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

All right. Welcome to the BofA second day of the Healthcare Conference. My name is Geoff Meacham, I'm the senior biopharma analyst here at BofA. We're thrilled today to have Kymera Therapeutics. And with me on stage is Nello Mainolfi, who's President and CEO, Nello, good to see you.

Thanks, Geoff. Thanks for having us here. Great conference.

S Yes. So give us maybe like the 5 minute or a couple of minute high-level focus for this year and going forward, and then we'll get right to some questions.

Yes. So we're -- Kymera is a company focused on taking targeted protein degradation and use it for creating a new generation of medicines, mostly focused on immunology and oncology. We have a lot going on, and we have a lot of upcoming data readouts in the next 6 to 12 months. So maybe starting with -- we have 2 oncology programs, that are really about to conclude our Phase I dose-escalation study. We have an update at EHA with our STAT3 degrader, KT-333, which I'm sure, we'll discuss. Some exciting data in heme that we're seeing. We have an update for our MDM2 degrader at ASCO. We have -- the abstract has not been released yet. Exciting data there in both heme and solid tumors. And then next year, we'll be really focused heavily on immunology. We have our KT-474 program in partnership with Sanofi and an IRAK4 degrader. We expect to have Phase II data in both HS and AD in the first half of '25. Then we have our STAT6 wholly owned degrader, we're starting Phase 1 in the second half of the year. We expect to have Phase I data in the first half of '25. We have our TYK2 degrader that we're starting Phase I in the first half of the year with hopefully data in the second half of next year. And we have a lot going on under the hood as they say, we might be able to share some new programs or new exciting research that we're doing at Kymera, maybe we'll share something in the first half of next year, too. We'll just have to see depending on how busy we get with all the clinical readouts. So maybe I'll pause the year and go from there.

That's perfect. Yes. So I guess, Nello, when you guys IPO-ed, there were a number of TPD companies out there, and I think investors kind of threw them all together with the idea that 1 company's technology sort of has read-through to another. And as it turns out, that's not really true. And so you guys have avoided a lot of the pitfalls from some of your competitors, give us a perspective on kind of how you view the Kymera platform and what you think is unique about it relative to other TPD companies?

Yes. So yes, so going back, we IPO-ed in 2020, August. We -- since then, we took 4 programs in the clinic. We've seen high fidelity of translation of PK/PD, safety and early efficacy. Not much that surprised us in the translation, mostly positive. I actually bring it back to -- we have been very focused on as a platform-based therapeutics company, I'd like to say instead of a platform company, we've been focused on what is the platform going to do for patients and how do we marry the benefit of the platform with the unmet need and the opportunity. And so we'll be much more, I would say, therapeutic focused than kind of trying to identify proof of concept for the platform. And I can't say that we got everything 100% right, but we focused on target that had not been drugged or drugged well where protein degradation is the best way or the only way to tackle them. And the targets that we believe were in areas where patients were looking for new opportunities. And while we're, I would say, between early and mid-stage development, I can say that if I go through the programs, if I start with IRAK4, I think IRAK4 degrader as a profile that is not seen in immunology. This is a Th1, Th17, even partially Th2 broad anti-inflammatory agent with the derisked safety profile based on human genetics that could be applicable in a wide variety of indications. We're starting in HS and in AD, but we can go way beyond. And we've seen some really early exciting data there. STAT3, we're seeing some exciting data in some indication in heme-oncology for a mechanism that hasn't really been explored before without any dose-limiting toxicity. Same can be said about MDM2 in terms of potential. If you think about STAT6, it's probably the perfect target for protein degradation, a dupi like in a pill. TYK2, again -- lots of promise for the mechanism, but I think the small molecules haven't delivered and I think we have a great opportunity there. So I don't like to speak about other companies, but I think for Kymera, we've been focused on first becoming master of the technology, and then importantly, applying it to the right targets where we know and we expect the biology to marry the technology well.

Is there a number of patients for -- across the board in I&I and oncology, once you hit a certain threshold, you'd feel pretty comfortable in sort of the target -- like the platform risk, so to speak, right? Look at tipping point of, okay, now we can move forward more aggressively to focus more on efficacy now that we have treated patients for a certain length of time.

Yes. That's actually a great question. So there is different ways to probably to answer that question. I would say that we've actually dosed -- drugs, I was just doing the math while you were asking the question, to probably north of 200 patients now across our programs, probably even more than that. And -- so I think there is 2 aspects. There is a -- how many patients you've dosed and then how long you've dosed your patients. For our immunology franchise so far, we've dosed a lot of patients, but only recently, we've started to dose 16 weeks in our Phase II study. And so that data is maturing and is evolving. We do -- we expect, given that we dosed that drug to 150 patients already, we feel pretty good about the profile. In oncology, maybe less patients -- but for longer, our STAT3 degrader has been dosed to probably as of the abstract about 40 patients now, but in many cases, for multiple months, I think we have patients with 10 cycles, so we're talking about close to a year. MDM2 kind of similar, and then we have extensive preclinical safety. I think what I can say about safety, if I look across the industry is that there is no protein degradation, specific safety concern. I think that has been already derisked by Revlimid and the ER degraders, small molecules that have been on the market for years. I think what we learned that depending on the target biology, you might see target-specific safety issues. And that's true whether you use the graders or you use small molecules, I think for biologics or RNA -- I think it's important, though, if you pick a degrader target, there is 2 paramount things that we at Kymera care about. First specificity it is critical that you're very specific for your target because it is a very powerful technology and you don't want to degrade other proteins. And then that you know very well what is the biology of your target. And when you do have the biology of the target can be so powerful that can go beyond the expected pharmacology. For example, think about MDM2 degradation. We know that MDM2 complete degradation 24/7 is noncompatible with a beneficial therapeutic effect. And so there, you have to get created with maximizing your therapeutic potential of the mechanism with the beauty of the technology. So for example, for MDM2, we know that if we give a degrader to a sensitive cancer cell, that cancer cell is going to die in a matter of hours, at least committed to apoptosis in a matter of hours. So what we have devised for a mechanism like this, we have this pulsatile dosing with dose once every 3 weeks with an MDM2 degrader, and we can see robust activity in the absence of any, for example, thrombocytopenia, neutropenia, things that are known to play MDM2 mechanism. So I think you also have to optimize and really think about how the technology works and then optimize how you dose this molecule when you work in mechanism that are fundamental to biology.

And is the conversation different? Are the markets different between I&I and oncology, I think from a risk-benefit perspective, right? I mean I&I indications can be obviously not lethal, but pretty severe and devastating right? But...

Yes. So I mean, look, I think our goal at Kymera is part of building a global player in immunology and other diseases as we continue to grow the company. Our goal has always been, if we build molecules like our -- if you look at our immunology franchise, these are meant to be oral degraders with biologics like activity our dream is that we can dose, we can treat as many patients as possible. So when I think about, for example, STAT6, which is a program that they wholly own and is in the IL-4/13 biology, there is about 150 million patients that suffer from Th2-driven inflammation. Now a subset of those that have moderate to severe, a large percentage of those have mild disease. A drug that has the potential to have dupi like activity and safety potentially with the convenience of an oral drug. Our dream is that we can put the drugs in the hands of as many patients as possible. And if you think about Th2 inflammation, that is a very severe disease when -- especially when it impacts small children. You just have to do a Google search to see 4 -- 3, 4, 2-year-old children with severe atopic dermatitis, children with severe EoE, these are life-changing experience. And I think we want to serve those patients with a convenient, effective and safe therapy. And that's the value proposition there.

Yes. Well, let's get into some of the programs. So 474, help us with kind of the -- how you view the target profile relative to -- there's obviously a pretty competitive landscape across many I&I indications, but you have good proof of concept.

Yes. I'd like to tell the story that when we started our IRAK4 program around 2017, we started talking more broadly, I would say, '19 -- and we were seeing our first indication, at least at that time, was HS, we were met with a lot of skeptics. I think at the time, there was only 1 drug in HS that was active, was HUMIRA that has some activity. And then the -- as I'm sure you recall, Geoff, we -- as a drug development industry had been phasing lots of failures in HS, it was thought to be an intractable disease. And now it's great to see many drugs -- more drugs approved, many drugs that are active. And now the fact that -- the notion is that almost HS is a competitive space, which obviously is good for patients. So what I would say is, sorry, a long story, but to get to the short part to it, the immunology landscape has been changed by biologics. Biologics have served 2 things. They have validated the biology. If you think about TNF, IL-17, IL-4/13, IL-23, IL-12. These are all huge mega blockbuster drugs that have told us the cytokine -- these particular cytokines and mechanisms are responsible for diseases. They've done that, but they've also changed the treatment landscape. 10 years ago, if you had RA, you wouldn't have almost any reasonable therapy. If you have psoriasis, you would have topical creams and some general anti-inflammatory agent. I think now we have targeted therapies that have changed the landscape. The future of immunology, I believe, is having oral therapies that will have much broader application. And so IRAK4, going back to your question, is a typical example of a drug that has a broad anti-inflammatory profile, IL-1, IL-18, 33, 36 TLR7, TLR8 TLR4, these are all agonists of this pathway that have shown to have activity in a wide variety of diseases. The goal here with an IRAK4 is to have an oral drug that can have a broad anti-inflammatory effect. And our goal is not that we need to be better than an IL-17 drug in HS. So we need to be better than DUPIXENT in AD. Our TPP is we don't want to have an active drug that is well tolerated that can be one of the key tools. Ideally, the first line tool for patients that, as you know, go through so many treatment paradigms to manage their disease over their lifetime. And so our goal is an active drug with a good safety profile that is convenient and accessible, right?

And when you have a derm indication, obviously, you sort of visually -- in theory, you could move faster, you could derisk faster, you could kill drugs faster. When you shift gears to say, STAT6 looking at either pulmonology or GI diseases, like how do you think about that in the context of the potency that you could achieve with the degrader.

Yes. So we've shown in derm, the beauty of -- so the beauty of protein degradation, you can monitor target engagement over doses over time. So you almost know in real time the level of degradation for example, in the case of our experience with IRAK4 in blood and skin after 1 dose, after 14 doses after 28 doses. And that tells you how you are impacting both the target and the downstream biology. And we've built a lot of knowledge and expertise around the correlation between the central compartment and the skin or other noncentral biomarkers. I think we have built enough knowledge, both in the clinic and preclinically to being able to be quite comfortable to generate data that can speak to other tissues. I mean in our preclinical species, we've shown robust degradation in lungs with STAT6 in both nonhuman primates and rodents. At concentration that are similar the ones that we see in blood at the same doses. So we know that we can see a one-to-one correlation between lungs and central compartment. We've done the same for GI, for spleen, so I think we understand enough about the compounds, both potency and distribution that we believe venturing outside of our initial foray in derm should be something that we can do -- that we can do comfortably.

Right. When you look at HS, I mean you brought that up, there's -- it's been recently a more competitive space. You see a lot of major pharmas, big biotechs go after more orphan indications, right, across I&I. Is that -- is that still, in your view, a faster path strategy? I feel like now FDA may not give you speed concessions, right? They still may require the same kind of derisking? Is that -- so is that something that you think over time you could go after more rare indications and with some speed?