Welcome, everyone, to Jeffrey's 2026 Global Healthcare Conference. My name is Roger Song, senior as I cover Smica Biotech. It is my pleasure to have the five-side chat with our next company, Calaris Therapeutics. We have a full crew here, new worker CEO, Roland Kovac, CSO, and then Hugh Davis, president. So welcome, gentlemen. Awesome. All right, Neil, why not you kick off, tell us what's the high-level overview of Eclaris as of now, and then what you're expecting to see in the coming months to here.
Sure. So, hello, everybody. Neil Walker, the CEO of Eclaris. And Eclaris is a biotechnology company focused on both large and small molecule therapeutics. We have three assets in the clinic, one on the way into the clinic. and getting into an IND in the back part of this year. Currently, we are running two 1B studies with our 052 bispecific. It's a T-slip IL-4R. Those are due to readout in the second half of this year. We are also moving our T-slip MAB through a moderate to severe atopic dermatitis phase 2 study that we'll readout at the end of the year. And then we have, on the small molecule side, ATI-2138 is our oral ITK JAK-3. We'll be starting up a study in lichen planus and that in the second half. And then finally, we have our next-gen ITK, where we've engineered out the JAK-3 that is headed towards an IND in the second half of the year.
Excellent. Well, you have a lot of kids in your house, and then maybe we pick one to start. Why don't we start with the bispecific? Because probably that's the one investor most interested and then probably have the biggest upside potential. Maybe we'll start from the field, right? So bispecific, multispecific is definitely the buzz right now for atopendomatitis. By the way, we just put out an AD landscape update a couple of days ago, right before the conference, and we did a pretty comprehensive doc survey and then talking about all the new modality. Your name is up there, so we put you there, And then I think you get some pretty interesting finding. Everyone, if they're interested, can take a look. And then maybe from your modality, which is T-cell plus L4 receptor. So we see data from Pfizer. We see data from Sanofi. Maybe just from your perspective, how you see the read-through from those, you know, competitors slash peers read-through to your program? Sure. Sure.
So I think, and by the way, it was a really well done assessment of the AD landscape. I read through it over the last couple days, so thank you for that. On the competitive landscape front, I think we've seen a few large data sets now, starting with J&J looking at an IL-4R, IL-31, which didn't meet the efficacy levels that they would have liked to see. And then later on in the first quarter, we saw Pfizer report out on positive, highly positive data with their tri-specific that hits IL-4, IL-13, and T-slip. And then finally we saw Sanofi report out data on their IL-13 T-slip in AD as well, which sounded a little bit mixed with the limited data disclosure. But I think the best read-through for us was the Pfizer data because our bispecific targets IL-4R, which by definition takes out IL-4 and IL-13, and we also hit T-slip, which is exactly the three inflammatory mediators that the Pfizer drug hits in a tri-specific format. And so we were excited to see that. We think that, in addition to a number of recent preclinical papers that show the advantage and the additive and synergistic effect, that one gets by targeting two different aspects of the same inflammatory pathway. So we think it makes sense to continue to pursue that in AD, and we're looking forward to reporting out on our 1B data.
Excellent. All right, you did report some SAMAD data early on in Healthy Volunteer. I think the PK looks pretty good. Half-Life is also supportive, the long-acting perspective, and then also ADA, the immunogenicity. I think that's probably one of the key components and appreciated, but I think that increasingly aware by the investor community, and so this is critical, particularly with the J&J's compound. So all of those aspects seems pretty good. I know you want to highlight the PD seems underappreciated by the people. So maybe, you know, here, Neil, you want to talk about the SAMAT finding and then why you think it's a lot more de-risking than other people think.
Sure, I'll take that.
So, right, we read out our Healthy Volunteers SAD and MAD data, and the pharmacokinetics was quite good. We see duration of PK that takes us out to 16 weeks. And so just from a PK perspective, you know, we think we could dose this drug up to monthly. I'm sorry, every three monthly. And then, yeah, the pharmacodynamics was really, took us a bit by surprise in that we could see by looking at both sides of the molecule, the T-slip binding side and the IL-4R binding side, that we could show complete inhibition of either T-slip or IL-4 activated TARC secretion at a hundred percent that took us and our mad studies took us out again for 12 weeks after the last dose and so our t-slip potency was really quite evident because it actually took us out throughout the whole 20 weeks of the study which was 16 weeks after the last dose and then on the aisle for our side side, it was also nice to see that by having this avidity to the target, the receptor, that we could also get 100% inhibition with the IL-4 stimulated TARC. So this molecule has the ability to really hit both sides, both targets in a much more impressive way, we think, that either is able to do alone.
What's the level of the ADA you have been seeing?
Yeah, so for the healthy volunteers, we saw very low incidence and very low titer of the incidence. We saw no impact on clearance in terms of the PK. In fact, our half-life is greater than three times that of DUPI. And then on the other side, this activity that we're seeing is really showing us that it's really a very potent molecule throughout the whole dosing.
It's pretty difficult to put into context in terms of PD comparison because everyone uses a slightly different assay. Maybe what's the closest head-to-head comparison we can make for the PD markers, understanding you're a healthy volunteer, ex vivo stimulation, so what should we look at because we don't make, you know, not necessary apple-to-apple comparison to other programs.
Yeah, I think the PDSA we have developed is, first of all, a very, very robust PDSA. So we are stimulating with IL-4 concentrations and TSLP concentrations, which are probably about 500 to 1,000-fold above the levels you would see in disease. Now, I think possibly other comparable PD effects is, again, our essays where you stimulate ex vivo with cytokines and you, for example, you look at downstream STAT6 phosphorylation that has been done in monocytes by others. I think that's probably an essay which is similar to what we have done here. We looked at CCL17 release. And then others have done simply receptor occupancy studies using flow cytometry. I think that's another way of doing it. But again, overall, we feel really, really comfortable with the results we have generated with our assay.
Okay, good. And obviously, you're not stopped at here, right? So, you just want to give us a little bit early kind of, you know, the indicator how the compound works. You are in clinic inpatient asthma and the endometritis. And we can ask about the expectation for in a minute. But interestingly, you also recently announced you want to move forward into phase two for asthma. So you already made that decision. The question twofold, why you want to do that right now, already start the phase two, at least the planning now, and then how you make that decision? You already see some data, or what's the maybe external risk you already think is enough to move into the asthma?
Yeah, I think it's based on what we already know internally, but the argument about whether a bispecific with a construct that hits IL-4R and T-slip will work in a setting where we already know Dupixent and Tezopelumab work quite well in that indication is a very easy argument to make. So all we're simply saying is we've got the ability to target both molecules within the same construct. And so from our perspective, that doesn't take a lot of thinking about. So if we had the balance sheet, we would certainly go forward with both AD and asthma at the same time. But in light of constraints there, we're going to operationalize on the asthma study. And with the recent capital that we raised, we will be, you know, actually starting that in the fourth quarter of this year. So we're excited about that. And that's, you know, next would be AD.
Got it. You start fourth quarter this year. That will be how the timing is going to look like compared to your phase 1b readout.
So, we get the 1B readouts in the early second half, and then we'd roll in towards the later part of the fourth quarter into the Phase II asthma study. Okay. Got it.
Okay. Let's talk about those Phase I-B data readouts. Maybe we start with atomy dermatitis. So, that is well designed. It's a placebo-controlled and then with decent size. And then what you want to see there and what will make you feel comfortable moving?
Yeah, I think from a baseline level, what I'd like to see, just given that it's a small study, is good directionality in terms of that additive or synergistic effect. That's what I expect to see in looking at the aggregate of the PD and clinical effects that we're studying in that particular study. In terms of, like, the next layer up, if we saw a 5% bump along a number of efficacy measures, measures, that would be kind of the next layer of upside, and I think the home run scenario is if we see basically a 10% bump on various efficacy measures, which would be quite clinically meaningful in that condition.
Got it. Great. And by the way, that resonated pretty well with the survey as well, so 5, 10, 15, I think for novel mechanism, multi-specific, people probably looking for 10% as the clearest superiority, but 5% start to think about it's different. OK, good. And then what would the next step look like for the ADA? I think this is a classical, a Claris type of the proof concept, fast, quick, and then the capital efficient way to do it. What would you think about, let's say this, what kind of scenario of the profile will make you what kind of decision for the next step?
Yeah, so I think if we hit, you know, even the base case, we're going to move forward into a topic. You know, we really believe in the power of this asset. We know that T-slip is a key component in the pathophysiology of this disease, and pairing it up with a downstream mediator like IL-4 just makes sense. And I think, you know, if we achieve the efficacy bump that we expect, this could absolutely represent first-line treatment option.
Okay, and then because this time you test one type of dose, right? And then how big the dose ranging you will do for the next step?
You want to comment on it?
Yeah, I mean, you know, your standard approach is going to be, you know, three different dosing exposures, if you will. And so, you know, honing in, and that's what the 1Bs are going to be able to do for us, honing in on the exposure response in a patient population in order to understand the dose and the dosing interval that can get us to that trough concentration, that's going to be meaningful. So your standard would be three active arms with a placebo, but you're going to have to figure out that dose and dosing interval and, you know, together.
And then potentially you will test every three months, but probably it's at the maintenance or a bit longer after the 16 or 24 weeks induction, is that the?
Yeah, I mean in AD you're gonna do induction. In asthma, you know, we're considering induction as well. Sometimes it's not done, sometimes it is. I think you can get to steady state faster and be more meaningful earlier in the trial with induction. But at the end of the day, it's really gonna be about what the maintenance is gonna look like in terms of continuing that, you know, the sustainability of the effect.
And then just confirming the base case is comparable to DUPI or you want to be 5% no?
No, I think we want to see directionality in terms of that additive or synergistic effect, so that would mean that we're better than DUPI. Better than DUPI, okay, got it.
Alright, so that's atopidermatitis. I think Fyther already made the decision moving to phase 3, so that's, as you said earlier, right, this is a more direct comparison to your approach that give us some of the confidence. And then on the asthma side, it's a single dose, right? So I understand why you want to do that because this is more validated. You just don't want to see if any surprise to you. Tell us what you want to see from that single dose phase 1b, and then, or you already made decision moving to phase 2, but on this side is what kind of profile will make you feel more or less confident for the phase 2?
Yeah, so like you said, in the asthma study, we are testing the single dose, and the end point is after four weeks of those administration, it's going to be, again, it's a small study, a 16-patient study, and we are enrolling moderate asthmatics that have high levels of T2 markers, high levels of phenol above 35 ppm, and then also eosinophils above 150 circulating eosinophils I'm talking about. So what we want to see in that short time period is a pronounced effect on these two biomarkers, the phenoreduction and the reduction in neosinophils, and as an efficacy marker, we're going to look at FEV1 improvement in that patient population, and based on, you know, other biologics within that time frame, we are expecting to see, you know, similar or better effects as S2P. I think that's roughly what the expectations are for us.
Got it, and then similar question, what kind of delta you want to see, you know, you feel good about a phase two.
Yeah, I think it's similar like in AD, if you see a little bit of a bump, 5 to 10% improvement, I think that that would be really great.
Okay, good. All right, you know, we do want to talk about your other kits. So before we move on to other pipeline, anything else you want to highlight for the O52? All right, good. And then the 45, so this is actually an even bigger phase two trial for AD, and then the same T-slip, but just a monoclonal antibody. So what you want to achieve there? Because it is you already have the respiratory study done in China, and then they report a positive data. And then what you want to see from that trial, and then what kind of profile you will think it's worthwhile continuing pursuing, and then also balancing the 52?
Yeah, I think we have to think about capital allocation in light of having positive data sets across the board, and I think if the data is spectacular with the T-slip map, then one would entertain moving that forward as a monotherapy. NAD, you know, particularly given the safety history with T-slip in general, you could definitely see a place for that as an orthogonal mechanism to something like a dupy. However, you know, that would probably be better done in a partner's hands with a full complement of respiratory and atopic dermatitis data. So, you know, we'd like to see stat sig and study. We'd like to see efficacy that is on par with DUPI. But I do think that the bispecific, if it keeps producing the data that we expect it to produce, will necessarily cannibalize the T-slip map. So I think we're going to be over-indexing on the spend on the buy-specific moving forward.
Yeah, makes sense. And then, you know, I know you want to over-index for the buy-specific, but if you do the partner for the T-slip map, would that create a competition? Or how you think about, I think you say something like this is best in class T-slip, and maybe you can, other company, your partner can use that combination.
Yeah, I think they're just different. You know, the market can be served in numerous ways, you know, just as we've seen with orthogonal mechanisms like out of companies like Nectar or Sanofi with Ox40 and things like that. So there's lots of different patient subsets that one could go after. And I think, you know, looking at a bispecific is very different if we're thinking about that as either first line or, you know, perhaps hitting those patients who are dupy failures. So, you know, I think there's room for both. This is a very fast-evolving market in the AD space, at least, and still a lot of room for multiple approaches.
Makes sense. And then the other thing is in terms of data timing, I think you just said Phase 1B for 052 is the early part of the second half, which is the coming weeks. And then in terms of the TSIB, it's still fourth quarter? Is that the...?
Yeah, the cadence of data will be the 1Bs will come first. You know, can't tell you which one will be first, but that'll be first. And then the last data readout of the year will be the T-slit map. Got it.
Thank you for confirming. And then we talked about this. You have a China partner. Basically, you license the, or they acquire the rights for the map. They did report, they did say top-line respiratory, you know, indication is positive. Do we expect to see any data from that program? Or, you know, have you seen how much you can disclose?
Yeah, not much in the way of updates on that from when we last talked about that at an earnings call, a few earnings calls ago. but we know that they're in two phase three studies with asthma and CRS with NP and a phase two study with COPD. As near as I can tell, those will be reading out sometime either late 27, maybe into 28, not exactly sure. but again just to reinforce what we had said a number of months ago everything we've seen to date is is quite encouraging and supports you know our position about the potency of the compound okay got it oh so for the phase 1b those two readouts you just say you may not wait for both to read out and then you can put them a one by one yeah it just depends when they when they both finish, and so, you know, it's very likely, just sitting here today, I would say that they would be reported at different times.
Okay, good. Okay, good. Maybe talk about the small molecule franchise. Sure. So, you have a lead. It's ITK Jax3, and then data, you know, I think for AD is also pretty encouraging, but also you decided not to move forward, rather to go to the alopecia or lichen alopecia planus indication, and then you also move forward with selective ITK. Just tell us a little bit more about this franchise.
Sure. So it's kind of followed a natural progression, if you will. The first molecule we had innovated around was ATI 2138, and you can think of that as a pretty large hammer. It hits ITK, TXK, and Jack 3, and it does so quite robustly, and so there's a lot of indications that we could have gone after. We used atopic dermatitis as a proof of concept in disease. We like the ITK Next Gen, where we've engineered out the Jack 3 as a better target product profile, just, you know, engineering out the jack for indications like AD. So recently we just completed a pretty lengthy indication down selection process and came up with lichen planus, which is a great mechanistic fit since 2138 is the only therapeutic that has jack inhibition in its mechanism that also hits the T cell receptor. And that's important. You know, just think of combining a cyclosporine hitting the T-cell receptor along with a JAK, mechanistically very potent in terms of anti-inflammatory activity. So lichen planus was great for that because part of its pathophysiology is antigenic stimulation through the T-cell receptor. So it has a very unique mechanism that's tailor-made for that indication. And then kind of the other factors there were just efficient clinical drug development. and there's nothing approved in that category. We have proof of concept with the use anecdotally with cyclosporine, with other JAK inhibitors, strong results there on the efficacy side. And there's three different phenotypes that one can go after within like implants. One is mucosal, which is pretty devastating when you think about some patients needing to be tube fed, that the ulcers get so burdensome in the esophagus and the oral mucosa. Cutaneous is the second phenotype, and then third would be that which affects the hair follicle and causes scarring alopecia. So I think it's pretty exciting. It's a way to go study and pick up three indications within one subset of disease, and it's just a beautiful mechanistic fit.
Got it. And then in terms of the current JAK inhibitor, any, like, off-label use or any anecdotes used for lichen planters?
Yeah, there's been some IIS studies done. There's been case series of people using, you know, various approved JAK inhibitors off-label, which is great because it just paints the picture for us of, you know, understanding the probability of success. success and that's even with what we would characterize as suboptimal mechanisms for this particular indication. So I feel really good about the probability of success there and the unmet need is clear and at the end of the day there's nothing approved. So we're deep into discussions with regulatory authorities on the most appropriate path but my guess is sitting here today we'll have some ways to expedite some of this development, which is great when we're talking about, you know, capital efficiency.
And then we definitely talk about the capital allocation, you know, if the O52 is positive, then how are you going to balance in the bi-specific or biological side versus the small molecule Yeah.
Well, you know, we think, you know, the two game-changer molecules in our portfolio are the buy-specific and the next-gen ITK, so I think what you'll see is a gradual shift of capital being allocated to those two programs, and we have to get the ITK next-gen through the IND in the coming months, but I think that once that happens, it unlocks a tremendous amount of value for the company, and it would behoove us to invest there like we're investing in the buy-specific.
Yeah, got it. Okay. And then for the selective ITK, you have one company is focusing on that. And then what do you want to achieve for your next gen selective ITK? and then, you know.
Yeah, so we're really excited about it. You know, ITK is a validated target. You know, us and others have shown that over the past couple of years. It's a, you know, when we think about STAT6 as a target, it's often referred to as kind of the oral dupie. You know, we would refer to this as an oral JAK inhibitor without the JAK inhibitor kind of safety or label baggage. change and we know how well JAK inhibitors work in indications like AD and others. And so I think it's really exciting to be able to offer patients a pill that can hit the TH2 side as robustly as ITK does but also importantly weave in the TH2 or TH1 or TH17 endotypes that we know exists in indications like atopic, like asthma, and many others as we're learning more about these diseases. So, and, you know, you found this in the research you just published. There is a clear kind of dividing line between those patients who want to be on orals and those patients who want to be on injectables. It's not, it's never been, you know, since I've practiced dermatology, and it never will be the case where one modality trumps all the others. There's some patients who just prefer orals and some patients who prefer injectables, and that's good. That means that there's a nice market opportunity for all these modalities.
Yeah, by the way, AD, as we preview or review, it can be $90 billion. So we talk about obesity, $100 billion, $150 billion. I think AD can be as big as the pricing, et cetera, the dynamic over there. Okay. I think we hit all the key high points, and Neil, anything else you want to highlight?
No, I would just say very active next 12 months in terms of catalysts across the portfolio. We have a lot of ways to win. We have $191 million on the balance sheet. were fully funded through the end of 2028, and that includes doing or conduct, starting and conducting a phase two study in asthma with the bispecific.
Awesome. All right. Thank you, gentlemen.