Good morning, everyone. Hope you're enjoying the final day of the conference. My name is Alex Buckley. I'm with the Healthcare Investment Banking Group at JP Morgan. And it's my pleasure to introduce Lawrence Klein, CEO of Oruka Therapeutics. There'll be some time at the end for Q&A. If you can just raise your hand, and a mic will be passed around. And with that, I'll pass to Lawrence.
Thanks, Alex. Thanks for having us. And thanks to all of you for joining us this morning. I'm Lawrence Klein, CEO at Oruka Therapeutics. I'm very happy to be here this morning to share an update from the company as we head into what could be a very important 2026 year for Oruka. These are some disclaimers on forward-looking statements that I may make today. Oruka Therapeutics is a company focused on advancing the standard of care in psoriatic disease, plaque psoriasis, psoriatic arthritis, as well as some associated inflammatory conditions, including hidradenitis suppurativa, or HS. Our pipeline is centered around two co-lead programs, ORKA-001 and ORKA-002 , which are each optimized extended half-life monoclonal antibodies targeting what we believe are the two best cytokine targets to treat psoriatic disease: IL-23p19 and IL-17A/F.
These are modeled off of what we consider the gold standard antibodies in the field today, target known mechanisms of action, establish targets to minimize biological or technical risk. We believe there's tremendous upside potential for products like these to offer improved product profiles for patients and also be very important in the market. 2026 will be a big year for the company. We're in the clinic with both programs now. We just recently read out phase I data from a healthy volunteer study for ORKA-002 earlier this week, which I'll talk a bit about today. We're planning to initiate two phase two studies, first in plaque psoriasis and then in HS with that program. We're currently in two parallel phase two programs with ORKA-001 in plaque psoriasis, which we call EVERLAST A and EVERLAST B.
Very importantly, later this year in the second half, we plan to release data from the EVERLAST A portion of that study, which I will share some detail on today. Our goal as a company is offering the greatest possible freedom from disease for patients with psoriasis. We like that phrase, freedom from disease, because it captures two aspects of what we're trying to deliver. One, the absence of disease symptoms. In plaque psoriasis, PASI 100 or fully clear skin, with the fewest number of administrations possible. We think we have data now to support that for ORKA-001 , we might achieve once yearly dosing, so a single annual subcutaneous administration to keep the skin clear. For ORKA-002 , twice a year dosing in psoriasis. I'll walk through some of the data to support that.
Part of the thesis behind Oruka is that psoriatic disease is an approximately $30 billion market that's growing. And there's an established track record that if you can bring a better biologic with a better profile, you can reward all stakeholders. I think the most recent example of that is Bimzelx, which launched just a couple of years ago and I think was underestimated in terms of its potential in the market. It has better efficacy than Cosentyx and Taltz by targeting the F portion of the IL-17 cytokine family and has been seeing incredible adoption in both psoriatic disease and HS. I think it's modeled now at something like an $8 billion peak consensus. So another mega blockbuster in this field. I think it validates the thesis behind Oruka in two ways. One is that this market will continue to reward biologic innovation.
The second is we have a half-life extended IL-17A/F inhibitor, which to our knowledge is one of only a few in the clinic with a differentiated profile. So the key is, can we differentiate over what we consider the gold standards in the field today in this very important market? In the IL-23 class, we look at Skyrizi as the gold standard. In the IL-17 class, we look at Bimzelx. The core of that differentiation that we're trying to offer is the ultra-long dosing interval, potentially once a year with ORKA-001 and twice a year with ORKA-002 . But we're not stopping there. We think there's much more we can offer for patients. We think there's a very good chance with the first program in particular, the IL-23, to achieve greater efficacy.
There's both retrospective and prospective clinical evidence that higher exposures of IL-23 antibody can lead to higher rates of skin clearance, and I'll walk through some of that. We think there's an opportunity to offer for the first time in psoriasis off-treatment remission. This is defined in the field as over one year with clear skin since last administration of a therapeutic for psoriasis. We think there's ample evidence now that through the sustained PK of our molecules with a durable PD effect caused by tissue-resident memory cell depletion, we might achieve some percent of patients having clear skin two years or more after just starter doses. We think that could be an incredible step forward in the field, and we're excited to try to bring that to fruition.
We also have in our plans a sequential combination of ORKA-002 and ORKA-001 , which we call ORKA-0 21, which we think could combine the best of both worlds of an IL-17 and IL-23 profile to offer further differentiation, so we believe dose interval alone could achieve multi-billion-dollar potential with each of these products. But again, we're not stopping there, and if we can achieve all of this, we really think the sky is the limit for this portfolio, so I'll then turn to each program and talk through our plans with ORKA- 001 and some of the data that we've shown to date and do the same with ORKA-002 , so both of these antibodies were engineered at Paragon Therapeutics.
They're a really world-class antibody engineering group that sort of has the raison d'être of taking well-established targets in very large, high-potential markets and perfecting the product profile. The aim here is not to take unnecessary biological risk, and so this antibody was engineered to bind a very similar epitope on IL-23p19 to risankizumab or Skyrizi and show very similar activity in a variety of different preclinical assays. We presented some of this data at EADV a couple of years ago. This is one of the assays we've done, but we've done multiple assays to show similar activity. What we think this does is give you confidence that on a molecule-to-molecule basis, one molecule of ORKA-001 should have similar activity on the disease as one molecule of risankizumab, but they're very different in terms of their PK properties.
I'll show the data, but we put this out at EADV last year that we have a half-life of about 100 days with this molecule in human. That compares to 28 days with risankizumab. We think that this PK profile that we've established in healthy volunteers could enable annual dosing, could give us a chance to achieve better efficacy via higher antibody exposures during the important period of establishing the response, and could unlock this potential for off-treatment remission. We're testing all of that in our ongoing EVERLAST program with data expected in the second half of the year. This is that PK data that we showed at EADV last year. You can see it's very consistent, very flat PK curves modeling out to about a 100-day half-life.
To our knowledge, that's the longest half-life of any monoclonal antibody, which we're very excited about and I think shows the power of the engineering that Paragon is able to achieve with these molecules. You can see very tight error bars and very consistent trajectories. We don't see any evidence of ADAs in any individual subjects on this study, and so we're very excited about that PK profile. We also showed some PD data showing ability to suppress IL-23 signaling out to the latest time point we had, which was six months, even at the lowest dose of 300 milligrams. You can see suppression of signaling showing that not only is there antibody at those late time points, it's also active and able to suppress the pathway, so all of that has enabled us to start rapidly our phase two program in plaque psoriasis.
Again, we call these studies EVERLAST- A and EVERLAST-B . The EVERLAST-A portion started enrolling this past summer. The design is fairly novel for a psoriasis study. Patient population is fairly typical, moderate to severe psoriasis. Size of the trial is around 80 subjects. It's placebo-controlled, but it's weighted towards the treatment arm. So subjects are randomized three to one into either active or placebo for induction. Subjects on the active arm will receive 600 milligrams of ORKA-001 at week zero, week four. That's a higher dose than standard dosing of Skyrizi. I'll talk through the rationale for that. But we think that could enable greater efficacy at week 16, which is a typical time point for an efficacy readout. The primary endpoint here is PASI 100. That's fully clear skin.
To our knowledge, that's the first time PASI 100 has been used as a primary endpoint in a psoriasis study. Typically, it's PASI 90. There's peer-reviewed research showing a quality of life benefit at PASI 100 versus PASI 90. We really think that should be the goal in the field today. Patients, physicians want fully clear skin. And maybe the most innovative part of the design of EVERLAST- A is that about six months, subjects who have clear skin will be randomized two to one into either a six-monthly maintenance arm. That's to sort of lock in our base case profile of twice a year dosing or an arm where they're not dosed until disease recurs. And as you can imagine, all those subjects will start out clear and will be essentially collecting a Kaplan-Meier curve of how long responses last without retreatment.
We think this will give us the opportunity to support a once-annual dosing profile for this molecule, and also, those subjects will continue on into an open-label extension where we could see the potential for responses to last for multiple years. We think it's quite possible here we could have 20%-30% of patients going two years or longer with clear skin after just induction doses. We think that would be an incredible opportunity to unlock in the psoriasis field, so this readout, second half of this year, will have all subjects to the primary endpoint of week 16. We also expect to have some subjects out to close to a year to be able to start to see that potential for once-a-year dosing and long-term responses.
We've also started a part B of this EVERLAST program, which is a dose range finding study where we study some different induction dose levels. This is primarily to justify a phase III dose that we take into a pivotal study. And so we've got a range of doses starting at what we believe will be a minimally effective dose of 37.5 milligrams. We're testing a 300-milligram dose and then that 600 mg, which we believe, based on all the data to date, should be the optimal regimen. But this will test some different dose levels. And this study began enrolling in December. So again, we think three different ways to win with ORKA-001 in plaque psoriasis: potential for greater efficacy, potential for extended dosing intervals, six months, we think once a year quite likely based on the PK, and then off-treatment remission.
I'll talk through a little bit of the data behind what makes us confident we might be able to achieve all of that differentiation. In terms of higher efficacy, there's evidence both retrospectively and prospectively that higher exposures of IL-23 can lead to higher rates of skin clearance. The KNOCKOUT study was an investigator-sponsored study run by Andy Blauvelt, who's a leading KOL in the psoriasis field. He's led and co-authored many of the phase three studies of important programs approved in psoriasis over the past several years. He had a hypothesis that Skyrizi was essentially underdosed in plaque psoriasis. He tested two to four X the approved dose of Skyrizi in around 20 subjects. He achieved pretty dramatically higher efficacy, so 20-30 percentage points higher efficacy than Skyrizi standard dosing. Skyrizi averages around 43% PASI 100 at week 16 across multiple studies.
He saw 67% at that time point. And that gap continued to widen out to six months. Now, it's a very compelling piece of data, but all appropriate caveats of it being a small cohort and investigator-sponsored open-label study apply. But it does fit a broader trend from the phase twos and phase threes of Skyrizi, where you see now thousands of patients separated into exposure deciles, and you see a clear trend of increasing efficacy with higher antibody exposure. We think KNOCKOUT just extends that curve further to the right. We're going to test exposures towards the top end of what was tested in KNOCKOUT in EVERLAST- A and EVERLAST- B with ORKA-001 .
Since I showed you on a molecule-to-molecule basis, you can have a high degree of confidence, should behave similarly, we think there's a very good chance we could achieve higher rates of skin clearance as an additional benefit to add to the very compelling dosing profile we think we could have here. We think we could have once-a-year dosing with this antibody. This is modeling showing that for the entirety of a year with a 600-milligram dose, we could keep antibody levels above Skyrizi trough levels. If Skyrizi trough levels are able to keep people in skin clearance, we think ORKA-001 should be able to for that entirety of that year interval. We will be going up to higher exposures with this regimen than standard Skyrizi dosing. There's a very unique situation here where Skyrizi is approved in ulcerative colitis and Crohn's disease.
There, it's used at much higher levels. You get around 3.6 grams of Skyrizi in induction for ulcerative colitis, for example. And so the antibody exposures you see there, that's an approved regimen, thousands of patients, no additional safety or tolerability profile seen at those very high exposures. It provides a very unique precedent for going to slightly higher exposures in psoriasis with the potential to achieve all of the differentiation we just talked through. Last piece of differentiation we might offer is this, I think, really compelling opportunity to, for the first time, offer off-treatment remission in psoriasis. I mentioned that there's evidence that higher doses of IL-23 inhibitors can deplete tissue-resident memory cells from the skin. Those are the cells that drive recurrence of psoriasis after it's cleared.
That's observed in randomized withdrawal trials shown here that you see an extended PD effect even when serum levels of the antibody have dropped to sub-effective levels. You have a combination with ORKA-001 of a very long PK, the 100-day half-life, with this potential for extended PD. This is what gives us confidence we might see some percentage of patients out for a very long period of time, maybe two years or more after just starter dosing, which fits the definition of off-treatment remission in the field. That's the picture with ORKA- 001. Again, phase II studies are ongoing, and we're laser-focused on a readout in the second half of this year on what we believe is a very compelling molecule. We have a second program that we're equally excited about in ORKA-002 . It's an extended half-life IL-17A/F inhibitor.
I just talked through the really incredible launch that Bimzelx has seen in the field, both in psoriasis and in HS. We designed ORKA- 002 in a similar fashion to ORKA- 001. Like analogies, ORKA- 001 is to Skyrizi what ORKA- 002 is to Bimzelx. It binds a very similar epitope on both the A and F cytokine. We've shown that here. We've done cryo-EM to establish that. It shows very similar activity in a variety of preclinical assays again. So here, you can have a very high degree of confidence that one molecule of ORKA-002 has a similar effect on the disease as one molecule of bimekizumab or Bimzelx. But they're very different in terms of their PK properties. Here, we've shown a 75-80-day half-life. This is data that we put out just recently on Monday of this year.
This is interim data from an ongoing phase I study. This is over three times longer than bimekizumab, and we think could enable twice-a-year dosing in psoriasis, quarterly dosing in HS, which is very different and so we think this could be a very attractive profile. You'll notice here that the mid-dose looks maybe a little proportionately lower than the others. There's actually a really good reason for that, as the mid-dose ended up having some higher body mass individuals in it, and it actually models out sort of perfectly from what you'd expect based on that difference, so really predictable PK that we're seeing here. Again, no evidence of ADAs in any individual subject.
We've also done some PD analysis here to show out to six months, we see full suppression of the signaling even at the lowest dose, which again, not only is there antibody out at those long-time points, it's also active and able to suppress the pathway, and so if we do similar modeling here to what we did with ORKA-001 , we think it supports twice-a-year dosing in psoriasis, quarterly dosing in HS. This is compared to once every two months for bimekizumab in psoriasis for low body weight or low BMI. It's once every month for higher BMI, and then in HS, compares to monthly dosing, and there's really, again, nothing long-acting in the 17 class. Here, we don't see as much logic in the data for higher antibody exposures leading to higher efficacy. It really looks like the exposure response has been maximized with bimekizumab.
But Bimekizumab is a newer molecule to the market, branded for a long-time horizon, nothing long-acting in the 17 class. We think this profile with ORKA-002 could be very, very well received in both of these indications. So we're excited to start those phase two studies, again, psoriasis in the first half of the year and HS in the second. This is ORKA-SURGE , playing off the ticker for the company and the names of our molecules. This is a dose range finding phase two study where we'll test three different doses of ORKA-002 and then evaluate twice-a-year dosing in the maintenance period. The last program I'll mention today in our pipeline is actually a combination of ORKA-002 and ORKA-001 . We don't think there's logic for combining these in a co-formulated, co-administered format, given their very overlapping pathways.
But we do think there's a very good rationale for thinking that sequential administration of these two could really be the ideal regimen to treat psoriasis. And we think we're uniquely positioned to do this because there's really no other company out there with a great 17 and a great 23. We've gotten great feedback from physicians on the potential of this approach. The rationale is these two pathways or these two targets behave slightly differently. IL-17 suppression clears the skin very fast, tends to be more potent, so able to clear people who have difficult-to-treat disease. It does come with some really nuisance-level tolerability events, the most common of which being oral candidiasis, that aren't present with the 23 class. And so 23s are sort of the ideal maintenance regimen.
The idea here is, could you induce with a couple of doses of ORKA-002 , clear the skin quickly, and then maintain on a once-annual IL-23? It could combine the best of both worlds, something we could very easily test in a proof-of-concept study. If it looks compelling, take it forward. We are excited to test that in the near future. It sets up a very exciting year for the company. We are very well funded. We disclosed over $500 million in cash at our last disclosure. We have a really nice cadence of important readouts coming up from the ongoing EVERLAST program data, second half of this year from the A portion. The B portion is ongoing, and we will have a readout next year.
ORKA-SURGE, the phase II study in psoriasis, will start in the first half, planning to start HS in the second half, funded through readouts from all of these studies, plus an additional year of runway beyond that, which we think puts us in a very strong position as a company. So I'll end there. And thank you all for your time and I'll be happy to take questions.
Thank you, Lawrence. And congrats on all of the progress to you and the team. Sounds like an exciting 2026. I'll open up to the room for questions. Otherwise, I've got some here. Maybe if you could talk about, is the intention to commercialize these programs at Oruka yourselves?
Yeah. I think great question. And I'd say maybe conventional wisdom, or sometimes people believe that only a few privileged large companies can commercialize effectively in these indications. We think there's really evidence that that's not the case. We look at Ilumya, which is an IL-23 inhibitor with lower efficacy than Tremfya or Skyrizi, marketed with a fairly small sales force in the U.S. by Sun Pharma, with really minimal DTC marketing. It's a $1 billion-a-year product, growing 20% year- on- year. We also look at what Arcutis is doing with a new topical in the psoriasis space. And we think it's very feasible for a small company to take these all the way through to commercialization. And that's the way we're building the company. We have conviction in the potential of these programs, and we think that's the way to build is for the long run.
At the same time, I mean, we see that these could be a great strategic fit for companies with a larger presence in these indications. And so we'll be open to other pathways as well.
Great, and convenience and frequency of dosing is obviously an important part of the story. You mentioned the Sotyktu launch. I'd love to hear your views on orals in these indications and oral profile and your differentiation, you think, to orals?
Yeah. Again, there's been sort of a conventional view that the next step in innovation in psoriasis is to get to orals that have similar efficacy to biologics, and then that would be the kind of winning profile. We actually think that's not the case. First of all, orals have really consistently failed to reach biologic levels of efficacy. Even the newer wave of orals really fall well short of Skyrizi or Bimzelx efficacy profiles, and then we think once you get to once- to twice-a-year subcutaneous administration, the vast majority of patients will prefer that over a daily oral, especially when you factor in things like a food effect where you have to fast around each administration. We think orals will continue to play an important role in these indications, but we think biologics will continue to be the primary preferred approach for moderate to severe disease.
We do think some of the new orals could expand the market, and we're excited about that. But we think ORKA-001 and ORKA-002 could have the ideal profiles.
Great. And then lastly, from my side, the EVERLAST trial has quite an interesting design, particularly that third arm. Is that quite a novel design in I&I generally? And is that something that you discussed with the FDA? Or what would they need to see, do you think, to really support that once-yearly dosing that you were talking about?
It is quite novel, and we don't know of anyone really testing that as the intended treatment regimen in psoriasis with the goal of getting something like that onto a label. There are other examples and other indications, though, in pemphigus, for example, with rituximab dosed that way. So this idea of treat and extend in certain diseases where you can have a disease-modifying effect is out there and is accepted. It's just it will be newer to psoriasis. It's definitely out there in the field, though, this concept that eliminating TRMs could lead to long-lasting responses. There's a lot of physician and patient excitement for that opportunity.
Great. Thank you. We'll open up again to the room if there's any others.
Lawrence, can you just explain why it's better to have sequential IL-17 and 23? Or if you put them together, would they just get up towards 100% responses across the board?
Yeah. Yeah. So great question. So basically, why not combine them? Co-administer versus sequential. We think it's just trade-offs. I mean, they're highly overlapping pathways. It's thought that in psoriasis, something like 90%-95% of IL-17 production is under the control of IL-23. So you're probably getting the vast majority of the benefit from the 23. Adding the 17 is going to come with the 17 tolerability profile and maybe not get you much on the efficacy side. So that may not be a winning proposition. We think it makes more sense to do the sequential and really combine the best of both.
The sequential was to have back and forth or just have?
Just once sequential. Just induce with the 17. And then what the proof-of-concept study would test is, can you retain those responses with 23 maintenance? I think there's good reason to believe you could because the kind of bar for maintaining a response is lower than for establishing a new response in active disease. If it is, that could be a really compelling profile to offer.
When you think about the ultra-long dosing and the hope to get that, how do you visualize a phase III? Because you might have to dose for several years, which would be impractical if you're trying to get approval. So how do you go about getting just a patient run until they?
Yeah. So the question is, I think, if you have a once-a-year dose interval, how long does your phase III program need to be? We want to have a one-year phase three program. We think there's a way to navigate this, which would be get six-monthly dosing on the label with a one-year program and then amend the label with one-year dosing when you have maybe 18 months of data so that people have gotten that maintenance dose. There's some precedent out there. There aren't too many biannual or annual treatments out there, but there are some. And so there's good precedent for approaching it that way. We do think there's a chance you could run a one-year study and establish one-year dosing. We'll have data from our phase II program to support that. And these are well-known targets, well-known pathways, well-known development paths.
So we'll evaluate different options when we have the phase II data. But we think the kind of base case would be you run a study, establish the six-month, and then add the one-year soon thereafter.
Then building on that for pricing, you won't necessarily know right at launch really how long you can go. How do you do pricing such that you don't lose a lot of the opportunity because a certain percentage of people might go for two years?
Yeah. Sure. I mean, I think we would be excited to introduce some pricing complexity for the advantage of having off-treatment remission for the first time in a disease that affects millions and millions of people in a market that's $30 billion and growing. It's a little early to talk about exactly how we would approach that. But again, there's good precedent for this. So I think there's a couple of recent examples of flexible dosing regimens that have done very, very well. Vabysmo in AMD, Vyvgart has a flexible dosing interval. Patients tailor their dose schedule based on when symptoms start to recur. And the way those were approached is you run a phase three program and you estimate what's a weighted average doses per patient per year. You'll have a confidence interval around that, so it may not be perfect.
But I think you'll get close enough to do very well if you can offer that kind of profile to patients. I think it also provides a really nice opportunity to engage with payers on. We're trying to do the right thing for patients, unlock a new opportunity for off-treatment remission. We're trying to have people take the right amount of medicine that they need to keep their disease in check. So I think you could structure risk-based arrangements around that, value-based arrangements where you say, if it ends up being more than that weighted average in the real world, you could offer a rebate. If it ends up being less, maybe there's a way to share in the upside. Others have done that. Argenx did that with Vyvgart. And so we're looking at those examples.
Again, we think it's an opportunity that's there in the field that could just be incredibly compelling to offer patients for the first time. We think there's ways to navigate the extra complexity of pricing around that.
Great. Thank you. If there are no further questions from the room, thank you, Lawrence, and good luck in 2026.
Thanks, Alex. Thanks, everyone.