Good day, and welcome to the Kymera Therapeutics Second Quarter 2024 Results Call. [Operator Instructions] Please note, this event is being recorded. I would now like to turn the conference over to Justine Koenigsberg, Head of Investor Relations. Please go ahead.

Good morning, and welcome to Kymera's quarterly update call. Joining me this morning are Nello Mainolfi, President and CEO; Jared Gollob, our Chief Medical Officer; and Bruce Jacobs, our Chief Financial Officer. Following our prepared remarks, we will open the call to questions. In order to have enough time to address everyone's questions, please limit your questions to 1 and a relevant follow-up. Before we begin, I would like to remind you that today's discussion will include forward-looking statements about our future expectations, plans and prospects. These statements are subject to risks and uncertainties that may cause actual results to differ materially from those projected. A description of these risks can be found in our most recent 10-Q filed with the SEC. Any forward-looking statements speak only as of today's date, and we assume no obligation to update any forward-looking statements made on today's call. With that, I'll now turn the call over to Nello.

Thank you, Justine, and good morning. Every day, we take important steps towards our goal of building a fully integrated global biotechnology company, demonstrating our ability to consistently deliver first and best-in-class programs that target validated pathways with the potential to address large underserved disease areas. The progress we've made over the past quarter highlights our novel approach to drug development that emphasizes innovative molecular design, fidelity of translation from preclinical settings to the clinic, data-driven development strategies and the commitment to maximize the impact of our signed to improve patients' lives. Our unique approach has led to the development of a pipeline of exciting degrader medicines with the potential to change treatment paradigms for multiple diseases as evident in our recent updates and presentations at major medical congresses and publication in peer-review journals over the past few months. Our STAT6 program, for example, was featured at both ATS and DDW, MDM2 at ASCO and STAT3 at AACR and EHA. In addition, we published data from our noninterventional trial, evaluating IRAK4 expression in patients with HS in the Journal of Investigative Dermatology. The findings we've shared across these forums highlight the differentiated profile of our programs. Before handing the call over to Jared for a more detailed overview, I wanted to highlight 2 important updates in our immunology pipeline. I will start with our IRAK4 program. As a reminder, KT-474, IRAK4 degrader partnered with Sanofi, the first heterobifunctional molecule to have been dosed in healthy volunteers and then HS and AD patients. We have shown in our Phase I study TYK degradation of IRAK4 in blood and skin resulting in impact on biomarkers of inflammation, both systemically and in the skin of HS and AD patients. This robust PD profile has resulted in clinical benefits measured by EASI and pruritus…

Thanks, Nello. Starting with KT-474. As mentioned, last month, we announced Sanofi's decision to expand the ongoing Phase II studies in HS and AD, following an interim analysis of KT-474 safety and efficacy by an independent data monitoring committee. This exciting development is a great outcome for Kymera and our IRAK4 program. Importantly, it not only reinforces Sanofi's strong commitment to the program, but also provides the potential to inform future registrational trials in a way that should accelerate overall time lines. But just to step back, the expansion effectively will allow a seamless transition into more expansive dose-range finding Phase II studies. The goal is really to structure the studies with the necessary regulatory perspective to enable dose selection for Phase III. While it will take longer to complete Phase II, these 2 expanded Phase II trials in HS and AD, will support moving directly to Phase III. Therefore, the overall time lines to Phase III and ultimately, to registration should be meaningfully shorter. Since the update last month, Sanofi is undertaking activities to update the protocols. And once this work is complete, we expect the new details will be posted on clinicaltrials.gov. Once that happens, we will be able to discuss updated timing related to trial completion and data releases. As a result, we expect the Phase II results, which will be shared in their entirety following this expansion, will be beyond our prior guidance of the first half of 2025. As Nello mentioned, KT-621, our first-in-class STAT6 degrader has the potential to be a once-daily oral medicine, capable of delivering dupilumab-like activity and safety in highly prevalent allergic diseases. We recently presented additional data at the ATS conference that demonstrated activity of KT-621 comparable to a saturating dose of the IL-4 alpha antibody dupilumab in an asthma…

Thank you, Jared. As I review our second quarter 2024 financial highlights, please reference the tables found in today's press release. Revenue in the second quarter of 2024 was $25.7 million. All of that was attributable to our Sanofi collaboration. With respect to operating expenses, R&D for the quarter was $59.2 million. Of that, approximately $7.3 million represented noncash stock-based compensation. The adjusted cash R&D spend of $51.9 million, which excludes that stock-based comp reflects a 22% increase from the comparable amount in the first quarter of 2024. On the G&A side, our spending for the quarter was $17.4 million, of which $7.1 million was noncash stock-based comp. The adjusted cash G&A spend of $10.3 million, again, excluding stock-based comp, reflects a 21% increase from the comparable amount in the prior sequential quarter. Finishing up with our cash balance at the end of the quarter was $702 million. Our cash balance is expected to provide a runway into the first half of 2027, and will enable us to execute on multiple data readouts, including oncology proof-of-concept results in 2024, KT-474, Phase II data and several clinical inflection points for our STAT6 and TYK2 programs expected in 2025. This concludes our prepared remarks, and we would be happy to now address any questions you may have. Operator?

[Operator Instructions] Our first question comes from Eric Joseph with JPMorgan.

Hi, good morning. Thanks for taking the question. Just wondering if you could elaborate a little bit further on the type of data you and Sanofi were able to review as part of their decision to expand the Phase II program. I'm wondering whether safety -- whether it was just based on safety or whether there was an efficacy component or some surrogate thereof. And I know that there are some moving parts to work through here. But I guess, do you have a loose sense of when there could be -- when we might see data from the Phase II trial after it's expanded and whether there might be interim readouts within?

Yes. Thanks for the question, Eric. So the -- so there was an interim analysis of both safety and efficacy, as we said. And as we've said, the companies, both Sanofi and Kymera had access to the blinded data there was IDMC that had access to both blinded and unwinded data. I can't speak to, again, the content of the review or the questions that were asked. But obviously, what we should conclude from this update that we provided a few weeks ago, and now we're obviously highlighting again is that the review of the data was supportive of further investment into the program. Don't forget that this is one of the few programs in the pipeline where Sanofi is running multiple phase and studies in parallel without having previously run a proof-of-concept study in a placebo-controlled manner. So it speaks again, I think, to the level of enthusiasm that we both have for this program. With regards to time lines, we hopefully, we'll be able to see an update on clinicaltrials.gov in the next -- in the upcoming months, and that will include also expected completion dates. And at that time, we should be able -- we will be able to comment on the time lines. As we said -- Jared said earlier, it's going to be beyond the first half of '25 that was initially guided to. But at this point, we're not able to provide more accurate guidance.

Our next question comes from Jeff Jones with Oppenheimer.

Good morning, guys. And thanks for taking the question. Just a quick one on the R&D and G&A trends. Obviously, picked up significantly from the prior quarter with the extensive work you have going on. Just how should we think about the trends there? And then a follow-up as well on the jump in collaboration revenues from Sanofi. How should we think about that moving forward?

Yes, sure. This is Bruce. Jeff. Thanks for the call. So in terms of the trends, there's nothing unusual there in terms of the growth quarter-over-quarter versus what we had expected. As the year progresses, obviously, we get closer to the start of the studies for STAT6, you'll see that come through in the R&D line. G&A is just modest growth either organization. We haven't guided towards annual burn, typically don't. But last as I looked at the street, they're generally in the right ballpark. But definitely for this year, a little more back-end loaded than front-end loaded. And that's typically how our care years have gone and represented what you'll see this year. In terms of the revenue, there was just a catch-up in revenue related to the Sanofi alliance, all the revenue is a result of that. So that resulted in a higher level this quarter, but I think it will be a little unusually high vis-a-vis the rest of the year, and you can do some calculations based on the deferred revenue balances on our balance sheet for how you might look over the coming year or so. So hopefully, that helps a little bit happy to take more offline as well if you'd like.

Our next question comes from Kelly Shi with Jefferies.

Congrats on the progress. And thank you for taking the questions. Maybe I'll start STAT6 program based on the multiple preclinical studies you have presented findings please? With your comment on more specific plans for the Phase I? Would it be like a single indication or multiple indications to all that this area has been made on the discoveries from preclinical studies, which one to prioritize?

Yes, thanks. Maybe I'll let Jared comment on the Phase I plans. We haven't described the details of our plans before the healthy volunteers. I think maybe just to remind what we -- the update that we're giving today on the program is really on the fact that we were able actually to accelerate our path to Phase I, and we're able to conclude and complete our IND-enabling studies. And so we are on track, if not earlier, compared to what we have said to start the Phase I study. Maybe Jared, you can provide some high-level description of our healthy volunteer studies.

Yes. So Phase I healthy volunteer study, being in healthy volunteers, we expect to be able to move through it quickly. It will be a traditional single ascending dose and multiple ascending dose Phase I study, the MAD portion will consist of 14 daily doses. Within that study as we did for the IRAK4 Phase I, we'll have a number of different pharmacodynamic measures which will be critical to that study in addition to looking at safety. And those measures will include looking at STAT6 for example, in blood and skin. And also importantly, we'll have an opportunity to look at several different TH2 biomarkers in the circulation, in particular, to be able to look at IgE and TARC, giving us an opportunity to show impact on the biology of the IF IL-13 pathway even in healthy volunteers.

Our next question comes from Vikram Purohit with Morgan Stanley.

Hi, good morning. Thank you for taking our question. We had two on the I&I pipeline. First on 474, just wanted to get your latest thoughts on when we can learn more from yourself and Sanofi on indication expansion beyond HS and AD and what might be flowing into those decisions? And then secondly, for the TYK2 program, just wanted to see how you're thinking about indication expansion or indication selection rather, I mean, how broad do you think the development program could be? And what will you be looking for in the initial Phase I data to help make those decisions?

Yes. Thanks, Vikram. So on the 474, as we said in the past, we believe this pathway has relevance in a broad variety of diseases. Our initial foray is in skin and derm. So with HS and AD again, based on pathway agents with existing proof of concept, we expect this pathway in this target to be relevant in respiratory in both asthma and COPD in GI inflammation, IBD as well as traditional, let's say, rheumatology, both RA and lupus. So the opportunities are vast. As we've communicated in the past, there is a process that has been ongoing within the collaboration to prioritize a series of indications that the team has the team has done. And I -- again, I cannot speak for Sanofi, who will be -- have the final decision-making on this. But all I can say is that the recent update and what we have seen, I think, continues to support the enthusiasm around the program and the potential eventual expansion. I'll leave it to Sanofi to speak to the timing of that. But I will say that at least we're getting closer to, hopefully, that decision. With regard to TYK2, again, as Jared said earlier, this program is really for us an opportunity to provide an oral molecule with biologics like profile and actually unique biologic-like profile. If you think about this pathway is involved in IL-23 or 12 and Type 1 interferon and being able to block those 3 pathways fully with a single oral small molecule should provide a highly differentiated profile. So there's lots of potential diseases that one could go after. The ones that others have gone after psoriasis, psoriatic arthritis, IBD, lupus, obviously are up there. There are potentially others that could be interesting. I think our goal will be in Phase I study to demonstrate that our mechanism of action is able to show food blockade of these pathways unlike any other agents that has been tested so far, and then our plan would be to do a proof-of-concept in an indication that will actually demonstrate the differentiated profile. But we'll speak with more details about that once we're closer to -- for Phase I studies.

Our next question comes from Brad Canino with Stifel.

Thank you. And two for me. First, and Nello just talk about this a little bit. But given the recent external news, can you discuss the confidence of TYK2 as a tractable target for IBD? And then second, maybe a bit of a strategy question, but years ago before this named pipeline really evolved to the shape it is today. I mean you actually highlighted a lot of the discovery efforts at Kymera. And I just want to pull back and ask, how would you characterize the degree of discovery efforts now? What are some of the areas of focus? And how do you maintain that while also asking a lot of questions individually and collectively across the clinical pipeline today?

Thank you. Jared, why don't you -- you want to take the first question, I'll take the second one.

Sure. Yes. In terms of your question around our approach to targeting TYK2 and our expectations for activity in IBD. I mean there have been some challenges with the TYK2 small molecule inhibitors to show activity in IBD. With deucrav for example, part of that might be due to the fact that while it's hitting, say, IL-12, IL-23 because it's also not selective just for TYK2, it's also hitting JAK, it's also probably affecting IL-10 which can be a real problem in IBD because if you block IL-10, you're going to interfere with mucosal healing, which is going to be an important component than any sort of therapeutic where you don't interfere with that. So we think one of the real advantages of our TYK2 degrader is that we can maximally block the key inflammatory pathways, IL-12, IL-23 and Type 1 interferon, while at the same time, completely sparing IL-10 signaling. And we think that, that will be a distinct advantage for our approach in this disease, and that's why we anticipate being able to show activity in IBD as well as in the other indications that Nello was discussing earlier, including the derma indications like psoriasis and room indications like lupus.

Yes. And just maybe to add a small statement on the recent data. I think it's important to look at the profile of the molecule tested and their activity, blocking the relevant pathways. And so it's difficult, as you know well, Brad, to compare or to use the other trials as a testament to the value of that biology in that particular disease without taking into the context of the actual molecule profile. With regards to the discovery efforts, I think one thing that we've been consistent with Kymera has been the focus on pathways that have high degree of validation, and within those pathways we're just going after targets that have not been drug of drug well. And I think if you look at the type of targets that we've gone after, what comes -- what really rises to the top are 2 main classes, transcription factors, and we have STAT3 and STAT6 as an example, or scaffolding protein IRAK4 TYK2. And I believe that general -- the general philosophy will continue to be the same. As we mentioned earlier in the year, we have increased substantially our effort to immunology. Again, we've talked about STAT6 with an amazing profile so far, we've talked about TYK2 with great potential. We've talked about IRAK4 for years now. You'll hear about new programs, hopefully, as early as next year, again, in the context of difficult to drug or impossible to drug targets with other modalities within the same immunology landscape. I think our goal and our vision and I have the highest degree of confidence where I sit today, is that we will have the best in industry oral immunology pipeline, if we don't already have that. And I think that's what the world should expect for us in the next few months and years.

Our next question comes from Marc Frahm with TD Cowen.

Hi, thanks for taking my question. Maybe one quick one on oncology. Just the 253 up ticking. Can you clarify, is the data presentation this year, just the biomarker approach? Or should we also expect the kind of the full clinical update this year to happen this year? Or is that going to be a next year event? And then maybe a broader question kind of on the I&I portfolio and just kind of Kymera's approach. Do you guys view the oral convenience of your molecule is so important that it's acceptable to develop molecules that end up having clinical profiles are maybe not quite as good as the leading injectables? Or is it the idea here that you really have to show every bit as much efficacy, if not more, than kind of anything that's out there?

So on your first question, what we've said is we've been talking for a while about our commitment to share a biomarker-based strategy for forward-looking recruitment strategy for 253 and MDM2 based on sensitivity biomarker so we will hopefully be able to share that this year at a medical meeting. What we said about our clinical data is our plan and our expectations are that we should be able to complete total escalation this year. As you know, that is -- doesn't depend only on us, but it depends on also the safety profile of our drug and how many doses would be required to reach MTD. As you've seen for STAT3, we actually ended up escalating probably more than we had anticipated because the safety profile was better than we had anticipated based on our preclinical data. And so for MDM2, again, our desire to share the totality of the escalation data. And so the reason why we're seeing, we shared thereafter that we complete the escalation. It all depends on when we complete the escalation. We expect that we should be able to do that by the end of the year, but it will depend again on the safety profile and the timing to reach MTD. The trial is recruiting extremely fast. And so that recruitment of patients is definitely not on critical path. It's really the profile of the drug. With regards to the immunology pipeline, I mean, I think we've said it early in the year, we have selected targets that are able to be superior to evolve, actually, I should say, or superior at blocking those pathways than upstream biologics. That is actually true for IRAK4, which should be superior to individual upstream IL-1 biologics even that you should be able to block the pathway…

Our next question comes from Kalpit Patel with B. Riley.

Yes, hey, good morning. Thanks for taking the question. You mentioned the expansion of the IRAK4 trials also includes testing of additional doses. Maybe help us understand the decision-making for that specifically and why more doses need to be tested now. And as a follow-up, if you can share. Can you give us any additional color if the new doses are outside of the 50 to 200-milligram daily dose range?

Great question, Kalpit. So as you know, in order to initiate a Phase III -- registrational Phase III study, it is expected from a sponsor to have a degree of dose ranging to establish the relationship between efficacy and safety. And so if you look at the existing, let's use HS Phase II study that we -- there is actually still now on clinicaltrials.gov, that actually had 1 dose and 1 placebo. It would have been extremely difficult, if not impossible, to go from that type of study into a Phase III registrational study without exploring multiple doses. So that's what's driving the addition of other doses is the acceleration of getting into -- after this study into a Phase III study. With regards to the type of doses, again, we're not in liberty to actually comment. I would also point to that actually in Europe, actually, the doses are revealed much sooner than in the U.S. So if you do some investigative work, you it's not that hard to figure out what the existing dose versus the new doses will be, but maybe I'll stop here. What I will say is that the doses will be within the range that you say. And unfortunately, I can't comment more on where they would be.

Our next question comes from Michael Schmidt with Guggenheim.

Hi, thanks for taking our question. This is Paul on for Michael. Just following up on a prior question on STAT6. Can you talk about how we should interpret that early biomarker data coming out of the healthy volunteers next year? For instance, is there a certain threshold of serum IgE or TARC reduction that you're hoping to see? Or are there any directional and dose-dependent reductions sufficient to give you confidence in that program? And then just as a follow-up, is the goal here just to establish proof of concept? Or could the PD data actually guide your thinking on target indication prioritization?

Yes. No, great question, Paul. So let me start with -- so obviously, we built a really robust preclinical package, right? We've shown in vitro first that we degrade this target fully with picomolar concentrations, in all relevant cell types. When I say relevant, I mean, cell types, human cell types, they are relevant to all these TH2 diseases, whether it's respiratory, derm GI. We've shown that if you look at pathway inhibition, so IL-4/13 biology downstream of the receptor, we're able to block that pathway actually more potently than dupilumab. If we go in vivo, we've shown either in atopic derm model or more translationally in the asthma model, that's a 30-day HDM model, we've shown that with 90% degradation of STAT6, we have an ability to block a plethora of TH2 biomarker as well as disease endpoints either equally or better than DUPIXENT. So we've shown preclinically in terms of pharmacology that this drug behaves like a very, very robust, probably best-in-class pathway inhibitor. We've also shown the safety profile to be so far, absolutely pristine, which we talked about early in the year, in January about that we haven't seen any adverse events in our non-GLP tox. Today, we're seeing as an update that even going through GLP tox, we haven't seen any adverse events in any doses that we've tested. So also the safety profile is quite compelling. So the goal of the Phase I study is to demonstrate that everything that we've done so far in preclinical species or at least most of the things that we've done in preclinical species, replicated human. And importantly is the PK that leads to a dose-dependent and robust degradation in blood and skin. And then we're using the biomarker that DUPIXENT has modulated. To just confirm, to be honest, it's totally expected, but confirm in humans that blocking STAT6 will lead to downstream biomarker changes, which, again, we've shown extensively in all sorts of preclinial models. If you look at the data that the pics that have shown, and I encourage everybody to kind of study that so they were aligned on expectations. You've seen that we do -- you can reduce the TARC and also IgE in 28 days. And so if you look at the data, somewhere between 20% and 40%, depending on the biomarker that you use. Again, it shows that there is a pathway in ambition even in healthy volunteers that don't have ongoing inflammation. And so it's a confirmation of target engagement. I don't believe we will use that data for any decision-making with regards to indication, given that those are again qualitative biomarker in a healthy volunteer population. Our goal will be to go in patients soon thereafter to establish a more robust both proof of mechanism and proof of fund.

Our next question comes from Ellie Merle with UBS.

Hi, this is Jasmine on for Ellie. Thanks very much for taking our question. We have two in oncology. So for STAT3, could you give a little more color and talk about your view on the potential opportunity in Hodgkin's lymphoma? And then secondly, on your MDM2 strategy, specifically in solid tumors, are we going to hear an update on this when you give your biomarker patient selection update this year? And just based on the [ mechanism ] of action, what can you say about what you see as the most applicable set of solid tumors?

Yes, maybe starting with your question on STAT3 and Hodgkin's. We've reported that we've seen complete responses in Hodgkin's lymphoma in patients who have been gone on to hopefully, curative transplant. So that very encouraging data and Hodgkin's is consistent with what is known about the genetics of Hodgkin's disease, where there's amplification of PD-L1 as well as JAK amplification, both of which would render those tumors potentially responsive to STAT3 targeting. So as we've guided previously, with the Phase I study, we have now completed dose escalation and enrollment now is really focused on enrolling additional Hodgkin's patients. We see there being several different development opportunities for the drug. If we continue to see the sort of activity that we've seen to date. Those include opportunities for the drug as a monotherapy in third line and beyond. So for patients who have had prior anti-PD-1 drugs or prior anti-CD30 ADC, and also a potential opportunity up line in second line in combination with anti-PD-1. So I think it would be very interesting in terms of what we see for the remainder of the study this year, we plan on reporting data later this year once we've completed enrollment, of those additional Hodgkin's patients that can provide both efficacy and safety update at that time. With regard to MDM2 and patient selection, I think Nello referred to this earlier, we have had an ongoing extensive effort preclinically to identify different solid tumor types that are specifically sensitive to the degrader mechanism of action. And we've been in the process of developing a biomarker signature of sensitivity using various solid tumor models. And our plan is to present later this year at a medical meeting, an update so that people can see sort of what those preclinical data are showing and how those are potentially guiding, how we plan to further enrich for certain solid tumor types for the MDM2 degrader program. So stay tuned for that presentation, hopefully later this year, where we can provide more details on what that biomarker strategy is going to look like.

Our next question comes from Andy Chen with Wolfe Research.

This is Brandon on for Andy. Congrats on the progress thus far. Would you mind -- can you please discuss some of the challenges in creating the STAT6 degrader? Where the hurdles you were first developing it? And if another to greater company puts their mind to it, how quickly could they discover -- go from discovery stage to IND and how difficult would that process be?

Great question. So first, I would say that STAT6 has been a target that has been on the priority list of the biopharma industry that I can at least remember for the past 10 years since the early proof of concept of dupilumab and this pathway relevant to TH2 inflammation. And I believe that most pharma companies have had an effort in this space. But we have spent years working on this program. We're not going to talk about details. But at some point, we will. And the depth and breadth of work that we've done in STAT6 and our ambition to own this target completely from all points of view of pharmacological blockade of STAT6, I think it's what's fundamentally driving all the effort that we've had so far. This is one of the best molecule we've made at Kymera in the past 8 years. And I think it's going to be difficult to compete both timing and quality with Kymera, given everything that we've shown so far, but I can speak to what it will take others. I don't know the capabilities that other companies have. I know that there is nobody, there is no company that is a clinical stage or almost clinical stages we are. And I haven't seen any data from any other company. So it's hard for me to comment on the competition.

Our next question comes from Kripa Devarakonda with Truist.

Hey, guys. Thank you so much for taking my question. Just following up on the previous question regarding STAT6 degrader. One of your peers is developing, it's not like you said, Nello, it's not in the -- anywhere close to the clinic, but they're developing a STAT6 degrader in collaboration with Sanofi. So from a big funnel perspective, obviously, they're trying to cost a wide net. But can you help us understand how Sanofi's collaboration can develop -- potentially develop a STAT6 degrader might or might not impact your collaboration for IRAK4 degrader? Do you think there could be any overlap? And then just a clarification on the KT-474 dose expansion that you announced, you're adding more patients, expanding the doses. It seems like you've talked about there being an acceleration towards Phase III study. Can you just clarify whether this has been discussed with the FDA already?

Yes. So thanks for the question. So on the first one, we -- Kymera and Sanofi have obviously different goals and different strategies to accomplish their goals. And we come together around IRAK4. But we -- everything else that we do as independent companies is obviously independent of each other. We know, obviously, we're aware that Sanofi is highly interested in the STAT6 impact. Sanofis are only competitor in the STAT6 world as they have licensed called the STAT6 agents that are available out there, given that ours isn't. And so that's -- I think from one point of view, if we need it, personally, I don't think we do, but to validate how important this target is and how valuable this target is for any company, again, given the Sanofi is at two collaborations with two modalities for the same target, right, a small molecule inhibitor and integrated. But we are -- we have a very strong relationship. We have an amazing team that works on 474 on both hands. And we don't believe, don't expect that our, let's say, our STAT6 competition will have any impact on 474. With regards to the doses that you've asked about -- so the goal for the expansion, as we said, is in order to accelerate the entry into a registrational study. And I think the -- I don't know if -- what was the specific question discussing there? Yes. So with regard to -- thank you, Jared. With regard to the FDA, I can't comment on that. Obviously, whenever there is a protocol amendment, there is a process. But given that Sanofi is the official sponsor, they're in charge of that particular path.

Our next question comes from Chris Shibutani with Goldman Sachs.

Right. Thank you very much. Many questions have been asked. Perhaps two on the bigger picture side, one, thinking about additional immunology indications from your R&D day started the year, you had a slide that included. The end market opportunities being very vast in some of the traditional indications like MS and rheumatoid arthritis, it would seem that there's a lot of existing therapies, combinations tend to be the playbook and the industry is also looking to figure out how to better identify patients, patient selection strategies. And my questions are twofold. One, how are you feeling about the potential to expand into CNS type indications, noting that degraders are small molecules, but larger? And number two, how are you starting to thread in patient selection strategies in terms of thinking about how you can enhance probabilities of success? I know that Sanofi is in control of the advanced clinical development, but is there any scientific work biomarker data that is helping inform what you think might be a way to sell out a better sort of patient population to study to enhance your success there?

Yes. Thanks, Chris. So I mean, this is front and center of what we do here at Kymera. I think our work with STAT6 and the ability to select patients with TH2 inflammation that in a way, although it's -- obviously something that comes with the mechanism, it's one of the few examples of targeted therapy in immunology. As you know, the example with DUPIXENT in eosinophilic asthma and COPD are just an example of how you can actually now prospectively select patients for this population. I'll address one more and then I'll let Jared comment also what we do in terms of patient selection. But on the brain on the CNS angle. I think we and others, I would say, have demonstrated extensively that degraders can access the CNS compartment. We have internal examples, several internal examples that we've shown preclinically. So I don't -- we -- the choice of going into CNS indications will be driven by the mechanism, the opportunity, the -- again, the unmet need and led by capability or the ability of the technology. Jared, do you want to comment a bit on, generally on target side?

Maybe in terms of on the patient selection sort of question, is applied to IRAK4 and the STAT6 and I think the TYK2 as well. I think it's a very important question, but I think it's also important to emphasize that our expectations regarding the activity of these oral degraders is that we should not have to narrow the patient population upfront in order to be competitive. If we are as active as upstream biologics, we believe that these drugs could be approved and used upfront for very broad populations of patients across these very large indications for STAT6 and IRAK4 and TYK2. With that being said, we are building in to our studies. We did this with IRAK4 and certainly, we're doing this with STAT6 and TYK2. To extensive pharmacodynamic assays in Phase I and Phase II that include proteomics and transcriptomics on blood and also, for example, on skin lesions for patients with skin diseases when they come on to our study, whether it be AD for STAT6 or psoriasis, potentially for TYK2. That will allow us to retrospectively look at these various proteomic and transcriptomics profiles because that help us understand whether there are patient subsets that might be benefiting even to a greater extent than the broader population, and that might be important in helping us differentiate from other therapeutics. This concludes our question-and-answer session. I would like to turn the conference back over to Nello Mainolfi for any closing remarks.

Thank you. So I just want to thank everybody. Actually, we made it almost the 9:30. So maybe just to highlight the key news of today, one which we had shared a few weeks ago on the expansion of the 474 Phase II programs in both HS and AD. We're very excited and thankful to Sanofi for their increased investment and confidence in the program. And then more recently, the news of today was they know we're really, really close to initiating our Phase I study with KT-621 and especially, showing that we've completed all the IND-enabling studies with great safety profile. And so we're really excited about updating you all next time on our progress towards our first in-human dose that should happen soon. So thanks again. We're available with any follow-up today.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.