Kymera Therapeutics, Inc. (KYMR) May 12, 2026 Conference Transcript

Okay, let's get started. So, good morning, everyone. Welcome back to the Bank of America Healthcare Conference. I am Tazeen Ahmad. I'm one of the senior biotech analysts here at the bank. For the next 30 minutes, we'll be sitting and chatting with Chimera Therapeutics. Up here on stage, we've got a couple members from the management team. We've got Bruce Jacobs, who's, of course, the chief financial officer, as well as Jared Golub, who is the chief medical officer. Gentlemen, thanks for making the trip over from Boston.

Thank you.

So maybe we can just start off with a quick overview of the company, maybe talk to us about, you know, atopic dermatitis is a very, very popular space to be looking at these days. That's just one of the many things that you've got going. Can you just talk in general about the platform and how you differentiate from others who might be pursuing similar indications, and then we can go into more specifics from there?

Sure. Thanks, Tazine. Maybe I'll start, and Jared can chime in. So it's a good time for that question. And Chimera actually, last week, celebrated our 10-year anniversary.

of the company's founding, May 4, 2016.

So it's been a great opportunity for us to reflect on all that we've accomplished over that time, but also what we still have in front of us. But the company obviously was founded at the time on the promise of targeted protein degradation. And since that time, I think we've been incredibly productive as a discovery engine. We've taken now six programs into the clinic. Over time, we've narrowed our focus really to immunology, where we think there's enormous And I think I've developed one of the better track records for targeting very unique, difficult to address targets with large opportunities, with clear biologic rationale, and human genetics supporting them, and puts us in a very good position with both the programs that we have in the clinic today, and I'm sure we'll talk about both STAT6 and IRF5, as well as those that will come in the future, and we still have an intention and goal to introduce at least one new program annually. So excited about where we are as a company. This is obviously every year is an important year for Chimera. This year is of particular importance as well because we've embarked on these phase two studies for KT621, one in atopic dermatitis and one in asthma. And I'd say the highest level of focus at the company right now is on executing on those trials. And we expect to complete the AD trial this year. I'm sure we'll get into that throughout the conversation. Asthma next year, and we'll have data, we expect, for both in 2027. So it's an exciting year for us in that regard. Going back again to the overview, IRF5, which is our next program after STAT-6, is in the midst of a healthy volunteer study. We'll be able to share data for that program in the second half of this year, and again, working to introduce one new program annually. At the same time, we have a couple programs partnered, one with Gilead, one with Sanofi, Those continue apace as well. So really, a lot of opportunity to progress all these molecules towards ultimately helping patients, which is the fundamental goal of the company.

Okay.

So for STAT6, you guys are, I think, the most advanced in terms of data that's been shown so far in atopic germ. But you're not alone. There's quite a few companies pursuing this indication. So you can look at it. That de-risks it because a lot of companies are willing to spend time and money on this. But on the point of differentiation, do you think that these molecules are meaningfully different from each other?

Yeah, I think in terms of, say, small molecule inhibitors, for example, of STAS-6 versus degraders, we think that there is significant differentiation because the pharmacology of degraders allow us to degrade STAS-6 completely and keep it down 24-7, which is really the sort of inhibition you need if you want to replicate what upstream injectable biologics do to the IL-413 pathway. So we're able to achieve that because of the catalytic mechanism of our degraders. Small molecule inhibitors, and we've looked at these as well preclinically, they're just not capable of that level of inhibition 24-7. Small molecule inhibitors, because there's a stoichiometric sort of relationship, you get waxing and waning of exposure after a dose, and therefore you get waxing and waning of pharmacology. So I think it would be very difficult for an inhibitor of STAT6 to hit the pathway completely and consistently and maintain that inhibition the way a degrader can. So I think that gives us a significant advantage pharmacologically over the inhibitors.

So, yes, you talk about degraders versus inhibitors. In a clinically meaningful definition, what do you think that would manifest as?

Well, I think ultimately it will have to come out on clinical efficacy, right? So the ultimate test will be in randomized placebo-controlled studies and looking at efficacy with standard ADM points, for example, or asthma endpoints, depending on the study. So I think it will have to come out in the clinic, ultimately. I think some of the early phase studies will be able to start to give a sense, perhaps, with inhibitors. There are several inhibitors in phase one now that might start to give people a sense for what degree of inhibition are you seeing, what sort of effect are you having on biomarkers, even in healthy volunteers like TARC and Eotaxin-3, how do those compare to what we showed in phase one. You'll start to be able to make some comparisons, but ultimately, I think, the true test is going to be when you're up against a placebo when you're in a dose-range-finding phase 2 study, and again, I think just because we're able to maintain deep degradation over time without any let-up, which is much more like what you see with biologists like DUPI, where the inhibitors, we don't expect to have that same level of suppression, we think probably we'll compare favorably, at least across studies, once there are phase 2 data out there.

Okay. If you think about how people describe 621, rightly or wrongly, they call it the oral DP. So I wanted to get your thoughts. Do you like that term? Do you think that the main difference is the dosing, and how are you thinking about the overall efficacy profile over time as you compare it to Dupixen, especially as that goes at some point biosimilar?

Well, I think obviously the history of that term is really rooted in the fact that we are stat 6 as a protein is downstream from IL-413, obviously the target of dupilumab, and there's good reason to believe that if we can fully block that target as we expect to be able to do, that we have the opportunity to come close and hopefully actually replicate both the efficacy and safety of dupi, so I think that's obviously the derivation of that. Obviously, it's up to us to show that. I can say that everything we've seen, both preclinically all the way up through our smallish patient study, the Phase 1B 22 patient study, has supported the fact that it does seem to look and act like DUPI. We've seen efficacy levels that look comparable, and the safety's been quite clean. But obviously, as I said, it'll be up to us to replicate that in these randomized placebo-controlled trials, which we're in the midst of doing right now. It's an exciting opportunity. You talked about AD. It's obviously a very prevalent disease, and as successful as dupilumab has been, the penetration is still quite low, and there is a large number, depending on what source you evaluate, 40 to 50 million people that have moderate to severe TH2 diseases that are effectively not on systemic therapies, and that might be for various reasons, aversion Needles. It might be insurance reasons. It might be just fear of having to admit that they have a serious disease. We think that's a great population for 621, should it achieve the TPP that we're hoping to see with the drug. And so a lot gets made about, you know, how patient volumes will shift from injectables to orals, how many and so forth. I think the point we try to make is that there's a A large number of patients out there available and, frankly, excited about an oral mechanism, and that's where we'll mostly be focused.

And I think, as Bruce said, you know, while, you know, the term duping a pill helps people to understand mechanistically what we're trying to do with 621, I think ultimately we feel that KT621 will stand on its own merits, essentially, independent of duping, and maybe those comparisons down the line will start to go away.

So based on the data that you've presented so far, can you talk to us about what you'd expect to see at the next data update for AD?

Well, I think so. For us right now, it all focuses on the phase 2B broadened 2 study, which is a dose range finding study. We have three different doses of KT621 versus placebo. It's 16 weeks of dosing, daily dosing, followed by a 52-week open-label extension. So this is the first placebo-controlled test for KT621. So, clearly, we want to see that the drug itself has superior activity over placebo. You know, the primary endpoint is percent change from baseline and EZ at 16 weeks and a number of secondary endpoints that look at EZ and pruritus and a number of other relevant AD endpoints in all different ways. And so, I think really what we want to see is that this is a drug that is superior to placebo. We want to see that safe and well tolerated. Of course, there There will be cross-study comparisons in terms of, well, what did we see, you know, versus what has been seen in prior doobie studies, but really the aim of the phase 2b is to pick the dose that we then bring into phase 3, not just phase 3 and AD, but potentially phase 3 across other type 2 indications, for example, other cutaneous type 2 indications that could include indications like CSU, whereas with the asthma study, which is separate, which is the breath study, which is ongoing, that's a phase 2b study, We'll also have a Phase III dose come out of there, and that Phase III dose will be used not just in asthma, but also in potentially other respiratory indications like COPD, CRS with NP, et cetera.

We were obviously very encouraged by the Phase I-B data, but that was, by its own right, limited in terms of the number of patients was not placebo-controlled. So I think this will be a real opportunity to really see what this drug is capable of delivering. And we were asked many times for that study to put, you know, what's our bar of success, and we're asked that again for 2B. I think the point is, as Jared mentioned, is really to be able to pick a single dose to move into phase three, but everyone will be able to look up where DUPI was at 16 weeks and make their comparisons, and then we'll see where it falls out.

Yeah, and the point of the safety profile, mechanistically speaking, would you expect to see conjunctivitis show up at a certain point?

Yeah, you know, we get asked that question a lot. It's a really, you know, relevant question. What we've said is that because we're blocking the same pathway IL-413, and we know that with DUPI or drugs that block IL-413, one does see conjunctivitis predominantly in AD patients. You know, our expectation is that we should also see conjunctivitis. We may see conjunctivitis because we're also blocking that pathway. Now, with that being said, the mechanism for conjunctivitis in AD patients in response to IL-13, IL-4 targeted agents is unknown. So we don't really know what causes the conjunctivitis, so it's always possible there could be something unique to the antibodies that might be different from small molecules that might contribute. But our base case is that mechanistically we would expect to see something similar. I think we'll learn a lot from the ongoing phase 2B study to really know, are we seeing it? And if so, is the frequency similar or not to what's been seen previously with 2B?

And we didn't obviously see any cases in the phase 1B, but it was 22 patients. And at that time point, 28 days, DUPI only has about a 5% conjunctivitis rate, so you might have expected, right, one patient. So the fact that we had none, it's hard to make the call whether it was truly nothing or just small numbers, but obviously we'll learn a lot from the phase 2Bs.

Yeah, so based on our feedback from physicians, they don't at this point consider conjunctivitis to be, you know, rate limiting in use. It's certainly not for dupixins, but do you think that that bar has been set by dupixins? I think it's 14% in the approved dose that you see conjunctivitis in general. The higher you go from there, does that kind of impact the way you think of the market opportunity for 621, if it's the case that it's higher?

Yeah, I think probably, you know, we'd like not to see a significantly higher rate of conjunctivitis or greater severity. You know, it's possible we could see the same, we could see less. And even though it is a sort of quote-unquote nuisance adverse event that usually doesn't lead to discontinuations or dose changes, you know, it is something that, you know, patients and clinicians are aware of. So, you know, if we're going to see it, we'd like to be in that same ballpark. We don't want to see more of it necessarily. Now, if we did see a little bit more, would it matter? You know, I think if our efficacy is strong and we have an oral drug, I don't think that would be an issue.

Are there any other side effects to be looking out for here?

Well, I think with dupy, I mean, you see a very low incidence of viral infections over time, you know, whether it be mostly herpes simplex. Sometimes you can see sort of facial eczema, facial rash in maybe 5% to 10% of patients who are getting dupy. Those are the main things that people have seen, maybe a little bit of arthralgia in a small percentage of patients. So those are some things that we'd be on the lookout for. The fact that we haven't seen any of this so far, either in our preclinical work or in our phase one, means that these are not for us sort of, quote-unquote, adverse events of special interest. But I think, you know, we will be looking for those because those are things that have been seen with DUPI.

I mean, the data that we've been able to generate through all the preclinical work and then into both the healthy volunteers and the phase 1B has been as good as we could have expected from a safety standpoint. I think that speaks to, as we said earlier, what's known about the pathway, also the selectivity and potency of the drug being what it is, and so, you know, we went into the human exploration here having dosed at 30 to 40 times the efficacious dose in preclinical studies without having seen any adverse events, so, you know, we come in feeling good, but obviously that's the point of these studies as well.

And again, you know, as we said earlier, the phase 2b, it's a dose range finding study, so the aim is to look at safety and efficacy across the three doses and look at that in composite and then make a decision about what is the appropriate dose to bring into phase 3.

Do you just want to have one dose?

Yes, ideally we'd like to have one dose in phase 3. I think we should be able to achieve that given all we learned about sort of exposure response relationship in phase 1 and what we'll learn hopefully from the three different dose levels that are in phase 2b.

Okay. So next year is a big year for the company, right? You've got both the AD and the asthma phase 2Bs revealed. I think you've guided to mid-year for AD and closer to year end for asthma. When you do show the AD data, do you think that de-risks the asthma study?

It's a good question. I mean, I think we think of those studies as being separate. It's interesting that in the Phase 1B AD study, we did look at some respiratory endpoints. So in that study, we had some patients with comorbid asthma and allergic rhinitis, and we were able to see a nice impact of the drug on those comorbid illnesses as well as a nice impact on a lung biomarker called fractional exhaled nitric oxide. So even in the AD patients, that started to give us confidence of what we think the drug could do In asthma, which we already knew pre-clinically, we had a very strong effect in the house dust mite asthma model. And so I think, yes, you know, I think the AD study can shed some light on potentially, you know, what we may end up seeing in breath. But with that being said, you know, the endpoints are different. You know, they're different populations. And so I think we have to sort of view them separately. You know, the AD readout first and see how we impact those AD endpoints. And then I think hopefully the breath study will stand on its own. The BREATH study, just as a reminder, also three different dose levels versus placebo. It's a 12-week endpoint, primary endpoint, which is change in FEV1 from baseline, and there are a number of other secondary endpoints as well for that study. And it's also for patients with eosinophilic asthma. We call it high EOs, high phenol. So I think we expect, hopefully, to see encouraging results from both, but I think they'll both be sort of standalone studies And we'll tell us a lot about, you know, the phase three dose to take into either AD or other skin indications or maybe even GI indications coming out of the AD study. And then the asthma study, if it's a positive study, telling us what dose to take into asthma, COPD, and other respiratory indications.

But I do think it's a fair statement, though, that if we indeed, the AD will read out first, right? So we started just a level set on timing. We started that study last year. We expect a complete enrollment by the end of this year. And then that'll, once we announce that, that'll start the clock for when you can expect to see the data. I think positive results from that AD study will certainly make us feel more confident of the likely outcome in asthma, just given what's known about the mechanism.

And it does seem like other, you know, mechanisms of action for approved drugs, it seems like it's part of the natural progression from AD to asthma and other related indications.

Yeah, exactly. If you look at DUPI and its impact across all type 2 diseases, Whether they be respiratory, cutaneous, or GI, it's also worked across the board, and so we do have similar expectations there as well. I think for us, it's more a question of what is going to be the appropriate dose to take into phase three on the respiratory side versus on the derm side.

And as you think about market opportunities for both of these, is there one that's meaningfully bigger as you sit here today for 621?

Bruce, go ahead. Well, no, I think that there's an enormous opportunity for both. We talked about the untreated, when I say untreated, but the population that is not interested for a variety of reasons in advanced systemic therapies is significant. The other area that we haven't talked a lot about is the pediatric population. Obviously, many of these diseases afflict children. For right now, we're approved in the AD study, adolescents end up. But you can rest assured that the pediatric population is going to be a big focus of our time, attention, and our investment going forward. So I think they're both significant opportunities. Asthma, in particular, is interesting because there's so much known about what they call the atopic march and how patients worsen over time. So the sooner we can treat patients, I think, the better for the prevalence of the disease. And if you talk to parents, and we have talked to many about the pain that both they feel and the children feel from having to give an injection, it's a real impediment and a traumatic experience for a lot of families. So we're excited about having the opportunity to intervene there with a small molecule oral approach.

Yeah, and certainly one of the reasons we chose to start with AD and asthma is just because those populations are so large, 80% of Doobie's revenues come from those two indications, and so it represents a very large opportunity for adults, adolescents, and pediatric patients. Obviously, the other indications are very important as well, but starting with those, I think, made the most sense.

There's a question that's becoming more and more asked in my conversations, which is whenever Dupixent has a biosimilar, in a world where there might be, you know, multiple different options for AD, does that, in your view, make it a little bit easier because you would be an oral option? And for insurance companies that are always looking to kind of have patients step through therapies, would this be something easier that it would be able to get insurance to initially let you use earlier?

It's a good question. I think time will tell how the market unfolds. I think most people believe and expect that Doopey, that Regeneron, Sanofi will do their level best to extend the timeline for generic entry. And we've heard anything from the early 2030s to 2033, 34, beyond. We expect that we will likely be entering the market before a generic dupie is on the market. So I think that's, in our expectation, the most likely scenario. Obviously, a lot has to come to pass for that to be the case. But, you know, we, again, going back to the patient population, I think we're focused intently on this large number of patients that are not on biologics today. Is it possible and perhaps even likely that some number of patients will likely want to switch, certainly? But we would certainly like to be, you know, an early line of therapy for a big number of patients, which is what our goal is.

Okay. I did want to touch upon 579, IRF-5. So mechanistically speaking, why does it make sense to pursue this for autoimmune disease?

So, you know, there's been a lot of interest in IRF-5 from both big pharma and biotech for years, in large part because of the very strong genetic association between mutations in IRF-5 and susceptibility to lupus, to IBD, and to RA. The real problem has been just not being able to drug it. It's difficult to drug because there are multiple IRF family members, so you want to be specific for IRF-5 if you want to have a drug with a good safety profile, and there are also multiple different isoforms of IRF-5 itself. You have to be able to block all of the isoforms of IRF-5. So that's been, you know, the main stumbling block. But IRF5 has been of great interest because it's selectively expressed in certain immune cells like dendritic cells and monocytes and macrophages and B cells, and it's involved in controlling type 1 interferon response, controlling reduction of pro-inflammatory cytokines like IL-12, 23, and 6, and also involved in B cell activation and autoantibody production. So you get all of that by targeting one protein. So again, I think the limitation has been being able to target it. But now that we have a degrader that is highly selective for IRF5, it hits all of the isoforms of IRF5, we've been able to show preclinically that we can degrade IRF5 completely and that it's safe and well-tolerated. And we've also shown, importantly, in preclinical lupus models, several different models, that we are even more active than either standard drugs that are approved or other active drugs that are in development. And we've also shown that recently in a model of IVD as well. So I think we have a real profound opportunity here for targeting IRF5 to transform how diseases like lupus, inflammatory bowel disease, and RA are treated with an oral drug that we think can be dosed safely to fully block IRF5, but by affecting multiple different pathways, not just single pathways, really have a transformative effect on the treatment of these diseases.

So as you think about the level of degradation that you think is going to be needed to produce clinically meaningful results, is that going to depend on the indication? Because I think this mechanism has been tried by others, and it's also been a little bit of a challenge to get good data. So you've talked about your view about differentiation of your platform, but how should we be thinking about level of degradation you're looking for?

Well, I think we've shown in our models of lupus and IBD that even, you know, 80, 85 percent degradation is enough to give us very strong activity. I think our expectation in the clinic, just as we've had the expectation for other programs previously, is that we want to see at least 90 plus percent degradation of the target, and we feel we'll be able to achieve that based on our preclinical results. Do we need that level of degradation? I think we still don't know whether we need 95, 98% degradation to impact these diseases, especially since our preclinical data suggests that 85 or so percent might be sufficient. But I think we want to understand in phase one, can we get at least 90% degradation? Can we push the dose to get higher levels of degradation? Are those doses safe and well-tolerated? And when we do see degradation, are we impacting the pathways that IRF5 is signaling through? So TLR7, 8, and 9 doing ex vivo stimulation assays as part of our phase one study to really show how degradation in vivo in healthy volunteers translates then into impact or hopefully inhibition of those TLR7 pathways, Which I think if we were able to show at least 90% degradation and blockade across these three different TLR pathways, that would hopefully translate into being able to see activity in a subsequent patient study.

Okay. So when is the next data update from that program?

So we're running the healthy volunteer study now, and the timing will be once we complete the MAD portion. Typically, we do a SAD, and then partway through SAD, we start MAD. Once we finish the last MAD cohort and collect that data, then we'll share it with everyone. So we've got it to the second half of the year. We'll be able to give more specificity as we get closer. It just depends on how many cohorts we end up enrolling. So we'll hopefully have that data then, and we also plan at that time, if we haven't already done so, to share more details around the plans for the next study, which, as we have said, is likely in lupus.

Okay. And then how many different indications do you think you'd want to pursue at the same time? Because I remember, this was in January, one of the questions that Nella was asked when we all met up in January was, how many different programs do you think the company can support, given the size of the company? So what's your thought? Because you're the chief medical officer. How comfortable are you going to be?

We'll do everything. No, no, I think for IRF5, I think it's going to depend on, first, let's see what we see in phase one. If we get the levels of degradation and pathway inhibition that we want with doses that are safe and well-tolerated, I think that'll bring us into our first patient study, which, as Bruce said, will likely be a lupus study. If we feel as though there's a pathway forward in lupus, then the question becomes as you're asking, okay, well, do we start to think about development in inflammatory bowel disease given the promising results we've seen in our preclinical models there? Or would we be interested in other type 1 interferonopathies like Sjogren's disease

where there's also strong genetic association or systemic sclerosis or even rheumatoid arthritis?

So I think that remains to be seen, so maybe I'll punt it a little bit, that I think these are all potential opportunities for us. I think what we see in phase one, what we see in the lupus proof of concept, and how our preclinical animal model data continue to evolve will probably inform, ultimately, whether we parallel track or not, you know, other indications along with lupus.

The premise of your question is a good one, which is that the breadth of the opportunity in some of these targets is significant, right? Obviously, we've talked about AD and asthma with STAT6, but there's, you know, COPD, there's chronic rhinocinus, there's EOE, and several others. We, Jared mentioned a couple with IRF5. I think, you know, we've obviously, we're a well-capitalized company, but there's also, you know, human resource constraints ultimately, and broadly pursuing all of these indications, and so I think we'll continue to be rooted in the science, what indications are most supported by the preclinical work we do with Obviously, a commercial lens as well, and then try to make the right resource allocation decisions as we advance both these programs through clinical development.

And I think Bruce maybe mentioned this up front, but in terms of how we build our development group, we always try to be very proactive, and now even though we're in Phase 2B, we're already looking ahead to Phase 3 and building our development group to be able to manage multiple Phase 3s. And then the same thing goes. If 579 ends up being a productive, successful program, then we want to be able to be staffed up to be able to support doing additional trials there across multiple indications.

Yeah. And so on that point, what's your view going forward as probably for Bruce on business development, either partnering what you have, continuing to partner what you have with others, or do you even think that there's a reason for you to bring in things that you don't have currently?

As you might imagine, because of the opportunity in both of these programs, there's been plenty of companies who have kindly offered to lend assistance to our development efforts. Thus far, we've been focused on keeping these two programs internally run and wholly owned, and that's the plan for the foreseeable future. I think the opportunity that we might pursue would be one where we could, I'd say, capitalize on the breadth of the opportunity in a greater way than we could do ourselves. But heretofore, we have the team and the capabilities, and importantly, we have the capital to execute in the case of STAT-6 on these Phase 2B studies. So we'll see what happens beyond that, but that's our intention. We have a business development effort as well that's looking at in-licensing opportunities. Mostly in areas in immunology that would be synergistic to the programs we have today, but that also has to compete with a very productive internal discovery engine as well, and there's a lot happening on that side as well. So nothing to project and predict, but just know that we're going to do what we think is the right, take the right strategic option to really maximize the opportunities in some of these very, very large opportunities in front of us.

Yeah, on that last point, on things that you would look at, would it be things that you're not trying to, like T-cell engators, would that be something that you would want to develop in-house? And would you be, do you think that could be complementary to anything?

Yeah, so I think we've tried to stay focused on our core competencies, which is really on small molecule development. And so it would be difficult for us to venture into areas that were not kind of our core area of expertise. So most of the internal work we have, as you might imagine, is around protein degradation or small molecules more broadly. Could we in-license something a little bit afield from that? Certainly if we thought there was an opportunity to perhaps, you know, combination therapy down the road is going to be an interesting area of development. That's one that we're exploring.

With that, we are just about out of time. So I wanted to say thank you again for making the trip out west, and thanks, everybody, for joining us for the session.

Appreciate it.