Conference Transcript - KYMR 2026-03-12

Ellie Murrell, Analyst — Barclays

Hi, good morning, everyone. Thanks for joining us on the final day of the Barclays Global Healthcare Conference here in Miami. I'm Ellie Murrell. I'm very excited to have Chimera Therapeutics here with us today. They have one of, I think, the most exciting platform technologies in biotech. Joining us from Chimera is Bruce Jacobs, Chief Financial Officer for Fireside Chat. Bruce, thank you so much for making the time. Maybe just high level to start, can you give us an overview of Chimera as a company and your growing pipeline in INI?

Bruce Jacobs, CFO

So, Ellie, so first of all, thanks for having us. I think this is the OG Miami March conference, so we're happy to be ending our week here. So thank you. Yeah, so it's a good time to ask that question. Chimera is actually coming up next month on our 10-year anniversary of the company's founding. From the beginning, the company was founded to really capitalize on this exciting new modality, targeted protein degradation. And we approached it in a, I would say, a little bit of a unique way with a very disciplined, and I would argue, strategic approach to target selection, where we went into this company formation, this endeavor with a focus on targets that had not been addressed with conventional technologies, conventional small molecule technologies, where there were large markets of unmet need, but where there were proven and known biological pathways. And we thought in doing so, we could really ultimately de-risk the molecules that we were developing. And the company started with an approach that had both oncology and immunology in our sites. But a few years ago, several years ago, I should say, when we met with some success in our first immunology programs, we really narrowed our focus to these immunology targets. And as a result, you see the pipeline that we have today. We built a team of upwards of 250 people with, I'd say, some incredible strength in lead discovery, in chemistry, and really capabilities across what you would need as a biotech company to prosecute this pipeline. And we're excited about the programs that we're developing, those that you don't know about but will soon, and really excited about the future.

Ellie Murrell, Analyst — Barclays

Programs that we'll learn about soon. Any more color on timing?

Bruce Jacobs, CFO

No, I think we've said that historically that our goal is always to introduce one new program annually. So this year hopefully will be no exception. We've recently said that we would expect probably in the second half of this year to introduce our next program, likely in immunology. But, well, you'll have to wait for more than that.

Ellie Murrell, Analyst — Barclays

Great. Well, we certainly look forward to that. There's a lot of companies in the targeted protein degradation space. Maybe I think is probably the leader in the space. can you talk about why you think your approach is differentiated? Sure. So to say it's

Bruce Jacobs, CFO

differentiated requires us to know everything others are doing. And that's sometimes from the outside hard to know. But I would say that probably from the beginning, the target selection approach that I just alluded to a moment ago is perhaps what made us unique. Now others have followed us. So we're not alone in many of the targets we're pursuing today. But across our existing pipeline, And I think what you see is really high-value targets that don't have good solutions. We'll talk about, I'm sure, about the STAT-6 program. We'll talk about IRF-5, I would guess. Those are long targets of great interest for a long, long period of time across pharma. And because of the capabilities we've built, again, in lead discovery and also in all the work we do in lead optimization, our chemistry teams and others, I think have unique capabilities to really prosecute those very, very difficult to address targets. And I think that's where a great opportunity is to ultimately achieve our goal, which is to bring drugs to market that serve these patient populations that are large, but with really significant unmet needs. So to me, that's where a lot of the unique aspects of Chimera come to the forefront. There's definitely a sense of urgency and intensity about how we have built the company and what we're trying to do, because I think you need to have that intensity and that urgency with the size and scale and scope of some of these problems that we're trying to solve.

Ellie Murrell, Analyst — Barclays

Absolutely. Well, it's a great place to talk about STAT-6. Walk us through the data that was seen so far, and, you know, in particular, like atopic dermatitis is becoming an increasingly competitive space, not that there aren't a lot of patients, but sort of, you know, where do you see STAT-6 fitting in this overall landscape?

Bruce Jacobs, CFO

Great. So last year, obviously, was a big year for Chimera and for our STAT6 program, both in June and in December. We had really, I think, important, and we would argue and believe, de-risking data releases, first in healthy volunteers in June, where our principal goal was to show that we could degrade this target, which, again, the first to show that, down to the lower limits of detection, really, and do it in a safe manner with really, I would argue pristine safety in that healthy volunteer study. And that helped us move then into a patient cohort, understandably small, 22-ish patients. But again, very, very compelling results, we believe, where the degradation, again, reached those lower limits, 94, 95, 98% range of degradation, almost to the point where it's very difficult to measure STAT6 in the blood and skin. And for the first time, we were able to show an impact on some of these clinical endpoints, easy scores, itch, quality of life measures, that while it's very difficult to compare across different trials, I think gave us increased optimism that this pathway does indeed do what we expect it to do, that it has the same similar impact as blocking the IL-413 receptors, but doing it by eliminating STAT6 that is downstream from those receptors. So very encouraging results, certainly in the intended patient population, which is atopic dermatitis. And we also had a chance, as you recall, to look at some patients with comorbid diseases, particularly asthma, which is the target for one of our phase two studies that's currently underway. And we saw some encouraging signs there as well. So everything that we saw in that patient cohort really supported what we've been able to build preclinically in terms of the overall package, which is that if you can block STAT6 fully, there's the potential to show activity that looks a lot like competitive biologics out on the market, obviously Dupy being the most significant one. And we do think there's a tremendous opportunity to bring an oral agent to this market. Dupy is an incredible drug, very efficacious, great safety track record. It does, though, obviously require injections, which is not ideal for all patients. And there are a large number of patients in the, if you look at the broader TH2 population, that are untreated, or at least treated with non-advanced systemic therapies treated with steroids and the like. And that tells you that there's patients looking for better solutions. And if we can, as a company, deliver an oral alternative that has comparable efficacy and safety profile, which again, we'll need to prove in future studies, we think the market opportunity would be significant. So we're excited about what we were able to share last year. This year is a big year for the STAT-6 program in terms of execution. We started the atopic dermatitis trial late last year. We're well on our way with that and plan to complete enrollment before the end of this year, share data by mid-2027. And the ASMID trial also has started. That began a little bit later. We just spaced them out more for operational reasons, but that began earlier this year and we'll enroll that trial through this year and into next year with a plan to have data by the end of 2027. So we're focused intently on executing on those two studies. Obviously, we have some other programs we can talk about, but for SAT-6 and KT-621, that's our primary focus this year.

Ellie Murrell, Analyst — Barclays

Yeah, absolutely. And those are certainly very, very important readouts next year that we're all very eagerly anticipating. But I mean, it's interesting, right, atopic derm. I mean, as an oral, you could show efficacy that's probably less than dupy and have a large market. But here, in my view, you're showing signs that you could potentially be better than DUPI. So how are you thinking about that in terms of what's been seen in the preclinical models and the data so far, how you think you compare? And I know it's early, and we'll have to wait for more data.

Bruce Jacobs, CFO

So you know us well enough to know that we try not to put very specific bars and hurdles out there, particularly for clinical activity. The primary focus of our efforts with these Phase II studies is to, first of all, show that we can translate everything we've seen in the smaller patient studies, in our healthy volunteer studies and animal models, into a broader trial, randomized placebo-controlled trial in AD patients. So we want to show that we can translate the level of degradation, and ultimately, hopefully, we'll see the similar clinical activity. The other goal, if not probably, frankly, the primary goal, is to allow us to select a single dose for a phase three study. So this will be three active doses. We haven't disclosed what they are, but three active doses and placebo. The objective would be for the AD side to move into a phase three study with one single dose in AD. Similarly, for asthma to move into a phase three study with one single dose. When it comes to the efficacy profile, I think, obviously, we will see. Our view is that we would like to be in the – we use the very scientific term in the ballpark of what DUPI has been able to show, whether it would be slightly better, slightly worse, comparable. I think, you know, that's what we'll learn from the data. But I think if we can be in the ballpark, I think we'll have a very, very competitive drug, given the size of the population out there that really would be excited about an oral alternative to these injectable biologics.

Ellie Murrell, Analyst — Barclays

And in terms of the Phase 2A data, I saw you have a late-breaker presentation coming up. What should we be looking to see there?

Bruce Jacobs, CFO

So we're very excited about that. Obviously, investors love data, so we don't always have the luxury as an earlier stage biotech company to wait for these big scientific meetings to share our data. So we shared the healthy volunteer data in June. We were able then to do a late breaker for that data last fall at the ADV conference, which was great because it really gave us the opportunity to present the data to a broad universe of clinicians out there. Similarly, for the patient cohort, which we shared with you all in December, we do have a late breaker at AAD later this month. And again, it's a great opportunity to share that data more broadly. The response out of EADV was phenomenal. We had a standing room only audience. We're hoping and expecting a similarly large following when it comes to AADV. AAD. And one of the intentions of the Phase 1B is to build some excitement around the program, which we think will contribute to excitement around the enrollment for the Phase 2 studies. And so having this data at the AAD conference, I think will help build some more awareness of and appreciation for the data. You shouldn't expect there to be anything incremental. It's really a kind of a rehash of what you all have seen. But again, for some of these folks in the audience. It'll be new. Aside from that, you know, we will expect to be active this year sharing data. Most of it is things you've seen, although we have a small Japanese study that was done in healthy volunteers that we haven't yet shared. We said it's consistent with what you've seen in U.S. healthy volunteers. We'll share that. We're also working on a couple of publications this year that we hope will make it through. And so it'll be an active year of getting the word out there about the STAT-6 program, but less so on incremental data. Okay, that's really helpful

Ellie Murrell, Analyst — Barclays

context. In terms of the data, I just want to, you know, we talked about atopic dermatitis, but I think what's so interesting about this target is the potential to work in so many different indications. Could you elaborate on what was seen in the atopic derm patients in the

Bruce Jacobs, CFO

subset that had comorbid asthma? Yeah, so thanks for asking that question. So one of the exciting, many exciting parts of the phase 1b study were that we're able to look at some comorbid diseases and the impact that KT621 had on those patients. And there was a small group of asthma, patients with comorbid asthma, four patients in total, so understandably a small selection. But we saw some impressive results there. So I would say a meaningful reduction in phenol over 50%. And I think that what that told us is the drug is getting into the lungs and has promise in that indication as well. Obviously, we saw some nice EG reductions and itch reductions that gave us increased confidence that AD is going to be obviously a very meaningful potential indication for 621. But getting this additional data in asthma in a study that was really designed around AD patients was a nice incremental piece of information. I think it was a surprise to investors. We hadn't talked a lot about doing it. But we felt going in, frankly, that given what we know about the pathway, that we had good reason to believe that 621 would be applicable and impactful in all the diseases where DUPI is approved. And I think that asthma data just put one more piece of data behind that confidence that we have in that likelihood. So we're excited about that. Again, another piece of data that hopefully will help build excitement around the enrollment in the asthma trial, which is ongoing right now. And so DUPI is approved in many more

Ellie Murrell, Analyst — Barclays

indications beyond just AD and asthma. So let's fast forward next year. This hypothesis plays out. We see positive data in AD and asthma, and you move forward into phase three in both of those indications. Then you're also sitting on the decision of how many more phase threes do you start and how much do these cost? So walk us through the calculus, how you're thinking about that indication selection and sort of the phasing of all of these phase three starts.

Bruce Jacobs, CFO

Sure. Great. Well, so if this drug is as effective and safe as we believe it will be, I think our ultimate goal is to be approved everywhere DUPI is approved. And so the question really then becomes what is the timing and sequence of those pursuits? It would require upwards of 20 phase three studies to achieve approvals in all of the indications. That's an endeavor that if you tried to do that concurrently, I don't think any company could do it, let alone Chimera. But that having been said, I think we have a very deliberate strategy about expanding the indications we're going to be pursuing. And it's predicated on a development strategy that has these two phase two studies in AD and asthma really effectively supporting subsequent work in both dermatology indications and in respiratory indications. And so the hope is that once we complete these phase two studies, it'll position the company to be able to start other phase three studies even beyond AD and asthma. And so we haven't shared a ton yet about the sequencing strategy. I would say that if you look at the current DUPI market, AD, asthma, EOE, COPD accounts for the lion's share of the market. So one can assume that those are probably likely to be prioritized by Cabrera, I can tell you that much. In terms of the exact timing, I think we'll share more as we move forward. The other really important part of our clinical development strategy will be finding a way as quickly as possible as we can into the pediatric population. And historically, the protocol is that you complete a phase three in adults and then subsequently move into phase threes with pediatrics. We will do everything we can to get this drug ultimately into the hands of younger patients as quickly as possible, understanding that ultimately the FDA will dictate how we get there. But that's just a market of enormous unmet need. Again, Doobie is a wonderful drug, incredibly efficacious and safe, but it's not a pleasant injection. And if you're a parent injecting your six-year-old, it's not a happy time. So I think if we can make this product ultimately accessible to that population, I think that's an area of enormous, enormous need. So that's, I guess, how we're thinking about the development strategy. But you can assume that we appreciate that there's an enormous breadth of opportunity here, and we're going to take advantage of it. We've capitalized the company in a way to allow us to do that. We have $1.6 billion on the balance sheet. That runway takes us into 2029 and really gives us the maximum opportunity to, maximum optionality to pursue these, you know, broader list of indications.

Ellie Murrell, Analyst — Barclays

Makes sense. That's a very helpful context. So in the second half of this year, you've said that we'll get data in healthies in IRF-5. Certainly, there's a lot of excitement when we saw data in healthies in stat 6. But walk us through sort of the biology of IRF5, what we can expect to learn and help these around the biology and target engagement.

Bruce Jacobs, CFO

So it's, you know, one of the kind of side benefits of having a year of execution on stat six has been that we've been able to get more focus and attention directed towards IRF5, which is an exciting target that probably didn't get its fair share of investor questions last year, but it's changed for sure this year. IRF5 is a great target. It's been long pursued as well in pharma, but also has been on drug. It's a very, very difficult and challenging target to address. There's multiple IRS that share many similarities that make having a selective IRF5 target difficult to achieve. And also within IRF5, there's many different variants, and so you want to hit all of those as well. So, you know, we've, I think, cracked the code there. We found a molecule that's, like our others, is highly selective and we think ought to demonstrate a really strong profile when it moves through healthy volunteers and ultimately into patients. IR5 is what we kind of call a master modulator of immunity. Importantly, it's got, first of all, it's got exceptional genetic support. It's very strongly linked with diseases like lupus, RA, IBD, and so that's obviously important and a critical part of our target selection strategy, so it certainly checks that box. It sits downstream from many important pathways, type 1 interferon, pro-inflammatory cytokines, autoantibodies. And while there's drugs and diseases like lupus that impact each of these pathways individually, we think RF5 could be one of the only ones that can impact all three of these pathways. So if we fast forward to the healthy volunteer study, which has commenced, we announced last month that we'd started dosing. as with all of our studies in healthy volunteers, the first goal will be to show that we can degrade the target fully and that we can do it safely. From our clinical studies, you know, from our preclinical work, we think we probably need 80 to 90 percent type degradation. So that's what we will hope to show, obviously, and that it's well tolerated. The other important part of this study will be looking at biomarkers. So IRF5 is only activated in disease settings, so we won't be able to show like we did for 6-2-1 reduction in those biomarkers, because again, it's not, the target isn't activated, the pathway is not activated in those healthy volunteers. But we will be able to do some ex-devo stimulation studies to look at some of the pathways that I talked about, type 1 interferon, these pro-inflammatory cytokines, etc. And I think that'll give us an indication if indeed degrading IR5 is having an impact on those pathways. So it'll be an important and exciting study. We'll have that data before the end of the year. Our goal then is to move quickly thereafter into our first patient study. We said that would most likely be in lupus, but our plan would be to share more details around that as we move into the latter part of this year.

Ellie Murrell, Analyst — Barclays

Great. That's really helpful. And so if you move directly into lupus, like what theoretically, if you could give a little bit more color on what that could look like, would that be a phase 1B? Would that be a phase 2?

Bruce Jacobs, CFO

Yeah, I think we'll probably save the answer to that question for an update later in this year. We've built most of the development strategy for that program. We just haven't shared it all broadly. I think we want to get a little further in the year until we shed more light on it, other than just to say that the most likely first indication will be lupus, which has, again, a very, very strong genetic association with IR5. And I didn't touch on this earlier, but we've done a lot of preclinical work that gives us excitement about the potential of targeting RF5 in that lupus population.

Ellie Murrell, Analyst — Barclays

Great. And yeah, if you could also talk about some of the target biology in IBD and RA and some

Bruce Jacobs, CFO

of the other potential areas that this could work. Sure. So it's a tad bit premature, other than to say what I noted earlier, that there's very strong genetic association. We have done, as I said, most of our preclinical work is centered around lupus. We have some additional work we've done an RA. And then we have some work that is ongoing in IBD that we plan to share as we move to the

Ellie Murrell, Analyst — Barclays

year, but we'll save that for a later time. Great. And just to wrap up on the portfolio more broadly, as you think about target selection from here, you obviously have this platform technology, but what are sort of the attributes of targets and indications that you think about

Bruce Jacobs, CFO

as you advance more programs into the clinic? Yeah. Well, thanks. So, you know, we're really focused on having the strongest oral immunology pipeline in the industry. We think we're there, but we also have great opportunity to expand upon the existing portfolio with new targets and new molecules. So as I said, we've got a few that we're working on today. I think everything that we're doing fits within the model that I discussed right at the outset, which is known biology. So we're not taking huge biology risks, big areas of unmet need. Many of these markets are dominated by biologics. And so because of the appeal of an oral daily molecule, and I'm sure you've seen all these studies that say that, you know, 75 to upwards of 90% of patients that are on biologics would prefer a oral mechanism if it were equally safe and effective. Obviously, that's critical. So we think there's great opportunity. So all of our targets meet those criteria. I'd say about 80% of our work is ongoing in immunology, and so it's most likely that you'll see some targets in that area, but we have some other things that are, you know, progressing through the pipeline as well. But really, you know, we're trying to build a pipeline with other targets that look like STAT-6 and like IRF-5 and that they have just really areas of big unmet need where an oral daily molecule would be a regimen that would be highly appealing to a group of patients who either are already on biologics and would love to find something maybe less invasive or, frankly, and more importantly, is that really broad population like you see in AD of patients who are untreated because they're just not satisfied with the alternatives out there. There might be orals that have safety baggage that they don't want to accept or, again, they don't want to deal with the invasiveness of an injection. So we're excited about the pipeline. We've built a great team and, as I said earlier, incredible capabilities in hit finding and in chemistry that give me great optimism that we'll continue to stick to that one new entity per year goal that we've had for a long period of time. Great. A question that I get

Ellie Murrell, Analyst — Barclays

from investors a lot is how to think about which assets you might want to keep wholly owned versus partner, because obviously you have a rich platform that can produce many assets. We've seen a lot of deals in the stat six space. How do you think about this strategically?

Bruce Jacobs, CFO

Yeah, well, we're building a company that we believe can and will be a fully integrated biotech company. We've capitalized the company. We've built the team and the capabilities to do this ourselves. So partnership is not something that is a priority for us, certainly not with the STAT-6 program. I think the question where that becomes more pertinent down the road is when we have multiple phase three studies going, we have multiple programs, how much can we as one company do ourselves? So I think if you see us partner in the future, it would be more likely because we've just reached the level of what we can progress through clinical development on our own. But it's really not central to our strategy, and given we're capitalized to take these through trials ourselves, it's not something you should expect in the near term great that's helpful

Ellie Murrell, Analyst — Barclays

context well awesome thank you so much for joining us today and sharing all

Bruce Jacobs, CFO

your insights thanks Ellie it's great to be here thanks everyone