Oruka Therapeutics, Inc. (ORKA) Earnings Call Transcript

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. 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 ORCA 001 in moderate and 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 the 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, Joe Goncalves, will walk through the study and the results. I'll come back to discuss what these data mean 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 seat of care in psoriatic disease. We think combining very high rates of disease clearance with much less frequent dosing and improve the treatment experience dramatically for patients. Our pipeline is anchored on 2 co-lead programs, leading IL-23P19 and IL-17A 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 ORCA 001, we envision a regimen with once to twice per year dosing and the potential for rate of response that exceed existing options. I'll share data today's that program that increasingly elucidates this profile. Orca 002 is our extended half-life IL-17 AF antibody with potential for twice-yearly dosing in psoriasis and psoriatic arthritis and quarterly dosing in hidradenitis super tivo. 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-17 AF inhibitor, [indiscernible] 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 ORCA 004, an extended half-life TL1A antibody that creates opportunities for combinations with both of our co-lead program. 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 results 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-23 P19 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. Last, 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 election and further evaluate ORKA-001 efficacy and safety in order to severe cap psoriasis. The study was conducted at 36 experienced sites across the United States, Canada, Germany and Spain 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-rising study. As an EVERLAST-A, the eligibility criteria was closely aligned with higher IL-2. Participants were at with a patio of well at his Tencent body service area involvement and an IGA score of at least 3. In exposure to an IL-23p19 inhibitor was not permitted. These questions allow us to study a population similar to those enrolled in the clinical development programs for established psoriasis therapy. The study enrolled 187 participants randomized in an equal ratio across 3 active regimens and placebo. The Hides group received 600 milligrams at week 0 and week 4. The same reduction regimen evaluated an EVERLAST-A. The middle dose group received 300 milligrams at those time points. And the Loss Group received 37.5 milligrams we early all doses were administered subcutaneously. We deliberately studied a broad range of doses to understand the relationship between dose and clinical response. [indiscernible] are endpoint was P100 at week 16, which represents completely clear skin. We continue to believe the complete skin clearance with the most meaningful goal for patients and dermatologists and it is particularly useful in distinguishing the performance of highly effective treatments. Beyond induction, ever last year will also provide information on durability Participants repeated P100 at week 28, a rerandomized decrease the annual 600-milligram maintenance, also a group that received no further dose until disease recurrence. Participants who have not achieved PASI 100 at week 28, which is 300 milligrams every 6 months. But CoseaGroup's very prospect active treatment that we with annual maintenance trend 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 dose on dosing every 6 months for those who may now more frequent dosing and user without further treatment. Today, we'll focus on the week 16 induction results. Based on characteristics, we're broadly balanced across the treatment groups and typical of motor severe psoriasis population. Disease severity was also comparable to Everlast A, so it is worth noticing that the participants in the 600-milligram dose group and EVERLAST-B were on average 9 kilograms or GBP 20 heavier than the comparable group in EVERLAST-A and had a high incidence of prior biologic use. Seeing similar results in these 2 patient population increases our confidence that the efficacy results with a high dose or reproducible across different baseline characteristics. Turning to the Par endpoint. The Hirose Group achieved the highest great complete concern the center parties reaching PASI 100 and week 16. In the Mid group, 44 in reached 100 and 43% in the low-dose group. While no participants on Persio reached PASI 100. ICA 0, which also represents completely Karski with identical at PASI 100 across the group supporting the robustness of the assessments in the study for PAC19, both the high and the dose groups achieved response rates in the mid- to high 80s, while the merger was 70%. None of the participants in the placebo group reached personality. IgA-01, response rate with similar to the opportunity across group. The high response rate 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 forward into Phase 3. The passion of response for the 600-milligram dose to remarkable consistency from Everlast A to EVERLAST-B. As you can see in the slide, overlaying the response curves from the 2 studies, the project we tracked very closely through week 16 for both PASI 100 and PASI 90. That consistency is especially encouraging, given the lipid side of the lab and the addition of European sites and Everlast B and it gives us confidence in the efficacy profile we have observed. We also see similar results across a lesion including AGI 01, responses in the mid-18 and PASI75 sponsord and numbered mites in both studies. In each case, the response rates are EVERLAST-B being were within a couple of percentage points of EVERLAST-A. The alignment of price end point 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-9 class. In the provoke treatment group, rates of treatment-emergent advertising, severe treatment-emergent adverse events and service events were comparable to placebo and not the effect a considerate treatment-related nest those depots were observed. The most frequently reported adverse events and participants C001, or upper respiratory has infection and de occurring at rates comparable to those observed in studies of approved IL-23 inhibitors. There was no injection fact reacting in any of the 001 group. And as a reminder, we saw 0 rejection at reactions and EVERLAST-A as well. Overall, these results support the favorable safety and horribility 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 of PK data from Everlast A in December. Those results will help us see how well the response with us over a full year and further supports the potential for annual dosing. Pending discussions and alignment with regulators, we plan for in this year 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 33 of the ongoing to 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 a recap.

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. Wooling 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 ever-last studies alongside relevant trials for other IL-23 inhibitors. SKYRIZI, TREMFYA and the recently approved daily [indiscernible]. While we acknowledge the limitations of cross-trial comparison, what stands out is that both ever last 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 TRIPRIFYA is roughly 20 percentage points. We also see a substantial difference on PASI 90 compared with the daily oral options 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've 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-23 P19 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 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 day 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 whatever 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. Your line is live.

Let me add my congratulations. Very good results, clear applications of the data from 2 studies now. So a couple of questions for me, if I may. First 1 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 01 looks clearly superior, not only on convenience, but on efficacy close to 20 points better. Is there a potential for doing some form of or conducting some from a head-to-head study, whether it's TREMFYA or Sky. 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 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 a 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 we're 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 100 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. Choices comparator is a very important aspect of that, and we will have planned to have an active comparator in that study. As of course, with results like these really exciting to think about potentially running it head-to-head against a leading IL-23 P19 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 II 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 01 and 02, 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 [indiscernible], which has sort of set that ceiling. It's, of course, a very different profile in IL-23p19 versus IL-17F played different roles in the indication space. We love the opportunity to have potentially both 01 and 02 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 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 have an active competitor. 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-23 P19 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 and 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 one-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 one-year product once your medication, which keep in mind, there's never been a once annually dose 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 your 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. [indiscernible], the majority of people will do great on a once annual maintenance. Keep in mind, PASI 100 Clearskin 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 may be 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 updates soon.

Thank you. 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 prior 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 it would separate from our desired Phase III dose.

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

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

Sure. Thanks for the question. Yes. And I think we would always qualify by saying it's our desired dose right now. Is the 600 weeks 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. 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.

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

This is Krishan on for you guys. Congrats on investing the sending data. Just had a quick question about sort of how should we think about the expectations for EVERLAST-B going into [indiscernible]

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.

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