Hi. Good morning, everyone. Thanks for joining us on the final day of the Barclays Global Healthcare Conference here in Miami. I'm Eliana Merle . Very excited to have Kymera Therapeutics here with us today. They have one of, I think, the most exciting platform technologies in biotech. Joining us from Kymera is Bruce Jacobs, Chief Financial Officer, for a fireside chat. Bruce, thank you so much for making the time. Maybe just high level to start, can you give us an overview of Kymera as a company and your growing pipeline in I&I?
Sure. Eliana Merle, first of all, thanks for having us. I think this is the OG Miami March conference, so we're happy-
Yeah.
happy to be ending our week here. Thank you. Yeah. It's a good time to ask that question. Kymera is actually coming up next month on our ten-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. 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.
We thought, in doing so, we could really ultimately de-risk the molecules that we were developing. The company started with an approach that had both oncology and immunology in our sights. 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. 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, you know, what you would need as a biotech company to prosecute this pipeline.
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.
Programs that we'll learn about soon. Any more color on timing?
No, I think we've said that historically that our goal is always to introduce one new program annually. 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 you'll have to wait for more than that.
Great. Well, we certainly look forward to that. It is 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. To say it's differentiated requires us to know everything others are doing, and
Yeah
that's sometimes from the outside hard to know. I would say that probably from the beginning, the target selection approach that I just alluded to it 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. Across our existing pipeline, I think what you see is really high value targets that don't have good solutions. If you talk about, we'll talk about, I'm sure, about the STAT6 program. We'll talk about IRF5, I would guess. Those are long targets of great interest for a long period of time across pharma.
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. 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. To me, that's where a lot of the unique aspects of Kymera 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.
Mm-hmm. Absolutely. Well, it's a great place to talk about STAT6. Walk us through the data that we've 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 STAT6 fitting in this overall landscape?
Right. Last year, obviously, was a big year for Kymera 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.
that helped us move then into a patient cohort, understandably small, you know, 22-ish patients, but again, 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.
For the first time, we were able to show an impact on some of these clinical endpoints, EASI 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, you know, the IL-4 receptor, but doing it by eliminating STAT6 that is downstream from those receptors. Very encouraging results, certainly in the intended patient population, which is atopic dermatitis. 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 2 studies that is currently underway. We saw some encouraging signs there as well.
Everything that we saw in that patient cohort really supported what we've been able to build pre-clinically 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 Dupixent being the most significant one. We do think there's a tremendous opportunity to bring an oral agent to this market. Dupixent is an incredible drug, very efficacious, great safety track record. It does, though, obviously require injections, which is not ideal for all patients. 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, you know, advanced systemic therapies treated with steroids and the like. That tells you that there's, you know, there's patients looking for better solutions. 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 the future studies, we think the market opportunity would be significant. We're excited about what we were able to share last year. This year is a big year for the STAT6 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.
The asthma trial also has started. That began a little bit later. We just spaced them out more for operational reasons. 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. We're focused intently on executing on those two studies. Obviously, we have some other programs we can talk about, but for STAT6 and KT-621, that's our primary focus this year.
Yeah, absolutely. 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 Dupixent and have a large market. But here it's, you know, in my view, you're showing signs that you could potentially be better than Dupixent. 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? I know it's early, and we'll have-
Yeah.
to wait for more data.
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, in animal models, into a broader trial, randomized placebo-controlled trial in AD patients. We wanna 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 III study. 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 III study with one single dose in AD. Similarly, for asthma to move into a phase III study with one single dose. When it comes to the efficacy profile, I think obviously we will see. Our view is that, you know, we would like to use the very scientific term in the ballpark of what Dupixent has been able to show. You know, whether it would be slightly better, slightly worse, comparable, I think, you know, that's what we'll learn from the data.
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.
Mm-hmm. In terms of phase II-A data, I saw you have a late-breaker presentation coming up. What should we be looking to see there?
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. We shared the healthy volunteer data in June. We were able then to do a late breaker for that data last fall at the AAD 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. It's a great opportunity to share that data more broadly. The response out of the AAD was phenomenal. We had a standing room only audience.
We're hoping and expecting a similarly large following when it comes to AAD. One of the intentions of the phase I-B is to build some excitement around the program, which we think will contribute to excitement around the enrollment for the phase II studies. 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 kind of a, you know, 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 to what you've seen in US healthy volunteers. We'll share that. We're also working on a couple of publications this year that we hope will make it through. It'll be an active year of getting the word out there about the STAT6 program. Less so on incremental data.
Mm-hmm. Okay, that's really helpful context. In terms of the data, I just wanna 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 subset that had comorbid asthma?
Yeah. Thanks for asking that question. One of the exciting, many exciting parts of the phase I-B study were that we're able to look at some comorbid diseases and the impact that KT-621 had on those patients. There was a small group of asthma patients with comorbid asthma, four patients in total, so understandably a small selection. We saw some impressive results there. I would say a meaningful reduction, you know, over 50%. 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 EASI reductions and itch reductions that gave us increased confidence that AD is gonna be obviously a very meaningful potential indication for 621.
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. We felt going in, frankly, that given what we know about the pathway, that we had good reason to believe that KT-621 would be applicable and impactful in all the diseases where Dupixent is approved. I think that asthma data just put one more piece of data behind that confidence that we had in that likelihood. We're excited about that. It, again, another piece of data that hopefully will help build excitement around the enrollment in the asthma trial, which is ongoing right now.
Dupixent is approved in many more indications beyond just AD and asthma. Let's fast-forward next year, this hypothesis plays out. We see positive data in AD and asthma, and you move forward into phase III in both of those indications. You're also sitting on the decision of how many more phase III do you start, and how much do these cost? Walk us through the calculus, how you're thinking about that indication selection, and sort of the phasing of all of these phase III starts.
Sure. Great. Well, if this drug is effective and safe as we believe it will be, I think our ultimate goal is to be approved everywhere Dupixent is approved. The question really then becomes what is the timing and sequence of those pursuits? It would require upwards of 20 phase III 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 Kymera Therapeutics. That having been said, I think we have a very deliberate strategy about expanding the indications we're gonna be pursuing, and it's predicated on a development strategy that has these two phase II studies in AD and asthma really effectively supporting subsequent work in both dermatology indications and in respiratory indications.
The hope is that, once we complete these phase II studies, it'll position the company to be able to start other phase III studies even beyond AD and asthma. We haven't shared a ton yet about the sequencing strategy. I would say that if you look at the current Dupixent market, AD, asthma, EoE, COPD accounts for the lion's share of the market. One can assume that those are probably likely to be prioritized by Kymera. 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.
Historically, the protocol is that you complete a phase III in adults and then subsequently move into phase III 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. That's just a market of enormous unmet need. Again, Dupixent 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. I think if we can make this product ultimately accessible to that population, I think that's an area of enormous need.
Mm-hmm.
That's, I guess, how we're thinking about the development strategy and. But you can assume that we appreciate that there's enormous breadth of opportunity here, and we're gonna take advantage of it. We've capitalized the company in a way to allow us to do that. You know, we have $1.6 billion on the balance sheet. That runway takes us into 2029 and really gives the maximum opportunity to maximum optionality to pursue these, you know, broader list of indications.
Makes sense. That's a very helpful context. In the second half of this year, you've said that we'll get data in healthy volunteers on IRF5. Certainly, there's a lot of excitement when we saw data in healthy volunteers on STAT6. Walk us through sort of the biology of IRF5, what we can expect to learn in healthy volunteers around the biology and target engagement.
Great. Yeah, thanks. It's, you know, one of the kinda side benefits of having a year of execution on STAT6 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 undrugged. It's a very, very difficult and challenging target to address. There's multiple IRFs that share many similarities that make having a selective IRF5 target difficult to achieve. Also within IRF5, there's many different variants, and so you wanna hit all of those as well.
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. IRF5 is a what we'd kinda call a master modulator of immunity. Importantly, it sits. First of all, it's got exceptional genetic support. It's very strongly linked with diseases like lupus, RA, IBD, and 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 I interferon, pro-inflammatory cytokines, autoantibodies.
While there's drugs in diseases like lupus that impact each of these pathways individually, we think IRF5 could be one of the only ones that can impact all three of these pathways. 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 could degrade the target fully and that we can do it safely. From our preclinical work, you know, we think we probably need 80%-90% target degradation, so that's what we will hope to show. Obviously, that and that it's well tolerated. The other important part of this study will be looking at biomarkers.
IRF5 is only activated in disease settings, so we won't be able to show like we did for KT-621 reduction in those biomarkers because, again, the target isn't activated. The pathway's not activated in those healthy volunteers. We will be able to do some ex vivo stimulation studies to look at some of the pathways that I talked about, Type I interferon, these pro-inflammatory cytokines, et cetera. I think that'll give us an indication if indeed degrading IRF5 is having an impact on those pathways. 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.
Mm-hmm. Great. That's really helpful. 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 I-B? Would that be a phase II?
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 wanna get a little further into the year till 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 strong genetic association with IRF5. 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 IRF5 in that lupus population.
Great. Yeah, if you could also talk about some of the target biology in IBD and RA and some of the other potential areas that this could work.
Sure. 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 in RA, and then we have some work that is ongoing in IBD that we plan to share as we move through the year, but we'll save that for a later time.
Mm-hmm. Great. 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 as you advance more programs into the clinic?
Yeah. Well, thanks. 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. 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 risk, 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. We think there's great opportunity. 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. We have some other things that are, you know, progressing through the pipeline as well.
Really, you know, we're trying to build a pipeline with other targets that look like STAT6 and like IRF5 in 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, 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 wanna deal with the invasiveness of a, 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 from investors a lot is how to think about which assets you might wanna 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 STAT6 space. How do you think about this strategically?
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. Partnership is not something that is a priority for us, certainly not with the STAT6 program. I think the question where that becomes more pertinent down the road is when we have multiple phase III studies going, we have multiple programs, how much can we as one company do ourselves? 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.
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 context. Well, awesome. Thank you so much for joining us today and sharing all your insights.
Thanks, Eliana. It was great to be here. Thanks, everyone.
Thank you.