please go ahead.

Thank you, operator. Please note that during this call, we'll be making forward-looking statements related to our current expectations and plans for the company and our clinical programs. These statements represent our views as of this call are subject to risks and uncertainties such as the final data from the Phase IIa clinical trial not being consistent with the interim data presented today, regulatory feedback regarding the company's planned clinical trials and other risks covered in our SEC filings. These forward-looking statements should not be relied upon as representing our views as of any date in the future. Please review carefully.

I'll now turn the call over to our CEO, Lawrence Klein.

Thank you all for joining us this morning as we announce interim results from EVERLAST-A, a study of ORKA-001, our extended half-life IL-23p19 inhibitor in moderate to severe plaque psoriasis. I'll start with a quick overview of Oruka and our goals for 001, and then our Chief Medical Officer, Jo Goncalves, will walk through the safety and efficacy data from EVERLAST-A. After that, I'll wrap up with a few closing thoughts on the opportunity we see with this program, and we'll open it up for questions.

Before I get started, I want to sincerely thank EVERLAST-A patients, their advocates, the investigators in our study and our team at Oruka, all of whom have gone above and beyond to get this study off to a great start.

So at Oruka, our mission is to advance the standard of care in psoriatic disease, and we have an aspiration that we might change the treatment paradigm. Our pipeline is anchored on 2 co-lead programs, 001 and 002, that we believe can set a new standard in these indications. Each of these are extended half-life monoclonal antibodies that target what we believe are quite clearly the best targets for psoriasis, IL-23p19 and IL-17A/F. These 2 programs apply best to fairly nonoverlapping subsets of a very large indication space. ORKA-001, we envision as a potentially annually dosed option for patients with predominantly skin psoriasis. And ORKA-002, we think can be a twice-a-year regimen for patients who have concurrent joint disease or psoriatic arthritis and potentially the first quarterly dosed option in HS or hidradenitis suppurativa.

Both of these programs are now in Phase II. 001 is in 2 parallel Phase II studies in plaque psoriasis, EVERLAST-A and B. And 002 has started its psoriasis Phase II and is anticipated to enter the clinic for HS in the second half of this year. Today, we're going to primarily focus on EVERLAST-A and the data up to the primary endpoint from the study at week 16.

So psoriasis is a very important disease area due to its high prevalence and impact on quality of life, and it's one of the largest commercial markets for pharmaceuticals at over $30 billion in total sales today and growing. There's been a thinking that the final answer in psoriasis treatment might be a highly effective oral medicine and major investments have recently been made toward that goal. However, orals have consistently failed to reach the disease clearance rates offered by the best biologics, and it's our belief that we can offer something potentially better with ORKA-001 and 002.

We think that most patients would prefer a once to twice per year biologic regimen with very high efficacy over a frequently administered oral. We've seen this biologic preference play out continuously in this market. And again, it is being validated by BIMZELX, which is projected to be another $5 billion to $10 billion mega blockbuster biologic in this field. Today, we'll focus on ORKA-001, but we're thrilled to have a long-acting IL-17A/F antibody with a similar mechanism of action to BIMZELX coming close behind in our ORKA-002 program.

Today, we will be presenting interim data from our EVERLAST-A psoriasis study of ORKA-001, an ultra-long-acting IL-23p19 inhibitor. I'm not going to steal too much of the thunder from Jo here, but I think it's safe to say that what we've seen so far has been quite remarkable. We think that 001 is showing an efficacy profile that could be best-in-class and on par with BIMZELX with clear potential for annual dosing and a safety profile consistent with the very high tolerability of the IL-23p19 class.

The headline figure from this data set is a 63.5% rate of PASI 100 or fully clear skin at week 16. This is unprecedented efficacy for an IL-23 inhibitor. And combined with the potential for annual dosing, another feature never achieved before in this indication, we think this could be a category-winning profile.

I'll hand it over to Jo at this point to take us through the data set in more detail.

Thanks, Lawrence. The results we will be reviewing today are 16-week interim data from EVERLAST-A, which is a double-blind, placebo-controlled Phase II study of ORKA-001 in moderate-to-severe psoriasis. EVERLAST-A is a rigorously designed study intended to enable a robust assessment of ORKA-001's potential in this indication. The study enrolled 84 participants with moderate-to-severe psoriasis from 26 sites across the U.S. and Canada, all of which have substantial experience in psoriasis clinical trials, including trials of approved therapies.

The inclusion and exclusion criteria used in this study were intentionally aligned with those of prior studies with IL-23 inhibitors to facilitate appropriate cross-trial comparisons. Importantly, the clinical trial population in psoriasis has remained consistent over time.

As a reminder, EVERLAST-A uses an innovative study design to evaluate the multiple ways in which 001 may offer a differentiated treatment option in psoriasis. In this study, we are assessing a single induction regimen of 600 milligrams of 001 administered subcutaneously at week 0 and week 4, at least 4x higher than the induction dosing of market-leading IL-23 inhibitors. This dose was selected based on evidence in the literature suggesting that higher exposures of IL-23 inhibition may lead to higher efficacy at week 16 and beyond.

Importantly, these dose levels and exposures remain well below those used in inflammatory bowel disease where safety and tolerability is similar to psoriasis, further supporting the favorable safety profile of the IL-23 class. All participants have now reached the week 16 primary endpoint with no discontinuations. And these data are the focus of today's presentation. Participants were randomized 3:1 to receive ORKA-001 or placebo, and the primary endpoint was PASI 100 at week 16. This is the first time that PASI 100 is being used as a primary endpoint in the Phase II psoriasis study. Prior biologic studies have typically used PASI 75 or PASI 90. However, we believe that achieving complete skin clearance should be the targeted therapeutic goal for patients as data demonstrated quality of life improvement at PASI 100 versus less stringent endpoints.

The study is ongoing and at week 28, participants will be assessed based on the PASI 100 response. Those who achieved PASI 100 at week 28 will be rerandomized in a 2:1 ratio to either a treatment-free arm in which participants are not dosed until disease recurrence or to a Q6 monthly maintenance dosing, the shortest potential dosing interval. The no dose arm will give us an indication of the potential for once yearly dosing and will evaluate whether 001 induction can lead to long-lasting duration of skin clearance in a subset of patients with a potential for off-treatment disease remission. We plan to provide a second update on longer-term data from this study in the second half of this year.

Meanwhile, placebo participants have passed over to active drug at week 16 and will progress on to a 12-month dosing regimen as part of the open-label extension, which will allow us to gather additional data with 001 as a once daily maintenance dose. Overall, EVERLAST-A provides multiple different ways to demonstrate differentiation with ORKA-001, including ultra-long dosing intervals, the potential for greater efficacy and long-term off-treatment disease remission.

The baseline characteristics in EVERLAST-A are shown here. The enrolled population was overall very similar to that in prior studies and the placebo treatment arms were well balanced with that expected variability due to sample size. A few variations versus prior studies are worth noting. The 001 group was towards the higher end in terms of the percentage of patients with severe disease or IGA 4. Meanwhile, weight, baseline PASI and percentage of patients with prior biologic use was slightly lower than prior study populations.

Notably, correlations between these characteristics and efficacy endpoints have been weak in subgroup analysis of prior studies, and we will show some analysis from EVERLAST-A, which shows similar results. Overall, we view this patient population to be readily comparable to prior studies in terms of expected efficacy.

Turning now to efficacy. I'll start with our primary endpoint, the proportion of participants achieving PASI 100 or clear skin at week 16 as assessed by nonresponder imputation. Out of the 63 participants treated with ORKA-001, 40 the primary endpoint, representing 63.5% of participants. In the placebo arm, a single participant out of 21 was assessed with PASI 100 at week 16. The p-value on the primary endpoint was less than 0.0001. The IGA 0 assessment was identical to PASI 100 for all participants. Both IGA 0 and PASI 100 indicate complete skin clearance with no signs of psoriasis and the alignment is important for ensuring rigor as well as consistency in investigator assessment.

Consistent with these high rates of complete skin clearance, we observed high response rates across various less stringent endpoints of efficacy. 52 out of 63 participants or 83% achieved PASI 90 at week 16. One placebo participant achieved PASI 90, the same individual with PASI 100. Across additional endpoints of absolute PASI less than or equal to 1, IGA of 0/1 and PASI 75, we observed high rates of efficacy in the active arm and low rates on placebo. Later Lawrence will put these results into context of what has been shown with other treatments in psoriasis. These are highly encouraging data that suggest that ORKA-001 has a differentiated efficacy profile.

Historically, baseline characteristics have had limited impact on efficacy. We've observed the same in EVERLAST-A. Shown here is an assessment of the impact of weight, baseline PASI and IGA scores and prior biologic exposure on week 16 PASI 100. In the case of baseline PASI and IGA severity, efficacy was similar in each subgroup. Higher body weight patients showed slightly higher rates of PASI 100, which could indicate that exposures on ORKA-001 have reached the effective plateau of efficacy where body weight no longer contributes to exposure response. Participants of prior biologic use actually had slightly higher efficacy than the overall population, which is largely attributable to the limited [indiscernible] that subgroup. Overall, these data indicate that small variations in baseline are unlikely to contribute to the high efficacy seen in EVERLAST-A.

In terms of safety, ORKA-001 has been well tolerated with a profile comparable to placebo and consistent with other IL-23 inhibitors. The overall incidence of treatment-emergent adverse events was similar across the groups with 50.8% of participants reporting an event on 001 and 57.1% on placebo. Most events were mild in nature and none led to discontinuation. There were no serious adverse events. There was one severe adverse event, a bone fracture and dislocation, which occurred on placebo. The only treatment-emergent adverse events occurring in 5% or more participants in either group with upper respiratory tract infection, which was well balanced between treatment and placebo. It's worth noting that the study was conducted during peak respiratory virus season in the U.S. and Canada.

Notably, there were no infection site reactions reported for over 200 injections of ORKA-001 and no evidence of an ADA effect on safety, efficacy or PK. Overall, these results are as expected with a favorable safety profile of the IL-23 class and support a very promising profile for ORKA-001.

The EVERLAST-A study is ongoing, and we are planning another data update in the second half of the year that will include all participants through week 28, a time point that could demonstrate further deepening of response. In addition, we plan to share data on a portion of the cohort of week 52, which could show the potential for annual dosing. In parallel, EVERLAST-B dose-ranging study is enrolling rapidly, and we anticipate a 16-week readout next year. Overall, we are tremendously excited by the emerging profile of ORKA-001.

I'll hand it back to Lawrence now to help put these results into context.

Thanks, Jo. I think it's safe to say that these are some very remarkable data. Putting them in context, what you'll see here are cross-trial comparisons of EVERLAST-A efficacy results next to approximately 15 prior studies with the leading IL-23p19 and IL-17A/F inhibitors. These are $5 billion to $10 billion products today or in the making. And across every metric, ORKA-001 shows higher efficacy than the rest of the IL-23 class. Most importantly, on PASI 100 or complete skin clearance, we have a roughly 20 percentage point delta to SKYRIZI historical results and over double the response rate seen with ICOTYDE, an oral IL-23 inhibitor that recently launched and is expected to be yet another multi-blockbuster product in this area. 001 appears to have 16-week efficacy on par with BIMZELX, which to date has set the ceiling on efficacy in psoriasis.

We also note a very high percentage, 76% of patients with absolute PASI less than or equal to 1. These patients are very nearly clear at week 16 and could have the potential to reach full clearance at week 28. Together with once to twice per year dosing and the clean safety profile of IL-23p19, this level of efficacy could be category winning.

Now because EVERLAST-A started last summer, we'll need to wait until later this year for direct evidence of 1-year durability. However, we're very encouraged by what we're seeing in terms of the PK from the molecule. This is updated data from our healthy volunteer Phase I study, which has now completed its full 52-week follow-up for all subjects. What you can see is highly consistent PK continuing to reflect an approximately 100-day half-life. And when we look at the 600-milligram dose, the mid-dose level here, you can see that antibody levels stay well above the trough for other approved IL-23 antibodies through the full year duration. This is highly supportive of the potential for annual dosing since this level of antibody in the serum should be sufficient to maintain disease clearance. Updated PD biomarker data from the study also supports this, showing suppression of IL-23 signaling out to a full year at the 600-milligram dose. At this point, we believe it's quite possible that many patients could maintain response with annual dosing of 001.

ORKA-001 showing a 63.5% PASI 100 rate at week 16 and the potential for annual dosing could represent a step change in the profile of psoriasis therapeutics. This is a market where successive waves of incremental innovation have yielded multiple $5 billion to $10-plus billion franchises. And against this backdrop, ORKA-001 could represent an even bigger step forward. We think this program has tremendous potential to deliver value to patients and reward all of Oruka stakeholders.

Now bringing it back to the full picture for the company, I want to remind you again that this is just our first program. And our co-lead, ORKA-002, is now in Phase II as well and could be an extremely valuable asset in its own right based on the success that BIMZELX is having in both psoriatic disease and hidradenitis suppurativa. We have a great cadence of upcoming readouts across the EVERLAST programs and the ORKA-002 studies over the next couple of years with meaningful data updates expected to come every 6 months or so.

We are well funded with runway over 1 year beyond at least 3 of these readouts, a longer-term update on EVERLAST-A, EVERLAST-B data next year and our ORCA-SURGE data in psoriasis, which will also come next year. Based on the data shared today, we are charting a fast path for 001 toward BLA. Psoriasis programs can move quickly through the clinic, and we think we can potentially set a new record with 001.

I'll now open it up to questions.

[Operator Instructions] Your first question comes from the line of Alex Thompson with Stifel.

Congrats on the data. I was wondering if you could talk a little bit about your expectations for EVERLAST-B as well in the context of baseline characteristics here. How similar do you expect EVERLAST-B baseline characteristics to be to EVERLAST-A? I guess, you do anticipate BSA and PASI at baseline to be a little bit higher based on some of the contemporary or least not contemporary, more with some of the SKYRIZI studies historically?

Thanks, Alex, for the question. I think we would expect EVERLAST-B to be similar to EVERLAST-A. I think this baseline is quite similar to other historical studies in moderate-to-severe psoriasis. And in particular, if you look at the more recent studies, I think it looks very, very similar in terms of baseline.

The approach here is we had 25 sites that enrolled subjects in North America. These are very experienced sites. We used inclusion/exclusion criteria that are essentially identical to prior studies. And I think we got a patient population that reflects the current moderate-to-severe population out there. And then when you look at those baseline characteristics, they historically have not shown strong correlations with efficacy, and we haven't seen those correlations in our study either.

Your next question comes from the line of Yatin Suneja with Guggenheim Securities.

Congratulations on the data and the execution. Maybe just a couple for me. So first one is on this dose exposure relationship, right? So you clearly validated the dose exposure relationship. Could you then talk now a little bit about the potential for driving remission? What does that look like? What is that potential for you, which we don't see it with other molecules? So that's one.

Second question is on the ADA. Could you -- I know you mentioned that there is no impact of ADA. If you can sort of help us understand what the rate were that will be helpful. And finally, I think I see you are emphasizing yearly dosing a little bit more today than previously. Like what more you need to see before you tell us, hey, look, we have a yearly versus 6 months?

Sure. So thanks, Yatin. So on the first, I'll try to go through all 3 of those. So on dose exposure relationship, I think what we've seen here looks quite similar to what we've seen in KNOCKOUT. And I think any time you see something like that twice, you have more confidence that, that's a reproducible effect. And I think that gives us confidence that as we move forward through development, we're likely to see similar results.

I think on the second question, which was the ADAs. Yes, we haven't on any individual subject seen an effect of ADAs on, like we said, PK safety or efficacy. We are assaying for ADAs, and we have a very low rate of ADA positivity here, which looks very promising. And I think historically, IL-23 as a target has had very low rates of ADAs and in particular, very low rates of ADAs that had any impact on the metrics that matter.

And then in terms of yearly dosing, yes, I think if you look at the PK, it's pretty hard not to get excited about the 1-year potential just because the 600-milligram dose stays well above the trough level for IL-23s for the entirety of the year. And so that gives us quite a bit of confidence. I think you can never be fully certain until you see patients that are a year out from last dose and still have clear skin. And I think the exciting thing is that we're not too far from that. We started enrolling EVERLAST-A last summer. And so in just a few months, we'll have some of that data. And I think it gives you a lot to look forward to in terms of the potential here.

Your next question comes from the line of Tyler Van Buren with TD Cowen.

Congrats on the incredible data. So the PASI 100 figure on Slide 12 shows that the rate is going sharply up and into the right through week 16, and it suggests that the rate could continue to increase past week 16 in a meaningful way. So how are you thinking about the potential for increased PASI 100 rate over time here with a longer follow-up given the higher exposure and significantly longer half-life with ORKA-001 relative to on-market agents? Could the dynamics here be unique? And I have to ask the second question, so I guess I'll call it a follow-up. How quickly do you believe that you all can get to pivotal trial initiation with ORKA-001?

Sure. Thanks, Tyler. I can address both of those. Yes, certainly, we noted that as well that the slope of the PASI 100 curve looks pretty promising for later time points. I mean I think when you think about week 28, I think going into this, we would have been happy with the 63.5% clearance rate at week 28. So I think if that improves from there, that's going to be extremely exciting. We do look at that absolute PASI less than 1, which was around 76%. Those are people who have really minimal disease at week 16. So we're certainly hopeful that a good portion of those make it to full skin clearance by the later time points.

Again, I think it just gives you something to get excited about in terms of data sets that will be coming from EVERLAST-A. And then based on these data, I think even prior to these data, we were trying to chart the fastest path forward towards pivotal studies. I think based on these data, we're certainly going to be as aggressive as we can with that. The EVERLAST-B study, as you know, started enrolling last December. It's the 16-week data from that study that will really be gating in terms of having an end-of-phase discussion with the agency.

We are lining everything else up that goes into pivotal trial prep, CMC, clin ops, et cetera, so that nothing else is rate limiting. And we think we can go fast. Psoriasis programs have gone very quickly through development. I think if you benchmark us to those time lines, we're pretty confident we can go even faster. I think so far, we have been with 001. So I'm not going to put any more firm numbers on that yet, but rest assured, we're going to go as fast as possible.

Your next question comes from the line of Michael Yee with UBS.

This is Kyle Yang for Michael Yee. Congrats on the data. So the first question is, how should we think about the expectations heading into the 28-week data readout, particularly around early signs of durability. The second question is, based on your conversations with physicians, how do you expect docs to use this drug, assuming you could repeat this data set in further clinical studies?

Sure. Thanks, Kyle. So I'll take the first one, and then I'll let Jo comment on the second. I think we've certainly seen a lot of excitement. On the first, in terms of later-stage data and durability, I think the important thing to note is we'll have another readout in the second half, so not too far away, and that will have everybody at that 28-week endpoint. So you'll see how efficacy has matured to that point.

And then by that point, we'll have part of the cohort out to over a year since last dose. And we'll probably report on a partial cohort there or show the whole cohort at different time points. But to give you a sense of how long responses are lasting, I think if you see a dozen or so people out to a year and a good portion of them have maintained their response. That's going to give a lot of confidence in once a year dosing potential. So we're pretty excited looking forward to another readout on this study in a few months that could be really impactful and just continue to kind of build on the differentiated product profile we have here, which I would say has been extremely well received by the physician community. But maybe, Jo, you could comment on what we're hearing.

Yes. Thanks, Lawrence. So all along, the dermatologists have been super excited about ORKA-001 and the potential profile. As you know, IL-23p19 inhibitors are the drug of choice for dermatologists when it comes to just purely skin disease. And now with the data that we are showing that shows higher than other IL-23p19s, I think this is very compelling and dermatologists will be very excited now about this profile even more.

Your next question comes from the line of Sam Slutsky with LifeSci Capital.

Congrats on these awesome data. Just a quick one for me. Just based on these results, there's a few angles for development and commercialization that you could take with 001, whether it's a 6- versus 12-month dosing interval and then in-clinic versus at-home subcu dosing. Could you just discuss how these data in the Phase IIb might inform which of these permutations you'd include in the Phase III program? And then I know historically, most drugs do placebo-controlled studies in psoriasis, but any chance that you're thinking about potentially using an active comparator in Phase III?

Sure. Thanks, Sam. So yes, we're definitely doing a lot of work right now on the specifics of the Phase III plan. I think we can keep all of those options on the table and get data on all of them from a Phase III program. We envision a label that could have both a once a year and twice a year dosing option. I think even if it looks like a once-a-year drug for the vast majority of people, I think having a 6-monthly dose option for maybe people who don't get fully cleared is a nice feature. And so we think there's a pretty straightforward path we could take to enable both of those. At this point, we're fairly bullish on the once-a-year potential based on what we've seen.

I think in terms of comparator in the Phase III, we would probably include an active comparator. I think which active comparator you choose is still something that we're doing work on. Certainly, with data like these, it's hard to avoid the thought of could you go head-to-head against some of the best products out there. But I think that hasn't been necessary for approval or commercial uptake in these indications historically. And so we're going to take a prudent path there in terms of Phase III design.

Your next question comes from the line of Yasmeen Rahimi with Piper Sandler.

Congrats on the outstanding data. Maybe help us understand on the PASI 100 and PASI 90 scores, like sort of what the error bars look like, specifically around PASI 100. If you had some patients who might have been -- like was it pretty uniform as you went from week 4 to week 16? Were there certain patients that got a greater response? Was there anything unique about them? I appreciate if you could conceptualize that.

Sure. Thanks, Yas. I think generally, we had 63 patients in the active arm across 25 different highly experienced sites. I think the rate of PASI 100 that we've seen at the different time points, it's pretty remarkable how closely it matches what was seen in the knockout study if you just overlay those curves. And that's something that I think stood out to us. I think any time you see a result twice, you sort of assign a higher credence to that in terms of how robust it is. And we think it's biologically plausible, certainly, when you look at the exposure response that more antibody needed in the serum to fully saturate the target in the tissue, in the epidermis in all patients. And it looks like we have a very potent molecule and well tolerated with 001.

Nothing really stands out in terms of patient segments. And we showed some of that today, which would kind of be the subgroups that you would expect, and we set cutoffs where they were historically for SKYRIZI, so you could kind of compare those. There's, obviously, kind of endless subgroup analysis you could do. But on a Phase II study, I think that stops really being useful pretty quickly. I think this is a pretty -- this is a representative population and the efficacy that we're seeing looks very different than other IL-23s. And I'm, overall, just thrilled with the results.

Your next question comes from the line of Roger Song with Jefferies.

This is Fiona on for Roger. Huge congrats on the data. Just a quick one from us. Can you comment on the baseline population, the prior therapeutics use? And how does it compare to other trials? And any comorbidity with psoriatic arthritis?

Sure. Thanks, Fiona. So on prior biologics, the percent with prior biologic use was a little lower than has been seen in some of the prior studies. Other metrics were higher like severity, Jo mentioned on IGA score of 4. But prior biologics, in some indications, prior biologics can really seem to correlate with efficacy outcomes. That's not the case in plaque psoriasis. I mean you can look at multiple analyses of prior studies like, for instance, in the SKYRIZI Phase IIIs, the people with prior biologic use actually had a slightly higher rate of PASI 100 than people who are naive to biologics. And that's actually what we saw in our subgroup analysis as well. We think it's probably just small end that you see a difference there. And -- but really, I mean, I think historically, you wouldn't expect that population to behave any differently, and that's what we've seen here. And then the rate of PSA, concurrent PSA was in the range that you typically see.

Your next question comes from the line of Julian Harrison with BTIG.

Let me add my congratulations on these results. First, I'm wondering if the data here changed at all how you envision ORKA-001 and 002 coexisting in psoriasis. Is there maybe an updated long-term vision there or with ORKA-021? And then second, I'm wondering if you could talk about your general outlook for price stability in the psoriasis market. I think it's interesting that Stelara biosimilars entered the market early last year, but SKYRIZI still saw 50% year-on-year growth. So I'm just wondering if you have any thoughts on why step edits are not part of the picture here and probably won't be by the time ORKA-001 and potentially 002 enter the market as well?

Sure. Thanks, Julian. So these really don't change how we see 001 and 002 in the market. I think, generally, the treatment algorithm in psoriatic disease is pure skin disease. Docs want to use an IL-23 inhibitor because of its sort of exquisitely clean safety profile. And it's really patients who have concurrent joint disease or highly recalcitrant disease where IL-17 play the best role and IL-17A/F with BIMZELX is really proving to be the preferred strategy for that group of patients. And it's a large group, right? So concurrent PSA is typically 1/4 or so of patients with moderate-to-severe skin disease. So if you don't have a 17, you're sort of missing the right drug for 1/4 of the patients in a very, very large indication space. And then you've obviously got the additional indications like HS where that applies.

So we envision these 2 coexisting complementary in the market. That's what you've seen with BIMZELX. I don't think it's taking share at all from SKYRIZI. I think it's taken some share from Cosentyx and Taltz. So they're really sort of different subpopulations in what overall is a very, very large market.

And yes, I think we're encouraged generally. I think this is a market that has historically rewarded successive rounds of innovation. And I think what we have here looks like it could be a bigger step forward, I think, than some of the steps in the past. I think we see the excitement around ICOTYDE and its pricing in the market and the expectations there. And we think that new product will do great and likely continue to grow this market. And we think that what we potentially have in once to twice a year biologics with what are now looking like some pretty impressive efficacy figures. It would likely be preferred by the vast majority of patients. So overall, we're just excited by what we're seeing.

I think you mentioned step edits. I think in psoriasis, typically shows up in your 20s or 30s and then it's with you for the rest of your life. And so you see oftentimes people going on biologics have been dealing with the disease for 15 years or so. And so oftentimes, they step through whatever therapies are required and there's sort of a steady kind of pool of patients moving through that progression. And I think what we're excited about here is we think we could have really the option that most people want to get on, and we want to offer that as soon as possible.

Your next question comes from the line of Etzer Darout with Barclays.

Congrats on the data. Just wondered if you had any information you could provide on the median follow-up of the patients on EVERLAST-A and whether or not you can draw any comparisons on the exposures from the updated Phase I data that you commented on today?

Yes. So far, what we're seeing in the Phase II is very consistent with the Phase I. It's still early data, and so we want to let that mature a bit. But I mean, I think in the Phase I, it's pretty impressive PK, approximately 100-day half-life. And when you look at that 600-milligram arm, it's not really close to the median trough. And keep in mind, that's the median level, that 1.5 line on that graph is the median level for SKYRIZI right before patients receive their next dose. So there's half the patients below that line with SKYRIZI. And actually, on the Phase I, every single one of the individuals was above that line in that group. And so overall, I think just a high degree of confidence based on the overall PK that we're seeing in the potential for once a year dosing for at least the vast majority of individuals.

Your next question comes from the line of Andy Chen with Wolfe Research.

This is Brandon on for Andy. So it looks like ikztoza is still meaningfully above ixekizumab C trough by week 52. And we know annual dosing is in sight, but is there any confidence that you could achieve something even less frequent than annual dosing?

Sure. I mean I think once a year dosing in terms of a maintenance regimen is what we're shooting for. I think that aligns perfectly with the kind of visit frequency that physicians expect to have with moderate-to-severe psoriasis patients. We do have an open-ended arm in EVERLAST-A where we want to see if there's a proportion of patients that could go even longer than that, which would fit the definition in the field of off-treatment remission, which is over 1 year with clear skins since last administration of a therapeutic for psoriasis.

And every drug in psoriasis today is sort of a fixed-dose regimen for the rest of your life. I think the chance to offer off-treatment remission could be an additional very compelling differentiator and sort of gives us 3 different ways we could differentiate with this profile, very long dosing once to twice a year, greater efficacy and then really the first time ever to have the potential for off-treatment remission. So that's something we're excited about seeing as the data matures and then we'll decide how exactly that fits into how we want to position the drug once we get there.

Your next question comes from the line of Martin Fan with Wedbush Securities.

Congratulations on the strong data. Thinking about the speed of recruitment and the depth of response that we've seen so far, what are your thoughts on going forward with 2 trials versus 1 trial and current discussions with the FDA for the Phase III program?

Yes. So we'll really have those discussions once we have that primary endpoint data from EVERLAST-B. That will be the right time to really have that engagement. We certainly noted the kind of move by the agency towards willingness to accept a single Phase III. Really actually what makes the most difference in these indications is the size of the safety database that you need. If you need the same size safety database, sometimes there's really not that much difference between the cost and efficiency of a single Phase III versus 2 different studies and 2 different studies could maybe give you the option to do those in slightly different patient populations that could broaden the label.

So we're looking at different options there, and we'll have some really focused engagement with the agency once we have the right data set to have that discussion. But we think what's nice is there's a lot of options on the table. And the pivotal studies are something we think are very feasible for a company like ours to access the resources needed to execute on those.

I will now turn the call back over to Lawrence Klein for closing remarks.

Thank you, operator. Yes, I'll just thank everyone for your attention and interest. We're thrilled by these data and really excited to be looking forward to the next year or so at Oruka, another update on this study in the second half of this year, which I think could really build on the great results we're seeing here, the IIb data, which would then enable a rapid Phase III start. And then 002 will start to be layered on to that. We're enrolling our Phase II psoriasis study right now and planning an HS study to start in the second half of the year. So just a lot of excitement over here at Oruka, and we'll try to keep these good results coming. I appreciate all your attention.

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.