I think we'll get started here with our next fireside discussion. My name is Derek Archilla. I'm one of the senior biotech analysts here at Wells. Next up, we have Kymera Therapeutics. From the company, we have President and CEO, Nello Mainolfi, and then also we have Jared Gollob, the Chief Medical Officer. So gentlemen, thanks so much for joining us, and look forward to the discussion.
Thanks for the invite.
Yep.
So maybe just to start off, Nello, maybe do you want to just provide a little bit of background about the company and, and kind of what you guys are working on, and then we can kind of dig into the more specific questions?
Yeah. So first, thanks for the invite. It's great to come to a Boston conference for us. We're a company that was founded with the mission of building an integrated biopharmaceutical company using targeted protein degradation to deliver a new generation of medicines. The beauty about TPD, targeted protein degradation , is that it combines the power of genetic-like knockdown with the flexibility of small molecules. So you can use oral small molecules that can distribute in the body, in any tissue, any organ of interest, to bring a disease-causing protein to the ubiquitin proteasome system, which is the recycling mechanism in our cells for degradation. So the sky's the limit for the technology.
The trick is really, or the challenging part is really where to apply the technology, what type of target, what type of protein, what type of diseases, what type of patients, and that's where we've been focused for the past seven years, selecting, we believe, the right targets, the right diseases, the right patients. So we have focused for the past few years, mostly in oncology and immunology. You know, the technology is protein type agnostic, so it's disease agnostic. It's target agnostic, as I said, but I think it's important, especially for an early company, to build capabilities and to be a credible drug developer.
For that reason, in the first phase of the company, we're focused on immunology and oncology, but it's probably obvious that at some point, as we continue to grow, and hopefully with further success, we will be able to expand beyond immunology and oncology. So for now, we have four programs in the clinic, we have several other programs that are approaching clinical development, and we focused on proteins that have not been drugged or drugged well before, within pathways that have been validated with both human genetics data as well as clinical data, especially with agents targeting other nodes in those pathways. We were the first company to take a degrader into a placebo-controlled, randomized, healthy volunteer study, as well as in patients with inflammatory diseases like HS and AD.
We took a heterobifunctional degrader against a transcription factor in the clinic with STAT3, that probably we will discuss soon. And, you know, we continue to be focused on targets that, again, have been difficult to drug. So our IRAK4 program is entering Phase II, and we have three programs in Phase I in oncology. IRAKIMiD program, STAT3, and MDM2. We're well-capitalized. We had $472 million as of Q2 of this year, which will allow us to get into the second half of 2025, and importantly, will allow us to read Phase II data for KT-474, we believe in both HS and AD, as well as proof of concept data for the three oncology programs.
We're really in execution mode across our pipeline, and so excited to, you know, share upcoming pieces of data across our pipeline in the next few months.
Great. Perfect. Thanks, Nello. Maybe to start off on some of the targets, and as you said, you guys, your strategy has been more to look at the undruggable versus kind of like validated, you know, maybe by inhibitors and, and things like that. So maybe, you know, one of these targets is STAT3. So maybe you can just provide a little bit of background about that target, why it's so hard to drug, you know, with the small molecule inhibitor approach, and, and again, kind of the genesis of your degrader program for that target.
Yeah, I mean, the STAT family of transcription factor is a family that we've been pretty keen on since the beginning of the company. STAT3 was our first program in the family of transcription factors for maybe I would say three reasons. One, it's one of the most well-documented undruggable target in the public domain. There are probably 25,000 publications pointing to the role of STAT3 in immunology, in fibrosis, in oncology, in heme and solid tumors, in immune regulation of tumor microenvironment. So we felt that it represented a great example of, you know, what target protein degradation can do that other technologies can't. So again, first reason is undruggable target with lots of literature around. Second, you know, not possible to drug with other technologies.
And third, we thought that it would allow us to build the franchise around the single target. As you know, we have started clinical development against STAT3 in oncology, but we hope and plan to expand beyond the early clinical data in oncology as we generate more data, both clinical and preclinical. The target has never been drugged well by other technologies because first, it's a widely expressed target, so you need an agent that can distribute in the body well, so you need either a small molecule or a highly permeable, in this case, degrader.
The other point has been that small molecule inhibitors are not able to block the total function of STAT3, given that STAT3 acts by protein-protein interaction, protein-DNA interaction, so small molecules are not able to block those interactions well. And so we thought that the degrader was really the only way to do it, to do it well.
Got it. So maybe you can talk about some of the data thus far that we've seen from the program, KT-333. And I guess, you know, what level of degradation are you able to achieve, and how are you thinking about that as it relates to efficacy in the future? I guess, what have you seen pre-clinically, like, what level of degradation do you need to see?
Joe, do you want to take that one?
Yeah. Maybe if I start with your second question in terms of the level of degradation needed for activity. You know, our sort of workhorse model has been STAT3-dependent T cell malignancies. And STAT3-dependent T cell lymphoma, anaplastic large cell lymphoma, ALK-positive, has been our workhorse model because it's very sensitive to STAT3 inhibition. And we've shown in that model that we need 90% + degradation for 48-72 hours to send those tumors into complete regression that's durable and lasting. So that's been our target level of degradation for STAT3-dependent T cell malignancies. And the ones that we're interested in are peripheral T-cell lymphoma, cutaneous T-cell lymphoma, and large granular lymphocytic leukemia. And all of those, you know, have genetic evidence as well as other phenotypic evidence that they're dependent on STAT3.
So maybe coming back to what we're seeing now in Phase I, a dose escalation, this study is open broadly to patients with solid tumors because we do believe that there's a solid tumor opportunity for STAT3 targeting, that might be more of a combination opportunity with immunomodulatory drugs like anti-PD-1. But we think that the monotherapy opportunity is really in T-cell malignancy. So our Phase I study is open to solid tumors, to all lymphomas, B- and T-cell lymphomas, as well as to leukemias. And we've been dose escalating. You know, we shared, you know, back at ICML in June, you know, our progress on dose escalation. You know, we've seen a favorable safety profile so far. We haven't encountered any dose-limiting toxicities, and we have seen robust STAT3 knockdown in the blood, where we've been able to reproducibly measure it.
We've seen knockdown that's averaged in the mid- to high 80s, with some subjects having knockdown as high as, you know, 90%, 91%, with knockdown lasting for at least several days. So that's been very encouraging that we can reach those levels of knockdown at the doses that we've got to so far with a safety profile that has been, you know, quite encouraging. And now that we're at those dose levels, we're making even more an effort now with our investigators to try to enrich for those malignancies that we think are most likely to respond to the drug as a monotherapy, so namely CTCL, PTCL, LGL leukemia. So we are actively recruiting those patients in addition to the other tumor types.
Our aim is to present, you know, data, you know, later in the year, preferably at a medical meeting, that would provide more safety, PK, and PD data, but also provide some of the first sort of clinical sort of antitumor data, especially in a handful of these target patient populations, these T-cell malignancies.
Like, how, how should we think about the total number of patients? And just going. You kind of started alluding to it, but, like, for that specific group of, of malignancies that you want to focus on, like, again, what percentage of the patients do you think have already kind of been enrolled with those specific malignancies?
Well, we can't really provide those specific details, but I think our aim is to be able to have sort of a, you know, a critical mass, a small handful of these patients, you know, represented within CTCL, PTCL, and LGL, treated at these higher doses, where we're seeing 90% or greater knockdown. That will allow us to start to see if there's an initial signal of activity in terms of antitumor response. And so that really is our goal, and that's what we want to be able to present later in the year.
Got it. And then just kind of from a mechanistic standpoint, by degrading STAT3, like, are there any, you know, potential liabilities or risks? I know you haven't seen anything, but maybe, you know, again, longer term, you know, how should we be kind of thinking about the safety?
Well, I think what's important is that we we're dosing the drug as an IV infusion once every week. And so we don't think that chronic, you know, deep suppression of STAT3 would be tolerated, so we're really utilizing this intermittent dosing regimen. And we've seen in our preclinical tumor models that dosing once a week or once every two weeks gives us a strong tumor regression in the STAT3-dependent T-cell malignancy. So that's our dosing paradigm, which in our preclinical tox studies has shown that we can mitigate, you know, tox from STAT3 knockdown. So, you know, the sort of tox that we saw preclinically was predominantly GI, you know, tox at higher doses.
But I think that, you know, our intermittent dosing schedule is probably allowing us to dose escalate without seeing, you know, a lot of those sorts of toxicities, or at least not having seen so far, dose-limiting toxicities.
Got it. So we get this data, we start to see some activity in those, you know, kind of target populations. What's kind of the next steps there? Is it more kind of, you know, more patients, kind of expansion around that specific dose regimen? Or how do you think about the regulatory path for these specific, you know, T-cell malignancies?
Nello, do you want to answer that part?
Yeah. I mean, so just to recap, right? The goal of the Phase I dose escalation is to identify a dose to take into further expansion. I mean, I think it's the responsible thing to do, is to try to recruit to these studies enough of the patient where you expect to see responses, so that you can also understand and appreciate what is the interplay between safety and early signs of activity. So that's really what we want to establish this year.
Now, with regards to further development, the goal is to expand in indications where we have either strong preclinical data or emerging clinical data, where we expect to see meaningful activity. And I think then as we expand, the opportunities of going down a registrational path will depend on the indication, on, you know, the standard of care, the regulatory pathways that one can envision, depending on, again, which type of tumor types we're going after. I think until we kind of commit to this expansion cohort, I think at this point it's too early for us to say, like, what's the end game towards registration for this program?
Got it. Maybe you can put some context around, I guess, the standard of care for those indications and, like, what would be, like, clinically relevant in terms of responses or, you know, things like that?
I mean, because we're not gonna be able. As, as Jared said, this year, best case scenario is, let's say CTCL or LGL will have a handful of patients, right?
Yeah.
Think about how many those cohorts. I think the. Our communication is not gonna be about what is the response rate in LGL leukemia or CTCL, because we're not gonna have enough patients to be scientifically credible to talk about response rate. We can talk about, look, we had, I don't know, X number of patients, we've seen-
Yeah
X number of responses, and we feel pretty good about that particular indication. Then once we go into expansion, where we have, you know, larger ends, then we can talk about response rates. So setting the stage for response rates right now, then we're not gonna be able to talk about it, seems like probably not the right time to do it. We can talk about what the, you know, the standard of care responses are in those indications when, you know, time is right.
Got it. So more focused on just activity and then.
You know, the focus is first proof of concept of a STAT3 agent in an oncology indication, which has never been done before.
Got it. Maybe just shifting gears to the other aspect of STAT3. So I know you guys have talked about looking at it for I&I. It might not be the three three three molecule, it might be, you know, others that you might have kind of, you know, floating around in the pipeline, but maybe you can just kinda talk to, you know, again, the biology there and how you guys are thinking about, is that something that you do yourselves? Is that a collaboration with a larger pharma to kind of move an I&I program on STAT3 forward?
So, let me give you two answers. One is kind of more, let's call it scientific, and one is more strategic. So the scientific answer is, we know that there are data that are in the public domain and data that we have disclosed actually extensively, maybe not as recently, but in the past couple of years, of how active a STAT3 degrader can be in a wide variety of autoimmune indications. I think we've shown data in a MS model. We've shown data in a rheumatological model. We've shown data in skin models. So we know that STAT3 depletion, and actually even suboptimal, you know, 50%-60% to even 70% of STAT3 degradation is sufficient to drive strong anti-inflammatory effect.
In fact, in fact, if you look at our data at ICML, we showed dose Level 1, 2, and 3, which, you know, hover around 60%, 70%, 80% degradation, have a substantial impact on circulating CRP level in patients that are, you know, probably similar to strong anti-inflammatory approved agents. So we know that this mechanism is extremely relevant. I think that the work that we've done, both pre-clinically and in the clinic, is first trying to understand better the safety profile. Obviously, the safety profile in cancer patients is not always gonna be directly translatable in non-cancer population, but it gives you an idea of what we've seen pre-clinically, how it translates clinically, and then trying to prioritize the route of administration and formulation to take into other potential non-oncology indications.
And so I would say that out of, you know, completion of a Phase I, dose escalation study and preclinical work that we're doing to refine formulation and route of administration, we hope to be able to talk about what is the development program outside of oncology. But we would only develop a STAT3 degrader if we have opportunity in meaningful indications that can help a lot of patients. But going to the strategic question, I think somebody asked me a similar question, and I feel like my answer was not clear enough, so I'm gonna try and do better this time. We're not going to partner every immunology program. That doesn't mean that we will not partner immunology program, but I just wanna be clear, just because it's immunology, we're not going to partner just because it's immunology.
It might turn out that STAT3 in immunology makes sense to partner, but I just wanna be clear, just because historically we have an IRAK4 immunology program that is partnered, then the oncology programs that are not, that is not our business model. It just turns out that at any point in time, there is a reason to partner a program, and it was only by chance that the only program that is partnered is in immunology. Our partnering strategy is, I would say, disease area agnostic. It's more of a business strategy decision than a disease area decision.
Got it.
Hopefully, that's clear.
That is very clear.
Okay.
Yeah, so just last on kind of STAT3 and IMiD, I guess, when would we kind of get more updates in terms of.
Yeah.
You know, kind of understanding a program, a development plan?
Yeah, no, I understand. Yes. So, I think we've said in our last quarterly call, we're planning to have R&D Day in early next year. Most likely, the focus of the R&D Day will be our immunology-evolving immunology pipeline.
Okay.
I think this is the first time I've said it. Hopefully, my IR team will not kill me. And so I think as part of that, it's possible that that will be part of it.
Okay. Got it. That's perfect. Maybe shifting gears away from STAT3, maybe just kind of an update on the 413 IRAKIMiD program. Obviously, similarly, you're gonna have data later this year, so if you can tee that up for us a little bit.
Yeah, maybe high level, and then Jared can help me. High level, it's quite similar to, you know, what we just said about STAT3. Although in 413, we have a more directed recruiting effort, B-cell lymphomas, non-Hodgkin's lymphoma. Within the larger family, our target population is MYD88 mutant tumors, which happen to be most likely diffuse large B-cell lymphoma , which is the larger, in terms of absolute number, population of patients, and 25%-30% have MYD88 mutation. We're also, you know, open to recruiting Waldenstrom patients, which, in terms of absolute number, are less, but in that population, 90% have MYD88 mutation. So, and also, there is primary CNS lymphoma. So within, again, the non-Hodgkin's B-cell lymphoma, we have a subset that is our patient population.
We hope to be able to recruit to the study enough MYD88 tumors to be able to prove the concept that an IRAKIMiD degrader is safe, well-tolerated, and leads to antitumor activity in MYD88 mutant tumors by the end of the year.
Got it. Jared, do you want to add anything to that?
No, unless you want more details on the study itself.
Yeah, we can get into that. I guess, also just I wanted. So it's sounding like you're confirming that we would learn whether it's gonna be wild type or mutant, like, in terms of the patients, and you'll kind of give that stratification with the data set.
Yeah, maybe just to be clear. Yeah, let me just clarify that. So we recruit without selecting patients just because the goal is to get to an MTD. We do then characterize patients on the study, and so we know, obviously, for sure, when we will present data, how many were wild type, how many were mutant.
Yeah.
And then we only expect to see activity in mutant, so then we'll hopefully be able to talk about that.
Got it. Yeah. And maybe, Jared, you want to just kind of, a little bit more color on the trial design.
Sure
Where you guys are in dosing and things like that would be helpful.
Yeah. So just as a refresher, the dosing regimen is, we give it as an IV infusion once every three weeks, and we're degrading, you know, IRAK4 and the IMiD substrates, Ikaros and Aiolos. And so we've been dose escalating on the trial, and we presented some data around the time of the ICML meeting, that was sort of an update on where we were with dose escalation. And at that time, we reported that, we were seeing, you know, fairly robust knockdown of all three targets as measured in peripheral blood.
In particular, our target knockdown for IRAK4 is in the 60%-70% range, and for Ikaros and Aiolos, in the 90%+ range, 'cause those are the levels of knockdown that led to tumor regression in MYD88 mutant models, and we were reaching those levels of knockdown in the blood with acceptable safety. And importantly, 'cause we often get asked: Well, are you seeing dose-limiting neutropenia.
Right.
Or GI tox? 'Cause this is usually what comes up with IMiD that are dosed chronically. We do have a potent IMiD built into the 413, but fortunately, we haven't seen that. So we haven't seen dose-limiting GI tox or neutropenia on the study as of that ICML update, despite the fact that we're seeing robust knockdown in the blood. So for us, that is sort of, you know, playing out nicely in terms of this dosing regimen, intermittent dosing, allowing us to mitigate classic IMiD toxicities and still get the knockdown that we think we need to get tumor responses.
Mm-hmm.
And so I think as we continue to escalate, our aim is to try to not just enroll a broad population of B-cell lymphoma, but where we can, also bring on MYD88-mutated patients, so we can again, have maybe a small handful or critical mass of patients by later in the year, where we can assess whether we're seeing any clinical antitumor activity in that population. And so I think that is a similar aim that we have for the STAT3 program, you know, to be able to report on that later in the year.
Is that IMiD, like, you know, really a knockdown, fairly similar to what you see with lenalidomide or pomalidomide? Is that or is it better? Like, again.
It's similar knockdown.
Uh.
In terms of the kinetics. It's probably even more potent than, say, pom and len, more of what you would see with some of the more, you know, potent, newer generation IMiDs. But I think the key is really the fact that we're not chronically dosing daily and keeping those, those targets knocked down.
Yes.
Which probably would not be tolerated well, and you've seen that with some of the results that have come out from, say, C4's.
Right.
You know, potent IMiD, where they had to sort of make alterations in dose and schedule. So far, we haven't encountered that, we think predominantly because we're using this intermittent every-three-week dosing regimen.
Gotcha. So, I mean, and, like, just, I guess, understand in terms of, like, again, you're not seeing that neutropenia side effect. I mean, was that something that you really didn't see, like, preclinically? Like, again, was it just like you nailed it with the dosing regimen pretty much?
I think pre-clinically, you know, in our GLP tox studies, you know, with higher species, you know, you do see a drop in neutrophil count, but the key is that you recover within three weeks prior to the next dose.
Yeah.
I think it's not that we're not expecting to see any change in neutrophils.
Right.
With dosing, but I think the key, at least that we learned from GLP tox studies, is that you get recovery prior to that next dose.
Right. Gotcha. So then kind of going forward, obviously, as you were saying now earlier, a little bit of a different kind of potential regulatory path here, maybe with, you know, kind of the focus on a specific population. You know, obviously, we'll get this data similar to maybe STAT3. This is more about activity, but can you just kind of elaborate on kind of the next steps here after that and, and what we'd kind of be looking for?
Yeah, I mean.
In the path.
You know, the fact that with protein degradation, we can, we can, select doses that are both active and, and hopefully well-tolerated, and we understand what is the PK, the PD, and the efficacy relationship. We believe that this will allow us to have a faster path, in also later development in terms of dose selection, with regards to, although obviously we'll have to interact with the agencies. With regards to path registration, we believe that this, this, this molecule and this program is well-suited, given that there are no targeted therapy for MYD88 mutant lymphoma, we believe that this is an opportunity to develop a first-in-class agent here, and so that should also allow us to potentially explore accelerated paths, to, to approval.
But again, this is still early in the process, and, you know, without interacting with the regulatory agencies, I can't, you know, commit.
Yeah.
To these type of statements.
Understood. And then maybe just lastly, in terms of the oncology, KT-253, the MDM2 degrader, and kind of where you are there with that and kind of your, you know, kind of, I guess, strategy around that target.
Yea.h. I mean, we started dosing in Q2, so we're.
Yeah.
Relatively still early in dose escalation. You know, I would say for each one of our program, we've been very thoughtful about getting to an early go, no-go, on the mechanism, right? So for example, just going historically all across our programs, the case with IRAK4 degradation, now going back outside of oncology, was we believe that degrading IRAK4 will have a differentiated biological signature than small molecule inhibitors, so we believe we have a path to having a best-in-class agent in that pathway. I think we've shown for sure pre-clinically, extensively, why we're differentiated and superior to small molecule inhibitor. I would argue also clinically, we have early signs of pretty strong differentiation versus small molecule inhibitors, or to be honest, a lot of other agents out there.
But again, this is something our goal is to be able to do in early development, right? So we feel we've done it with IRAK4. For STAT3, the question is, can we drug this target safely and effectively? We should be able to answer that in a Phase I study. For the IRAKIMiD, can we build a targeted therapy for lymphoma in a tolerated manner? We should be able to answer that in early clinical development. For MDM2, it's another simple question: Can we build a therapeutic index where that will allow us to fully explore the biology of p53 without hitting dose-limiting toxicity, which happens with small molecule? We should be able to answer that in Phase I study.
So obviously, the full clinical and commercial potential of all of these programs will be fleshed out in later clinical development. But the early go, no-go, are we doing what we designed these drugs to do, and is the biology translating the right way? We wanna be able to do early because we don't wanna spend $10 million or $100 million . And this goes back to the philosophy about target selection. Yes, you can go after a target that has been drugged by a small molecule where you don't have a biological rationale to be superior. You're gonna find out in a Phase III study if you're superior or not. That's not the business we wanna be in. So for MDM2. Sorry, this was.
No.
Something I had in the back of my head here. MDM2, again, it's also, I think it's a very easy question to ask. So the mechanism is validated. There is no- I think everybody in the world of oncology, if you talk to them and you say, "If you increase p53 levels in p53 wild-type tumors, do you expect to see antitumor activity?" 95% of people will tell you, "Yes." There's no question about it. Probably the same 95% of people will say: Can you do that safely, right? And that's where the small molecules have a trouble, because as soon as you hit the levels of p53, you don't discern between cancer cells and many, healthy cells, especially bone marrow-derived cells and sometimes GI, highly dividing cells. So, and why is that?
Because small molecules hit the target, and what happens as soon as you increase p53, you have a feedback loop that increases MDM2. So now you're trying to inhibit MDM2 as you continue to increase MDM2, and you end up hitting safety as soon as you start hitting efficacy. Mostly because with this small molecule inhibitory mode, you're mostly driving cancer cells to cell cycle arrest, which is the same phenotype of bone marrow-derived cell. They both go into cell cycle arrest. You have no therapeutic index. With a degrader, this is a catalytic mechanism that knock out the protein the same way as genetic agents that have validated this target for now, you know, 10, 15 years, we're able to drive cells into a apoptotic response because we remove MDM2 completely, we overcome feedback loop.
With KT-253, we increase the levels of p53 hundreds of fold above what has been seen with small molecule, and we drive cancer cells that are sensitive to this mechanism into apoptosis while healthy cells, at best or at worst, go into cell cycle arrest. That's the therapeutic index that we built. You combine that with infrequent dosing, with dose once every three weeks, then we build this therapeutic index. So the question we wanna answer in Phase 1A is: Can we drive antitumor responses in a subset of tumor patients or tumor types that are sensitive to this mechanism before we hit those limiting toxicity.
Got it.
You know, generally, that's not the goal of a Phase I study. Like I've told you, for other mechanisms, we're trying to differentiate to get to an MTD and understand how you further develop. But those are first-in-class mechanism, right? You're still evaluating what is your responder population here. We're really trying to differentiate from small molecule inhibitor, and so we need to show that differentiation early on.
Got it. Makes sense.
Hopefully, we'll be able to share that next year. I think this year it's gonna be early data, mostly around degradation and early safety.
Got it. Okay. And then maybe the last couple of minutes, did wanna touch on 474. I know you alluded to earlier. Again, partner, Sanofi, is gonna start two of those trials. Maybe you can just kind of give us an update on those programs and just your working relationship with Sanofi. I mean, how much input do you have into the trials and also, you know, kind of indication expansion for 474.
Yeah.
Beyond HS and AD?
I mean, you know, we, we were fortunate enough that, the relationship with Sanofi has been, has been always very strong, professionally and personally. And we're fortunate enough that they allow us to, contribute to, study designs and inclusion, exclusion criteria, and all the things that one considers in mid to late-stage development. Obviously, now that they're responsible for the development, they do have the final say, but, but I, but I, but I will say that they've been quite open with our team. So we're very excited about, you know, I can - I'm gonna say finally, starting these Phase II studies. I think we're, we're very close. We're excited about going into two indications that, don't really have approved, a well-tolerated, active, small molecule oral drugs, and that's really what we're going after, in terms of TPP.
And we believe we have really blockbuster potential in both indications and beyond. I think your question around going outside of HS and AD, it's obviously something we're very keen on. We're not gonna talk about it because now we're focused on HS and AD, but rest assured that I can say from myself here, that if the drug continues to be well, both in efficacy and safety, this will be a large pipeline in a molecule. That's Kymera's commitment that we will continue to work with our partner on.
Got it. I mean, do you see also just kind of, again, the move into a large indication like AD chronically dose, like, again, to kind of vote of confidence on the profile thus far, and, and particularly the safety profile?
Yeah, I mean, you know, I think for the. We've been very transparent with the data. I think that's one of the things that you can say about Kymera historically. So you guys have seen all the data we have seen. The molecule is well tolerated. It's been in 150+, the studies recruit 154, I think, subjects between healthy volunteers and patients. We have dosed for 28 days, so clearly we need to build more experience on chronic dosing. But what we've seen so far, the molecule seems to be really well behaved. We have seen this transitory that I call it subclinical QT effect, that reverses naturally with continued dosing.
So we'll continue to monitor that in Phase II, but we're very excited about the program, the molecule, and what Kymera and Sanofi for this program can do in immunology, and what Kymera can do in immunology beyond IRAK4, which, as I said, will be the topic of our R&D day early next year.
Got it. Maybe just last question, more of a platform question. I mean, you guys are kind of, you know, swimming in both lanes in terms of like, you know, PROTACs and glues and the ability to kind of look at, you know, both of those kind of modalities within TPD. I guess, like, one, how robust is that platform on, on both of those? And then ultimately, like, what drives your decision for either just depending on the target?
Yeah, I mean, first, our heterobifunctional degrader platform is best in class. I can't, you know, I can't imagine a company that has been more productive than us at discovering and putting degraders in the clinic. Regarding molecular glue, I will say it's an emerging platform at Kymera, but we made a ton of progress in relatively short amount of time. Probably more progress than most small companies in the molecular glue space. But we have a very high bar with regards to how we make decisions at Kymera, and we have also a simple bar. Heterobifunctional degrader programs, we use it for molecules that we can find small molecule binders, because that is the most rational perspective and predictable path to developing drugs.
For proteins that we cannot find small molecule binders, we then exploit protein-protein interaction-enabled degraders. So you will never find us degrading a kinase with a molecular glue, or building a heterobifunctional by trying to build a heterobifunctional molecule for an unligandable protein. That's the demarcating line.
Got it. Perfect. Well, we'll leave it there. Gentlemen, thank you so much.
Thank you.
Thank you.