Kymera Therapeutics, Inc. (KYMR) Earnings Call Transcript & Summary

Back to School Conference. So we're thrilled today to have Kymera Therapeutics. We have CEO at Nello Mainolfi, and we have Bruce Jacobs, CFO. So guys, welcome. Good to see you.

Yes. Thanks for having us. Back to school.

Yes, exactly. So we'll give us -- for those that may not be as familiar with the story, just give us kind of the 2 minute. I know you're kind of long-winded, so we'll try to keep a buzzer there.

Good. Starting with Geoff. All right. So the long story is we started the Kymera 10 years ago, so I'm going to go year by year now. And -- and the idea was high level, really simple. There is tons of targets that have not been drugged. There is tons of genetics information we have but we have lacked the technology to go after these targets effectively selectively and potently. And we thought that targeted protein degradation, which is a small molecule modality that can remove disease cars in protein was going to be that unlock in technology. And so we spent the past 10 years, we put actually, I think, by now, 7 molecules in the clinic. And we've shown that you can degrade specifically, potently, selectively and with patient impact. Proteins that have historically been undrugged. In the past, let's say, 5, 6 years, we have decided to focus almost completely in immunology for a couple of simple reasons, one of the biggest markets lots about -- dominated by biologics, the tons of opportunities to change the treatment paradigm and impact millions of people around the world. And so we've developed, I think, one of the most exciting immunology pipeline in industry with STAT6, which is obviously downstream IL-4 receptor alpha. And we believe one of the most exciting drugs, it's not the most exciting drug for type 2 inflammation, which is tens of millions of patients. We have an RFI program, which is targeting this incredible access where several pathways signal through B-cell type 1 interferon and downstream -- and other inflammatory cytokines. We have other programs that we haven't disclosed. And partnership with Sanofi and Gilead. So this is a big year. We have big readouts for both RFI and for STAT6. So I'll pause here, and we can go from there.

Well, let's talk about the -- so the data for STAT6 by the end of the year. Help frame kind of what -- how you think about this? I mean, obviously, the most people are thinking about this from a DUPIXENT contact store from other standards of care. But at this point, though, is there -- does oral convenience sort of outweigh the is that -- obviously, you want efficacy, right? But does the oral anchor the differentiation piece or maybe help us with the profile?

Yes. So a great question. So taking a step back, so there are indications in which DUPIXENT has been approved. And if you look at worldwide, we're talking about more than 100 million patients. And so when you think about actually STAT6 and KT-621, we need to remember, this is one of the few mechanisms. The other one is IL-4 receptor alpha, which is DUPIXENT, that had potential to address several comorbidities of patients with type 2 inflammations. And many patients, even north of 50%, in some cases, they have comorbidities. So I would start there. Just an important description of the opportunity. Then if we just take one of those indications, let's say, AD, atopic dermatitis. Let's see, if we do the math, so in the U.S., there is about -- depending on the literature you use between 6 million and 9 million patients, actually, 6.5 million and 9.5 million patients with moderate to severe AD, 12 and up. So let's use 7 million as the number. There has only been about 400,000 patients that have been dosed with an advanced systemic therapy. And this is dupi library Rinvoq and others. So roughly about 5% penetration in the moderate-to-severe atopic dermatitis patients. So why such a small penetration. Because most patients -- and this is work that we've done. So this is not me speaking, this is market analysis that we've done. I'm still speaking, but it's coming from others. Why such a small penetration because most patients and most prescribers feel that I'm not severe enough to be on an injectable biologic or on a drug that has black box warning. So what are they looking for safe, effective oral drug. It actually goes Geoff, exactly to your question. save effective oral will transform this space. It's not about dupi like or not. It's about safety, efficacy, and we have millions of patients that are untreated or poorly treated with messy topical. So this is going to be -- has the potential to be the first in line drug for millions of patients that right now are under-treated or untreated. And if you look at -- sorry, other comps, I'll actually get to your question eventually. If you look at other comps in the space look at psoriasis, icodide, great launch, psoriasis much more mature market still one of the best launches in the space. Why? Because it's a safe and effective oral not because it's actually the same efficacy of biologics, it hasn't. So if you ask me to scientifically, where do you expect KT-621 to land in terms of impact on signs and symptoms of AD I will say that will likely be in the dupilumab ballpark because that's what we've shown for the past 5 years. But I would say we don't need to do have a successful drug.

Right. Yes. And then let me just follow up on that. If you think about getting into maybe healthier, slightly less severe patients what would you anticipate maybe a duration of therapy for a safe, effective oral to be? I mean, would it be 2x, 3x what we see with dupi. And the second part of that is that -- are there lessons to be learned for the patients that maybe dupi stops working? Or are they -- is it tolerability or whatever that you have a stoppage of therapy that you could mechanistically maybe use TPD, use the mechanism a little bit more broadly?

Yes. So I mean that's a lot in there. So let me start with the second one. So we know that people start injecting themselves with DUPIXENT. That's a fact. I think that happens sometimes because you lose insurance coverage, and we've seen patients on our study that come on to our study because the insurance doesn't cover it DUPIXENT anymore. People stopped DUPIXENT because they don't want to inject themselves anymore. And then I think some people, although I actually don't know the exact number might lose the level of efficacy that we're seeing early on. So what we allow our clinical trials are the patients that have stopped taking DUPIXENT not because they have stopped responding, but for other reasons. So we have nonrefractory patients on our study. And it's important to have them because we believe it gives us people also data to believe that they can stop those type of drug and come on to our drug. With regards to dupilumab refractory patients, I don't think it's well understood what the biology is -- we know -- I believe there was a study that was run, I believe, by Eli Lilly with library that showed that 50% of refractory patients with dupilumab showed activity with lebri. So there's clearly maybe some level of biology that is maybe irrespective of the pathway and then there is some that is probably have to do with the pathway. But I wouldn't say that for a drug like ours, this is a first-line drug in the broader moderate-to-severe population, that's not really the problem we're trying to solve. We're trying to expand access to many more patients that right now are not on biologics right.

Maybe talk about the BROADEN trial. How should investors kind of compare the BROADEN2 kind of population versus prior DUPIXENT kind of studies in terms of baseline and prior treatment published and just to see like what differences are these trials that could kind of remind the results for BRODEN2?

Yes. So one thing to remember, if you look at dupilumab trials from 10 years ago or so, that was actually the first systemic product that was -- or the first targeted systemic drug that was developed in atopic dermatitis. So obviously, all naive patients with generally higher severity. In fact, the mean easy baseline in those studies were high 20s, early low 30s. If you look atopic dermatitis studies in the past few years, you see the mini EASI at baseline, it's more often than not in the mid 20s. And that's a natural evolution of the patient population. We go to all these clinical sites where patients have access to advanced systemic therapy. So the more severe patients are on advanced systemic therapies, that these are still moderate to severe patients, they're just generally milder. So I think there is a school of thought that would say if you have less severe patients, actually, your probability of showing reduction of EASI is lower because you start from a lower -- I'm personally not a believer in that. I think that's a extremely weak argument. I think if you have a strong drug, you should work in severe patients or less severe patients, and we've shown it in the Phase Ib, although very small lands. Regardless of the severity, we saw the same EASI reduction. With regards to others, I mean, it's all naive versus naive patients. As I just said, we allow on low response biologics experience that were responders on our study. And so obviously, there is a population that was not studied back then in those days. But otherwise, I think moderate to severe patients, we should be able to assess in a robust manner, the safety and the activity of the drug. And again, I'm trying to stress that the focus should be less about how it compares to other drugs, but more on, is it a safe and effective oral they can be the first in line, the post-topical drug in atopic dermatitis today because there are no drugs like this even in development.

You mentioned safety. I mean one of the kind of safety issues with DUPIXENT is conjunctivitis. Maybe talk about high level, what kind of expectations you have for this oral drug in terms of range of conjunctivitis you could expect? And what's the commercial kind of viable option in terms of the rates you could get for conjunctivitis?

Yes. So I think historically, what we've learned is that drugs that hit this pathway, whether they actually IL-4 receptor alpha, which blocks IL-4 and 13 or IL-13 only, patients in atopic dermatitis studies and not in other indications. They develop -- there is an imbalance between placebo treatment and are more conjunctivitis. I believe this is my personal view that these rates of conjunctivitis have been generally consistent across studies. While the numbers may appear different, I think just the way that now conjunctivitis is diagnosed in these studies is probably higher than it used to be back in the dupilumab studies where it wasn't yet an AE of interest. So I will just say that, I've said this for years now, so it's hard for me to know actually, even if I look at all these studies, whether there is a dose response, concentration response to conjunctivitis, it's not clear to me. So I'm naively thinking that I think it's kind of all the same. So now if you bring a new mechanism on the table, STAT6 degradation, same pathway. What do you expect? So in the Phase Ib, we did not see any cases. It was 22 patients for 28 days. Usually, in 28 days, the rates are very low in the 4%, 5%, so it should have been 1 patient. So have we seen and not seen it, it's not conclusive. Generally, I've said this again for a long time. I expect to see it because every drug in this path we have seen this imbalance, but we'll see. I think the data will tell us. With regards to the impact on different rates I guess it depends on what they are. I haven't had conjunctivitis, so I can't speak for patients. From what I've heard from dermatologists, it's not a reason for starting and stopping treatment of DUPIXENT. So I don't expect this to be a big data set in terms of the impact of any potential conjunctivitis adoption of these drugs. But I guess we'll see again for static, what we see and then we'll go from there.

Now will give us the range of what you're thinking for Phase III as you look to the -- at least the AD kind of study? Is there a potential for maybe an interim trigger on that just to get to call it early? Is it multiple doses? Do you feel comfortable? And just using one, I know, obviously, it depends on the Phase III.

Yes. Yes. The Phase II, obviously, one of the goals -- so we had 2 equally important goals of this Phase IIb study. One was to establish safety and efficacy in a global population in a placebo-controlled randomized manner and at the same time, selecting a Phase III dose. So ideally, I mean I think it's not surprising if I say that ideally, we'd like to take one dose to Phase III because it's easier, cheaper and faster. But many drugs actually in these pathways have taken more than one dose in Phase III and Regeneron and Sanofi did the same because they wanted to make sure that they would select the right commercial dose. So we'll see. I think we're trying to figure out how we get distract the market as quickly as possible, again, assuming success in the Phase II because patients want this drug with this profile. And so we're thinking about creative ways to get the market as quickly as possible. That includes how we design say Phase III how do we get to the right safety database to enable NDA. And obviously, we have and we will continue to have regulatory interactions to ensure that we're holding hands in this process. It's too early for me to comment on specifics. But that's one -- obviously, the goal is to get the market as quickly as possible. Even if it's a month quicker, we'll do everything that we can to do so.

So atopic derm, then asthma, obviously, data dependent. For the range of other indications, is there a path to run sort of a basket? Do you have to do a formal Phase II? Can you go right to Phase III? I'm just trying to think of ways to kind of because there's tons of indications that you have seen?

Yes. So there are a ton of indication. In reality, 4, 5 indications are 90% plus of revenues of DUPIXENT. So there is a component of impacting patients, creating values and then there is a component of going as proudly as possible. So if we think about 4 or 5 indications, our goal now that has to be vetted with regulatory agencies not to run any more Phase II studies and go directly into Phase III across these indications that we will disclose as we go into them. And we believe that the AD and asthma, those ranges will allow us to inform Phase III dose selection beyond those 2 indications.

Is there -- maybe if you tie it to the mechanism, is there -- would you need different -- are some of these diseases more severe? In other words, would you need a higher dose for, say, PN or for EoE or sometimes -- I think of like linking that to the kind of STAT6 and...

This is a dangerous question because this could be a long-winded answer, just so you know -- because this is a great scientific question. So first, what we learned from dupilumab is actually they have approved the same once every 2-week dose in all indications besides EoE where they're actually going every week and every 2 weeks, we actually did not work. And so you may be starting there, why I don't think it's ever been understood. Our hypothesis is that DUPIXENT is more sensitive to the local concentration of IL-4 and 13, we don't believe and we have data to show that our mechanism is not sensitive to local expression of IL-4 and 13. So we might not actually see dose discrepancy across indications. But what actually we will be able to see that other technologies cannot do is looking at systemic and when possible local degradation of STAT6 and then what that correlates in terms of efficacy. So those ranging studies would be critical to establish their relationship. Once that relationship isn't being established, I think we can go confidently into these Phase III studies that are repeating. So the ability to have this direct PD effect, we believe, gives us an opportunity to be a bit more aggressive with the late development design.

But you'd say atopic derm is pretty similar to asthma and COPD in terms of the dose...

So the reason why we're doing those ranging in AD and in asthma is because getting into the skin and getting into the lung is different. And we want to make sure that you really need the same dose and the same degradation profile. So I would say the AD 0 is different from asthma and AD is different from COPD, maybe asthma is closer to COPD, so you can use asthma for COPD. I wouldn't use AD for COPD, for example.

The Phase Ib data, you had AD patient, but you also had asthma data along with [indiscernible]. Is there a channel that we could see similar data in Phase II or the patient population is completely different and...

No. Yes. I think a large percentage of patients with AD will have comorbid asthma. We'll have comorbid allergic rhinitis. We had 4 patients that comorbid asthma out of 22 that's about 20%, which is in the range of what's seen in the general population. It's actually usually a bit higher. I think it's 30%, I might be wrong. So we definitely will have comorbidity. And again, I say it again, the comorbidity story for this program is critical. So we will assess comorbidities. What we cannot do is do deep assessment of comorbidities because dermatologists are now going to do pheno measurements in a big global studies. But there are other measurements that we will collect. And again, assuming success, we'll disclose them in the right meetings.

And then Phase 2 enrolled really fast. I mean you were able to push forward the kind of read out like by quite a few months. Is there a possibility to do something similar in Phase III where you'd expect like faster enrollment, faster kind of process versus other trials historically in AD?

Well, obviously, we've set an internal buyer. The team knows that expectations for Phase III will be that we roll fast. I'm not going to say how long it's going to take us. But we have used the information to project Phase III. And obviously, again, I think we assume that in the presence of positive data, Phase III should enroll even relatively faster because now we have placebo-controlled, randomized safety and efficacy data.

Let me ask, I know that the focus has been maybe to the more mild to moderate AD. But if you look at the moderate to severe end of things, is a dupi refractory patient, the same as a SKYRIZI refractory. If you look at the different mechanisms, do you think that...

So just to be clear, we are still looking at moderate to severe patients. Mine not part of the equation. Again, the refractory to DUPIXENT, it's still is a biology that is not well understood. I think there are many companies including us that are doing studies to understand what happens. I think there are hypothesis. If you look at the literature and you look at transcriptomic data of patients that have been on DUPIXENT for 16 weeks or longer. You see some upregulations of other pathways, like IL-17, IL-22, in some cases, IL-18. So there is, in some patients, some skewing from type 2, Th2 to Th1, Th17, is that the solution, we don't know yet. I think there are studies there are other companies are doing. There are combination that we're doing in research to understand and explore whether we capture broader and deeper efficacy with combinations. So I think that story is yet to be told completely.

It's just odd that in I&I, you see sequential therapies for the most part, you don't see tons of combinations like you do in a cost...