Conference Transcript - ORKA 2026-06-03

Roger Song, Analyst — Jefferies

Welcome, everyone, to Jeffrey's 2026 Global Healthcare Conference. My name is Roger Song, senior analyst, cover SMICAT Biotech. It is my great pleasure to have the next conversation with Ruka Therapeutics, and then we have our CEO, Lawrence, with me.

Lawrence Klein, CEO

Thanks, Roger. Thanks for having us. Thanks for being here.

Roger Song, Analyst — Jefferies

Awesome. Lawrence, I have to say, you over-delivered your recent data readout and then beyond everyone's expectation. You know, maybe take a step back and where is Ruka right now? What is the overall corporate strategy to develop a drug for the patient? And then we can dive into the details.

Lawrence Klein, CEO

Thanks, yeah. So 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, aisle 23 and aisle 17 AF, and really with a 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. And I think you alluded to our Everlast A data, which was phase two data for our 001 program, which is IL-23 antibody, which we released back in April. And 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. And so I think what we saw was highest in indication rates of disease clearance, so really on par with Bimzelix, 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 INI, 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. And so 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 2 studies, sets up a very exciting next couple years for the company.

Roger Song, Analyst — Jefferies

All right. You have IL-2, long-acting, super long-acting, and then deliver L17, the best L17, like the efficacy and the safety profile is also L23. So 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, and maybe some patients follow even longer. So how should we think about the next data set and then what the expectation you want to set?

Lawrence Klein, CEO

Yeah, so the Everlast Days study started enrolling patients last July, so 2025, finished enrolling in December. The data we shared in April was the 16-week data for that study, and then patients are continuing on 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, and then some portion of that cohort at that point also out to a year or more since starting on the 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, but that could be then direct evidence for what percentage of patients maintain response out to a year.

Roger Song, Analyst — Jefferies

So by the way, before the data, we did a preview to build a PK exposure or the efficacy, the coloration. I think your data came in the right ballpark. So one thing we've been talking with the investors is how should we think about the exposure from 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, do you, you know, how, what's your response to that?

Lawrence Klein, CEO

Yeah, I think we don't know what to expect as we go further on in this study. I think, you know, you can do modeling. Sometimes it shows you, you know, the actual result. Sometimes it might not. So well done to you for getting that right. But I think there's a couple different ways to think about it. You know, we did dose higher, so you might imagine that you get more of the response early on and then maybe there's less you know deepening I think what we've seen with prior biologics all 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 I mean if we have 64% at week 28 you know Skyrizzy ranges like 50 to 55 percent at week 28. So that's already, you know, far higher than what you see with the best IL-23 out there. You know, if you get more, I think that'd be fantastic, but I think

Roger Song, Analyst — Jefferies

it's a good setup for us. Yeah. I think just to reiterate the point is before the data, the expectation is you are comparable to scurrency. You don't even need to have any delta. Delta, 10 percent is great. It's basically superior to the current drug or scurrency as a standard care. But at the 28 even longer if you get to similar level of screening that still could be a very profile a

Lawrence Klein, CEO

very good profile for the 101 yeah I mean what we've said from the beginning and we think remains true is six monthly dosing equal efficacy is a multi-billion dollar asset and 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. But I think those fundamentals are still true, that that profile would be very successful in this market.

Roger Song, Analyst — Jefferies

And then between every six months and every year dosing, do you see the big difference in terms of patient, physician will choose the drug with similar kind of efficacy and

Lawrence Klein, CEO

Yeah, once a year consistently surveys better for us than once every six months, but both do very, very well in terms of expected, you know, 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. and so we're sort of a scenario where whatever percentage we get out to once a year would be would be great I think higher is better though based on all the market research we've done and I think once a year potential does start to capture the imagination in a different way you know you hear things like you know that could be the closest we get to a cure in this indication I mean that 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.

Roger Song, Analyst — Jefferies

Yeah, kind of put psoriasis in your mission. I think we saw the conversation at the EAD for a couple of years already. Okay, good. And then 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? And then on the other side is, you know, this is initially it's a physician office, maybe a buy-and-build kind of a model. So how should we think about, you know, the inventory or the investment, offering investment for those kind of physicians?

Lawrence Klein, CEO

Yeah, so the way we're planning to study it right now is 600 milligrams as the annual dose and then 300 milligrams for the six-monthly dose. So it ended up being the same. So it's kind of two pens for once a year, one pen for a six-month. and so the annual price which is how you know insurers typically look at it would be the same for either dose regimen so that's kind of convenient and 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 aisle 23 out there today called Illumia Sun Pharma markets it in the US it has lower efficacy than Skyrizi or Trimphia. It's dose quarterly. It did a billion dollars 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, you know, best in indication efficacy with a once to twice a year dosing, that opportunity could grow, you know, several fold. It's also a channel within the market that has a different dynamic in terms of access. You know, Sun doesn't do a lot of direct-to-consumer advertising, whereas I think we've all seen the Skyrisi and Trumfaya advertisements. I think it's an interesting path you might pursue if you were an independent, you know, small company entering this market where you could establish a pretty, you know, sizable presence without the same dynamics. You can actually, it's not an either or, either you could enable both of those. And so that's something we're looking at very carefully as we move into, you know, phase three study design and things like that.

Roger Song, Analyst — Jefferies

And then by the way, you are thinking about self-administration at home and then that's just a, may not at the initial launch, but not going to be too far from the launch.

Lawrence Klein, CEO

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.

Roger Song, Analyst — Jefferies

Okay, good. All right, so, and then the Avalast B is also, you know, ongoing, and then, you know, should we, you know, how much we should expect any difference between A and B, and then, you know the expertise to be the similar comparable efficacy as the base case and then if you get to the you know I will ask the a level that's that's certainly

Lawrence Klein, CEO

another upside yeah I mean I think expectation at this point is ever last day was a very robust study 25 sites North America you know sizable cohort replicates you know in some ways an effect that was seen in some investigator sponsored work previously so I think our expectation for Everlast B is it should look like Everlast A we're using you know a lot of the same sites some new sites as well we're doing we're testing a couple different doses but you know for the 600 milligram dose our expectation going in should be look similar again it doesn't need to to to be a very compelling product profile but I think that should be everyone's expectation going into that study that study started last December. Enrollment's been very good, you know, similar to what we saw with Everlast A. We think we'll get a very similar patient population, and yeah, excited to, you know, have that in the works, which is really then the main gating item to starting phase three studies, which is something we're, you know, actively working on right now.

Roger Song, Analyst — Jefferies

Yeah. Okay, great. So that's a confidence, right? So you think Everlast A can replicate it in the Everlast B. And then in terms of phase 3, it is long acting. You have many different way to position the drug in terms of the induction, maintenance, long-term kind of remission. So what's the current high-level thoughts about phase 3? You say the Everlast B data is needed before you can start phase 3. What kind of data you are looking for to

Lawrence Klein, CEO

validate? Yeah, the primary purpose of Everlast B is to have dose ranging data that can support our dose selection for the phase three. Right now we think the 600 milligram dose, week zero, week four, and then 600 milligrams annual maintenance, 300 milligrams every six months maintenance. We have a very high degree of confidence that that's a great dose. And, you know, if it were up to us, we'd probably just start the phase three with that dose today but 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 milligrams week zero week four and 600 milligrams week zero week four we think there's two scenarios one where those separate and 600 looks better where we would you know strongly make the case that we want to go forward with that dose given what we also saw in the part If those don't separate, which is possible, you could then go with the 300 milligram dose. We think that's a very viable dose as well, and that's a possible scenario. So it just gives us optionality to have a phase three dose that is supported by dose-ranging data and that the FDA would endorse or give their blessing on. So that's essentially the plan. And then other nuances of the phase three 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, you know, not quite ready.

Roger Song, Analyst — Jefferies

Yeah. You mean the maintenance portion or that's, yeah?

Lawrence Klein, CEO

Yeah, maintenance portion and, you know, how many studies, what exact kind of population, all those kind of details.

Roger Song, Analyst — Jefferies

Yep. Got it. Okay. Great. So in order to start a phase three, any CMC or any other gaining factor outside of Everlast B and then your internal kind of strategy and then refine the protocol?

Lawrence Klein, CEO

Yeah, 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. So, you know, lining up CMC well ahead of time, You know, ClinOps, all of those other aspects of getting the studies going so that we can be in a, and we're 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.

Roger Song, Analyst — Jefferies

Yeah, got it. And then in terms of, because it's long-acting, right, particularly you were thinking about once a year dosing, which is good for commercial and then patient, but from the regulatory perspective, would they ask you to do a longer follow-up before they can get an initial approval, or they're okay with the initial, you know, whatever the time point they want to look at it, and then you just give them longer follow-up, you know, as you get the first approval?

Lawrence Klein, CEO

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. So 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 will determine what exact path we take. But I think either one is very viable.

Roger Song, Analyst — Jefferies

You don't want to get a penalty because you are super long-acting and then getting delayed on the initial approval. But no, that's just that.

Lawrence Klein, CEO

We definitely want to file a BLA based on a one-year study. 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, you know, a little bit later, that's perfectly fine.

Roger Song, Analyst — Jefferies

Yep, got it. And then with the potential remission or remittative effect, would you put that, you know, fact that into your pricing strategy? Because, you know, we're thinking about chronic dosing from current biologics, and there's certainly a benchmark. But on the other side, if you can dose once a year, maybe some patients, they don't need to dose for a longer term. And then how should we think about the pricing?

Lawrence Klein, CEO

Yeah, probably a little too early for us to comment on specifics of how we would price. I mean, 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. So, you know, I think being the first medicine that could offer off-treatment remission in psoriatic disease, and we've got to show that data, we're not there yet, but we think there's a possibility with the O1. We're very excited about that. How exactly we decide to factor that into, you know, the value recognition, we're not quite there yet.

Roger Song, Analyst — Jefferies

That's a good problem to have, right? So once you have the data, I know I can think about it. And then you do have a second program. It's also kind of in the clinical, you know, moving along, and the O2, which is L17. So now you have a fantastic data from the O1. And then how you think O2 can fit into the whole portfolio, you know, kind of strategy?

Lawrence Klein, CEO

Yeah, we're very excited about O2. We view them as very complementary. even in, you know, when you're talking about psoriatic disease, where they do, you know, 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. And then 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% to 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, but 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. And so 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 months ago, the phase 2 study. And then the 002-17-AF 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, you know, 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.

Roger Song, Analyst — Jefferies

Yeah, I always think IL-23 is the perfect target for long-acting, particularly from the safety perspective. In the IL-17, you know, it's still pretty relatively clean, but compared to IL-23, it's less so. How do you think about IL-2 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?

Lawrence Klein, CEO

Yeah, I think it's all relative. You know, IL-23 is probably the perfect target for an ultra-long-acting. IL-17 AF is very, very good as well. You know, when you stack it up next to some of the other mechanisms that are used in rheumatology or, you know, severe dermatology conditions, it's a very, very good safety profile. And really, the events that show up are largely in the kind of nuisance category, like oral candidiasis. You know, oral candidiasis is the most frequent event that's seen. That's the one that gets the most focus. treatable once it resolves tends to not recur in patients very very few patients see recurrent episodes of oral candidiasis and so it you know i think it hasn't impacted bimzelix at all right it's done incredibly well in its first couple years of its launch and so we think a a long-acting option in the 17 class where there's really nothing there's nothing longer than once every two months today um we think it could be very very well received okay good um and then uh in

Roger Song, Analyst — Jefferies

terms of the uh the combination maybe i take that back so you just recently announced some deal uh you know more modification of the uh the alignment agreement with the paragon uh and then with your brother company or sister company so uh i maybe you just give us some high level uh what's the rationale behind that? What's the strategy behind that? Because I think IL-17, you own the whole rights in terms of all cross-order indication, but the old one is you only do the derm or skin

Lawrence Klein, CEO

disease. That's right. So 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. And that restriction was put in place because Spire 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. And this was done early days to sort of ensure the two companies would focus on their primary indication areas of focus. And in the last two and a half years, that's what we've done. Inspire has 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. And this is something, 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. And this felt like the right time where we're both now we've got phase two 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, very compelling lead program for RUCA, and so we're very excited to have announced that amendment.

Roger Song, Analyst — Jefferies

Awesome. I know the timing is always interesting, so you say it's been in talking for some time, And then also to the both company reporting some very good data from phase two. And then how should we think about the strategic discussion will play into that, you know, speculation. But, you know, you can say whatever you feel comfortable to comment.

Lawrence Klein, CEO

Yeah, probably not going to say too much. I mean, people are free to speculate, but I wouldn't read too much into it.

Roger Song, Analyst — Jefferies

Okay, good. And 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? But on the other side is, you know, maybe different indication and how should we think about the priority there?

Lawrence Klein, CEO

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, you know, 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 or ORCA21. You know, that's something that we've got the plans for. We will eventually run a proof of concept study with that program. But 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. just that much more excited about oh one and we want to do everything we can to move that so if you go you know in the company right now everybody's focused on phase three planning for oh one running the phase two's for oh two we will get around to running orca 21 it does move down a bit in terms of priority based on

Roger Song, Analyst — Jefferies

you know everything we've seen so far yeah honestly all one is the off the charts gray and then you know if you are comparable efficacy you think okay I Maybe I can squeeze that a bit more on the efficacy side compared to the R23. But if not, then what's the benefit of doing the combination and things you don't need to? Okay, good. And then maybe just last minute or two, anything else we haven't highlighted you want to highlight on the other side is what's the cache and then how much is supported for your current development plan?

Lawrence Klein, CEO

Yeah, no, I think we covered most everything. I'll just maybe the kind of catalyst map or milestones, you know, from here. You know, I think we've got a very action-packed next couple of years for the company. So additional data on Everlast Day, that's the 28-week, and then evidence for once a year potential in the second half of this year. And then next year we've got Everlast B to facilitate the phase three start, and then psoriasis data for 002 as well. So three really exciting catalysts in the next 18 months or so and plenty of cash to get through all of that and then some. So pro forma, we've got over a billion dollars 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 threes and things. So that's an incredibly strong position to be in as a company. I 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.

Roger Song, Analyst — Jefferies

Given your planning for the BOA submission, how should you think about the partnering strategy? Is that necessary for you to even launch the drug by yourself?

Lawrence Klein, CEO

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 Illumia out there that kind of show how a non-large, traditional large cap pharma can have a meaningful share in these markets. So that's absolutely what we're executing towards. At the same time, you know, 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. And so this license amendment, I think, is a nice, you know, move in that direction of clearing up anything that could prevent something. So we want to keep both paths open. I think that's the best strategy.

Roger Song, Analyst — Jefferies

No speculation, but got it. Okay, great. Thank you, Lawrence. Thank you, everyone.

Lawrence Klein, CEO

Thanks, Roger. Thanks, everyone.