Welcome to Kymera Therapeutics Quarterly Conference Call. Leading the call from management are Nello Mainolfi, Founder and CEO; Jared Gollob, Chief Medical Officer; and Bruce Jacobs, Chief Financial Officer. After management's prepared remarks, we will open the call to your questions. [Operator Instructions] Before we get started, I would like to remind everyone that some of the comments that management may make on this call include forward-looking statements, as outlined in the press release. Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those set forth in Kymera's most recent filings with the SEC and any other future filings that the Company may make with the SEC. You are cautioned not to place any undue reliance on these forward-looking statements and Kymera disclaims any obligation to update such statements. I will now hand the call over to Nello Mainolfi, Founder and CEO.

So thank you, operator, and thanks everybody for joining us on our first quarterly results conference call. We look forward to using this forum every quarter to update all our stakeholders on the progress we're making in building Kymera into a best-in-class, fully integrated, degrader medicine company. Before we transition into the program updates, I just wanted to take a moment to reflect on some of Kymera's achievements since we founded the Company just over five ago, and also as we near almost our two-year anniversary since our 2020 IPO. When Kymera was founded in 2016, we had bold ambitions for the Company we wanted to build. As you'll likely know by now, the foundation of the Company was predicated really on leveraging what at the time was an emerging area of science, targeted protein degradation. While we weren't then, and certainly are not now, the only company engaged in TPD, I think it's fair to say that we've approach it in a very unique way. And as a result, we believe there are several important points of differentiation with respect to our strategy and our approach that still holds true today. From a target selection standpoint, we've been guided by strict criteria, which we believe has led us to focus on unique, high-value targets, where there is a clear advantage to using a degrader versus small molecule inhibitor or another technology, several of which you know well and we will discuss today. We remain acutely focused on those targets that address high unmet needs, have biology that has been well validated and, where possible, can be addressed with the precision medicine approach. We also embarked on this mission with the belief that to truly harness the full potential of TPD, we needed to invest thoughtfully, but aggressively in building…

Thanks, Nello. Starting with our oncology programs, we are pleased to report that the three disclosed oncology programs STAT3, IRAKIMid and MDM2 are all tracking as expected. First, I will discuss our STAT3 program. KT-333, as mentioned, is our lead STAT3 degrader. As brief background, STAT3 is a transcriptional regulator that has been linked to numerous cancers and other inflammatory and autoimmune diseases, and it is a target that has long been considered undruggable. Our focus here is on developing selective STAT3 degraders for the treatment of hematological malignancies and solid tumors, as well as autoimmune and fibrotic diseases. We believe our STAT3 degraders have the potential to provide a transformative solution to address multiple STAT3 dependent pathologies. In terms of a clinical update, recall that we received IND clearance from FDA in 4Q '21. The first clinical site was activated in 1Q '22, and the trial is actively recruiting patients. As a reminder, KT-333 is being evaluated in adult patients with relapse refractory liquid and solid tumors, including aggressive lymphomas. Dose escalation is expected to proceed throughout 2022 and we look forward to presenting the first patient data, including preliminary safety and proof-of-mechanism clinical data, in the second half of 2022. Moving now to IRAKIMid, KT-413 is a novel heterobifunctional degrader that targets degradation of both IRAK4 and the IMiD substrates, Ikaros and Aiolos, with a single small molecule. KT-413 was designed to address both, the IL-1R, TLR and the Type 1 interferon pathways synergistically to broaden activity against MYD88 mutant B-cell malignancies. KT-413 is on a similar time line in STAT3 having received IND clearance from FDA late last year. The first clinical site was activated in 1Q '22 and patient recruitment is underway. As a reminder, the Phase I trial for KT-413 is focused on adult patients…

Thanks Jared. I will keep my comments here brief. For the quarter, we recognize $9.6 million of revenue. This total reflects revenue recognized pursuant to our Sanofi and Vertex collaborations. At the end of the quarter, our deferred revenue total on the balance sheet was approximately $93 million. That reflects partnership revenue that we expect to recognize over the next several years. With respect to operating expenses, R&E for the quarter was $35.9 million of which about $3.9 million represented non-cash, stock-based compensation. The adjusted cash R&D spend of $32 million, which again, excludes the stock-based compensation, reflects about a 5% decrease from the comparable amount in the December quarter. Our G&A spending for the quarter was $10.6 million, $4 million of which was non-cash stock-based comp. The adjusted cash G&A spend of about $6.6 million, again, excluding stock-based compensation, reflects a 2% decrease from the comparable amount in the December quarter. And finally, for my part, we exited 1Q with cash and equivalents of approximately $523 million. That provides a runway based on our current anticipated spending levels into 2025. And please recall, we do not include in our cash runway, any payments for milestones that we have not yet received. I'll now turn the call back to Nello for some concluding remarks.

Thanks, Bruce and Jared. In conclusion, I think I can clearly say that we're very excited about where Kymera is at the moment. We have an exciting first-in-class pipeline that is progressing hrough the clinic; a best-in-class platform and discovery engine of which we'll continue to hear about as we disclose more programs and data; productive partnerships with Vertex and Sanofi that allow us to expand across multiple disease areas; and as you've heard from Bruce, a very strong cash position that enable us to continue to invest in high-value programs and generate several important data sets in the next few years. 2022, we're looking forward to generating key proof-of-mechanism data in two oncology clinical programs, KT-413 and KT-333 against two undrugged targets and pathways, IRAKIMiD and STAT3, both with broad franchise potentials. We're also very excited to add our fourth clinical program later in the year with our MDM2 degrees, KT-253, which we believe will have large clinical potential. With regards to KT-474, as you've heard from Jared, after consultation with the FDA, we've extended our Phase I patient studies to 28 days to generate even more potentially de-risking data, including the possibility of early clinical proof of concept. We strongly believe that this mechanism has the potential to be best-in-class, small molecule, anti-inflammatory drug, and excited to explore clinical activity in HS, AD and eventually in a wide variety of additional indications. I'd like to thank first of all, Kymera team for every day, pushing boundaries in a completely new drug modality, and for continuing to execute on our very ambitious goals. I would like to thank our collaborators for enabling us to operate efficiently in a globally challenging landscape; our partners for the rich contributions; and last but not least, all the healthy volunteers and patients that allow us to advance the development of our potentially transformative therapies. Finally, I would like to thank all of you that have taken time this morning for our first quarterly call and looking forward to a rich Q&A. I'll now hand the microphone back to the operator so that we can take your questions. Thank you.

[Operator Instructions] The first question comes from Eliana Merle with UBS. Please go ahead.

Congrats on all the progress. Maybe just first on the 28-day patient cohort, I guess, do you still anticipate enrolling 20 patients or given, sort of, the lengthening of the study, do you anticipate perhaps enrolling more patients as well? And then if you could just comment on the anticipated mix between atopic derm and HS patients within that cohort? And then second, just on the QT prolongation, can you give us just a little bit more color on what was seen, sort of, like the number of patients, which dose levels, and I think you said it wasn't considered grade 1, even" I mean, just any more color would be helpful? And I guess also when you did the unwinding of the safety data, just maybe what dose levels the mild heart palpitations were seen at?

Cool. Thanks Ellie. This is Nello here. So maybe, I'll just give a brief overview and then I'll let Jared here comment on the specifics. So as we said, the extension of the study to 28 days was done mostly driven by our desire to pursue an opportunity to understand even further the PD and potential clinical profile of the molecule, given the competitive space, and to be honest, given the profound pharmacology that we've observed so far. Also after un-blinding the study, we wanted to take the opportunity to extend the duration of dosing to further our understanding of the safety, which so far has been actually quite promising. Maybe Jared, you can comment a bit on the un-blinding, what we've learned as well as I think Ellie's question was also about this modest finding that we have with QTc, which doses and how it was detected.

Sure. Yes. As we described on the call, we were always planning to un-blind and really have a comprehensive look at all the safety data once we decided that we wanted to dose escalate further and when we were going to then choose our dose to bring it to Part C. The un-blinding really showed that really the adverse events that we saw with the blinded analysis still remained the primary adverse event that we saw in a relatively small proportion of patients, including headache that was predominantly; mild palpitations that were also predominantly mild and self-limited, as well as several subjects with nausea. It turned out that the adverse events, these in particular, we're seeing in the drug arm, not in the placebo arm, and that was not unexpected. And again, just to note that these were relatively few in number, they were self-limited and they were predominantly mild. In terms of the QTc finding, as we described, this was not seen in the SAD portion of the study, and it was not seen following the first dose of the MAD, it was only seen after multi dosing. This was a modest effect. This 10 msec to 20 msec increase is a modest effect. This change in QTc is well below the 60 msec threshold that is associated with risk of arrhythmia. And also importantly, the QTc interval itself remain less than 450 msec, which is essentially within the normal range, which is also well below the 500 msec threshold which confers risk of arrhythmia. So, we note this modest change in QTc, but it's important to note that this is well away from the threshold associated with any sort of possibility of sort of clinical adverse events such as arrhythmia.

Okay, thanks. Maybe I will just add one thing as we go, Bruce, if we go to the next question here. So, why are we sharing a non-adverse event in this call today, as obviously, never made to the table of adverse event, and actually we only learned it afterward, and the reason that we're doing so is just because we want to keep our kind of style of communication transparent and continue to maintain high level of rigor and credibility. Obviously, we can discuss over the next half an hour, this particular finding but hopefully we get to talk about the other things as well.

Thank you. Your next question is from Brad Canino with Stifel. Please go ahead.

On the newly added clinical endpoints for KT-474, I've seen data with the TNFs and IL-1 agents in HS, particularly where improvements don't max out until about eight weeks. So do you have any HS benchmarks in mind when you're thinking about the four-week time point? I'm especially asking in consideration of Pfizer's announcement to discontinue their IRAK4 small molecule this morning? And then looking forward to the other development opportunities for 474, I'd like to ask about your takeaways from the recent Nature publication, they implicated TLR7 as the central signaling pathway in lupus, and whether that might change your disease development prioritization at all?

Yes, thanks Brad. As always, great questions. So, I'll take a bit of it and then I'll let Jared comment on the more specific points. I just would like to kind of reiterate the 28 days. So, we're not running a 28-day study to produce definite proof-of-concept data. I think as we said, we have given our preclinical talk studies. We have opportunities to extend the duration of those into 28 days to firm up PK, PD as well as early time of clinical efficacy with also the safety profile, and to really fully -- maybe not fully, but to further appreciate the risk-reward profile of the molecule. So, I would not comment specifically on other drugs in four weeks of study, but I think it's fair to say, both across AD and HS, then within four weeks, active drugs, you start to see some separation from placebo in well-controlled studies. And so, we feel like it will be probably shortsighted of us not to measure clinical endpoint. Again, not with the expectations for us to say we have clinical proof-of-concept, just because I want to reiterate this would be an open label study, but just to start to further create a strong relationship with RPD and again, as I said, early potential clinical endpoints. So, it's to further that relationship that we've been trying to build from the early days of the development of this program. And I'll let Jared comment on where are the comps that he's keeping an eye on. I wanted to address you made the Pfizer point and the other indications. With regards to Pfizer, yes, we've learned it today as well, 20 minutes ago, I think half an hour ago, that maybe just not to correct you, but to specify, I think their HS study -- the HS development seems to be halted, but the RA trials continues to move forward. I don't want to speculate, especially not on this call. Clearly, the important thing, it doesn't seem to be, at least based on the fact that other studies are ongoing, a safety concern. And then we really don't know the data in HS versus that the three-arm study with the JAK inhibitor and TYK2. So, I don't know whether there's been some prioritization in that pipeline, but we'll have to see. And then with regards to the breadth of opportunities, as you know, we have a slide on our deck that points to several opportunities in TH1, TH17, TH2 biology. Yes, we're well aware of TLR7 data, recent human genetics data pointing to a really strong correlation to lupus. Lupus is one of those diseases that we're exploring with our partner Sanofi in terms of priorities. And so, as we continue to advance the program, we will do our best to exploit fully the potential of this mechanism. Jared, any comment on the, let's say, the comps.

Yes, maybe just to touch on this in terms of why extending also the 28 days. I think one of the main drivers for our decision to extend the 28 days of dosing came from our review with the pharmacodynamic data, where we saw that while knockdown in peripheral blood really reached steady state after seven days of dosing. In skin, we had not reached steady state after 14 days of dosing. And so being able to extend dosing to 28 days would give us the opportunity to dose long enough to reach steady-state knockdown in skin. And since in Part C, what's very important to us, is it now obtains skin biopsies of active, inflamed skin lesions, and being able to show not just knockdown the IRAK4 in the skin, but also impact on disease relevant inflammatory biomarkers in the skin. We thought it was important to extend the 28 days to give us the best chance of really showing that sort of pharmacology in diseased skin. Now in terms of the comps, at 28 days, we know, for example, in the Humira pivotal studies in HS and the Dupixent pivotal studies in AD, if you look at the curves for their various primary endpoints or even their secondary endpoints, you can see that at 28 days, as Nello was saying, you can start to see separation clearly from placebo. So, we think that there is potential opportunity to detect an initial sort of exploratory signal of clinical efficacy. And what would be nice for us is to be able to connect a signal of efficacy with pharmacodynamic effect with proof of biology showing impact of IRAK4 and inflammatory biomarkers in both the skin and the blood. So being able to make that connection of Part C, we think would really help to further de-risk the program.

Thank you. And your next question comes from Michael Schmidt with Guggenheim. Please go ahead.

This is Paul on for Michael. I have one on your IRAKIMiD. There's been some renewed focus recently on tolerability with the [indiscernible] generation of [indiscernible], particularly on neutropenia. So just wanted to get a sense of your expectations around digital safety for 413, given how you designed the molecule and any read-through, if any, from the competitive landscape. And then secondly, you mentioned STAT3 has some potential in inflammatory and fibrotic diseases. Just wondering, if there's any gating factors that you're thinking about the potentially initiating development outside of oncology, and if there's something we can expect if the PD and safety data from the Phase I look good?

Yes. Thanks, Paul. So great questions. So the first one, I'll just share some thoughts. So, every -- I think everybody's well aware of the pharmacology of IMiD. And I think we're well aware of the strategies that Celgene, that -- or now Bristol has taken to develop those drugs. So, I'm personally not surprised by seeing the pharmacology of IMiD play out in different clinical studies, depending on the potency of the compound. And I think, as we've said in the past, our goal has been to maximize the synergistic pharmacology between the IRAK4 degradation and the IMiD degradation in a way that we would be able to maximize activity while managing safety. And in fact, we based on the potency, the PK, the distribution profile of our molecules, we've optimized this molecule to be dosed once every three weeks, which is obviously very different than how IMiDs are dosed. So we feel very confident, going into the study, that we'll be able to really explore and understand how the preclinical study will translate into clinical, both safety and activity. And we believe that we spend a lot of time running non-human primate study to really understand how to walk the line between efficacy and safety. So, we're confident going into the study. And again, before the end of the year, we will update -- we will be updating everybody on how the data is evolving. On the STAT3 questions, so we've invested heavily on that program. There was a nice review the other day up there on all the other efforts that are in the space. And I think it's probably fair to say that our selective degrader is probably the most de-risked approach to targeting selectively and specifically STAT3. We also spent, I would say a couple of years actually, under trying to fully understand pharmacology and safety of STAT3 degradation, running multiple efficacy and safety studies across many type of disease states. And so, the reason why we've separated oncology from non-oncology indications is because we have come to the conclusion that the degradation profile needed in oncology is actually quite different than the degradation profile needed outside of oncology. And so, the reason why molecule that will be developed outside of oncology are slightly behind is because we're, again, firming up the PK/PD safety to then advance better towards the clinic. So, I don't know if that's a satisfying answer, but that's really the story to the STAT3 program right now.

Thank you. Your next question comes from Vikram Purohit with Morgan Stanley. Please go ahead.

This is Gospel on for Vikram. We have two questions. So, the first one pertains to Sanofi. I mean, could you walk us through the mechanics of how your decision-making process with Sanofi will unfold, following the release of the KT-474 data in second half of 2022? Specifically, I mean, how long does Sanofi have to review the package and how will you be working with them to prioritize the indication to evaluate in Phase II? And when do you think this disclosure could be provided to the Street? And then how are you thinking about the timing and process for your opt-in decision?

Okay. Thanks. So first question, what's the process. So as we've shared in the past, and nothing has changed, so when we -- we are in the very close communication with our partners. We do that with every one of our partners. And so, they're obviously well aware and they're part of key - whether it's regulatory interactions or an internal decision. And so when we complete -- when we will complete the patient cohort that we just described that we've extended to generate even more data, I strongly believe to generate hopefully key de-risking data, then we will be very quickly presenting Sanofi with a full data package, which, just to remind everybody, includes all preclinical as well as Phase I data. So it's actually a large document. And then, we haven't disclosed how many days, but there are X number of days. It's not like half a year. It's definitely less than that, to make the decision of whether to advance 474 interface 2. We expect that at least our firm goal is to present that complete dataset to Sanofi before the end of the year. And then, hopefully, that decision will be swift as, again, they're up to date with all the development of the program. Then I think there was a question about Kymera's opt-in, if I understood well. And so that will - the mechanism for that is if and when, hopefully Sanofi decides to advance KT-474 into a randomized placebo control Phase II study, or multiple Phase II studies, then at the end of the first one, with proof of concept study in hand, Kymera will have the opportunity to decide if we want to co-develop and commercialize in the U.S., sharing profit and loss 50:50. And that decision will have to be made before the beginning of Phase III so that we can operationally and financially contribute to Phase III study.

Thank you. Your next question comes from Kalpit Patel with B. Riley. Please go ahead.

One, just one question on your IRAKIMiD program, I think another drug developer Curis had a clinical hold placed recently on their IRAK4 inhibitor on safety concerns for rhabdo. I guess, does that in any sense, impact your thinking about how you're advancing this IRAKIMiD program? From my understanding that Curis drug is more of a dirty kinase inhibitor that might have been responsible for the safety concerns, but do you have any evidence of elevated CK levels in your preclinical studies with the IRAKIMiD program?

Yes. Thanks for the question. No, I think it's a good question. I think as you mentioned, the Curis compound is a multi-kinase inhibitor and addition to IRAK4. One, it's key target is FLT3. And there have certainly been published reports of rhabdomyolysis occurring with other FLT3 inhibitors. So we think it's highly likely that the rhabdomyolysis that they're seeing and that's problematic and potentially dose limiting for them is because of the FLT3 targeting. With regard to IRAK4 targeting, we, and others, have not seen any rhabdomyolysis with either IRAK4 targeting or the use of IRAKIMiD in our preclinical studies. As you know, in our IRAK4 Phase 1, we are engaging the target quite robustly and knocking out of the target by 98%. We have not seen any rhabdomyolysis. We are not aware of any reports of rhabdomyolysis from Pfizer, with their IRAK4 kinase inhibitor and their various clinical trials. And as you also probably know, there are IRAK4 no individuals who, as adults, really have no clinical phenotype and certainly have no muscle pathology. So, we don't think that there's a connection between IRAK4 targeting and rhabdomyolysis. And what Curis is seeing, again, is probably due to off-target effects and most likely FLT3 targeting.

Thank you. Your next question comes from Divya Rao with Cowen and Company.

Divya on for Mark. First one is, could you talk about what [indiscernible] meaningful degradation for IRAK4 in the AD/HS population? And then, do you think the levels of IRAK4 needed to drive this meaningful clinical benefit is different between the two? And then just like a little bit more broadly, are you willing to comment on the venues you plan to present the updates on all three clinical updates coming later this year? Would it be like a medical meeting or possibly another R&D day?

Great. So you broke up to the point, so I'm going to repeat the question. Hopefully I got it right. So the first part was, do you expect the degradation profile needed to be different between HS and AD? I'll let Jared take that one. And then I want to answer the presentation venues. So, we have always said that we like to present scientific data at scientific medical meetings. We've also said that our commitment to time line and, again, going back to the point that I made about transparency and credibility, is paramount. So if we said that we're going to present the data before the end of the year, which is true for all three programs, we're going to try our best to do it in a medical meeting. If not, if for time line reasons or abstract admission, etc., we won't be able to do, then we'll find another venue, whether it's an R&D Day or it's a focus meeting. It's not our preference by far, but, again, I just want to say that as a company, we like to commit to the time lines that we give, unless, obviously, some operational issue arises and we can't deliver on the time lines, which is not the philosophy we have at Kymera. Jared, do you want comment on a degradation profile?

Yes. Yes, I think it's a really important question. I think that we anticipate that the degradation that we need for clinical impact should be similar for AD and HS. We've learned from our preclinical mechanistic models of inflammation that 85% or greater degradation really has an impact on inflammation and the induction of various inflammatory cytokines that drive inflammation. We've also learned from our Phase I healthy volunteer study so far that a similar threshold, 85% or greater, degradation is associated with an impact on ex-vivo cytokine induction. So, we think that really what's important is how much degradation is needed to impact the function of the TLR IL-1R pathway and importantly, the particular function that we're interested in is the induction of pro-inflammatory cytokines and chemokines. And so, we anticipate a similar threshold of knockdown, at least 85% or greater, in blood and in skin for us to really be able to impact inflammation in both of these diseases. And we feel from what we've seen so far in the healthy volunteer study, with the dose that we plan on taking into Part C, that we should be able to readily attain those levels of IRAK4 degradation.

Thank you. Your next question comes from Eric Joseph with JPMorgan. Please go ahead.

I wanted to revisit the first question on QT, specifically the dose levels where you observed the extension or the prolongation and how it resolved. I guess, did it resolve on consistent dosing or was dosing modified in any way? And do you anticipate having to conduct a QT, a thorough QT study as part of the Phase I package prior to [indiscernible]?

Thanks, Eric. Great question. I think it's created an opportunity to clarify this point. So, I'll just want to clarify one thing and then I'll pass it to Jared. So, I think what we've said, that this is a non-dose-responsive, self-limiting, modest finding that never became an adverse event, not even a great one for QTc. And again, I repeat, the reason why we're sharing it is for being transparent as a company. Maybe Jared, you can comment on those adjustments, resolution and all that stuff.

Yes, I think importantly during the conduct of the SAD and MAD, again, there were no ECG adverse events. There were no changes in QTc interval that rose to the level of being an adverse event. It was only after we completed those parts and then undertook a more thorough analysis of ECGs prior to selecting the doser Part C that we noted this modest QT prolongation, again, that was not adverse. I think importantly, and as I mentioned earlier, this was not associated with prolongation that reached any sort of threshold that would be associated with arrhythmia. I think it's also important to note, as we said, in order to be open and transparent with FDA, we did share these data with them. And we have to go ahead to go into Part C with a very robust dose, 100 mg, that should help us to really maximize pharmacology. We're continuing with daily dosing. We're now extending dosing to 28 days and including clinical endpoint. I think in terms of your question around whether we need a thorough QT study. I mean, it's very common for companies to do through QT studies. Sometimes the T-QT studies can be bypassed by having enough ECG information from your Phase I study to be able to determine whether there is any sort of QT effect. It is a possibility that we might do a thorough QT study. I think that will depend in the future on what we see in Part C. But I think that certainly is on the table, but at least we have some understanding right now that whatever QT effect we're seeing is very modest, and currently is not being -- has not met the threshold for being adverse, it's not even close to that.

Thank you. Your next question comes from [Richard Low] with Credit Suisse. Please go ahead.

I have two questions. So regarding the QTc observation, did the FDA ask for any mitigation plans if that re-occur again? And at what point would that trigger some sort of intervention? And then the second question I have is on KT-474. Can you share with us any updated changes to time line or preliminary discussions you had with Sanofi regarding the Phase II plans, like in terms of what type of patients will you be exploring? And also you mentioned the RCT trials. Would that be any head to head studies with biologics?

Yes, no, thanks. I just want to clarify again, the first point. So we actually did not have to share this QTc finding with FDA, but we decided to do -- we have a really strong relationship, our regulatory group, it's really strong. We've had four -- almost four -- close to four MD submissions, several other follow-ups. So, we try to be also, as we do also with FDA, transparent and collaborative. We obviously had to engage them to amend the protocol. And when we did, we also submitted all the safety, PK/PT, and all the data that we generated. We really didn't receive much of comments with regards to how we're proposing we continue to explore the safety of the drug. I think they generally align with our proposed plans and there was no particular mitigation plan that was discussed. This was our study design protocol. And there was a general alignment in a big picture. With regards to Sanofi, again, we are very close to the team, to the development team. And I think where we are today is that, as we have always said, we have some really high priority indications. There are several but what we've discussed often is the chest, AD, RA. We talked last week a lot about lupus, for example. And I think what we agree, and it makes sense, we're both data-driven companies, we will continue to see how data emerge from this patient study. Obviousl,ynow this patient study is much more powered in terms of data that we generate. And I think with that data in hand, we will refine the strategy and the selection for the right dose -- sorry, for right priorities that we'll have for Phase II and beyond.

Thank you. Your next question comes from Zhiqiang Shu with Berenberg.

I have two questions. First one on the STAT3 program. In the past year, you have communicated potential accelerated approval seen on the CL. I guess based on the data that you're seeing or have you hold that view? And also on the program, I see you have amended the protocol to include a combo study. Can you discuss more -- provide more color on how you want to go with that combo study?

Yes, it was a bit noisy, but I think Jared, the question was. What is the path to potential accelerated approval that we're planning with STAT3? And then the combo, like, what is the plan on how to develop the combo?

Yes, I think with STAT3, we see the rapid development opportunity in STAT3 dependent key malignancies, especially certain T-cell malignancies like peripheral T-cell lymphoma and cutaneous T-cell lymphoma and LGL leukemia, where you tend to see activating mutations in STAT3 or in JAKS or even just hyper activation of the pathway. So our preclinical animal model data where we've seen very robust, and then tumor activity with STAT3 degraders and monotherapy, and because these are areas with very high unmet medical need, we think there are rapid approval or accelerated approval opportunities with our STAT3 degrader, KT-333 as a monotherapy. In terms of combination, we tend to think more about combination in solid tumors where we have shared very interesting data where the immunomodulatory properties of STAT3 synergize with anti-PD-1 drugs to show sort of synergistic anti-tumor activity and various solid tumor models, sygeneictumor models, such as colorectal cancer. So we think there could be an even larger opportunity for combination development with checkpoint inhibitors and solid tumors. Those paths may not be as accelerated because those are combination studies as monotherapy path, but we think that those are also very attractive and represent even larger opportunities for the degrader.

I'm going to [indiscernible]. And also your IRAKIMiD program, have you seen -- I know, it's early days -- have you seen any QTc findings in those programs?

Yes, so far, we're early in - we just opened our Phase I. So, we were not in possession of any human safety data. Generally, what I would say is that QTc prolongation is not a signal that we've had to deal with, within our pipeline. So, it's not something that is present in our portfolio molecules broadly.

Thank you. And I'm not showing any further questions in the queue. I would like to turn the call back to Nello Mainolfi for his final remarks.

Yes. So thank you. First, I want to thank everybody for tuning in today. I realize it was a very busy day in the biopharma space in terms of calls. So thanks for calling in. I just want to reiterate, so we're a company that is almost six years in. We have a rich pipeline of programs across a variety of indications. Again, we've talked about HS, AD, T-cell lymphoma, T-cell leukemia, solid tumor, diffuse rash B-cell lymphoma, and then soon, with MDM2, other indications. So you see that we're obviously a company that is trying to build into a fully integrated business that takes protein degradation into the space where it should be, which is really changing people's lives. We're here for any follow-up, for any questions that others might have during the day or in the next few days. I want to thank the team here, Bruce and Jared, and the team at Kymera for continuing to generate really best-in-class data every quarter and wish everybody a good day.

Thank you, ladies and gentlemen, for participating in today's call. You may now disconnect. Have a wonderful day.