ARCA biopharma, Inc. Aktie

Thank you for standing by. My name is Jordan, and I'll be your conference operator today. At this time, I'd like to welcome everyone to the Oruka Therapeutics presentation of interim EVERLAST-B data. [Operator Instructions] I would now like to turn the call over to Alan Lada. Please go ahead.

Thanks, operator, and good morning, everyone. During this call, we'll be making forward-looking statements related to our current expectations and plans for the company and our clinical program. These statements represent our views as of this call and are subject to risks and uncertainties, including the possibility that final or longer-term results may differ from the interim data presented today, regulatory feedback regarding our 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 the disclaimers in today's presentations and our SEC filings carefully.

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

Thank you all for joining us this morning as we share interim results from EVERLAST-B, our Phase IIb dose-ranging study of ORKA-001 in moderate to severe plaque psoriasis. When we presented data from EVERLAST-A earlier this year, we showed an efficacy profile that we thought could be a major advance for psoriasis treatment. Today, we're very pleased to share that our candidate showed highly similar results in a second independent study while also generating the dose-ranging data needed to support moving this program forward into Phase III studies.

I'll start with a brief overview and the headline findings. Then our Chief Medical Officer, Jo Goncalves, will walk through the study and the results. I'll come back to discuss what these data mean for 001 and our development plans, and then we'll open it up for questions. Before getting started, I want to thank the patients, investigators and study teams who have made this work possible.

At Oruka, our mission is to advance the standard of care in psoriatic disease. We think combining very high rates of disease clearance with much less frequent dosing can improve the treatment experience dramatically for patients. Our pipeline is anchored on 2 co-lead programs targeting IL-23p19 and IL-17A/F, mechanisms that we believe will remain the gold standard in psoriatic disease treatment and that are each suited for complementary segments of the patient population.

With our IL-23p19 inhibitor, ORKA-001, we envision a regimen with once to twice per year dosing and the potential for rates of response that exceed existing options. We'll share data today from that program that increasingly elucidates this profile. ORKA-002 is our extended half-life IL-17A/F antibody with potential for twice yearly dosing in psoriasis and psoriatic arthritis and quarterly dosing in hidradenitis suppurativa. 002 is now in Phase II in both psoriasis and HS with the first psoriasis results expected in the first quarter of next year.

We're encouraged by the continued success and adoption of the first approved IL-17A/F inhibitor, BIMZELX and believe that a long-acting option in the IL-17 class could be something very new and beneficial for patients. In addition, our pipeline now also includes ORKA-004, an extended half-life TL1A antibody that creates opportunities for combinations with both of our co-lead programs. Following healthy volunteer studies, we plan to initiate our first Phase II combination study with 004 sometime next year.

Today, the focus will be on EVERLAST-B and the week 16 results from that study with 001. The headline result for today is that the 600-milligram dose delivered 61% PASI 100 and 86% PASI 90 at week 16. Those results are highly consistent with EVERLAST-A. We now have 2 studies showing complete skin clearance in more than 6 out of 10 patients and an extremely high rate of PASI 90 or near clearance with a favorable safety profile consistent with the IL-23p19 class. The body of safety evidence continues to grow, and we have now dosed over 250 subjects and accumulated over 100 patient years of experience with ORKA-001, increasing our confidence in the profile we've observed.

EVERLAST-B also gives us the dose-ranging evidence we set out to generate. The 600-milligram dose produced the highest rate of complete clearance, and we plan to advance that dose into Phase III in the first half of 2027. Our vision remains an annual maintenance regimen with a 6-monthly option. The next important test of that goal is the week 52 EVERLAST-A readout coming in December. Taken together, we think today's data are a substantial step forward for the program.

With that, I'll hand it over to Jo to walk through the results.

Thanks, Lawrence. EVERLAST-B is a randomized placebo-controlled Phase IIb study designed to support Phase III dose selection and further evaluate ORKA-001 efficacy and safety in moderate to severe plaque psoriasis. The study was conducted at 36 experienced sites across the United States, Canada, Germany and Spain, fewer than 30% of the sites overlapped with EVERLAST-A. This provides an opportunity to evaluate the same high-dose regimen in a new group of sites with a broader geographic footprint and in the context of a dose-ranging study.

As in EVERLAST-A, the eligibility criteria were closely aligned with prior IL-23. Participants were adults with a PASI score of at least 12, at least 10% body surface area involvement and an IGA score of at least 3. High exposure to an IL-23p19 inhibitor was not permitted. These criteria allow us to study a population similar to those enrolled in the clinical development programs for established psoriasis therapies.

The study enrolled 187 participants randomized in an equal ratio across 3 active regimens and placebo. The high-dose group received 600 milligrams at week 0 and week 4, the same induction regimen evaluated in EVERLAST-A. The middle dose group received 300 milligrams at both time point and the low-dose group received 37.5 milligrams at week 0 only. All doses were administered subcutaneously. We deliberately studied a broad range of doses to understand the relationship between dose and clinical response. The primary endpoint was PASI 100 at week 16, which represents completely clear skin. We continue to believe that complete skin clearance is the most meaningful goal for patients and dermatologists, and it is particularly useful in distinguishing the performance of highly effective treatments.

Beyond induction, EVERLAST-B will also provide information on durability. Participants who achieved PASI 100 at week 28 are re-randomized equally to annual 600-milligram maintenance or to a group that receives no further dose until disease recurrence. Participants who have not achieved PASI 100 at week 28 received 300 milligrams every 6 months. The placebo group then crossed over to active treatment at week 16 with annual maintenance planned as part of the open-label extension. This design allows us to assess how long clearance persists after induction and also allows us to gather additional evidence on annual maintenance dosing on dosing every 6 months for those who may need more frequent dosing and on period without further treatment.

Today, we'll focus on the week 16 induction results. Baseline characteristics were broadly balanced across the treatment groups and typical of moderate to severe psoriasis population. Disease severity was also comparable to EVERLAST-A. So it is worth noting that the participants in the 600-milligram dose group in EVERLAST-B were on average 9 kilograms or 20 pounds heavier than the comparable group in EVERLAST-A and had a higher incidence of prior biologic use. Seeing similar results in these 2 patient populations increases our confidence that the efficacy results with a high dose are reproducible across different baseline characteristics.

Turning to the primary endpoint. The high dose group achieved the highest rate of complete skin clearance with 61% of participants reaching PASI 100 at week 16. In the mid-dose group, 44% reached PASI 100 and 43% in the low-dose group, while no participants on placebo reached PASI 100. IGA 0, which also represents completely clear skin was identical to PASI 100 across the groups, supporting the robustness of the assessments in the study.

For PASI 90, both the high and mid-dose groups achieved response rates in the mid- to high 80s, while the low-dose group was 70%. None of the participants in the placebo group reached PASI 90. IGA 0/1 response rates were similar to those for PASI 90 across groups. The high response rates across endpoints observed with the 600-milligram dose, together with the consistent results from EVERLAST-A and the safety findings, which I'll review shortly, support our plan to take the 600-milligram dose forward into Phase III.

The pattern of response for the 600-milligram dose showed remarkable consistency from EVERLAST-A to EVERLAST-B. As you can see in the slide, overlaying the response curves from the 2 studies, the trajectories track very closely through week 16 for both PASI 100 and PASI 90. That consistency is especially encouraging given the limited site overlap and the addition of European sites in EVERLAST-B, and it gives us confidence in the efficacy profile we have observed.

We also see similar results across other measures, including IGA 0/1, responses in the mid-80s and PASI 75 responses in the mid-90s in both studies. In each case, the response rate in EVERLAST-B were within a couple of percentage points of those in EVERLAST-A. The alignment across these endpoints further establishes the reproducibility of ORKA-001's efficacy profile as we move towards Phase III studies. In terms of safety, 001 was well tolerated with findings consistent with the IL-23p19 class.

In the pooled ORKA treatment group, rate of treatment-emergent adverse events severe treatment-emergent adverse events and serious events were comparable to placebo and none of the SAEs were considered treatment related. Notably, no dose-dependent trends were observed. The most frequently reported adverse events in participants receiving 001 were upper respiratory tract infections and headaches, occurring at rates comparable to those observed in studies of approved IL-23 inhibitors. There were no injection site reactions in any of the 001 group. And as a reminder, we saw 0 injection site reactions in EVERLAST-A as well.

Overall, these results support the favorable safety and tolerability of ORKA-001 that we have seen to date. The 600-milligram dose demonstrated the best benefit risk profile, and we therefore plan to advance it into Phase III. The next major ORKA-001 update will be the week 52 data from EVERLAST-A in December. Those results will help us assess how well the response persists over a full year and further support the potential for annual dosing.

Pending discussions and alignment with regulators, we plan to initiate Phase III in the first half of 2027 using the 600-milligram dose. We plan to release additional results from EVERLAST-B in the second half of 2027 once participants have completed week 52 of the ongoing 2-year study. We are very encouraged by the consistency of the results across these studies and by the opportunity to bring this profile into a pivotal Phase III program.

I'll hand it back to Lawrence to discuss what we believe this could mean for Oruka.

Thanks, Jo. Across EVERLAST-A and EVERLAST-B, more than 100 participants have now received the 600-milligram induction regimen in 2 independent studies with highly consistent results. Pooling those results gives us approximately 63% PASI 100 and 84% PASI 90 at week 16. That is a remarkable level of efficacy for an IL-23 inhibitor, essentially the highest level of efficacy ever seen in this indication.

The dose-ranging results give us a clearer basis for moving forward with 600 milligrams as our chosen Phase III dose. For Oruka, the importance of today's readout is the confidence it has in the 001 profile as we prepare for Phase III and the next assessment of long-term durability. Putting the results in context, this slide shows the EVERLAST studies alongside relevant trials for other IL-23 inhibitors, Skyrizi, Tremfya and the recently approved daily oral Icotyde. While we acknowledge the limitations of cross-trial comparison, what stands out is that both EVERLAST studies show an efficacy profile above the historical experience with prior IL-23 inhibitors and among the highest response rates observed for any mechanism in psoriasis.

On complete skin clearance, the separation from Skyrizi and Tremfya is roughly 20 percentage points. We also see a substantial difference on PASI 90. Compared with the daily oral option shown here, roughly twice as many patients achieved complete clearance at week 16. This is unprecedented efficacy for an IL-23 mechanism, particularly when it comes with the potential for once or twice yearly administration. It is becoming increasingly clear that ORKA-001 could offer a very compelling trifecta of disease control, safety and convenience.

Our body of experience with 001 continues to grow. We have now reproduced very high rates of complete clearance in 2 independent studies. On the tolerability side, we've observed a profile consistent with the IL-23p19 class and no injection site reactions across several hundred administrations. We have also seen no apparent impact of antidrug antibodies on PK efficacy or safety. The approximately 100-day half-life we've observed in healthy volunteers supports the potential for annual dosing.

The clinical durability data are the next piece of that assessment and December's readout will be our first look at direct evidence for annual dosing potential. We're preparing to move quickly into Phase III with the aim of bringing this treatment option to patients as efficiently as we can.

New and improved biologics in psoriasis have repeatedly become highly successful commercial products. Successive improvements in efficacy and dosing have created multiple franchises with annual sales of $5 billion to $10 billion or more. The product on this chart illustrate just how much value has been created by improving treatment for people with psoriatic conditions.

With ORKA-001, we think there's an opportunity for a substantial further advance. We've seen the potential for higher clearance rates than of the leading IL-23 therapies, and we are working towards a maintenance schedule as infrequent as once per year. We believe patients would find that profile extremely attractive. We also think it could be compelling for physicians who want to maximize disease control while reducing the burden of ongoing treatment. If we can deliver that combination, we believe that 001 could have a category-winning profile in a very large market.

Now bringing it back to the full picture for Oruka, we have several important milestones coming in close succession. The week 52 EVERLAST-A data are expected in December, followed by Phase III initiation in the first half of next year. In addition, we'll see the first Phase II results for ORKA-002 in psoriasis in the first quarter of 2027. 002 is also progressing in HS, and we continue to see substantial potential for that program across multiple indications.

Finally, we expect ORKA-004 to enter Phase I around year-end with combination studies expected to begin in 2027. Our cash balance of more than $1 billion at the end of Q2 is expected to provide runway through an ORKA-001 BLA filing, allowing us to pursue these plans from a strong financial position. We're very pleased with what EVERLAST-B has shown us thus far. We've reproduced a highly differentiated efficacy profile, added to the safety experience and generated the dose-ranging data to support the next stage of development. Thank you again to everyone participating in our studies and to all of you for joining us today.

With that, I'll hand it back to the operator, and we'd be happy to take your questions.

Your first question comes from the line of Yatin Suneja from Guggenheim Partners.

Let me add my congratulations. Very good results, clear replication of the data from 2 studies now. So a couple of questions for me, if I may. First one is regarding -- I mean, obviously, there is a lot of focus on the 52-week data. So I would love for you to maybe articulate a little bit about how should we think about the 52-week data going forward?

And then the second question is more around your Phase III program. I mean, given that the profile of 001 looks clearly superior, not only on convenience, but on efficacy, close to 20 point better. Is there a potential for doing some form of -- or conducting some form of a head-to-head study, whether it's Tremfya or Skyrizi? How do you think about that? And then obviously, the data look as good as an IL-17. And how does it sort of change your conviction or view on your second asset, 002?

Thanks, Yatin. So 3 parts there. We'll go through each of them. I mean I think with the 52-week data, today, we're just -- we're thrilled with the 16-week results and the reproducibility across 2 independent studies. I think it's really fantastic and speaks to a really important part of the differentiation we think we can provide with 001, really unprecedented activity in an IL-23 mechanism. We're excited that fairly soon now, we'll get some clinical data to suggest just how many patients can do well on a once annual regimen.

I think with the PK we've observed, we have quite a high degree of confidence that this can be a once per year administered medication for at least some percentage of patients. And the question will be, can it really be a once a year for essentially everyone with a 6-month option just to provide the flexibility? Or is it more of a once a year with a 6-month option for people who need it type of profile. When we look at the 52-week data, the arm from EVERLAST-A now that's going to provide the clearest evidence of that is the group that were clear at week 28 and then go forward with no additional dosing.

And there's benchmark data that you can look at to sort of say what is perfect maintenance in that group, which is around, we think, around 80% maintenance of those PASI 100s and then what is a range where you might have a once per year regimen with a 6-month option. And so we're very excited to be approaching that readout and really, at that point, I think, have a very full picture of all 3 legs of the stool of differentiation that we could provide with this asset.

On your second question, in terms of Phase III, that's something we're working on right now, and we're obviously going to engage with regulators to finalize Phase III plans. Choice of comparator is a very important aspect of that, and we will have plan to have an active comparator in that study. It's, of course, with results like these really exciting to think about potentially running it head-to-head against a leading IL-23p19 inhibitor. There's, of course, multiple different aspects that go into that decision, and it's really about maximizing the benefit and risk you're taking in a Phase III study. So it may not make sense to do something like that in Phase III, but that's something that we're working through, and we'll share more detail on that once we've discussed with regulatory authorities.

And on your third question in terms of 001 and 002, I mean, I think what we've seen here is efficacy that's essentially at the ceiling that's been reached in moderate to severe plaque psoriasis. And considering the amount of development that's been done in this disease, that's pretty remarkable in the type of profile we have. It really is on par, we think, with BIMZELX, which has sort of set that ceiling. It's, of course, a very different profile, an IL-23p19 versus an IL-17A/F play different roles in the indication space. We love the opportunity to have potentially both 001 and 002 available in psoriatic disease.

We think they ideally fit complementary portions of the patient population where IL-17s play their best role in individuals with concurrent psoriatic arthritis, which is a sizable segment of the population, 25% to 30% of people with moderate to severe skin disease. So we continue to see a fantastic opportunity for both of these product candidates in the psoriatic disease space, and we think it could be a huge strength to potentially have the best biologic for any patient with psoriatic disease. That's what we're trying to create.

Your next question comes from the line of David Risinger from Leerink Partners.

So let me add my congrats on the results. And I guess it would be helpful to just get a little bit more color on a couple of the things that were already discussed. So specifically, Lawrence, if you could talk about the range of possibilities for the 52-week results. And then second, I heard your comments on potentially having an active comparator in Phase III, but I thought that you previously said that, that wasn't necessary and was unlikely. So if you could provide some more color on that as well, that would be great.

Sure. Thanks, Dave. I'll take the second part first. I don't think we've ever said it would -- I think we've always said we'd have an active comparator. I think it's just a question of what that active comparator would be. And I don't think we've ever -- we haven't locked down our Phase III designs. We need to discuss with regulators. I think the decision there would be, do you run head-to-head against another IL-23p19 or do you run head-to-head against something that's, for instance, going to be biosimilar on the time line that we intend to launch?

I think there's different puts and takes in how you think about the benefit in terms of access and adoption versus risk of always having some amount of unpredictability in a head-to-head study like that and also the size and cost changes with how you'd have to power things. So that's something we're working through and it won't be too long before we share all the details on those designs in the future.

In terms of 52-week, I think we've been pretty clear on kind of viewing it as 2 categories where you could say if we see close to 80% maintenance in that no-dose arm of the PASI 100 and minimal disease in people who do see some fluctuation, that could be perfect maintenance essentially. That's on par with a frequently dosed maintenance regimen, what you see. That could be a once-year product for basically everyone. And we still would want a 6-month option on the label. We've always said that because this is a preference-driven market and having flexibility, we think, would be beneficial.

We do believe that there is a very meaningful window south of that where you would have a once-year product, a once-year medication, which keep in mind, there's never been a once annually dosed medication for a chronic immune disease. I mean we think that would be incredible to even have something like that available for the first time in an indication space like this. But a profile where you'd say this is a once a year product.

And then if you do need 6 monthly maintenance, we have that available in order to maintain your desired level of response. And so we think there's a window, call it, 50% up to that 80% maintenance, where you'd say the majority of people will do great on a once annual maintenance. Keep in mind, PASI 100 clear skin, extremely high bar for efficacy. Many patients very happy with responses even in the kind of PASI 90 range. So we think of it as those 2 categories. I mean if it's south of that, it's probably a twice year dose regimen. But I think we've always said based on the PK that we see, we would be surprised to be in that category at this point.

Got it. Super helpful. Well, congrats again on the results this morning, and we'll look forward to the additional update soon.

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

This is Sam on for Tyler. Congrats on the data. So I was wondering if you could just provide some additional color on the low-dose efficacy you saw. Were you surprised to see it achieved comparable efficacy to the 300-milligram dose? Or is that what you expected based on either like IL-23 data or modeling of the exposure response relationship?

Sure. Thanks, Sam. Yes, I think if you haven't looked at a lot of prior IL-23 data, the 37.5 milligram response could look surprising. I think if you look back at some prior dose-ranging evidence, there's clearly this dynamic where a small amount of IL-23 inhibitor can lead to pretty significant responses, but then to drive the optimal response, you need much higher exposures.

And so we point to, for instance, the Skyrizi Phase II, they tested 18 milligrams delivered once. And that, of course, has a much shorter half-life than 001. So if you compare those on an exposure basis, we're about 4x higher. And that low dose of Skyrizi reached 15% to 20% PASI 100 and like 50% on PASI 90. So the fact that at 4x higher than that, we're seeing the efficacy we see here is in the range of what we thought was possible for that dose. And part of the reason we sort of went that low to give a higher degree of confidence that it would separate from our desired Phase III dose. Yes, next question.

Your next question comes from the line of Alex Thompson from Stifel.

This is Patrick Colton. Congrats on the data. I guess just on the Phase III, 600-milligram is the take-forward dose. Are there any expectations to test the single-dose arm? And maybe what would you expect from a single 600-milligram dose?

Sure. Thanks for the question. Yes. I think we would always qualify by saying it's our desired dose right now is the 600 week 0, week 4. We've got to have those discussions with regulators and align on path forward. But I think we think -- believe this data set is highly supportive of that decision. We like the 04 regimen. We think it's an opportunity, and we've done a lot of kind of market research on this. We think it provides an opportunity at that 1-month mark to check in with the physician and see how just the responses are starting out. We do see pretty significant responses at the week 4 mark in a lot of patients. So we've always liked that as an induction regimen. I think all current or the vast majority of current regimens are dosed that way, and there's a lot of familiarity with it. So we don't have any plans to pursue a single dose. Next question.

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

This is [indiscernible] on for Yas. Congrats on the data. I had a quick question about sort of how should we think about the expectations for EVERLAST-B going into second half of '27.

Yes. So 52-week data second half of next year, we've got a lot of exciting stuff between now and then that we'll be focused on. But I think there'll be some similarities to what we're seeing with EVERLAST-A when we go out to that year mark. So this one, again, separates into 2 different arms. So if subjects have PASI 100 at week 28, we have a no-dose arm. And then we have a 1-year maintenance arm, whereas in EVERLAST-A, it's a 6-month maintenance arm. So at the 52-week mark, you'll have a lot of subjects that haven't received a dose for a year. And I think that will be exciting to see how responses deepen and then sustain in that population. So that will be the primary thing we'd be looking at that point. Next question.

The next question comes from the line of Michael Yee from UBS.

Maybe 2 questions since we've pretty much reviewed the strong data in psoriasis today. Maybe 2 different questions. On the IL-17A/F data, your second asset with some exciting data coming up in Q1, the range of the competitors, they may have a range of PASI data. Can you just comment on your expectations for similar like PASI efficacy, similar tolerability? And would you comment in your disclosure around any psoriatic arthritis data that you might have in that readout in Q1? That's the first question.

And then the second question is more strategic. Previously, I think this summer, you previously had a very nice disclosure around the change in the license agreement with Paragon allowing you to also do IBD in the future. And I think your other related company also sort of amended their licensing agreements. Can you just remind us is that, that was due to various business development topics that had come up and sort of the rationale around that given that your efficacy looks super strong here? So naturally, the question is, what would that mean in other indications?

Sure. Thanks, Mike. Yes. So excited to first quarter next year is the plan to release data from ORCA-SURGE, which is our Phase II study with 002 in psoriasis. I think it's interesting what we've seen here with 001, efficacy looks very similar to BIMZELX in terms of week 16, low 60s PASI 100, mid-80s, PASI 90 leads us to wonder whether that's sort of the ceiling you can reach by inhibiting the IL-23, IL-17 axis. And that sort of fits with what we've seen with BIMZELX, if you look at the exposure response, it looks like they're sort of maxing that out at their current dosing. So it could be that, that sort of complete shutdown of the pathway, what you tend to see.

And there is some variation in the BIMZELX data. So our Phase II has 3 different dose arms, fairly well matched to the BIMZELX Phase II dose-ranging data. And it's around 160 subject study, so 40 patients per arm. So I think generally, what we're looking for in the efficacy profile is to see something that looks similar to the BIMZELX activity. Of course, in a study that size, you might see some variation from arm to arm, but we're expecting an overall picture that looks consistent. Don't have expectations for higher efficacy because, as I said, there doesn't seem to be room in the exposure response relationship there. And we think that a long-acting entrant into the IL-17 class could be extremely impactful.

And on tolerability side, again, we'd expect to see something in the range of what they've seen. I think oral candidiasis is probably the event that will get the most kind of attention. But just overall, we'd expect to see a tolerability profile fairly consistent with that. Maybe at the end, I'll let Jo comment on whether there's any psoriatic arthritis assessment in that.

And then on the [ TL1A ] amendment, that was a deal that we struck together with Paragon and Spyre to essentially open up potential use of 001 for us in any indication, including IBD. That was sort of a long-term desire, I think, for both companies to have access to all indication rights eventually for that candidate. We don't have any near-term plans to start an IBD study. And in fact, in that agreement, we're restricted from doing that until at the earliest, the middle of 2028. But excited to have that opportunity longer term, and we are branching out now with our HS study with 002, which started earlier this year and then do intend to branch out beyond that as well with combinations with 004 and the breadth that our pipeline could offer.

I'll come back then to ask Jo to comment on whether there's a psoriatic arthritis assessment in the 002 ORCA-SURGE study.

Yes. We're just looking at baseline PsA and not really following in the Phase II. That's certainly something that we continue -- will continue to explore in the Phase IIIs and do a little bit more in the Phase III program. These studies are too small to look at that.

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

Congrats for the data. So given the timing of the Phase III start first half next year and then you will have data from EVERLAST-B 52 weeks second half. So just curious what kind of data will make you to further enhance the Phase III design, if anything, you can incorporate that based on the EVERLAST-B 52-week data?

Maybe I'll ask Jo to take that one as well.

Thanks. Echo. So we have all the data. I'm just going to pause and see if we can see what that's up to. Let me try again.

Roger, do you mind going on mute quickly?

Yes. I am on mute.

Okay. Let me try again. There still seems to be quite a bit of an echo.

Yes, I can take it.

Okay. Is that better? Okay. Sorry about that. So yes, importantly, I think the data that we required for the Phase III program was the dose selection, and that's what EVERLAST-B has provided us with. We believe we have a strong case in taking the 600 milligram as our proposed dose. So with that, we are actively in preparation for our End-of-Phase and look forward to Phase III in the first half of next year.

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

Congrats on reproducing the Phase IIa data. A couple for me. I guess as we think about Phase III maintenance and getting both the 6-month and 12-month dosing regimen potentially on label, would that dosing strength be the same in maintenance? Or would they differ? And then a reminder on plans for in-clinic versus at-home use commercially and the commercial benefits of having both options? And then just real quick on 002, just how you're thinking about the speed of indication expansion given BIMZELX seems to do great on the launch across indications.

Sure. Thanks, Sam. So yes, we definitely want a Phase III design that could allow us to get both annual and twice year dosing on the label. We think we have an efficient plan to do that, but that's one of the key aspects of the design that we want to discuss with the FDA, and then we'll share more details on what that plan looks like once we have that engagement and alignment.

In terms of in-office versus at home, that's another one where we think there's an opportunity to potentially offer both of those options. And we think there's clearly a desire opportunity for in-office administration, medical benefit access to psoriatic disease medications that's apparent in the market. Todd Edwards just joined us as our Chief Commercial Officer a little earlier this year, has a lot of experience in this field. And so he's digging into those opportunities and helping us understand how we maximize the potential of 001 across potentially both of those channels.

And so more to come on that, but we definitely do see an opportunity for both of those channels. And then on 002 indication expansion, that's something we're excited to be already embarking on with the HS study. I think we view PsA and HS as the top 3 indications that we would certainly want on label eventually for 002. I think PsO and HS makes sense as the first 2 to kind of go after because I think people understand that there's activity in PsA if you show the PsO results, but we would want to seek that label eventually as well. There's some other indications we could think about exploring beyond those 3. But for now, those would be the focus.

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

On these data. A few from me. First, I'm wondering if you saw any relationship between efficacy and patient weight in the 600-milligram arm of EVERLAST-B. Second, you had more biologic experienced patients in B versus A, but still had a pretty resilient top line efficacy result. Have you had a chance to look at the naive versus experienced subgroup efficacy in EVERLAST-B yet? Is there anything notable there? And then finally, I know this is a call focused on ORKA-001 in psoriasis, but I'm curious if you have any reflections on ORKA-002's potential as a monotherapy in hidradenitis following an IL-1 Phase III data set shared last week.

Sure. Jo, do you want to take those on subgroup and then I'll speak on HS.

Yes. Thank you, Julian. I think, first of all, we're really pleased that the patients that were enrolled in this study are very consistent with patients in moderate to severe psoriasis. There's always a little bit of variability across the groups, and we looked at the different subgroups, and there was really nothing there. I think importantly, when you look at historical data in psoriasis studies, baseline characteristics really don't play an impact on the outcome and the efficacy. And as you saw in the 600 milligrams, I think this is a really nice bit of evidence to demonstrate that.

When we look at EVERLAST-A, as you pointed out, the weight was a little lower, 10 kilograms lower and the prior biologic use was less compared to EVERLAST-B. And despite that, the efficacy was replicated in A and B. So that really gives us a lot of confidence that what we're seeing here is a true effect of the drug and that these baseline characteristics really don't have an impact on the outcome.

And then on IL-17 002 in HS, we think there's a huge opportunity. I mean we're watching, obviously, what BIMZELX is doing. It's incredible. And I think there's only a few clinical A/F inhibitors out there and really nothing long-acting in the IL-17 class. So we get fantastic feedback for a quarterly dosed option. And I think 17A/F remains the leading target in that indication. And we don't see that changing in the near future. We do think it's an indication that's going to support multiple different mechanisms of action, and it's going to grow considerably here as there are more treatment options available for patients, and it's a really exciting time for that field.

We do think the TL1A data is probably the next best relative to 17A/F and less experience, obviously, with it, but exciting data there recently. So excited to have 004 coming as well and look at potential combinations down the road. But we see a huge opportunity with 002 monotherapy in psoriatic disease, absolutely in patients with concurrent psoriatic arthritis and then in HS. So very excited about that program.

That concludes the question-and-answer session. I would now like to turn the call back to Lawrence Klein for closing remarks.

Okay. Well, thanks, everyone, for joining us today. Exciting day for the company, and I hope you all have a great rest of your day, and we'll see you again soon for more data from Oruka.

This concludes today's meeting. You may now disconnect.

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.