Good afternoon, everyone, and welcome back to Oppenheimer's 36th Annual Healthcare Conference, day 2. I'm Jeff Jones, one of the analysts here on the biotech team, and I'm delighted to be joined by Bruce Jacobs, Chief Financial Officer, and Jared Gollob, Chief Medical Officer of Kymera Therapeutics. Gentlemen, thank you for taking the time to join us this afternoon.
Thanks, Jeff.
Thank you, Jeff.
Kymera has really transitioned over the last 12 to 18 months from more of an oncology story to a leader in degraders for IMiD today. Maybe if you would just give a brief introduction for those who are less familiar with the story, just about in terms of how you're positioning the story today.
Sure, Jeff. Great. Maybe I'll start, and then we'll take it from there. First of all, appreciate being here. Great to have the opportunity to present. Yeah, I would agree. Over the past 12 to 18 months, certainly some things have changed, but there's also much that has stayed the same. I think what is unchanged is that Kymera continues to be extremely disciplined with respect to, you know, how we select our targets. We're focused, as we have been in the past, on large markets, where there's very known and established biology, and where there's frankly, no good solution, no perfect solution. Oftentimes, protein degradation can be either the only solution and/or the best solution. Over this time, I would argue we've been very productive as a company.
We've now put six programs into the clinic. I believe we have an IMiD pipeline that is compelling and will only grow as we announce new programs. Over that time as well, we've run clinical trials that I think have delivered results that really have validated our strategy. Just in general, you know, I think we've, as a company, have executed very well. As you mentioned, definitely some things have evolved at Kymera, one of which is our strategic focus, which is now squarely on IMiD. We're there and focused there for a number of reasons. I should note that this focus goes back a number of years.
You just don't wake up one morning and decide you want to be an IMiD company, although maybe some others are doing that these days. We made strategic investments in both our programs and in our people multiple years ago, and you're seeing those manifest themselves today. That was all with the goal of developing small molecules that we felt and hoped could deliver biologic level of activity. While we focused on IMiD, we decided to stop some activities that did not have quite the same opportunity, either as measured by the size, by the competitive dynamics, the regulatory pathway, whatever may have been.
Instead, with this investment in the IMiD market and some of these programs, I think we've built what we believe is the best small molecule pipeline in IMiD right now, including what we believe, and I'm sure we'll talk about shortly, what we think could be one of the most valuable programs in the industry. At the same time, we've capitalized the company. We have $1.6 billion in cash and runway to 2029 to really take on these large opportunities, which are very, very exciting. Hopefully that gives you a sense for how, you know, how we're focused and where we sit today.
Fantastic. Talking about that opportunity, you know, the story in the last several months has really been about the STAT6 program or STAT6 targeting and KT-621 with the data you showed end of last year in atopic dermatitis, which included some patients with asthma. Maybe could you highlight the data that you showed back in December and then how that drives that program forward? That's clearly, you know, the primary focus of folks, I think, on the story right now, despite a lot of other really exciting things in the pipeline that we'll get to as well.
Sure. Maybe I'll go ahead and hit on that. You know, last year in 2025, we essentially had two major data sets, you know, from our phase I program. We had the healthy volunteer data that we presented last June, and then, of course, the phase Ib AD data that we presented in December. I think both of these were important steps for us, right, in helping to really de-risk, the next stage of development, which is phase IIb. I think the phase Ib AD trial, in particular, you know, arguably took an even larger step, you know, toward that de-risking, you know.
What we saw in that phase Ib study, that open label study of 22 patients with moderate to severe AD, where we brought two different doses, 100 and 200 milligrams in from the phase I. We saw remarkable internal consistency between degrading STAT6 strongly in blood and skin lesions, impacting Type two biomarkers in blood and skin and in the lung, and having an impact on a variety of different clinical endpoints, both for AD, as well as in patients with comorbid asthma and allergic rhinitis for those diseases as well. Within all of that, especially the biomarkers and clinical endpoints, being able to show an effect across all of those that were comparable to, or sometimes even numerically superior to what has been seen with dupilumab.
All of that really gave us an enormous amount of confidence, you know, in how this was translating from healthy volunteers to patients. Also a lot of confidence in our selection of doses for the current ongoing phase IIb studies in AD and asthma, which are really the important pivot points now for the program that will hopefully then lead us to selecting single, you know, doses for phase III campaigns across not just AD and asthma, but also, you know, across, you know, multiple other Type two allergic diseases. Maybe, you know, as you refer to, I'll just mention, you know, the impact that we saw in.
asthma and allergic rhinitis, those comorbid conditions, it was very interesting to us that in this AD study, we not only saw an impact on AD, we saw an impact on this important biomarker, fractional exhaled nitric oxide, which was showing us that we were hitting the IL-4/13 pathway in the lung and having an impact even in atopic dermatitis, an even bigger impact on FeNO in asthma patients. We saw important impact on various patient-reported outcomes in asthma and allergic rhinitis. We really, yeah, took the opportunity from that phase Ib study to learn about the activity of our drug, not just in AD, but also in respiratory diseases like asthma. That's why I think this de-risks, you know, the program, you know, at large, not just AD, but the asthma side of things as well.
Yeah, that's fantastic. obviously, folks have talked about the AD data in a great deal of depth, and you have obviously. On the asthma side, maybe could you talk a little bit about the FeNO biomarker, the FeNO signal that you saw in those patients, and where that plays into, sort of endpoints and evaluation in asthma for folks who are maybe less familiar with FeNO as a biomarker?
Sure. FeNO, you know, is an important biomarker in Type 2 allergic diseases, especially in respiratory diseases like asthma, you know, where FeNO is used, you know, either to classify patients, you know, with Type 2 disease or Type 2 asthma, you know, high FeNO, for example, FeNO that's over 25. It's also been used to follow response to therapy, and can be a good predictor, you know, of response to therapy, not just in terms of impact on lung function, but also impact on exacerbations. That's why there's a lot of interest in FeNO. We think of FeNO as a broader sort of Type 2 biomarker.
We were very interested in looking at it in AD, we were the first ones to do that because we wanted to get a sense for whether or not we could detect a change in FeNO, even in AD patients without comorbid asthma. It wasn't really clear whether we would see changes in that population, but we noticed that, you know, at baseline, those patients had FeNO levels that were in the 15 to 20, 25 part per billion range, which is sort of mildly elevated, and we saw about a 25%-35% reduction in FeNO across the board with our drug. When we looked specifically at the asthma patients, their baseline FeNO levels were close to 50, and in those patients, we saw about a 55% reduction in FeNO after just those four weeks of treatment.
For us, it was an important way to show that treatment with KT-621 has a systemic effect on the IL-4/13 pathway, including effect in lung. It also starts to give us that important initial insight into how we're impacting FeNO and how we're even impacting, for example, measures of disease control in asthma, which we measured using the ACQ-5, which I think now carries over to, you know, the level of confidence in what we hope to see in the phase IIb asthma study. Just as a reminder, that phase IIb asthma study is focused on a subset of eosinophilic asthma patients that have what we call high FeNO, high eos.
FeNOs of greater than 25, greater than equal to 25, eos of greater than or equal to 300, which is a population shown, you know, to respond exquisitely well, to drugs like Dupixent. This gives us an opportunity to have a study that where FEV1 is our endpoint. It's a 12-week endpoint, so it allows us to have a faster, more efficient study by enriching for that population in phase IIb. Subsequently, in phase III, we would anticipate a more traditional eosinophilic asthma population that has, you know, an eos of at least 150 or greater at baseline.
Okay. Yeah, that really helps and answers half the questions I was gonna ask about the phase IIb study design, so that's great. When we think about Dupixent, in AD, and, you know, it's approved in a host of indications, these populations have changed over time, in terms of Dupixent originally approved, you know, maybe 10 years ago, in the AD population, obviously very well adopted there. Changes the sort of recruitable population, as you're looking at your phase II. How do you think about the different populations you may be recruiting, and when people are then going to try and cross-compare to what Dupixent has shown?
Bruce, do you wanna start with that, or?
No, you can go.
Jeff, I mean, maybe starting with AD, because I think, you know, the AD population, you know, of course, you know, we're focused on moderate to severe AD, you know, in both our phase Ib and now in our phase IIb as well, and eventually in our registration studies. As you're alluding to, you know, over the past, say, 5 to 10 years, you know, that moderate to severe population has changed somewhat. You know, it still represents a range of disease severity, but whereas maybe 10 years ago or so before Dupixent was approved, the mean EASI scores in patients coming onto those studies were probably in the low 30 range.
You know, in more recent studies, they're now more in the sort of the, you know, low to mid-20 range, which I think reflects the fact that, you know, certain subsets of patients with very severe disease in certain regions of the world are going on Dupixent, and they're not eligible to go on to these clinical trials. There has been somewhat of a shift in terms of the population for that reason. I think overall, you know, clinical trials in AD, you know, are still going to be able to enroll a range of moderate to severe patients. Our hope is that we see activity of our drug across that range.
That was one of the important learnings from the phase Ib, albeit in a small study that did not have a placebo control, was that, you know, our impact on EASI was across the board the same, regardless of whether patients came in on the lower end of EASI or the upper end of EASI, or the lower end of TARC biomarker or the upper end. I think that tells us that we should be able to see with an active drug, an impact across a full range of moderate to severe disease. Even if there's been some shift overall in the severity of that population on average, it shouldn't affect our ability to show activity of our drug in AD.
Okay, really helpful. Obviously, in AD and asthma and potentially several other indications, you're thinking about 621 as being a therapy for long-term use. Safety is always a question. Story seems very clean. I guess just can you comment on what you've seen in terms of safety, so far?
I think safety, you know, I mean, pre-clinically, first of all, you know, that our drug has been very clean. Now we just reported today that we now have not just, you know, 4-week and 4-month GLP tox data. We now have 6 and 9-month chronic tox data in rats and non-human primates, where, again, pushing to high doses that are giving us systemic, you know, full STAT6 degradation. We're not seeing any adverse findings at all in any tissues, either, you know, clinically or histopathologically. So that gives us a lot of confidence in the safety of the drug that goes along with the clean profile we've seen so far in the clinic.
You know, both in our placebo-controlled phase I healthy volunteer study, where we dosed for up to 2 weeks, and then in the phase Ia, where we dosed for 4 weeks. We really did not, you know, see any significant signals at all, you know, clinically or on labs or ECGs. Actually, in the placebo-controlled healthy volunteer study, safety in the drug-treated subjects looked exactly the same as those in the placebo arm. Again, that all looked the same in the phase Ib study. We're glad now that we have our, you know, phase IIb is ongoing, where, you know, for the AD study, for example, it'll be a 16-week endpoint, and then patients will be able to roll on to a 52-week open-label extension afterwards.
This will truly give us, you know, long-term safety and even more confidence in the tolerability of the drug. You know, the other thing I'll say is, from a safety standpoint, people, you know, have asked us, you know: "Well, hey, it's great that in phase Ib you didn't see any conjunctivitis among the 22 patients, which is something you can see with Dupixent and AD patients.
You know, what does that mean for the future of the program?" The way we answer that normally is to say, "Look, you know, because it was a small study, because, you know, even with Dupixent, you know, the incidence of conjunctivitis is probably in the, you know, 10%-15% range, and it usually tends to, you know, see it in that range after more than 4-8 weeks of treatment. It's still too early for us to know whether we will or will not see conjunctivitis." We do expect, overall, our safety profile should be comparable to Dupixent, I think with longer-term treatment, that'll be necessary before we really understand the full safety profile.
All right. That's really helpful. One question that I get occasionally on the degraders really as a class, is around the CRBN targeting, and potential, you know, concerns or warnings there, you know, based on teratogenicity and things like that. Just going way back historically, obviously, you guys have a very clean safety profile to date. Just is there anything that you've seen or discussions you've heard with the agency that flags this as a, as a real concern?
Well, you know, even though we haven't discussed, you know, which E3 ligase we're using specifically for the STAT6 program, you know, we do harken back to the IRAK4 program when this comes up. You know, that was a program where we do use a cereblon-based degrader. You know, there's a recent publication that we put out, you know, at the end of last year, that really goes through all the work that we did to show why a degrader like the IRAK4 degrader that uses cereblon as E3 ligase does not have any risk of teratogenicity. There are a number of reasons for that, you know, which include the fact that the cereblon binding ligand that we use for a degrader like IRAK4 is functionally neutral.
It binds cereblon, but it doesn't redirect it to any neosubstrates. You don't get, you know, degradation of substrates like SALL4, which have been associated with teratogenicity. We've also done a number of embryo-fetal development studies in multiple species, that have shown no effects whatsoever. Of course, you know, we've done detailed proteomics showing that we don't degrade anything else aside from the target protein, IRAK4, despite, you know, using cereblon. I think all of those results, you know, have really, I think, for that program in particular as well, not raised any red flags with FDA.
We had multiple discussions with FDA, either when we were doing it on our own or with Sanofi, when the program was partnered with Sanofi, in which FDA themselves were able to see that full data set, and they themselves had no concerns around there being any risk of teratogenicity, you know, for our IRAK4 degrader, even though it was using cereblon. I think all of that information, I think, you know, should put people's minds at ease, that if one is using a degrader that co-ops cereblon, but the ligand is functionally neutral, you know, this should not raise, you know, questions around concerns, either on the part of clinicians or on the part of regulators, about whether there'd be any any risk of teratogenicity or other concerns of that sort.
Yeah, I appreciate you taking the time to address that. Thinking about just the market for a minute in the AD space, with Dupixent.
... you know, Dupixent is obviously an enormous drug. There's a lot of patients who are either Dupixent failures or who come off Dupixent for tolerability or other reasons. Just as you think about the market, where are you thinking of being focused? Is this go head-to-head versus Dupixent, which from efficacy seems like an opportunity? Or do you focus on Dupixent failures, or do you focus on those patients going in early for treatment and moving them to an oral first versus an injectable?
Yeah. Thanks, Jeff. Maybe I'll start with this one, and Jared can chime in. The point that we like to make on the opportunity, and actually, we talked about this even on our call tomorrow, is that this market is far from a zero-sum game. There are on the order of 140 million patients with Type 2 diseases, probably 50 million or so of them are moderate to severe, and which would be our focus and is Dupixent. Only a couple million of those are treated, it's amazing that Dupixent, a $20 billion drug already, has such low penetration relative to what the real patient need is.
I think that speaks to the enormous untapped market opportunity for solutions that really come in and address these unmet needs that are clearly not being adequately solved with existing therapies. As we've said this morning, whether we're slightly better, slightly worse, close to the same, if we have a safe drug that has efficacy in the ballpark of dupilumab, you know, we really believe that the ability to offer an oral daily molecule, that will appeal to a large number of patients. That's why we think, you know, what Dupixent is doing today, which I should say is amazing, is really only the beginning of the opportunity for our STAT6 program. You know, I don't think we'd look... You mentioned, you know, Dupixent failures, in front of Dupixent.
Wherever it may be, I think the key is that there are so many patients out there with unmet needs, that if we can deliver on the TPP for this program, I think it's gonna be a very, very appealing opportunity. It has an opportunity, frankly, to be one of the larger drugs in immunology if we hit that.
All right. Just before we move away from 621, I'd be remiss if I didn't give you the opportunity to flag timeframes for data coming out in AD and asthma, then just Jared, you briefly mentioned sort of plans to expand afterwards. If you could just touch on that.
Yeah, maybe, Jeff, I'll take the first part, then I'll let Jared talk about the expansion opportunity. We started the trial in AD first, that was last October, we just started the AD trial earlier this year, very beginning of this year. We mentioned today that both trials are very much on track. one of the many reasons that we, you know, we undertook this phase Ib study was to get data out there that would generate excitement and enthusiasm around the target and the drug. Clearly, from what we're seeing out in the market with these trials, that has served its purpose.
There's incredible enthusiasm amongst patients and investigators for an oral solution, we think the, you know, the story has definitely resonated. We have said that the AD trial should enroll this year, and we're on track with that. We expect to share that data by mid 2027, so, you know, you could say in the first half of 2027, is the hope. For asthma, that because it started later and is a little longer to enroll, is likely in later 2027, the later part of 2027. Those will be the first two areas of focus. You know, I guess, Jared, I'll pass it to you if you want to just talk quickly about how we're thinking about other indications beyond AD and asthma.
Yeah. Yeah, I think, you know, our overarching sort of clin reg strategy to allow us to, you know, efficiently accelerate development for a drug that we think is incredibly promising is to only have to do 2 phase II studies, these phase IIb studies, one in asthma and one in AD, in order to then open up multiple phase III campaigns after that. You know, out of the phase IIb asthma study will come a recommended phase III dose. Out of the phase IIb AD study will come a phase III dose. Whether those are the same or not remains to be seen, they might end up being the same.
Those phase III doses will be used not just to then run subsequent phase III studies in AD and in asthma, but then to allow us to then parallel track, you know, phase III studies across multiple other respiratory and GI indications based on the phase III dose that comes out of the AD phase IIb study, and then other respiratory indications like COPD or CRSwNP, you know, based on the phase III dose that comes out of the asthma study.
Perfect. All right, that's great. Moving on in the pipeline, the IRF5 targeting program, you announced this morning, has started dosing. The opportunities there, again, I, but a slightly different subset of indications. Maybe if you can touch on that, and I think you've spoken a fair amount about the preclinical data that has you excited there.
Yeah, maybe, you know, in a nutshell, I mean, this is an incredibly attractive target, you know, for pharma as well as biotech, just because of the strong genetic association between IRF5 and diseases with high unmet need, like lupus, RA, IBD, other type one interferonopathies like Sjögren's. On top of that, now we have this very selective, potent degrader of IRF5, where in preclinical models of lupus, multiple preclinical models of lupus, as well as RA, we're seeing substantial activity that seems to go beyond even what's seen with sort of current standard of care or other active drugs out there.
You know, we're very excited about the potential for IRF5, you know, the fact that it controls signaling through these various TLR pathways that are driving type I interferons and pro-inflammatory cytokines and B cell activation and autoantibody production, each 1 of which has been clinically validated by other drugs that are out there. You know, all of these 3 pathways can only be addressed 1 at a time by individual drugs, whereas now we have a drug in IRF5 that can address all 3 of these pathways at the same time, and we think that's a real value proposition. Not only does that provide that opportunity from an activity standpoint, but from a safety standpoint, because IRF5 is very selective in its expression in immune cells and is only really activated, you know, predominantly in the context of pathologic inflammation.
We think it should be very safe to knock down IRF5 and to have an effect on these three different pathways that are important in diseases like lupus without there being safety issues or infectious complications. That's already been borne out. If you look at IRF5 knockout mice, or if you look at our preclinical tox data, including our four-week GLP tox study, where we saw no adverse findings across all the doses, it gives us a lot of the confidence that we can have a real novel oral drug, you know, for diseases like lupus that could be highly active and well-tolerated.
Right. Another exciting data set, and this is the healthy volunteer study that's enrolling, just in terms of timing for a data update there and, you know, what the, what the next signal is beyond that, similar to, say, the 621 program and your phase IIa data.
I think we're expecting you know, as we said, we've already started dosing, you know, in the healthy volunteer SAD/MAD. We expect to have data on that in the second half of this year, those data will then be supportive of moving into our first proof of concept study in patients, which, as we indicated on the call, will most likely be in lupus, given, you know, all of the preclinical data that we've generated and the strong genetic association and the high unmet need there.
Got it. You guys, at some time back, shelved the TYK2 program. TYK2 has certainly gotten a lot more interesting in the last few months, with some interesting, at least preliminary, top-line press release data out of Takeda and Alumis. Just curious, you know, those are both oral molecules, obviously, and curious, you know, how you might think about TYK2 and fitting into your strategy.
Yeah, sure, Jeff, I appreciate that. I mean, for sure, those results, we would argue, are validating of our views of the target which were and continue to be very positive. I think where we stand strategically, you know, from a company standpoint, I think we're sufficiently occupied with all that we're doing, that it probably doesn't make sense at this point for us to change course. You know, the team is certainly well aware of that data, so we'll take it into consideration. I wouldn't expect any big strategic changes from us there at this point.
All right. Fair. I guess, you know, with a minute and a half left or so, any other programs you'd like to flag? Obviously, you have the partnered program with Sanofi on IRAK4, the Gilead program with CDK2. Just anything else you would like to flag from a pipeline perspective?
Yeah, I guess I would just, Jeff, make the overarching comment that, you know, we are as excited as investors and analysts are about the STAT6 program. We think, you know, it's an enormous opportunity, maybe even could end up being unprecedented in small molecules. You know, we have so much more beyond that. Obviously, we talked about the IRF5 program, where we're excited to start that study and have data later this year and start a POC study shortly thereafter. You mentioned our two collaboration programs, IRAK4. Sanofi will be moving into phase I this year with our second-generation IRAK4 degrader. Gilead has an option decision shortly on the CDK2 glue. Beyond that, our pipeline is robust and active as it's ever been.
We have a plan to introduce a new development candidate to you all at some point, probably in the 2nd half of this year. You know, we've never had more happening at Kymera, and, you know, it's on us to continue to execute, which I believe we will. We couldn't be more excited about all that we have in front of us. As I mentioned earlier, you know, we're well capitalized. We have $1.6 billion in the bank. That'll take us into 2029 and cover all of the phase II studies for STAT6 that we're running, will fund almost the 1st full phase III study, everything we've discussed on IRF5, as well as our pipeline, and obviously growing the organization to support all these programs.
We don't think we could be in a better position financially and strategically than we are today.
Well, gentlemen, thank you very much. I think we're up on time, you know, really excited about the Kymera story, and you guys have got your head down with an enormous amount of work and clinical work ahead of you this year. You know, fantastic data so far on STAT6, and everybody watching that story closely, as it continues to evolve, and people chase you, frankly. You know, congratulations again, and thank you for taking the time this afternoon.
Thanks so much, Jeff.
Yeah, thank you.
All right.