Hey. Welcome, everyone, to Jefferies 2026 Global Healthcare Conference. My name is Roger Song, Senior Analyst covers Mid-Cap Biotech. It is my great pleasure to have the next conversation with Oruka Therapeutics, and then we have our CEO Lawrence with me.
Thanks, Roger. Thanks for having us.
Awesome.
Thanks, everyone, for being here.
Awesome. Lawrence, I have to say, you over-delivered your recent data readout and beyond everyone's expectation. Maybe take a step back and where is Oruka right now? What is the overall corporate strategy to develop a drug for the patient? We can dive into the details.
Thanks. Yeah. Our goal when we set up the company a few years ago was to have potentially best-in-class assets in psoriatic disease, going after what we think are the two best targets in that indication space, IL-23 and IL-17A/F, really with the goal to sort of perfect the product profile of agents that could inhibit those pathways, with the goal of offering patients the greatest possible freedom from disease. We like that kind of phrase because it captures two aspects of what we're trying to offer, which is highest possible rates of disease clearance with the fewest number of administrations of a therapeutic possible. I think you alluded to our EVERLAST-A data, which was phase II data for our 001 program, which is an IL-23 antibody, which we released back in April.
I think what we showed is really delivering, as you mentioned, at the higher end of what we thought was possible in terms of that differentiated profile. I think what we saw was highest in indication rates of disease clearance, so really on par with BIMZELX, which offers the highest possible efficacy so far in psoriatic disease in the form of an IL-23 inhibitor, which has basically the cleanest safety profile of anything in I&I, in a format that could potentially be dosed once a year and maybe offer off-treatment remission to a decent percentage of patients as well. We really think that is the higher end of what we thought could be possible and very likely could be the best biologic in psoriatic disease space in a few years' time.
Followed closely behind by our 002 program, which we're also very excited about, which is now in phase II studies, sets up a very exciting next couple of years for the company.
Excellent. All right, you have IL-23 long-acting, super long-acting, and then deliver IL-17, the best IL-17, like the efficacy and the safety profile is also IL-23. This EVERLAST-A is 16 week, right? Data is high end of the expectation, and then you continue to follow those patients to 28 week later on, maybe some patients follow even longer. How should we think about the next data set, and then what the expectation you want to set?
Yeah. The EVERLAST-A study started enrolling patients last July, 2025. Finished enrolling in December. The data we shared in April was the 16-week data for that study, patients are continuing on the study. We've guided to an additional data update in the second half of this year, where we'd have all of the subjects through the week 28, which is about six months data point, where you sometimes see deepening of response beyond what you see at week 16. Some portion of that cohort at that point also out to a year or more since starting on this study, which could start to give direct evidence. We've seen evidence from our PK profile that looks very supportive of once-a-year potential. That could be then direct evidence for what percentage of patients maintain response out to a year.
By the way, before the data, we did a preview to build a PK exposure or the efficacy, the correlation. I think your data came in the right ballpark. One thing we've been talking with the investors is, how should we think about the exposure for low patient and then get to the highest level they can get, and then later on, you keep following them with the exposure not necessarily will further increase the efficacy. What's your response to that?
Yeah. I think we don't know what to expect as we go further on in this study. I think you can do modeling. Sometimes it shows you the actual result. Sometimes it might not. Well done to you for getting that right. I think there's a couple different ways to think about it. We did dose higher, so you might imagine that you get more of the response early on, and then maybe there's less deepening. I think what we've seen with prior biologics, IL-23s and 17s, is you do see some deepening from week 16 to week 28. I think based on the curves that we were seeing, we would expect to see some deepening. I think the nice setup that we have is even if we don't, we have an amazing profile.
If we have 64% at Week 28, SKYRIZI range is 50%-55% at Week 28. That's already far higher than what you see with the best IL-23 out there. If you get more, I think that'd be fantastic, but I think it's a good setup for us.
Yeah. I think just to reiterate that point is, before the data, the expectation is you are comparable to SKYRIZI. You don't even need to have any delta. Delta 10% is great. It's basically superior to the current drug or SKYRIZI as a standard care. At the 20A, even longer, if you get to similar level of screening, that still could be a very good profile for the 001.
Yeah. What we've said from the beginning, and we think remains true, is six-monthly dosing equal efficacy is a multi-billion-dollar asset. I think all the modeling, all the survey work, market research you do will support that. I think what we've seen so far out of this molecule, you start to believe a lot more than that is possible. I think those fundamentals are still true, that that profile would be very successful in this market.
Then between every six months and every year dosing, do you see the big difference in terms of physician will choose the drug, with similar kind of efficacy and safety?
Yeah. Once a year consistently survey's better for us than once every six month, but both do very well in terms of expected new patient starts and switches. We envision having a label that has six months and once yearly dosing options on it. Even if a very high percentage of people can make it to a year.
We want to have a six-monthly dosing option on the label just to offer additional flexibility.
Right.
We're sort of a scenario where whatever percentage we get up to once a year would be great. I think higher is better, though, based on all the market research we've done. I think once a year potential does start to capture the imagination in a different way.
You hear things like, "That could be the closest we get to a cure in this indication." That's really never been seen before for a therapeutic for a chronic immune condition. I think that would be amazing to be the first ever annually-dosed medicine for a chronic immune disease.
Yeah. Kind of put psoriasis in remission. I think we saw the conversation at the AAD for a couple of years already.
Yeah. Okay, good. Maybe on the more practical commercial setting, let's say you have the label every six and every 12 months dosing. How should we think of the pricing strategy over there? On the other side is, this initially is a physician office, maybe a buy and bill kind of a model. How should we think about the inventory or the investment, upfront investment for those kind of physician?
Yeah. The way we're planning to study it right now is 600 mg is the annual dose, and then 300 mg for the six-monthly dose.
Yeah.
It'd end up being the same. It's kind of two pens for once a year, one pen for a six-month. The annual price, which is how insurers typically look at it, would be the same for either dose regimen. That's kind of convenient. Then your second question was on the medical benefit side.
Yeah.
We think this is a really interesting opportunity for 001. There's a medical benefit IL-23 out there today called ILUMYA. Sun Pharma markets it in the U.S. It has lower efficacy than SKYRIZI or TREMFYA, and it's dosed quarterly. It did $1 billion last year in sales, and it's growing 20% year-over-year. That shows you that there's a place for a medical benefit in-office delivered IL-23 in this market, even with a profile that you might look at and say is somewhat inferior to the best IL-23s out there. I think if you could imagine improving on that to best in indication efficacy with a once to two times a year dosing, that opportunity could grow several-fold. It's also a channel within the market that has a different dynamic in terms of access.
Sun doesn't do a lot of direct-to-consumer advertising, whereas I think we've all seen the SKYRIZI and TREMFYA advertisements. I think it's an interesting path you might pursue if you were an independent, small company entering this market, where you could establish a pretty sizable presence without the same dynamics. It's not an either/or. Either you could enable both of those. That's something we're looking at very carefully as we move into phase III study design and things like that.
By the way, you are thinking about self-administration at home, and then that's just may not at the initial launch, but not going to be too far from the launch.
Yeah. There's examples of drugs out there that have done this, where you have a PFS that launches first as an in-office format, and then you introduce the auto-injector soon after as a pharmacy benefit option.
Yeah. Okay, good. All right. The EVERLAST-A is also ongoing. How much we should expect any different between A and a B, and then the expectation still be the similar comparable efficacy as the base case. If you get to the EVERLAST-A level, that's certainly another upside.
Yeah, I think expectation at this point is EVERLAST-A was a very robust study, 25 sites, North America, sizable cohort. Replicates in some ways an effect that was seen in some investigator-sponsored work previously. I think our expectation for EVERLAST-B is it should look like EVERLAST-A. We're using a lot of the same sites, some new sites as well. We're testing a couple different doses, but for the 600 milligram dose, our expectation going in should look similar.
Yeah
to be a very compelling product profile. I think that should be everyone's expectation going into that study. That study started last December. Enrollment's been very good, similar to what we saw with EVERLAST-A. We think we'll get a very similar patient population. Yeah, excited to have that in the works, which is really then the main gating item to starting phase III studies, which is something we're actively working on right now.
Yeah. Okay, great. That's a confidence, right? You think EVERLAST-A can replicate it in the EVERLAST-B. In terms of phase III, it is long-acting. You have many different way to position the drug in terms of the induction maintenance long-term kind of remission. What's the current high-level thoughts about the phase III? You say the EVERLAST-B data is needed before you can start a phase III. What kind of data you are looking for to validate?
The primary purpose of EVERLAST-B is to have dose-ranging data that can support our dose selection for the phase III. Right now, we think the 600 mg dose, Week 0, Week 4, and then 600 mg annual maintenance, 300 mg every six months maintenance. We have a very high degree of confidence that that's a great dose, and if it were up to us, we'd probably just start the phase III with that dose today. If you took that plan forward to the agency, they'd ask to see your dose-ranging data, and we don't have that data right now. That's what's in the works with EVERLAST-B. EVERLAST-B has two viable induction doses, 300 mg Week 0, Week 4, and 600 mg Week 0, Week 4.
We think there's two scenarios, one where those separate and 600 looks better, where we would strongly make the case that we want to go forward with that dose, given what we also saw in the Part A. If those don't separate, which is possible, you could then go with the 300-mg dose. We think that's a very viable dose as well, and that's a possible scenario. It just gives us optionality to have a Phase III dose that is supported by dose-ranging data and that the FDA would endorse or give their blessing on. That's essentially the plan. Other nuances of the Phase III design we haven't put out yet. It's something we're doing a lot of work on right now to finalize that, and we will do that in the future, but not quite ready.
Yeah. You mean the maintenance portion or? Yeah.
Yeah, maintenance portion and how many studies, what exact kind of population, all those kind of details.
Yep, got it. Okay, great. In order to start the phase III, any like a CMC or any other gating factor outside of EVERLAST-B and then your internal kind of strategy and then refine the protocol?
There's a lot of work ongoing, but we've been very thoughtful since early days of not letting anything else be rate limiting other than that dose-ranging data from EVERLAST-B. Lining up CMC well ahead of time, ClinOps, all of those other aspects of getting the studies going so that we can be feeling good about all that, where we can be in a position where we have the Part B data to start the phase III studies very soon thereafter.
Yeah. Got it. Then in terms of, because it's long-acting, right? Particularly you are thinking about once a year dosing, which is good for commercial and then the patient, but from the regulatory perspective, would they ask you to do a longer follow-up before they can get initial approval? They are okay with the initial, whatever the time point they want to look at it, and then you just give them longer follow-up as you get the first approval?
Yeah, we haven't had that direct discussion with the agency yet. I think there's two possibilities. One is where they could let you do one-year maintenance based on a one-year study. I think there's also a possibility that to have one-year maintenance in the label, they'd want a longer study than one year so that you've dosed people with that maintenance dose and then seen follow-up, whether that's an 18-month study or a two-year study. If that's the case, I think there's a very clear path where you could get the six month on the label first and then have a longer study that you then amend the label with the annual dose as well and get both on the label.
We're mapping out both of those possibilities, and then based on the discussions we have with the agency, once we have the data in hand, that'll determine what exact path we take. I think either one is very viable.
Yeah. You don't want to get a penalty because you are super long-acting and then getting delay on the initial approval.
We definitely want to file a BLA based on a one-year study.
Yeah.
That's what all the other products have done. If that means we start with a six-monthly dose and then get the one year on a little bit later, that's perfectly fine.
Yep. Got it. With the potential remission or remittive effect, would you put that and factor that into your pricing strategy? We're thinking about chronic dosing from current biologics, and there's certainly a benchmark. On the other side, if you can dose once a year, maybe some patient, they don't need to dose for a longer term, and then how should we think about the pricing?
Yeah, probably a little too early for us to comment on specifics of how we would price it. We certainly think that that is potential additional benefit that 001 could offer that we're just very excited to potentially offer to the field for the first time, right? Every medicine for psoriasis today is a fixed dose for the rest of your life. This is a disease that affects millions and millions of people and a huge commercial market for pharma. I think being the first medicine that could offer off treatment remission in psoriatic disease, I mean, we've got to show that data. We're not there yet, but we think there's a possibility with the 001. We're very excited about that. How exactly we decide to factor that into the value recognition, we're not quite there yet.
That's a good problem to have, right?
Yes
We can think about it. You do have a second program, it also kind of in the clinical, moving along in the 002, which is IL-17. Now you have a fantastic data from the 001, how you think 002 can fit into the whole portfolio, the kind of strategy.
We're very excited about ORKA-002. We view them as very complementary. Even when you're talking about psoriatic disease, where they do address the same indication, they are fairly non-overlapping patient segments. Most physicians, if you talk to them, will use an IL-23 if a person has purely skin disease, so meaning no psoriatic arthritis. For patients who also have psoriatic arthritis, they'll lean towards using the IL-17 because IL-17s tend to have better efficacy, especially in the joint aspects of the disease. I would say that's 80%-90% of physicians would agree with what I just said. There are some that just love IL-17s and will use them for everybody, and that's fine. They're great products. That kind of makes it two fairly non-overlapping segments.
It's about 25% of people who have moderate to severe skin disease also have psoriatic arthritis, and so if you don't have an IL-17, you're sort of missing that population, at least, having the best option to offer them. We think the two coexist very nicely in the psoriatic disease space, and so we're pursuing 002 aggressively in psoriasis. We started the study a couple of months ago, the phase II study. The 002 17A/ F also has additional indication expansion potential. The first one that we're pursuing is HS, where we think we could be a quarterly dosed option in an indication that is in desperate need of new medicines for patients, and everything today is very frequently dosed, so that could be highly differentiated. We're ramping up the work to start that study in the second half of the year.
Excited to be branching out now from psoriasis into some other indications.
Yeah. I always think IL-23 is the perfect target for long-acting, particularly from the safety perspective. IL-17, it's still pretty relatively clean, but compared to IL-23, is less so. How you think about 002 in terms of safety profile? You think as a long acting, actually, it can be maybe better than the current kind of biologics in terms of the IL-17?
Yeah. I think it's all relative. IL-23 is probably the perfect target for an ultra long-acting. IL-17A/F is very good as well. When you stack it up next to some of the other mechanisms that are used in rheumatology or severe dermatology conditions, it's a very good safety profile. Really, the events that show up are largely in the kind of nuisance category, like oral candidiasis. Oral candidiasis is the most frequent event that's seen. That's the one that gets the most focus. Easily treatable. Once it resolves, tends to not recur in patients. Very few patients see recurrent episodes of oral candidiasis. I think it hasn't impacted BIMZELX at all, right? It's done incredibly well in its first couple of years of its launch. We think a long-acting option in the 17 class, where there's nothing longer than once every two months today.
We think it could be very well received.
Okay. Good. In terms of the combination, maybe I take a step back. You just recently announced some deal, more modification of the alignment agreement with Paragon, and then with your brother company or sister company.
Maybe you just give us some high level, what's the rationale behind that? What's the strategy behind that? I think IL-17, you own the whole rights in terms of across all the indication, but 001 is you only do the derm or skin disease.
That's right. We had one restriction in our portfolio when the company was set up, is that we couldn't take 001 into IBD. That's the only restriction. Everything else is free and clear, all indications globally. That restriction was put in place because Spyre Therapeutics also has an IL-23 long-acting that was developed by Paragon, and they had a complementary restriction where they couldn't take theirs outside of IBD.
This was done early days to sort of ensure the two companies would focus on their primary indication areas of focus. In the last two and a half years, that's what we've done. Spyre's been focused primarily in IBD and invested heavily in that area and had great data with their first program recently. We've invested heavily in psoriatic disease and now have great data. That restriction is something that Cameron and I have been talking about since the early days, of potentially seeing a path to eventually have that go away to sort of maximize the value for both companies. This felt like the right time, where we're both now we've got phase II data, we're advanced, we're committed to these indications.
There's a delay period on it as well, so that we can't immediately go into IBD with 001, but eventually we can, and that's great, and that's exciting. That opens up more opportunity for what we believe is a very compelling lead program for Oruka. We're very excited to have announced that amendment.
Awesome. I know the timing is always interesting. You say it's been in talking for some time, also to the both company reporting some very good data from phase II. How should we think about the strategic discussion will play into that?
Yeah
You can say whatever you feel comfortable to comment.
Yeah, probably not going to say too much. People are free to speculate, but I wouldn't read too much into it.
Yeah. Okay, good. Then you do have those two assets in your pipeline. How should we think about the combination strategy there? I know maybe not necessary at all, right? On the other side is maybe different indication, and how should we think about the priority there?
Yeah. With 001 and 002, a natural thing to think about is could you combine those?
I think a direct combination of those two doesn't make a ton of sense because they're very overlapping mechanisms of action, and also because in psoriasis, it's not as clear that there's a need for combination therapy, right, especially in plaque psoriasis. Whereas IBD, some of these other indications where the efficacy bar isn't quite as high yet, combinations could make a lot of sense. In plaque psoriasis, I don't think there's as much clear need for that. I think perfecting the product profile against these monotherapy targets is the way to go. The one thing that we have thought a lot about and eventually plan to do is a sequential combination.
where you use basically an IL-17 in induction and then an IL-23 for maintenance, so 002 followed by 001. We call it 021. ORKA-021.
Very cool.
That's something that we've got the plans for. We will eventually run a proof of concept study with that program. Based on the data that we've seen with 001, it's fallen down in terms of relative priority. We're still as excited about it. We're just that much more excited about 01.
Yeah
to move that. If you go in the company right now, everybody's focused on phase III planning for 01.
Yeah
running the phase for 002. We will get around to running ORKA-021. It does move down a bit in terms of priority based on everything we've seen so far.
Yeah. Honestly, 001 is off the charts great. If you are comparable efficacy, you think, "Okay, maybe I can squeeze a little bit more on the efficacy side compared to the IL-23." If not, what's the benefit of doing the combination since you don't need to. Okay, good. All right. Maybe just the last minute or two, anything else we haven't highlight, you want to highlight on the other side is what's the cash and then how much is supported for your current development plan?
Yeah, no, I think we covered most everything. I'll just maybe the kind of catalyst map or milestones from here. I think we've got a very action-packed next couple of years for the company, so additional data on EVERLAST-A, that's the 28-week, and then evidence for once a year potential in the second half of this year. Next year, we've got EVERLAST-B to facilitate the phase III start, and then psoriasis data for 002 as well. Three really exciting catalysts in the next 18 months or so. Plenty of cash to get through all of that and then some. Pro forma, we've got over $1 billion in cash on the balance sheet, which what we've said is that takes us through BLA for 001, and that's assuming a kind of fully loaded plan, including taking 002 into phase IIIs and things.
That's an incredibly strong position to be in as a company. We feel very privileged to be able to say that, and allows our team to really put our heads down and focus on generating additional great data sets, like we showed in April, and see how far we can take this.
Given your planning for the BLA submission, how should we think about the partnering strategy? Is that necessary for you to even launch the drug by yourself?
Yeah, not necessary, and that's the way we build the company, and we think about it internally as we envision pursuing these as an independent company. I think we have conviction in these assets, and that we can do that. We have the capital certainly, and I think there's interesting proof points like ILUMYA out there that kind of show how a non large traditional large cap pharma can have a meaningful share in these markets. That's absolutely what we're executing towards. At the same time, I think these assets could fit really nicely into large pharma pipelines as well, and we also want to make sure we don't do anything that is an impediment to that path for a small company. This license amendment, I think, is a nice move in that direction of clearing up anything that could prevent something.
We want to keep both paths open. I think that's the best strategy.
No speculation, but got it. Okay, great. Thank you, Lawrence. Thank you, everyone.
Thanks, Roger. Thanks, everyone.