Kymera Therapeutics, Inc. (KYMR) September 2026 Conference Transcript

Good morning, everyone. I think we'll get started here with the first fireside of the day. My name is Derek Archilla. I'm one of the Wells Fargo biotech analysts. I'm very excited to have Chimera Therapeutics. We're from the company. We have Nelofalphi. It's too early this morning. No coffee. President and CEO. And also we have Terrence Rooney, the new chief medical officer. All right. Got that one. All right. Well, probably one of the most consequential catalysts in small cap biotech this year coming up for the Broaden II trial. So, Nelo, maybe just sketch out for us, you know, kind of where you are with your STAT-6 program and maybe just a little bit about Broaden II before we get into the more specific questions.

Yeah, maybe that's that so thanks for the invite and great to be here in Boston sometimes So maybe let's take a step back just a minute on Chimera for people that don't follow the company closely so we're a company that was founded about ten years ago with the goal of using and building and evolving and Advancing a new drug modality called targeted protein degradation To deliver a whole new generation of medicines. These are the small molecule oral drugs that can degrade targets with the Efficiency the specificity that you can see in for example oligo based therapeutics, but with obviously the convenience of oral small molecule, so You know as part of our target selection strategy we have really focused on pathways with high degree of validation targets that have strong human genetics but undrugged or poorly drugged and so stat 6 coming back to your question stat 6 is we believe one of the perfect targets for protein degradation is a transcription factor traditionally difficult to drug it's in a pathway that has been extensively validated by multiple agents but most importantly by dupilumab which is an IL-4 receptor alpha monochromal antibody and again a pathway that and a target that would potentially give the first oral drug in this space so we have generated a plethora of pre-clinical data demonstrating that targeting stat 6 can block IL-4 and 13 just as effectively as an upstream biologics we've generated early clinical data that confirmed that KT621 is a potent specific and highly effective stat 6 degrader again a first-in-class degrader and also we've shown in a small phase 1b AD trial that the level of stat 6 degradation lead to a deep the level of degradation that we achieved which was you know very robust uh uh lead to a very robust impact on type 2 downstream biomarkers which eventually correlate to meaningful improvements in signs and symptoms of atopic derm comorbid asthma comorbid allergic rhinitis so all of this data all these two minutes or three minutes of my talk has given us the confidence and the excitement to initiate two global face to studies. One brought in two that you mentioned, this is a global dose-ranging placebo-controlled study in moderate to severe atopic dermatitis patients, and another study is BREATH, which is a global dose-ranging phase-to-bit study in eosinophilia, because actually I should say in type 2 asthma patients, so patients with high eos and ifino so i think as you said and i completely agree i think it's one of the most exciting programs our set six program and namely with the acceleration of enrollment we have been able to move up the data readout from middle of next year to as we said at by the end of 2026 so that's what we are today we've you know we've the goal of this study is number one to evaluate the safety and efficacy of kv6 to one in a much bigger study and just as importantly to select those for our phase three program got it so a lot to unpack on you know the trial but maybe first just in terms of your comments there around the enrollment and why in and it rolled so much quicker than expected, despite the fact that you were doing a lot in the trial kind of enrollment criteria to kind of mitigate placebo and things like that.

So maybe talk about those kind of pushes and pulls and why that's so exciting that the enrollment is so fast.

Yeah, I mean, I would start by saying that our projections were based on general execution of any topic dermatitis studies in this day and age, And also included what we expected the timeline would be in a study that is set up to ensure that quality and speed are equally important and not speed is the most important parameter. So I guess we expected that because of some of the measures that we had put in place to control, let's call it patient quality, that that would have impact enrollment. And what we've learned, that while all those measures that we put in place obviously were not changed alongside the execution of the study, they actually did not impact enrollment. And the enrollment went at least as well, if not actually way better than we anticipated. And mostly, I think, because there is a big desire from the AD community to have an oral drug. I think there is a level of comfort that investigators and eventually patients, I assume, have in this pathway and also the appreciation of the data that we've generated so far. Gotcha.

So, you know, in a lot of these AD trials, the more contemporary ones, you know, we've seen placebo responses kind of increase and, you know, that presents kind of an execution risk or at least a risk to the trial. So maybe you can kind of walk through some of those quality controls that you were just talking about in terms of the trial that you guys have employed. And I guess, you know, again, what you kind of are thinking about in terms of placebo response in this day and age for an atopic dermatitis trial.

I mean, I think we've seen, I mean, I would say more recently, the placebo responses have been generally within, let's say, the historical range. yes higher but not dramatically higher than historical rates we've had maybe two and a half years ago so a couple of really really bad study sorry really really bad placebo rates that I think spooked everybody I think investors and companies and I think so the reflection if you do a kind of a historical analysis I think it is true that from the early days of AD development which I think we should say dupilumab was the first systemic targeted therapy in a topic term so let's say from those days the placebo rates have increased and I think what is a fact is that the severity of baseline of patients that enrollment into these studies has generally increased the decrease the severity and that's mostly because in many of these sites we all use generally the same sites these sites have patients have access to these advanced therapy this biologic so generally the very very severe patients are treated with biologic so in these sites where you end up seeing are you know moderate to severe patients but maybe it's severity is less than the first study in atopic term so we've seen the mean baseline easy go from you know the low 30s into the mid 20s again these are still squarely in the mother to severe population but I think with that you see probably more disease fluctuation as the disease gets less severe and so that probably plays into what we've seen increased placebo rates I think another important reason is that because the space is so competitive I think in some cases not in all cases I think you have maybe some poor quality of both you know how sites and investigators and these studies you know measure the endpoints or heterogeneity into the measurements because there are many people involved in the studies and so I guess just driven by the competitive landscape maybe some of the quality has been reduced and so when you put it all together what are the things we can control obviously we cannot go and let's see patients which you know I love to do but we can't and so it comes down to ensure that that patients on our study have confirmed atopic dermatitis which you know believe it or not is still something you need to correct for and we have put measures in place to ensure that that the severity is in the generally again you can really the sponsor can get involved into that assessment but you can put system in place to make sure the severity is in the range that you're studying and then I mean a lot of it a huge amount of it is site and CRO oversight which you know I think we employed, as much as we could, a high-touch approach that hopefully will lead to a successful study. So everything I said, I think we've done. Some of the more creative things that have been done recently, the proof will be in the pudding, so we'll know soon enough. I know you've characterized kind of the expectation of having efficacy kind of around DUPI in the trials that they've produced that data in atopic dermatitis. so i guess to you what's in the range for for dupy does it need to be dupy like or can it be slightly lower than dupy because it's an oral yeah so maybe i'll take a step back and then i love to terence also to provide this view given that he's been involved in lots of studies with with oral drugs and biologics so i'll give you my perspective so so first uh i think something that we have learned by being in the field of type 2 inflammation and more in this case more closely AD is that what really patients and prescribers are looking for is a inactive and safe oral drug and so while from a scientific perspective you know the narrative of oral dupy has actually been quite successful one from a both communication and actually the data that we've generated I think what we have been met extensively is yes you know that that would be cool that would be great but actually what we need is an active and safe oral so in a way what we believe will be an amazingly successful program is a program that is strong activity and good safety and maybe we could talk about you know parallels in psoriasis maybe Terence can touch on it now from a technical perspective I'm not going to shy away from commenting on your question what we've shown to date has been that you know the mechanistic studies that we've done pre-clinically and everything that we've done clinically you know KT621 seems to be able to block IL-4N13 just as well as upstream biologics and again namely dupilumab so when i say from a technical expectation meaning from a scientific expectation you know to be in their range is like you know again i don't know because you know numbers can be different but you know i think when you look at the again solo one solo two data i think you can see the easy 75 iga01 you can see even across the two study there is a bit of a range so I think in that in that range that someone would think it's reasonable is where our expectation lay again from a point of a phase three and commercial success we're not fixated on the DUPI range we're fixated on efficacy and safety but before I say everything Terence why don't you share some of your views yeah look I just amplified there's

very reasonable grounds to expect scientifically that pathway blockade would be commensurate with the likes of dupilumab. And Nella already told you the story. We've seen that pre-clinically. We know from just expected pathway biology, and we've seen evidence of that in the clinic. However, I think we're learning more and more as we speak to patients, providers, and other stakeholders that there's just such an appetite for a safe, effective oral in this space that precisely having to meet exactly the efficacy bar produced by upstream injectables not necessarily required. You don't have to look too far around the industry for some examples in the dermatology space. If you look in an even more mature market, more severe plaque psoriasis, you've seen the recent launch from my old friends and colleagues at J&J of icotide, icotrakinra, targeted oral peptides selectively blocking the IL-23 receptor.

The launch appears to be going extremely well with a data set that arguably doesn't precisely meet all of the injectable biologics that came before so on the one hand we have very reasonable grounds to be optimistic on the other hand as you say I don't think you need necessarily to be at the same bar makes a lot of sense and then I guess you know one of the important things that we hear from investors is around like so you have three doses in the trial this is a very potent drug so I mean you know I think do we need to see a dose response I know you're trying to go lower to maybe kind of find a less efficacious dose essentially which might might be a good problem to have, but walk us through that and kind of your expectation.

So just to, I think I've said this before, but if not, I'll say here first. No, I mean, we didn't design the study to deliver a dose response. We designed the study, we believe, to select the best phase three dose. And when you think about phase three dose, you want to have the lowest most active dose possible and so I think if you think about the doses that we've selected I would say probably you know the let's let's call it the middle dose is that those where we believe we are achieving maximum pharmacology then you as you do if you don't have concerns about safety which we haven't uh so far uh you know we asked the question if you go above that pharmacological dose do you see more do you see the same so obviously we don't expect again we can be surprised i wouldn't expect to see a dose response in that let's say middle and high dose and then we select a lower dose where we expect to see less activity so again maybe it's not a perfect dose response but hopefully it's clear that you know we didn't explore this huge you know range to demonstrate that dose response we're really focused on selecting the best phase three dose possible gotcha and then maybe just to piggyback off the comment on safety so you know maybe just walk us through you know so far we've seen decent safety short trial very good very good very

good safety thank you for correcting me but so it's still limited data set yeah so as this will be you know longer 16 weeks but you know is there just going based on like the preclinical data what should we think about from just kind of loss function models but you know is there anything that we should be thinking about just in 16 weeks and then you know going forward to your open label which is gonna go out even longer so but yeah I think that's obviously for chronic therapy we'd want to see a lot of patient years of data so what are you trying to amass and what's the strategy there well i mean uh yeah so high level maybe it's worth summarizing the safety that we've generated so far so um from a pre-clinical perspective and

you know even looking at human genetics we know that gain of function of stat 6 leads to severe allergic diseases so that is a sign that the target is responsible for type 2 inflammation and nothing else at least as you're looking at those humans we know the heterozygous loss of function is completely no as a completely normal phenotype from a pre-clinical perspective we've run you know all the tox that is actually needed to initiate a phase three study including chronic toxin in all of these studies we have really not seen any anything to note and in the clinical space obviously as you mentioned the longest study that we run before the face to be have been the 28 day study and obviously we've with those probably close to 200 subjects between healthy volunteer and patient so we have lots of ends but short duration so as we go into these larger studies obviously our strategy is to amass as much long-term safety data as possible to being able to file an NDA as quickly as possible so the reason for having not only obviously people in 16 weeks but all of these people are able to join an open 52 week of a label extension on both the AD and the asthma study is to as you said amass as much safety information as possible so again we don't have you know besides the pathway events that have been seen in the past for example we know that agents in these pathways have generated some imbalance in conjunctivitis between placebo and treatment are in AD not in other indications besides these that we know obviously we were curious about and on the lookout for we don't have other things that were you know going into the study expecting or being worried to see so we're obviously very focused on generating the data but you know again we don't have something that we're trying to de-risk per se. Should the base case be that we see conjunctivitis in this trial? Well I'll share my view and then I'll let Dr. Rooney share his medical view so my non-medical view is that if I look at this pathway all the drugs that have targeted this pathway have shown some level of conjunctivitis so in a way I've said this for a couple of years and in a way I expected but who knows you you we just don't know actually what's driving it so it's hard for me to rationalize one way or the other I would say the asset has behaved well providing complete and exclusive inhibition of a keynote that completely and exclusively serves signaling of the upstream 4.13 pathway.

We've learned a lot. It's been very well characterized, the safety profile, across a variety of inhibitors of that pathway. Therefore, while we've seen no events to date of things like conjunctivitis, it would not be unreasonable to expect that we would see some as we move along in development. It's a learn and confirm paradigm, and we learn a lot from phase 2b.

Just to be clear, today refers to the phase 1b. Yeah, in case people want to read into it.

Yeah, getting a little jumpy. So, yeah, so I guess maybe talk about, so data readout, positive data. I mean, so you've already kind of operationalized, you know, gathering more safety. You know, how fast can you get into phase three and, again, basically walk us through kind of the phase three strategy post data?

Yeah, I mean, just on the timing, I let Terrence speak to the strategy. Obviously, we're not sharing details, but to the timing, we've said we should be able. Obviously, there is a regulatory interaction to be had, apparently. But I think we said by middle of next year, we'd like to start our phase 3. Terence, maybe we can talk about our strategy.

Yeah, so the phase 2b studies that are running at the minute that Nellor described, of course, are in atopic dermatitis and in moderate severe asthma. Our strategy would be that that would unlock a suite of confirmatory studies across the spectrum, potentially, of type 2 inflammation indications in DERM, in RESP, and in gastroenterology. Obviously, the first readout will come towards the end of this year, and the readout of the asthma study will come during 2027, and we'd be looking to move aggressively across indications from there.

So, I guess in your view...

And, you know, just to add, it's obvious, you know, AD, because it's moved faster, you know will hopefully be the first indication that we move into phase three and we plan to move aggressively into that and when you think about the trials there I mean so I know you guys are talking about going into pediatric and then a formulation there you already expanded brought into into adolescence so like you know like again the number of trials you need to kind of get the full spectrum you know for for AD yeah I mean so the pediatrics opportunity is one were very keen on for multiple reasons first I would say that children the patient population that I think has the hardest time with injectable and so we almost feel or I shouldn't say almost but we do feel the responsibility to provide children a convenient option to manage their disease and we've met we know we had we had a five-year-old severe AD patient come and visit us with it with his parents and you know it was clear the struggle that the family goes through even to be treated with existing injectable effective therapy so there is a huge amount need for the population and so the pediatrics program is a priority for us as you said we have adolescents on the 2b which we wanted to generate the experience to then make the case the regulatory agencies to accelerate the plan for younger children so I can't comment on where we are with those plans because we're still obviously in discussions and obviously the face to be there that would be critical but rest assured that as part of our phase three campaign obviously moderate to severe adolescents and adult ad patients would always be the first just because it's a well uh established path but the the younger patients are our priority now the timing on when those studies will start we're not in the position to comment yet and to be fair our uh priority uh for for children extends to other diseases we're just the ers we had an ad board for pediatric asthma just again to think about how to enable that for example if you think about EOE another disease with a huge impact in young children so and so not only we're thinking about plants but we're operationalizing the right formulation as well in order to being able to support those studies got it and I guess you know thinking about AD

success, then how translatable should that be for asthma?

Ferens.

So obviously the pathway is well characterized upstream across both of those indications, including the dose-response relationship across indications for pathway inhibitors upstream of STAT6. However, obviously we're conducting a dedicated Phase IIb trial in asthma. It would be our hope that when we unlock the Broaden II study in atopic dermatitis, as we mentioned a moment ago, that would enable us to move quickly, at least into dermatology indications, beginning with atopic dermatitis. It will give us a lot of information, I think, about what we are likely to expect when we open the envelope on the BRETT phase 2b study in asthma just a few months later, but that would be the ungating event then for the respiratory indications. And then to fill in the gap between derm, RESP, and GI, is in for the esophagitis, for instance, in the middle, we think generally we'll learn a lot from the dose-response relationship in the first readout in AD to let us make good guesses about where to go in EOE. So generally, strategically, that's the way we'd be thinking.

Can you talk through, you know, the BRUTH trial design and how it kind of differs from some of the other, you know, more contemporary asthma trials?

Sure. Yeah, sure. So it's a study in patients with moderate to severe asthma. We selected for a group of people with type 2 inflammation phenotype. Some people say eosinophilic asthma, but we prefer the term type 2 inflammation. We've indexed on delta FEV1 as the readout through 12 weeks. It's a more efficient study design for dose ranging. We've got good information, again, about upstream pathway inhibitors and how delta FEV1 might translate into other longer term outcome measures ultimately a registration program would be based around exacerbations but we think we can learn more than enough about through a Delta FEV1 efficient week 12 readout in type 2 inflammation high patients to make good to make good decisions about phase 3 design and readout will be coming in 2027 and we'll be looking to move swiftly to regulatory interactions from there now from the original you know phase 1b you shared some pheno data from those patients is that something that you would share potentially for some of the

atopic derm patients that might have you know some asthma symptoms or you know some asthma yeah maybe a flag so the obviously we we were the first company to measure pheno in ad patients that's a pretty involved operational requirement so we were not measuring pheno in the broadened tooth study because it will it will mean that all these the sites will have to have a pheno machine which is basically impossible there are other measures of asthma comorbidities and others that we're capturing I don't believe they will be shared in the top line but eventually we'll make sure we'll share and as Terrence was saying you know those are things that we will learn that will obviously we believe continue to de-risk the asthma program.

Gotcha and then so you were kind of hinting at this Terrence but in terms of like after you know proof of concept in AD, proof of concept in asthma, the regulatory strategy post that is just to start phase three trials and really accelerate development. So I guess we got a playbook from 2P, which ones do you feel like are the ones that I guess are priority for you and ultimately are probably the most de-risked from the two trials that you guys are currently doing?

Yeah, I mean, I think we look at that. So obviously there are, I think now, nine indications in which the Dupilumab has been approved in if you look at probably the first four or five still account for 90 plus percent of dupilumab revenues so if you look at AD, asthma, CRS, EOE and probably eventually COPD that's probably close to almost 95% plus I would say those are the kind of indications we're thinking about and the sequence again some of those obviously we're still refining time etc but as Terence said the sequences AD will allow us to go into all the other derm indications ideally directly into a registrational study we believe the EOE can be informed enough so that we can move swiftly through a potentially creative registrational studies so we'll talk more about that maybe early next year definitely after the broadened to data and then as soon as we unlock asthma we have you know asthma crs with mp and potential copd that can be unlocked so we're we're trying to actually do as much in parallel as possible but we have these gating factors which are the phase 2b data and the phase three dose because while I think it's fair to assume that the phase three dose for AD is the same as the phase three dose for asthma we're gonna have to make that as a data-driven decision and so if we have different doses obviously will require different kind of approaches for this derm versus respiratory diseases gotcha so maybe with the next five minutes we can talk about 579 so another program IRF5 maybe why why do you like this program why this target and you know in terms of your you know kind of vision to be you know powerhouse and I and I like what does this unlock for you yeah maybe I'll touch a little bit on it and then I'll let Terence speak to the to the program per se so first remember this is going to be our next data set we've said that the rf5 phase one day that will be before the broader two data so that would be on the lookout for that um you know the beauty of this target is the fact that again it's another transcription factor undrugged highly pursued by the industry with strong human genetics and with opportunities across multiple indications and so i think while if i can complain a little bit, while it's, I think, completely underappreciated, I think is one of the most innovative programs in the industry in immunology right now. Maybe Terence can speak to the biology and clinical opportunities of it.

So it's a node that sits downstream of a number of validated pathways. I should say upstream in some ways, upstream and downstream. So it's got strong genetic validation in a variety of rheumatic diseases and in gastroenterology. So that includes lupus, rheumatoid arthritis, Sjogren's disease, and inflammatory bowel disease. If you look at where it sits in pathway biology, it's downstream of a variety of pattern recognition receptors, and upstream of at least three pathway areas that have been clinically validated. That includes type 1 interferon signaling, a variety of cytokines, including TNF-alpha and the 1223 cytokines, as well as IL-6, and then finally B-cell biology, including autoantibody production. So you can imagine the penumbra of indications that might potentially touch. So in development, we're, as Nello flagged, planning to graduate from phase one this year and intend to reveal those data before the end of the year. And what we have expected to see from data generated in the past, aligning with what we've seen with our previous clinical degrader is fairly complete degradation greater than 90 percent of the target inhibition of downstream pathway relevant cytokines which we generate in phase one in healthy volunteers and we've guided to seeing and to being to expect it to see somewhere 80 percent plus inhibition of those downstream cytokines and obviously a well-characterized dose, PK, and safety profile from phase one. All being well with that, we would look to proceed to show proof of mechanism, proof of biology, and maybe some proof of concept in a relevant disease. And I've mentioned some of the diseases earlier on that might be in scope, so look forward to announcing that soon, but I'd amplify what Nello said. I think there's tremendous opportunity there, first-in-class molecule and a great target to select for a degrader.

Gotcha, and then maybe just the last question, the high level question for Nello so you know obviously as I said very consequential year for you guys and I think the industry as a whole you know in going into the broad and to read out but you know kind of taking it all together in terms of you know what the platform's ability to do with stat 6 IRAC 5 and other you know targets that you guys have pursued like where do you want to go with this like what's next and in terms of you know other opportunities and disease sets within an INI yeah I mean first I would say thanks for the question we want to build a commercial global biopharma company that can do innovation and deliver what patients are looking for which are

effective oral drugs and that's our mission we feel the responsibility were I think well set up very financially and we now have to execute and generate great data so I think stat 6 I believe and I think this is probably shared by many people in the industry is one of the most exciting targets and potentially one of the most compelling medicines in type 2 inflammation IRF5 I think can open up completely new opportunities for patients that suffer from these diseases that Terence was talking about you know another again an area that we often discussed is I think another pillar of immunology which are diseases driven by other antibodies so I know you keep talking about a target you might be right or wrong but that area is an area that we're very keen on and and and we continue to do work on and hopefully soon enough we'll be able to talk about it we are very keenly looking at what how how do we allow patients to continue to be treated in the most effective way and so what is the the right synergistic biology for either having deeper responses or broader responses in this heterogeneous patient population so combination therapies oral combination therapies which I don't know that anybody is doing right now we're seeing a lot of bispecific and trispecific I think that's another frontier that we're to be exploring in the next few years and we have lots of novel targets that we're working on and hopefully be able to disclose in the next few months and years.

Excellent well Nelo, Terence thank you so much for joining us really appreciate it.

Thank you pleasure.