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

Good afternoon, everyone. I'm Ellie Merle. Welcome to the UBS Healthcare Conference. Very happy to have Kymera Therapeutics here with us today. Joining us from Kymera is Nello Mainolfi, President and CEO; Bruce Jacobs, Chief Financial Officer; and Jared Gollob, Chief Medical Officer. Thank you guys so much for joining us here today.

And I guess maybe to kick it off before we jump into the programs. High level, what is it about targeted protein degradation that you think is so exciting and potentially disruptive as a novel modality?

Thanks, Ellie. Thanks. Can you guys hear me? I think so. Thanks for inviting us. Actually, this is a great podium here. So let's start with what's not exciting about protein degradation. Now in reality, the opportunities -- we should start viewing the opportunities in protein degradation at different levels. I will start with a very simple one. In the past, maybe 50 years where there's been really disruptive innovation in biopharma, we really haven't had a novel small molecule-based modality. This is the first one where you use a small molecule to do something different than inhibiting a protein. So this is very technical. In terms of the impact, for the first time ever, one can remove a disease-causing protein from its cellular localization without changing your genome. That hasn't been done before. So once you understand the technical aspect of the technology, then the application, I think, are almost endless. And I think the promise and the probability of impacting patients is really down to how one uses the technology. So we're focused on as someone else says, the higher hanging fruit, which is targets where there is or pathways where there is high degree of validation, but where key nodes have not been dragged or drugged well with other technology where protein degradation can be unlocking that solution. You will not find us working on targets that have been fully drugged before where there is a theoretical improvement of activity, if you use a degrader. I think that's maybe a proof of platform program but not a therapeutic program. So it's really about how one can impact patients more broadly is by going after targets where no other technology can do. The additional opportunity with protein degradation is to use the technology itself to ask new therapeutic hypotheses. So generally, the technologies known as using a small molecule lig into a protein to degrade that protein. We just talked about it. But now as someone -- as we continue to increase our understanding of the technology, we can move into what else can the technology do. And what we are focused on at Kymera and we have been for the past 4 years, at least, has been can we evolve the technology so that we can do more than what the technology can do today. And our angle has always been using E3 ligase expression to develop a selective pharmacological agent. So agents and drugs that selectively or restrictively can degrade proteins. And I don't know if to explain why that's exciting. Obviously, if you can degrade proteins only where it's therapeutically relevant, you will increase the quality of life of every patient that takes that drug.

Absolutely. And maybe just kind of high level, in maybe 5, 10 years, where do you see protein degradation as a field?

Yes. I think the closest that I can imagine protein degraders to, if I can imagine trajectory of protein degraders, the closest that I can think about is how antibody discoveries evolved in the past 20 years, where there was an early kind of technology understanding, an appreciation of the limitation about antibodies and then understanding what's the sweet spot. And then obviously, as you guys see the top 2 probably top -- in the top 5 drugs, unfortunately, for a small molecule like [ myself ], they're mostly antibodies. I think that's the type of trajectory. I'm not saying that the exact numbers will look the same, but that's the type of trajectory that protein degradation is on. It's all about are we learning enough from the early clinical experience and are we applying it to the right type of targets?

Absolutely. And I mean we could sit here and talk about IRAK4 and QTc for quite some time. But maybe in lieu of that, let's start with STAT3 when it comes to your programs. Maybe just starting with STAT3, can you tell us a bit of how this has historically been an undruggable target and why this could potentially be such a high-value target in the context, I guess, starting with oncology.

Yes. Thanks, Ellie. And obviously, we're happy to discuss any aspects of our pipeline. So starting with STAT3. So there is -- there are a few targets in the oncology space that have been pursued heavily in the past 20 years because they were thought to be key nodes of either cancer cell proliferation or immunomodulatory nodes in both oncology and actually, in this case, also inflammation. And STAT3 has always been one of them. Actually, I think there is 25,000 papers on that target pointed to its role in a wide variety of biologies. And what's limiting STAT3 has been really the chemistry to effectively and selectively target that transcription factor. This is an atypical protein because it doesn't bind to any substrate or secondary metabolite, but actually binds to DNA after phosphorylation. So the protein is not trained to bind to small molecules. So it's been challenging to drug. I think Kymera, while not the first to try the drug STAT3 has been -- I would say, the best, but I would say so far, has been the company that has been able to develop a specific STAT3 agent that is highly specific and selective. And the opportunities are broad, and I think actually most of the work that we've done in the past 3 years has been hard to prioritize opportunities. I think there is a relatively simple translational hypothesis around protein targets that are highly sensitive to either mutation of STAT3 or upstream regulation of the pathway. These are mostly in the lymphoma and leukemia space. There are targets that are -- the protein targets that are dependent on STAT3 as a mechanism of resistance. And then there are a series of proteins that are in targets and biologies that are dependent on STAT3 from a context of immune regulation. We found that this immune regulation of STAT3 in oncology is very synergistic with the immune regulation of immune checkpoints, especially PD-1 immune checkpoints. So these are the trials that are ongoing right now at Kymera in the U.S. now with our agent, KT-333. There is also another large opportunity in indications that are in immunology and fibrosis. And generally, I would say, in inflammation driven by the JAK/STAT pathway. Obviously, we're all aware of the JAK kinase family and its activities across a wide variety of indications. I think STAT3, you have a much more specific node that actually we've seen at least it's very different biology, also in immunology from JAK inhibitors.

Yes, it's exciting biology. And maybe just what we've learned from other modalities in STAT3, whether it's anti [indiscernible] or if there have been prior inhibitors and what can give us confidence from what we've seen so far.

Yes. I'm going to let Jared take this one from a clinical perspective as well. But I would say that I am personally not aware of the highly specific cell type agnostic mechanism to block STAT3 biology. There have been molecules that have been pathway inhibitors, but we've characterized all the molecules that are claimed to be STAT3 agents. And unfortunately, we haven't been able to confirm any. The ASO from AstraZeneca or actually from Ionis and then went to AstraZeneca was or still is an interesting drug. I think it's been difficult for that drug to distribute to tissues with high level of efficiency. And so it's been seen as in -- mostly an immune specific type of agent with limited target engagement according to what we've been able to learn.

All right. I don't know, Jared, if you have any other [indiscernible].

No, I think Nello covered pretty well.

Maybe I guess just thinking about the initial Phase I/II dose escalation of the STAT3. Obviously, you're beginning dosing either or have dosed the first patient.

Yes. We -- look, we've said a few -- I don't know, weeks ago that we were recruiting patients. Now obviously, things have evolved. I think we'll disclose at some point. But yes, things are ongoing.

Okay. Well, soon to dose or have dosed the first patient?

Soon to be confirmed.

Soon to be confirmed. How should we think about the initial study design and any initial data that we could be getting this year? I know, obviously, early to think about things like responses, but just anything in terms of proof of biology, target engagement, safety and what we should be looking for there?

Yes. So maybe to start, so KT-333, which is our STAT3 degrader in Phase I is given intravenously, and we're going to be giving it once a week. And this is based on our preclinical data in tumor xenograft models of STAT3-dependent T-cell malignancies where we've shown that weekly dosing leads to complete tumor responses in those model systems. So we know that STAT3-dependent T-cell malignancies should be very sensitive to this drug, if we can achieve greater than 90% knockdown in the tumor with a weekly or even every other week schedule. So our Phase Ia is a dose escalation study that's including both liquid tumors, lymphomas as well as solid tumors. And within that particular study, we expect as we dose escalate to gather, obviously, safety, PK as well as key pharmacodynamic data focused on STAT3 knockdown in blood and where we can get tumor biopsies in tumor as well. We anticipate later in the year being able to present data that will show our progress in dose escalation and show, hopefully, that we're achieving substantial levels of STAT3 knockdown in blood and tumor with a safety profile that is favorable. This is what we expect based on our preclinical data. It will probably be more towards the early part of next year when we're at closer to perhaps our recommended Phase II dose and expanding there, starting to bring on our target patient populations, which include peripheral T-cell lymphoma, cutaneous T-cell lymphoma and large granular lymphocytic leukemia. These are malignancies where there's a significant prevalence of STAT3 oncogenic mutations, that's when we'll start to probably be able to share antitumor activity next year. Our plan, once we finish Phase Ia dose escalation is then to bring a recommended Phase II dose into Phase Ib expansions. Those expansions will be in these STAT3 dependent heme malignancies, as I just mentioned, and also in solid tumors as well. And we'll also have an opportunity in Phase I, probably through an amendment to start to look at combinations, especially the anti-PD-1 combination that Nello referred to, given our very strong preclinical data showing synergy and tumor responses in -- using PD-1 in combination with our STAT3 degrader in syngeneic colorectal cancer models, for example, that this will give us an opportunity to explore a combination like that in Phase Ia and then to bring that into a Phase Ib expansion as well into solid tumors.

Got it. It's exciting. And then maybe just moving to the IRAKIMiD program. Maybe if you guys could tell us a little bit about this molecule kind of maybe a more unique contract to the traditional heterobifunctional and the biological rationale in the MYD88 heme malignancies.

Yes. So I just go back to target selection when we invested in these 2 pathways, and this was actually almost 6 years ago when we started the company. The idea was to have franchises within each pathway by targeting those key nodes. And we are strong believers as we were 6 years ago that the myddosome complex and STAT3 are key nodes that will develop -- will allow us to develop large franchise opportunities. And with the IL-1R/TLR pathway and the myddosome complex, the idea was in diseases where the upregulation or the activation of this pathway happens through receptor activation. This is what happens in immunology. You have IL-1 cytokines that signal through the receptor, or you have 2 TLR agonists that signal through the TLR receptor, you block the myddosome complex effectively, and you should be able to block fully pathway activation. In oncology, where was the other side of our, let's call it, franchise, we know that activation actually happens differently in a subset of lymphomas in diffuse large B-cell lymphomas, but also in other indications or subpopulation, we see activation at actual MYD88. This actually adapter protein gets mutated, and its mutation activates the myddosome complex and that complex fires continuously through NF-kB and drives proliferation. So our initial hypothesis was the blocking myddosome complex through IRAK4 degradation would be sufficient to drive single-agent activity. What we've learned actually through preclinical studies that IRAK4 degradation alone in oncology is insufficient to drive single-agent activity in MYD88-mutant lymphoma, not because it doesn't block the pathway fully. But because pathway blockade in lymphoma is insufficient to block proliferation and we found that you can use actually 2 other pathways quite effectively almost in the same way to then basically block this compensatory pathway. And one of them was the IMiD driven pathway. And we thought that by blocking both with a single molecule, we could use cereblon to degrade Ikaros and Aiolos and to degrade IRAK4 would be able to have this combo in a single degrader. And that was the biological and kind of technical rationale for the program. And so far, because these molecules, just going back to the molecule question, these molecules have a very exceptional potency and PK, we're able to dose this molecule once every 3 weeks and drive some really, I would say, best-in-class antitumor response. It's at least preclinically over any other agent that has been tested or approved in MYD88-mutant lymphoma.

Exciting. Maybe can you tell us a little bit more about MYD88 lymphomas and maybe just from the clinical side, sort of the prevalence and how to think about the path forward? Because theoretically, this could be a high unmet need, [ possible. I know ] these are my words, not yours, but like potential single-arm accelerated pathway type population. So just any more color on the patient population, standard of care prevalence?

Sure. We know that the MYD88 mutation is seen in about 25% of diffuse large B-cell lymphoma. So a drug developed here would be the first drug going after a genetically defined subset of DLBCL. We know that this mutation confers a worse prognosis in these patients that outcomes to first-line therapy in terms of survival are quite poor for patients with MYD88 mutations. So there is clearly a very high unmet medical need. We know there are active agents in combination regimens in relapsed/refractory diffuse large B-cell lymphoma. But despite that, most of them are not curative. And many of these patients are going on to third and fourth-line therapy. So there still is a high unmet need. Even at higher unmet need, I would argue for a drug that is going after a genetically defined subset of patients. Based on our preclinical antitumor activity, we see profound complete tumor responses in multiple different CDX and PDX (patient-derived xenograft) models of MYD88-mutant lymphoma, where we see complete tumor responses that are durable. This is almost unprecedented for other drugs that are put into preclinical experiments in these sort of model systems. So we think that this should predict for a really transformative antitumor activity preclinically. We have a Phase I study now in the clinic that is going to be additionally dose escalating across a wide variety of B-cell lymphomas and eventually going into a Phase Ib expansion focusing on MYD88-mutant DLBCL. And we think that if we have a robust response rate and a robust duration of response, which we expect from our preclinical data, we could have a clear pathway to accelerated approval with a single-arm Phase II that could come after a completion of our Phase Ib expansion.

Got it. That's helpful. And how should we think about what to look for in the initial data? Obviously, early and continuing to dose escalate, but what we could potentially see, say, by the end of this year, and what we should look for heading into next year?

Probably along similar lines to what I just described for the STAT3 program, which is also in Phase I. In some ways, they're both sort of neck and neck. So we would expect towards the end of the year to be able to share data from dose escalation -- Phase I dose escalation data regarding safety, PK and initial pharmacodynamic activity, where we're looking at knockdown of the 3 targets, IRAK4, Ikaros and Aiolos in both blood and in tumors where we can get tumor biopsies and to be able to show that we can knock it down to an extent which is correlated with antitumor activity in vitro and that we show in the clinic is safe and well tolerated. I should also mention that the Phase I study ultimately will give us an opportunity to also look at select combinations. I mean we have preclinical data showing that our drug in combination with rituximab, for example, anti-CD20 or in combination with Venetoclax, a BCL-2 inhibitor, also shows very profound antitumor activity. So that's another potential strategy for us. In addition to ultimately after we show activity in MYD88-mutant DLBCL to look at other key MYD88 mutated malignancies with a very high prevalence of this mutation that includes primary CNS lymphoma as well as Waldenström’s macroglobulinemia.

Got it. It's exciting. And then I guess turning maybe to MDM2. I mean can you elaborate a bit on the target biology here as well as the time lines?

Yes. I mean with MDM2, I go back to the same. So think about IRAK4 is a target that actually has been pursued for many years because it thought to be a key central obligate protein through which every signaling of the IL-1 receptor and TLR had to go through, we've learned that small molecule inhibition isn't enough to block the pathway. Our hypothesis has always been degraded will be a way to do it. We've shown data. And so it just tells you how to use the technology, I think, in the right context. STAT3, I just mentioned the same way, you can really [indiscernible] at all degradation through a nonactive small molecule binder can get you there. MDM2 is along the same line. So cancer genetics have told us for the past 10, 15 years that in patients that have p53 wild-type, removal of MDM2 leads to high dependency and cell death. So cancer become very dependent on MDM2 in the presence of p53 wild-type. P53 is the largest tumor suppressor gene. So stabilizing p53 will be transformative. I think the mistake that we made as an industry was believing that cancer genetics could be replicated by small molecule inhibition. We learned that you can't. You can't inhibit MDM2 and expect to see the same data that we've seen with cancer genetics. So what's the other way to actually replicate cancer genetics, which means which is the way that you can remove MDM2 is through protein degradation. So the data that we generate shows you that in a context of p53 wild-type, which is more than 50% of all cancers, the removal of MDM2 through degradation leads to highly -- high dependency on the protein and so it leads to really fast commitment to apoptosis. The important thing though that I want to be absolutely clear is that not all 50% tumors have the same response to lack of MDM2. And that's important. So we have seen that some both in liquid and solid tumors are extremely sensitive. And when I say extremely sensitive is that within hours of the removal of MDM2, cancer cells die very, very quickly, in vivo, you see complete responses very quickly that never returned. And what we're doing right now at Kymera and hopefully, we'll share this towards the end of the year too, is prioritizing indications where we see this phenotype. For example, in AML, which has historically been the place where many inhibitors have been, we do see this phenotype, which again is very different than small molecule. But we've also seen other indications where we've seen a similar type of really acute response. And those are the ones that -- where we want to develop this drug were also like we're doing for KT-413, we can dose as infrequently as once every 3 weeks and still maintain really profound antitumor effect.

Interesting. So a lot going on in the pipeline. I guess turning back to your lead program, the IRAK4 degrader. I know it's been a topic of much conversation recently. Maybe high level, after kind of the update on the signal with QTc prolongation, I guess, what drives your confidence that in the development path forward for this molecule and confidence in the safety profile?

Yes. Thank you. So I want to start with the target rationale. I don't want to bore you with things that I've said already half an hour ago. But just to remind everybody, there aren't many pathways in innate immunity that have human genetics validation and human pharmacology validation. This is one of them. IL-1R/TLR pathway, lots of drugs targeting cytokines that signal through the receptors that are either approved or post POC. So if you have a drug that can block all of those cytokines with a single or a small molecule, you expect to see clinical activity. So we expect to see clinical activity. Human genetics data tell us that people -- and there's been more than 100 that have been characterized. There are people that are born with [indiscernible] mutation on this gene that basically are born without IRAK4. And those people have no phenotype for sure, they have no [ cardiac ] phenotype. The only phenotype that you actually observed early in life is higher susceptibility to a subset of infections, which eventually, first of all, all treated with antibiotics. But as these kids grow, theoretically through the adaptive immune system, that susceptibility goes away. So clinical validation of the pathway, human genetic validation in terms of safety and developability and relevance across a wide variety of diseases, going from HS, AD, RA, lupus, gout, IBD. So clearly, the potential for this target is large. I would say, probably similar, if not larger, than JAK inhibitors with a better safety profile. So what gives us confidence of the safety profile? So we've characterized KT-474 in preclinical species extensively as far as even recently, we concluded the chronic tox study and that we've never actually seen dose limiting toxicity. We've also characterized this drug in humans. We recruited more than 100 subjects to our clinical studies so far. And our safety profile is really, really promising. We have no serious adverse events, and we've had some mild, I think there was 1 or 2 moderate adverse events that were really nonobjective adverse events such as headaches, nausea or palpitations. So what are we talking about here? We're talking about Kymera disclosing a nonadverse event, which we decided to do of this modest subclinical QT prolongation that was, in terms of QT interval within the normal range, 450; In terms of QTc data, was 10 to 20 millisecond. And we always, if you follow QT, usually between 0 and 10 is usually the [ noise ]. So it's just above that [ noise ]. The important thing is that it was never dose responsive, never concentration response, was not driven by Cmax of our drug. If you take sixfold of increase of exposure, you don't see any increase of QTc. So the confidence comes from the fact that we've never seen any subject enter risky areas of QT prolongation. There are drugs that are approved that have this QTc range. We can't -- we don't know of any drug that has been approved that has no increase of QT with increase of exposure. So this is self-limiting. So that's a further derisking over the approved drugs. Many of these drugs are approved outside of oncology. Some of them are used in chronic dosing in inflammatory conditions. So where we are right now, if the profile stays as it is, we have no concerns of being able to develop this drug in a wide variety of indications. But what we are doing, and I'm sorry if this is too long, we are doing everything that we have to do and we need to do to make sure that we are monitoring and that we're putting patient safety first in all the studies that we're doing. And we've aligned with FDA, with our partner Sanofi, we've been able to select a very active dose without having to take the QT as a limiting signal for our dose.

Okay. That's very helpful. And maybe just could you help us understand at least your current hypothesis around what caused this? Is this target specific, molecule specific related to degradation? And what drives your confidence that this won't affect other programs potentially in the future?

Yes. So great question. So what I probably didn't say before, although probably you could assume. So we did not see QT prolongation in our safety studies preclinically. Maybe because [indiscernible], we didn't pick it up. That's our current hypothesis. We know that this drug degrades IRAK4 and IRAK4 only. It does not degrade anything else, any ion channels or any other potential protein that might lead to this according to all the data we've generated so far. We know that it's nothing to do with IRAK4, both for human genetics and also some experiments that we've run internally. What I can say is that we have the only hypothesis that we have right now is driven by a modest affinity that this molecule has for an ion channel that happens at concentration that are really high, but it's possible that within the distribution over time, we might reach some saturated level of drug. As you see, the reason why it's self-limiting because probably it reaches a level and then the drug cannot go above. And maybe in those saturated level, we have a very, very mild inhibition or blockade of an ion channel. That's our current best hypothesis because everything else right now doesn't have scientific basis.

And sort of this like low affinity for this ion channel, is this something you've seen with other molecules? And how should we think about this going forward and what to look for in some of your other readouts as well?

Yes. We -- so obviously, this is -- every program goes through extensive preclinical characterizations. We have -- when we think about development risk, [ this is a ] reason to a risk level for our pipeline. So I wouldn't -- with confidence, I can say we don't expect QT risk to be a platform issue.

That's good to hear. Maybe just in terms of both the [ food ] study as well as the clinical studies, can you tell us a little bit about some of the monitoring that you're doing and maybe kind of your confidence level around the fact that this affinity might be saturated at the dose levels that are being studied or is it potentially already sort of hitting a plateau and we won't see further QTc prolongation.

Sure. You mentioned the [ food ] study and maybe just to touch on that just for a moment, which is that we're currently in the midst of doing one additional signal ascending dose cohort in order to determine what is the dose equivalent of 100 milligrams in the fasted state, that's a dose we plan on taking into Part C was the equivalent dose in the fed state. We did see some food effect in our signal ascending dose study. So we're doing one additional cohort just to determine what that correct dose is in the fed state. Because our plan in Part C, because it's a 28 days of dosing, and these are now in HS and AD patients, all treated on an outpatient basis. It's not practical to have them fasted, so they'll be fed in that study. Within Part C, that this is going to be a 28 days of daily dosing, we plan on doing fairly routine ECG monitoring. So the monitoring that we do standard several times a week for the first 2 weeks and then weekly thereafter. And these ECGs will be obviously looked at closely as they always are in order to look for any sort of QT effect. So we're not doing anything really beyond routine testing. We don't need to do 24-hour Holter monitoring. These patients are not put on telemetry. There's no inpatient or confined portion of the study. It's all done on an outpatient basis. This is what we described when we submitted our package to FDA, they were completely aligned with our plan for Part C and our plan for monitoring.

Got it. And I guess, to ask the million-dollar question, what are you looking to see at this data, the 28-day data from a potential efficacy perspective as well as also a safety perspective to give you guys confidence in the profile?

Well, I think for us, what's most important is confirming PK and PD that we saw in healthy volunteers and confirming that in patients. Obviously, in patients, we have the opportunity to look at pharmacodynamic effects not just in normal skin as we did in the MAD part of the Phase I study, but now in actual diseased skin, patients with inflamed lesions, both in HS and AD to look at the change in IRAK4 expression and also now to look in vivo at changes in pro-inflammatory gene transcripts, biomarkers of inflammation that are now clinically relevant because we're looking at them in vivo. So what we'd like to be able to see is IRAK4 knockdown and an impact of that knockdown on the expression of these different pro-inflammatory gene transcripts within these active skin lesions. Being able to see that would for us be a real success in Part C in addition to monitoring for safety. The fact that we extended the 28 days beyond 14 days, one of the reasons was we found in the MAD with 14 days of dosing that we were not reaching steady-state knockdown at 14 days. And so we anticipate being able to reach steady-state IRAK4 knockdown in the skin by 28 days. We reached that at 14 days in the blood in the MAD 14-day but not in skin. So by extending the 28 days, we now give ourselves the opportunity to see maximal knockdown in the skin, which should increase our chance of seeing impact on inflammatory biomarkers. And in addition, with 28 days of monitoring that from a safety standpoint, we can confirm, hopefully, that the plateauing of this modest impact on QT that we saw after day 7 in the MAD that we now continue to see that out to day 28. In terms of the exploratory clinical endpoints, we've added those in large part, because we've extended the 28 days, we know from prior studies of Humira in HS and Dupixent in AD, these are 12- and 16-week studies for registration, but they have been able to show some separation from placebo as early as 4 weeks or 28 days. Here, we're not planning to compare our data directly to those larger studies given the fact that those are indeed larger studies and even the baseline characteristics of our small number of HS and AD patients, 10 of each will probably be different from what's reported out in those studies. So our aim is not to do a head-to-head comparison, but really to be able to potentially show a correlation between impact on IRAK4 in the skin, impact on inflammatory biomarkers in the skin and a potential clinical signal across these different endpoints in AD and HS. So to be able to sort of make a connection between pharmacodynamic effect and preliminary clinical activity. But the aim is not to show clinical proof of concept in a small study like this, which is without a placebo control.

Can I just add one more thing? So someone asked me like what good looks like at the end of the year and maybe -- I don't want to speak with Sanofi, but I would say that we're looking for the same type of effect is this dose that we've selected showing -- showing the same level of knockdown that we've seen in healthy volunteer and predictable impact on downstream cytokines or transcripts. And is the safety profile in line with what we've seen in healthy volunteer. For me, that's a win. Everything else we can discuss for days, but that's the win for us.

Makes sense. And I guess for you, Bruce, maybe just on the cash runway and how to think about, obviously, a lot of potential areas to invest in from the platform as well as the clinical programs, how you're thinking about sort of capital allocation as well as cash runway and the time frame in which we could learn about a potential Sanofi opt-in?

Yes, sure. So we're fortunately well capitalized right now. So we have exited quarter with $523 million of cash that takes us into the first quarter of 2025, and we've consistently not included any milestones from our partnerships in that runway. So anything that we achieve there would be incremental. The really key, I guess, data point or time point for that will be Sanofi's decision about moving the program forward into Phase II. And we haven't disclosed exactly how much time they have to decide. But essentially, when we complete the patient cohort, we'll then get together with them and make a decision jointly or obviously, it will be ultimately their decision about moving it forward. Outside of that, as I said, no near-term financing intentions. I think from a BD standpoint, we've always been open to discussions where there's some value add to partnering. But suffice to say that we're capitalized -- well capitalized enough to take all of our programs through to some of these key inflection points that you've heard these -- to you guys discussing over the next few quarters and into next year.

Awesome. Well, with that, I think we're out of time, but thank you guys so much for joining us.

Thanks, Ellie. Thanks, everybody.

Thanks.