Oruka Therapeutics, Inc. Q1 FY2026 Earnings Call

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 Oroca Therapeutics presentation of interim data from Everlast A. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star, followed by the number one on your telephone keypad. If you would like to withdraw your question, press star 1 again. Thank you. I would now like to turn the call over to Alan Letta. 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 2A 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 ORCA001, our extended half-life IL-23 P19 inhibitor, and moderate to severe plaque psoriasis. I'll start with a quick overview of ARUCA and our goals for 001, and then our chief medical officer, Joe Gonzalez, 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 Aid patients, their advocates, the investigators in our study, and our team at ARUCA, all of whom have gone above and beyond to get this study off to a great start. So at ARUCA, 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 two 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-23T19 and IL-17AS. These two programs apply best to fairly non-overlapping subsets of a very large indication space. ORCA001 we envision as a potentially annually dosed option for patients with predominantly skin psoriasis. And ORCA002 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 hydrogenitis superteva. Both of these programs are now in phase 2. 001 is in two 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 ORCA001 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 Denzelix, which is projected to be another $5 to $10 billion mega blockbuster biologic in this field. Today we'll focus on ORCA001, but we're thrilled to have a long-acting IL-17-AF antibody with a similar mechanism of action to Denzelix coming close behind in our ORCA002 program. Today we will be presenting interim data from our Everlast-A psoriasis study of ORCA001, an ultra-long-acting IL-23-P19 inhibitor. I'm not going to steal too much of the thunder from Joe 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 Dimzellix, with clear potential for annual dosing, and a safety profile consistent with the very high tolerability of the IL-23 P19 class. The headline figure from this data set is a 63.5% rate of PASI 100, or fully clear soon, 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 on this indication, we think this could be a category-winning profile. I'll hand it over to Joe at this point to take us through the data set in more detail.

Thanks, Laurence. The results we will be reviewing today are 16-week interim data from EverlastA, which is a double-blind, placebo-controlled phase 2 study of ORCA001 in moderate-to-severe psoriasis. EverlastA is a rigorously designed study intended to enable a robust assessment of ORCA001'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 the 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 mg of 001 administered subcutaneously at week 0 and week 4, at least 4 times 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 inhibitions 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 iel 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 three to one to receive orca 001 or placebo and the primary endpoint was pussy 100 at week 16. this is the first time that pussy 100 is being used as a primary endpoint in a Phase II psoriasis study. Triapologic 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 demonstrate a 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 their PASI 100 response. Those who achieve PASI 100 Week 28 will be re-randomized in a 2-to-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 the subset of patients with the potential for off-treatment disease emissions. 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 crossed over to active drug at week 16 and will progress onto a key 12-month dosing regimen as part of the open-label extension, which will allow us to gather additional data with 001 as a once-yearly maintenance dose. Overall, Everlast A provides multiple different ways to demonstrate differentiation with Orca001, including ultra-long dosing intervals, the potential for greater efficacy, and long-term of 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 and treatment arms were well-balanced with, as 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 IGA4. Meanwhile, weight, basalmpathy, and percentage of patients with prior biologist 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 analyses from Everlast A, which showed 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 non-respondent imputation. Out of the 63 participants treated with AUKUS001, 40 met 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 RGA0 and PUSTI 100 indicate complete skin clearance with no signs of psoriasis. And their alignment is important for ensuring rigor as well as consistency in investigator assessments. Consistent with these high rates of complete skin clearance, we observe high response rates across various less stringent endpoints of efficacy. 52 out of 63 participants, or 83%, achieved PUSTI 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 or 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 suggests that ORP-001 has a differentiated efficacy profile. Historically, baseline characteristics have had limited impact on efficacy. We've observed the same in Everlast A. Dome here is an assessment of the impact of weight, baseline TUSCY and IGA scores, and prior biologic exposure on week 16 TUSCY 100. In the case of baseline TASI and IGA severity, efficacy was similar in each subgroup. Higher body weight patients showed slightly higher rates of TASI 100, which could indicate that exposures on ORCA001 have reached the effective tassel 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 likely attributable to the limited N in that subgroup. Overall, these data indicate that small variations in baseline are unlikely to contribute to the highest efficacy in an everlast egg. In terms of safety, ORCA001 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 were 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 discontinuations. There were no serious adverse events. There was one severe adverse event, a bone fracture and discercation, which occurred on placebo. The only treatment-emergent adverse events occurring in 5% or more participants in either group was 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 injection-type reactions reported for over 200 injections of ORCA001 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 ORCA 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 after Week 52, which could show the potential for annual dosing. In parallel, Everlast B dose ranging study is enrolling rapidly and we anticipate the 16-week readout next year. Overall, we are tremendously excited by the emerging profile of ORCA001. I'll hand it back to Lawrence now to help with these results into

context. Thanks, Joe. 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-trop comparisons of Everlast A efficacy results, next to approximately 15 prior studies with the leading IL-23 P19 and IL-17 AF inhibitors. These are $5 to $10 billion products today or in the making, and across every metric, Orca 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 Skyrisi historical results, and over double the response rate soon with Ikotide, 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 Vimzelix, 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 by 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 Days started last summer, we'll need to wait until later this year for direct evidence of one-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 this study also support 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 make same points with annual dosing of 001. Orca 001, showing a 63.5% TISE 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 to 10 plus billion dollar franchises. And against this backdrop, Orca001 could represent an even bigger step forward. We think this program has tremendous potential to deliver value to patients and reward all of Aruca's 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, Orca002, is now in Phase 2 as well and could be an extremely valuable asset in its own right, based on the success that Bimzelix is having in both psoriatic disease and hydrodonitis supertiva. We have a great cadence of upcoming readouts across the Everlast programs and the Orca 0-2 studies over the next couple of years with meaningful data updates expected to come every six months or so. We are well-funded with runway over one year beyond at least three 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.

At this time, I would like to remind everyone, in order to ask a question, press star, then the number 1 on your telephone keypad. we request to limit yourselves to one question and one follow-up we will pause for just a moment to compile the Q&A roster your first question comes from the line of Alex Thompson with Steve Hill your line is open a great good

morning and congrats on the data I was wondering if you could talk a little about you know the expectations for you know Everlast B as well in the context of baseline characteristics here how similar do you expect you know Everlast B baseline characteristics to B to Everlast A. I guess if you do anticipate BSA and path BF baseline to be a little bit higher based on some of the contemporary, or at least not contemporary anymore, but some of the Skyrizi studies historically. Thanks. Sure. 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. In particular, if you look at the more recent studies, I think it looks very, very similar in terms of baseline. You know, 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 thank you your next question comes from the line of Fiatie and Sunaya with Guggenheim Securities your line is open

hey guys congratulations on 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. 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 six months.

Sure, sure. So thank you.

Yeah. So on the first, I'll try to go through all three of those. So on those exposure relationship, you know, I think what we've seen here looks quite similar to what was seen in knockout. And I think anytime you see something like that twice, you have, you know, more confidence that, you know, that's a reproducible effect. And, you know, I think that gives us confidence that, you know, as we move forward through development, you know, we're likely to see similar results. I think on the second question, which was the ADAs, yeah, we haven't on any individual subjects 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, you know, very promising. And I think historically, IL-23 as a target has had very low rates of ADAs, in particular, very low rates of ADAs that had any impact on the metrics that matter. and then in terms of yearly dosing yeah I think if you look at the PK it's pretty hard not to get excited about the one-year potential you know just because the 600 million dose stays you know well above the trough level for IL-23s for the entirety of a year and so you know 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 Day last summer. And so in just a few months, you know, we'll have some of that data. And I think it gives you, you know, a lot to look forward to in terms of the potential here.

Your next question comes from the line of Tyler Von Byrne with TD Common. Your line is open.

Hey, guys. Good morning. Congrats on the incredible data. So, the POSI 100 figure on slide 12 shows that the rate is going sharply up and to 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 POSI 100 rate over time here with the longer follow-up given the higher exposure and significantly longer half-life with Oracle 1 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 a follow-up. How quickly do you believe that you all can get to pivotal

trial initiation with Work01? Sure. Thanks, Tyler. We can address both of those. Yeah, 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 a 63.5% clearance rate at week 28. So I think if that improves from there, that's going to be extremely exciting. You know, we do look at that absolute PASI less than one, which was around 76%. Those are people who have really minimal disease at week 16. So we're certainly hopeful that, you know, 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, you know, 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. Remember, it's the 16-week data from that study that we'll 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, you know, CMC, ClinOPS, et cetera, so that nothing else is rate limiting. And we think we can go fast. You know, psoriasis programs have gone very quickly through development. I think if you benchmark us to those timelines, 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. Your line is open.

Hey, guys. This is Kali Yee for Michael Yee. Thanks for taking our questions, and 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? Thank you.

Here, thanks, Kyle.

So I'll take the first one, and then I'll let Joe comment on the second.

I think we've certainly seen a lot of excitement. You know, 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, you know, not too far away. And that'll 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, you know, 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, you know, how long responses are lasting, I think if you see, you know, 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.

Yeah, thanks, Lauren. So, yeah, you know, all along, the dermatologists have been super excited about ORCA001 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-23 P19s, 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. Your line is open.

Hey, good morning. Thanks for taking the questions and 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 sub-q dosing. Could you just discuss how these data in the Phase 2b might inform which of these permutations you'd include in the Phase 3 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 3?

Sure. Thanks, Sam. So, yeah, we're definitely doing a lot of work right now on the specifics of the Phase III plan. You know, I think we can keep all of those options on the table and get data on all of them from a Phase III program. You know, 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 six-monthly dose option for maybe people who don't get fully clear 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 three, 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 three design.

Your next question comes from the line of Yasmin Rahimi with Piper Sanford. Your line is open.

Good morning, team. Congrats on the outstanding data. So, maybe help us understand on the PASI 100 and PASI 90 scores, like sort of what the air bars look like, specifically around PASI 100, if you had, you know, 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.

Thanks, guys. You know, I'd say generally we had 63 patients in the active arm across 25 different highly experienced sites. You know, I think the rate of PASI 100 that we've seen it 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, you know, 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, you know, how robust it is. And, you know, we think it's, you know, biologically plausible, certainly when you look at the exposure response that more antibody, you know, needed in the serum to fully saturate the target in the tissue, you know, in the epidermis in all patients. And, you know, it looks like we have a very potent molecule and well-tolerated with 001. You know, nothing really stands out in terms of patient segments. I mean, 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 SkyRizzy, 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 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.

Thank you.

Congrats.

Your next question comes from the line of Roger's song with Jeffries. Your line is open.

Good morning. This is Fiona on for Roger. Huge congrats on the data, and thanks for taking our question. Just a quick one from us. Can you comment on the baseline population, the prior therapeutic 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. You know, other metrics were higher, like, you know, severity, Joe mentioned on IGA score of four. But prior biologics, you know, in some indications, prior biologics can really seem to correlate with efficacy outcomes. That's not the case in flexoriasis. I mean, you can look at multiple analyses of prior studies. Like, for instance, in the Skyrisi Phase 3s, 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 n that you see a difference there. 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. Your line is open.

Hi. Let me add my congratulations on these results, and thank you for taking the questions. First, I'm wondering if the data here changed at all how you envision ORCA1 and 2 coexisting in psoriasis. Is there maybe an updated long-term vision there or with ORCA21? 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 still are biosimilars to enter the market early last year, but SkyRidzy 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 ORCA1 and potentially 2 enter the market as well.

Sure. Thanks, Julian. in. So these really don't change how we see O01 and O02 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-17s play the best role. And And IL-17AF with Benzelix is really proving to be the preferred strategy for that group of patients. And it's a large group, right? So concurrent PSA is, you know, typically a quarter 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, you know, a quarter 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 two, you know, coexisting complementary in the market. That's what you've seen with BIMZELX. I don't think it's taken share at all from SkyRiszy. I think it's taken some share from Cosentix and Taltz. So they're really sort of different subpopulations in what overall is a very, very large market.

And, yeah, 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. You know, I think we see the excitement around Iketide and, you know, 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, you know, 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 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. You know, I think in psoriasis typically shows up in your 20s or 30s and then, you know, it's with you for the rest of your life. And so you see oftentimes people going on biologics that have been dealing with the disease for 15 years or so. And so oftentimes they've stepped 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 Edzer Derroth with Barclays. Your line is open.

Thanks for taking the question and 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 one data that you commented on today.

Yeah, so far what we're seeing in the phase two is very consistent with the phase one. You know, it's still early data, and so we want to let that mature a bit. But, I mean, I think in the phase one it's pretty impressive PK, you know, approximately 100-day half-life. And, you know, 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 SkyRizzy right before patients receive their next dose. So there's half the patients below that line with SkyRizzy. And actually on the phase one, every single one of the individuals was above that line in that group. And so overall, I think just 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 Wolf Research. Your line is open.

Hey, this is Brandon for Andy, and thanks for taking the question. So, it looks like exposures are still meaningfully above chizumab C-trough by week 52. We know annual dosing is in sight, but is there any confidence that you could achieve something even less frequent than annual dosing?

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. You know, we do have an open-ended arm in every last day 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 one year with clear skin since last administration of a therapeutic for psoriasis. And, you know, 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 three different ways we could differentiate with this profile. You know, 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, you know, how we want to position the drug once we get there.

Your next question comes from the line of Martin Fan with Whitbush Acurities. Your line is open.

Hi, everybody. Thanks for taking that question, and 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 two trials versus one trial and current discussions with the FDA for the safety program?

Yeah, so we'll really have those discussions once we have that primary endpoint data from Everlast B. That'll 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, you know, the cost and efficiency of a single Phase III versus two different studies. and two different studies could maybe give you the option to do those in slightly different patient populations that could broaden the label. So, you know, 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 Lauren Sline for closing remarks.

Thank you, Operator. Yeah, I'll just thank everyone for your attention and interest. We're thrilled by these data and really excited to be looking forward to, you know, the next year or so at ARUCA, another update on this study in the second half of this year, which I think, you know, could really build on the great results we're seeing here. The 2B data, which would then enable, you know, a rapid phase 3 start. And then 002 will start to be layered onto 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 Uruka, and we'll try to keep these good results coming. Appreciate all your attention.

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may not disconnect.