Welcome to the 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. [Operator Instructions] Before we get started, I would like to remind everyone that some of the comments that management 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 to Nello Mainolfi, Founder, President and CEO.

Thank you, Operator and thank you, everybody, for joining us today. We're very excited to share with you the progress we've made over the last quarter and how it contributes to achieving our mission to building best-in-class, fully integrated global degrader medicine company. We recently completed the patient cohort portion of our KT-474 Phase I clinical trial which concludes the Phase I campaign for this drug. Jared will share more details in his remarks but with the study completed, we're currently in the process of collecting and analyzing all the data. We plan to share, as we always do, the data and the analysis of the data with our partner, Sanofi. And as announced, we will subsequently share the data publicly on a company webcast on the morning of December 14, 2022. As we have reiterated in the past, the objective of the patient cohort is to confirm that PK/PD and safety in patients with AD and HS is consistent with what was demonstrated in the healthy volunteers in the SAD and MAD cohorts. As we announced last month, we plan to update investors also on our clinical oncology pipeline on the December 14 call. As I believe you all know, we have 2 clinical-stage programs, IRAKIMiD KT-413 and STAT3 KT-333 and 1 program that we expect to enter the clinic soon which is our MDM2 degrader KT-253. With respect to the ongoing trials, the KT-413 and -333, they're both in dose escalating stages of our Phase I portion. As a reminder, the objective in this early dose cohort is to demonstrate what we call a proof of mechanism which we define as the ability to degrade the proteins of interest which obviously is STAT3 for 333 and for 413 is IRAK4 and even substrates Ikaros and Aiolos, with an…

Thanks, Nello. I'm excited to share updates on our 3 clinical programs. I'll begin with our IRAK4 program. KT-474 is a potentially first-in-class oral degrader of IRAK4, a key protein involved in inflammation, mediated by the activation of toll-like receptors in IL-1 receptors. KT-474 is being developed for the treatment of TLR/IL-1R-driven immune inflammatory diseases, such as hidradenitis suppurativa, atopic dermatitis and potentially others. As you may recall, Part C is an open-label study of KT-474, administered daily on an outpatient basis for 28 days, with patients followed through Day 42. As we shared last month, we've completed dosing in the patient cohort, or Part C of our Phase I trial for KT-474. Additionally, we can confirm today that all patients have completed their last visit, or Day 42 of the study. The Part C patient cohort followed the dosing of over 100 healthy volunteers in the single ascending dose and multiple ascending dose portions of the Phase I trial. In the SAD and MAD studies, we demonstrated near-complete IRAK4 degradation in peripheral blood mononuclear cells and skin, robust inhibition of multiple ex vivo stimulated disease-relevant cytokines and a favorable safety profile. Part C includes patients with either moderate to severe hidradenitis suppurativa or atopic dermatitis and is examining the safety, pharmacokinetics and pharmacodynamics of KT-474, while also exploring early signs of clinical activity. Patients received a daily dose of 75 milligrams of KT-474 in the [indiscernible] state. This dose is expected to provide a plasma exposure that is approximately equivalent to that achieved with a 100-milligram per day dose in the fastest state in healthy volunteers in the MAD portion of the trial which showed maximal or close to maximal degradation in blood and skin and broad disease-relevant cytokine inhibition ex vivo. As previously mentioned, the goal for this…

Thanks, Jared. For the quarter, we recognized $9.6 million of revenue, a total that 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 $77 million. That reflects the partnership revenue we expect to recognize over the next several years, excluding the receipt of any future potential milestones. With respect to operating expenses, R&D for the quarter was $43.9 million. About $4.9 million of that represented noncash stock-based comp. The adjusted cash R&D spend of $39 million which again excludes the stock-based comp, reflects a 7% increase from the comparable amount in the June quarter. With respect to G&A spending for the quarter, it was $10.6 million, of which $4.2 million represented noncash stock-based comp. That adjusted cash G&A spend of $6.4 million, again excluding stock-based comp, reflects a 5% decrease from the comparable amount in the June quarter. We exited the second quarter with a cash and equivalents balance of approximately $596 million. Recall that we do not include in our cash runway any payments from milestones that we have not yet achieved. Our guidance for cash runway of at least into 2025 incorporates the completion of our $150 million pipe but we do plan to update this runway guidance, in particular, the specifics around the extent of runway extension driven by the financing, closer to year-end. With that, I'll turn the call back to Nello for some concluding remarks.

Thanks, Bruce and Jared. As we look forward to providing a clinical update on our December webcast, it's clear that Kymera has successfully transitioned into a new phase, one in which we can observe our science in action in patients. We are excited to begin to assess the impact that 3 of our programs may have in patients with cancer and immunological conditions and to finally demonstrate the advantages of our platform over traditional medicines. With all the progress made this quarter, we're just getting started. In addition to our 3 clinical programs, we're on track to clear an IND for our MDM2 degrader, KT-253, this year and we're advancing several earlier programs with clear degrader rationale and significant commercial opportunities. So with the productive partnerships in place with Vertex and Sanofi, with our recent financing, we continue to maintain an array of pipeline investment opportunities to maximize the potential of our best-in-class platform and discovery engine. At this point, I'd like to thank the Kymera team as well as our partners, the patients who are participating in our clinical trials and, finally, all of you for participating in this call and I look forward to your questions. I will now hand the microphone back to the operator so we can take your questions. Thank you again.

[Operator Instructions] Your first question comes from the line of Brad Canino from Stifel.

First, can you tell us when you expect to deliver the data package to Sanofi in relation to that December 14 date you've set up? And will the package be based on the 28-day data cut? Or will it include the 2 extra weeks of follow-up? And then, Nello, I want to go back to your R&D Day last year. You set an ambitious suite of goals for 2022 which included the first tissue-restricted, E3 ligase-enabled program in development. Can you just update us on that status and perhaps share any comments regarding the critical decision points remaining for the target in E3 ligase selection for that first candidate?

Great. Thanks, Brad. Two great questions. So one at a time. So the first one, so we plan to deliver to Sanofi the complete data package. So obviously, that will include also the follow-up period of the extra 2 weeks of observation. I think today we're saying and it's also on the clinicaltrial.gov, that we have completed that phase as well. So when we say the study is completed, we mean that every patient has gone through also the 2 weeks of follow-up. What we've also said today, that we're still collecting and analyzing data. So the phase of data collection is not completed yet. As soon as we complete that phase, we will share the totality of the data with our partner. So we haven't said when that will happen because, to be honest, we haven't completed all the work that we're doing internally. Maybe the only thing I would add, we've always had a very close relationship and communication with the Sanofi team. So we try and be as helpful as possible also in this time when we're still collecting data to make sure that we share anything meaningful as we collect things. To your second question, as I said, we have several programs in the preclinical stage, many of which are actually close to entering preclinical development. And one of those programs entails the use of an E3 ligase that has a restricted expression in the body that will allow us to actually overcome the dose-limiting toxicity of a well-known oncology target. I think our plan, although we haven't firmed it up yet, is to provide an update at some point next year on where those programs are. Maybe we'll disclose. We'll see 1 or 2 of them, depending on which stage of development they are. So I guess it's not super satisfying but I'd say stay tuned, as more information will be shared on that.

Your next question comes from the line of Chris Shibutani from Goldman Sachs.

Just to be clear in terms of the optionality for Sanofi and the decision that they'll make, we may hear from them that they would proceed with both programs, one or sequentially, the way that you've structured your relationship there? Just so that we can frame the different scenarios that could play out, that would be helpful. And secondly, on the KT-333, there is scientific premise for pursuing indications outside of oncology. Any thinking there in terms of how you would pursue that? Would that be with partnerships? And does Sanofi have any opportunity to explore that as well?

Chris, if you can stay on the line for one more second, can you clarify your first question, when you said 2 programs? I'm not sure I fully understood the question.

Just thinking about the 2 indications for AD and HS. And so perhaps clarifying that we shouldn't be thinking that the decision from Sanofi is singular and binary but that there's sort of an option set.

Sorry, Chris. I missed that. So thank you. So going back to the question then, so as you know, we are in this partnership with Sanofi on IRAK4 degraders outside of oncology and immunology. That's actually the spirit of the contract. And both Sanofi and Kymera have large ambitions. We believe that this mechanism has potential to be one, if not the best, small molecule anti-inflammatory drug in a wide variety of diseases. Obviously, we'll have to generate data to support our beliefs here but that's what we're doing. So when Sanofi will make the decision to transition, if and when make the decision to transition, KT-474 into, we call it, late development, it's a decision to invest into the global development of the drug. And so it's not indication-based but it's in the late development. We, as a partnership, we've always been aligned that the reason for Sanofi and Kymera to partner is to use and benefit, at least from Kymera point of view, benefit from the broad both clinical and commercial footprint that Sanofi has built in immunology. And as they say publicly, they want to be the number one immunology company in the world. And so the spirit of the collaboration has always been to try and pursue several indications. But obviously, we would like to look at the data and then with Sanofi decide how to prioritize indications, going forward. But I would say their decision is in global development of, we hope, to be multiple indications. STAT3, outside of oncology. So we have been talking about this program for a couple of years. We've released data in different conferences. This is something we're very keen on. And I think we'll share some data as we firm up our kind of clinical strategy around this asset. For now, this is something that Kymera is leading independently from any other existing or any potential new partner. But obviously, time will tell if things go in different ways.

Your next question comes from the line of Divya Rao from Cowen & Company.

This is Divya on for Mark. We have one on the oncology program and then one on KT-474. So just for the oncology programs, what data can we expect at the R&D Day? And then could you remind us what level of degradation you would expect to see to translate into clinical activity? And then for 474, with the Part C now completed, I know that you guys are doing some analysis and that is still ongoing but is there anything else data-wise that still needs to be generated before presenting the data package to Sanofi this quarter?

Great. Jared, do you want to take the oncology question?

Sure. For both oncology programs, the aim is for us to be able to show what we call proof of mechanism which is knockdown of the intended targets to a level that hopefully is associated with preclinically antitumor activity and to show that we can accomplish that knockdown at doses that are safe and well tolerated. Your question around what are the target levels of knockdown for the various programs. For the IRAKIMiD program, we've seen that knockdown of IRAK4 in the IMiD substrates Ikaros and Aiolos in the 60% to 80% range is sufficient to give us activity in MYD88-mutated DLBCL. So that's a level of knockdown that, ultimately, we'd like to see in that program. For STAT3, we've shown in STAT3-dependent lymphomas that greater than 90% knockdown maintained for several days is sufficient to also induce significant tumor regressions in that context. So those are the sort of benchmarks that we'd like to ultimately see. But from the standpoint of what we'll be presenting at R&D Day, our hope will be that we'll be through enough dose levels to be able to show initial proof of mechanism at doses that are safe and well tolerated.

And maybe I'll take the other question, first, thanks, Jared, on 474. I just want to maybe take the opportunity to remind what the purpose of the study was and is. And it's really to demonstrate that transitioning from healthy volunteers to patients were able to maintain a good both PD, PK/PD relationship and safety profile to advance the drug into Phase II. And so that means that our key goal is to actually collect data to demonstrate that there is a -- continues to be a strong relationship between exposure and PD that can inform our Phase II dose selection, that the PD has now defined, let's say, a direct [indiscernible] degradation in blood and skin that PD results into impact on disease-relevant, pathway-relevant chemokines or cytokines that we believe will create that new now correlation, given that in healthy volunteers we weren't able to do that. So correlation between, we call it, let's say, target engagement and something that is disease-relevant as the biomarker. And then, as we said, just so that I obviously don't dismiss it completely, we've also said that we will be collecting clinical endpoints with the goal of trying to establish a potential correlation again with some PD, some biomarkers or anything that can be tied to clinical endpoints that obviously would be highly exploratory given the size and the design of the study. Now going back to your question, sorry, we are actually still collecting data. So there is some data that you can imagine is easily accessible in an open-label study. And then there is some data, especially with regards to PD, that actually takes weeks to generate. So we are generating data. We're not just analyzing data. And so it would take us more time to fully collect all the data. And that's the only reason for having a December call, because we wanted to have the totality of the data in hand before sharing it, again, both with Sanofi to get their approval to share the data and then with all of you.

Your next question comes from the line of Joseph Eric from JPMorgan.

It's Eric Joseph from JPMorgan. Nello, I'm assuming that some of the additional data you're gathering is perhaps the intermittent dosing data in healthy volunteers. I know you added this additional cohort looking at biweekly or every-other-day dosing. Is that specifically the data that you're gathering? And I guess, should we expect those data to be presented at December 14? And then, I guess, can you just talk about the rationale for evaluating that regimen specifically with 474?

Thanks, Eric, for bringing that up, actually. So the answer to your first question is no. I mean, we're focused on the patient cohort. And as I said, just maybe to be even more transparent, in this study you can get initial read on safety and clinical endpoint quickly. There is obviously a data lock and a cleanup that takes time even to do that. And what is taking longer, as it does and as it has done in the past, is generating all the PD and biomarker data. These are not simple assays. In fact, these are cutting-edge things that we're doing in the industry. I don't believe other companies have ever done what we're doing in HS and AD patients. And I have to thank Jared and his team for all the work that they've done in actually designing and executing and hopefully eventually generating the data. With regards to the infrequent dosing, as I've said in the past, this was a PK/PD experiment that we wanted to run before the eventual transition of the program to Sanofi, where we will lose the ability to run clinical studies. And this was a study that we wanted to learn not just for KT-474 learning, given that in the SAD we learned that has extended degradation after a single dose. So we wanted to learn how far and how reliable it would be dosing less frequently. But also for us, it was a big platform question. But I don't expect that that will be part of our disclosure. I think we'll be focused on -- unless there is anything relevant to that to the development of the program but we'll be focused on the patient data and how hopefully that will be informing further development.

Okay, great. I appreciate that. Maybe just a follow-up, if I could, on the oncology programs. And thanks for sort of setting...

We can't hear.

Excuse me. Just a follow-up on the oncology programs and thanks for framing expectations into December 14. I'm just wondering whether as part of the presentation you might be at a point where you can detail recommended Phase II dose. Really, how close a line of sight do you have on when you might start enrolling the expansion cohorts for 333 and 413?

I think it's -- first of all, at this point, it's probably not appropriate for us to comment. So we might comment on this in December. But what I would say is we're still in the dose escalation phase and we're focused on it. So just maybe to take a step back, the beauty of this technology and the reason why many of us are here is because it allows you to do drug development in a completely different way. It allows you to do a data-driven drug development where you know at any given point in your clinical trials, if you design them right, where are you versus your expectations or versus your prediction or your data-driven expectation of what kind of degradation do you need to achieve the type of efficacy that you're looking for. So the ability that we have in dose escalation, instead of blindly escalating to an MPD [ph], we have an opportunity to escalate and learning where we are versus our expectations on level of degradation needed to achieve efficacy. So the goal of this year is really to see if the translation of the PK/PDs, let's say, as good as we've seen with KT-474, where we degrade the protein in a reliable, predictable and dose-responsive way and the safety that goes with the degradation profile is in line with what we've seen preclinically. Because if that is the case, we will have really bullish prospect on the potential clinical success of these drugs. Because the mechanisms are well known in oncology and here is really getting the PD and the safety right for both of these drugs in oncology. And I think if we can show that, I think it will be a large derisking event for this program, moving forward. Now I don't want to dismiss your question. I think we will comment on there but I suspect that next year we will continue to do both some escalation and some expansion at the time that maybe we will discuss more in December.

Your next question comes from the line of Vikram Purohit from Morgan Stanley.

Following up on KT-474, I just wanted to see if there had been any more exploratory work done on the palpitation and QTC signals that you reported earlier with the healthy volunteer data set? And if so, if there's any update to communicate out here on anything more you might have learned versus your prior update on what the mechanistic rationale for these findings could be? And then secondly, on the same program, going back to your prepared remarks, you mentioned that you won't be seeing steady-state degradation until the second half of the dosing interval in Part C. So given that, how would you advise people to interpret the efficacy data here versus some other 28-day dermatology data sets that are available in this space?

Great. Thanks, Vikram. Maybe, Jared, if you want to comment on the first question. The only thing I will say maybe before passing it on to Jared, we have never draw a line of correlation between palpitation and QT. But I'll let Jared comment on anything else that we want to share on our understanding of the mechanism, on the QT at least.

I think what we've described previously, right, based on our in vitro data, is that with iPSC cardiomyocytes we have been able to see an effect on current that's consistent with a mild herd effect of high concentrations that is somewhat delayed and that is sort of consistent with the sort of effect that we saw in the clinic, where we have a delayed effect that's not, in the clinic anyway, dose- or exposure-dependent and appears to plateau after Day 7 and then remain steady until the end of the dosing period at 14 days. And so we don't really have anything new to report on those lines in terms of our understanding mechanistically of what's going on. I think what will be important for us in Part C is to really -- as we continue to observe now out to 28 days of dosing, past 14 days that we did in Part B, do we continue to see sort of a plateauing of that QT effect. And I think that will further inform us as to what sort of clinical impact, if any, there is of this subclinical non-adverse QT effect that we saw in Part B.

And maybe then to get back to you on the efficacy question, I mean, the question you asked is really why we continue to say that expecting clear efficacy readout from this study is, I think, kind of unfair for how we've designed the study and the purpose of the study. And it's really difficult for us kind of scientifically to take the eventual data set and compare it to other agents, given that this is a different mechanism, new pathway, small numbers, no placebo and, again, for a new mechanism, relatively very short time. But I think what we want to be able to do, if possible and again we'll have to generate the data and see, is to see if there are any trends between what we see in terms of PD and biomarker changes, any early signs of differences in clinical endpoints. It would be really hard, if not impossible, for us one way or the other to say that the drug works or doesn't work in HS and AD based on comparison with other studies, just because this is a different study.

Your next question comes from the line of Eli Merle from UBS Financial.

On MDM2, maybe if you could just elaborate on what a potential initial trial design would look like and any commentary on data timeline, say, if we could, assuming IND clearance, see data next year. And then also just in terms of the biology, how you're thinking about what tumor types this would make the most sense in and be best suited for as you had planned on initial dose escalation and thinking about expansion cohorts that you might be looking at.

Thanks, Eli. I enjoy talking about also other programs in our pipeline. So for MDM2, we have -- we're really excited about this program. Obviously, not more or less than others but it's really I think another program that we've built to demonstrate that this technology can be used to do things that other technologies cannot do. And so hopefully, everybody appreciates that has been our philosophy in terms of target selection all the time. And when we disclose our next 3, 4 programs that are in a really good stage preclinically, you'll see that that philosophy continues to be true. So with MDM2, this is not a super small molecule. This is just a different biological intervention at that pathway that is looking to eventually and finally replicate the genetics data that shows that absence of MDM2 generates high level of sensitivity in p53 wild-type tumors which is not what has been seen with small molecule inhibitors. And as we said, the one way that we're able to do is because we remove the protein quickly, we overcome this feedback loop and we drive cell to apoptosis in a way that small molecules are not able to do. So I'll let Jared comment on the clinical trial design, although it's something we haven't fully disclosed but maybe he can give you a high-level overview. But what I would say, our strategy there is to focus on indications where we see a very rapid apoptotic response that allows us to maximize efficacy and safety for this mechanism. And what I will say is that we have several indications in both liquid tumors and solid tumors that have this type of response. And I believe today our ASH abstract is out, I believe, at 9:00 a.m., highlighting a bit more work on AML which will be one of the indications of interest. Jared, do you want to give maybe just a high level overview?

Definitely. Just to give a high-level overview and just as a reminder that because of the unique mechanism of action of degrading as opposed to just small molecule inhibition, we're able to sort of dose intermittently. So we're planning on bringing in an intermittent IV dosing, so infrequent IV dosing, into the Phase I. And the trial design, it will be sort of a standard Phase Ia dose escalation, followed by a Phase Ib expansion. But importantly, the Phase Ia will be able to set us up to understand safety, tolerability and PD both in heme malignancies as well as in solid tumors. And we will have opportunities to put on indications of particular interest, both in heme malignancies and solid tumors, within Phase Ia. And then eventually, once we do come up with a recommended Phase II dose or maximum tolerated dose to then bring that into a Phase Ib expansion, that will likely involve expansion then in malignancies, especially AML but potentially others, including lymphoma, as well as in solid tumors.

Your next question comes from the line of Geoff Meacham from Bank of America.

This is Joe [ph] on for Geoff Meacham. On KT-253, are you hoping to achieve a tumor-agnostic label? And can you provide any additional information on patient selection and your breakdown between liquid and solid tumors?

Joe, that's a great question. We unfortunately are not in the position to comment on the specifics but rest assured that that is one of our ongoing translational works, being able to potentially get to that type of tumor-agnostic development and approval. But we're not in the position right now to comment on where we are. And this is something we hope to share at different meetings, hopefully next year. I know the team is working on, obviously, generating data and also identifying the right medical meetings to start to discuss what our translational strategy is.

Your next question comes from the line of Rich Law from Credit Suisse.

Can you comment on what were the stopping rules in place for Part C? And can we rule out all Grade 3 or Grade 4 adverse effects? And also a follow-up question is that you mentioned earlier that you are still preparing data for Sanofi. Can you confirm that Sanofi hasn't seen any of the data yet and there was no piece-wise data or real-time safety data that they already saw when the study was ongoing?

What was the first part? Ah. So I think we've said it in the past, we can't really comment on the specifics. Obviously, if there were events that impacted the study's success, we would have obviously had to share them. With regards to Sanofi, we really are not in the position to share what we have or haven't shared with them. But again, as I said earlier, you can assume that we're in constant communication, as we've been throughout the collaboration. So, I'll leave it at that.

Your next question comes from the line of Michael Schmidt from Guggenheim.

Just a couple from us. On KT-333 which is your STAT3 program, other than on target degradation in the Phase I study, are there any other PD markers related to STAT3 that you're looking at that could potentially further validate this target?

Jared, do you want to take that one? Thanks, Michael.

Thanks for the question, Michael. So in addition to looking at STAT3, yes, we are also looking at the impact of STAT3 degradation on the actual STAT3 pathway. We'll have the best opportunity to look at that in serial tumor biopsies. We can look at the impact either looking at phospho-STAT3 or looking at gene expression profiles for STAT3 pathway activation. So that will give us an opportunity to show not only that we can hit the target but that by hitting the target we're able to impact the pathway itself. We'll also be doing genotyping of these patients in order to see whether specific genotypes, for example, STAT premutations or other mutations affecting the pathway, correlate at all with clinical responses as we get into higher doses when we can start to assess the clinical responses and where we can start to bring on the target patient population, especially those patients with T-cell malignancies.

So expect that to be part of a kind of our global assessment of a comprehensive Phase I study. Obviously, it's not something that we can do in every patient.

All right. Got it. And then a question on your MDM2 program. It sounds like you are focusing on AML and then perhaps other solid tumors as well. And I know with this class of drugs, there has been some on-target toxicity; in particular, myelosuppression. And I was just wondering with the degrader mechanism and I think you mentioned the intermittent dosing schedule that you're looking at, I guess just given the PK and PD around degradation, do you think you can avoid some of those safety issues that have been associated with some of the other drugs in the class?

So just to clarify, Michael, AML is one of the indications of interest, not the main indication. It's just one that we've generated -- let's say, we're sharing data of and will obviously, as we said, be part of our clinical strategy. Going back to your question, the second part of your question, that's the point that I was trying to make before. We want to use protein degradation to do things that the small molecules or antibodies or RNAis or gene editing technologies cannot do. In this case, actually have a safe and effective therapy, at least much more effective than you can do with other agents. And let's say, the trick there is really to have a very profound effect very early on, very, very quickly which, again, small molecules cannot have and then allow for recovery. So Jared mentioned we dosed infrequently. So we dosed once every 3 weeks. And we have seen that that's enough to lead tumor cells to extremely rapid apoptosis and we also see healthy cells being able to recover because they're obviously less sensitive to cancer cells. And so we are able to manage the safety with maximizing efficacy. In a way, although not exactly similar, how we're developing our IRAKIMiD and how we're managing neutropenia with the IMiD part is theoretically, or philosophically, exactly the same way. And this is why we've built these drugs to be dosed infrequently. These are drugs that have been designed at the molecular level to have extended PD so that you can dose them infrequently but also with a dosing paradigm that will allow recovery of noncancer cells. So what we're doing at Kymera is not just pushing the envelope of protein degradation in immunology but what we're trying to show is that actually you can push the envelope on cancer biology through probably very, very thoughtful drug development, using the technology to change the paradigm on how one can think about affecting the biology in tumor.

Your next question comes from the line of Kelly Shi from Jefferies.

A follow-up question regarding the efficacy rate out of 747 [indiscernible]. So how many lines of prior biologics actually allowed for the trial according to protocol? And do you expect most of the patients had a prior DUPIXENT or [indiscernible] treatment for AD and HS patients, respectively? And to further complicate the efficacy interpretation, besides the difference of PK/PD and also the other [indiscernible] of 474 compared to any other AD and HS drugs.

Thanks for the question. We actually did not restrict number or type of prior treatments for either AD or HS patients. So the Part C of the Phase I allowed patients either who had not received prior therapy or prior systemic therapy as well as patients who had received prior therapy, including biologics. If patients had received any prior systemic therapies, they required a washout period before coming on to the study. So we did not allow concurrent therapy along with our degrader. That would have compounded the results. Again, because this is a small open-label study, we were not trying to control baseline characteristics in terms of prior treatment. That would have been difficult to do and probably not appropriate for such a small study. And because clinical efficacy is not the primary endpoint of Part C, we didn't feel it necessary to do that. However, when we do look at the results, we will of course pay attention to what the prior treatments of any were for patients with either AD or HS. And as we interpret results, especially exploratory endpoint results, we will certainly keep that in mind.

Thanks, Jared. And just to confirm, so we do not expect -- we know that we won't have any impact from previous therapies because every patient, if they were on previous therapies, would have been washed out. And so there will be no previous drug on board when they received KT-474.

Your next question comes from the line of Mike Kratky from SVB Securities.

Having completed the dosing portion in Part C, can you provide any details on the split between the total number of AD versus hidradenitis patients in the study and whether those baseline characteristics are largely consistent with your expectations?

Well, I mean, I think we're close enough to sharing the data at this point, we're just going to not comment on the split. I think baseline characteristics, Jared, we've always said moderate to severe, right? So I think that's consistent.

Your final question comes from Zhiqiang Shu from Berenberg.

The first one, I was wondering if you can tell us more about the difference in terms of biology between HS and AD. And I guess on your December data set, would you be able to differentiate the potential in these 2 types of disease and provide prioritization at that point? And then the second set of questions around the safety. Given you have been worried that the less frequent dosing schedule in your [indiscernible] MAD study, can you comment on any change or any safety signal in terms of QT prolongation in that cohort? And finally, on that, also related to QT, can you confirm for your oncology program, STAT3 and also IRAKIMiD, that the QT prolongation signal should not be expected?

Thanks. So maybe I'll start from the last. And then maybe, Jared, if you can comment on the first and the HS [indiscernible] biology. So the last one is easy. We don't expect that QT has anything to do with the platform program, broadly. As we've shared already, we have characterized for KT-474 this weak [indiscernible] that we believe is compounded by a higher-than-expected exposure in the cardiac tissues in humans that leads to this very, again, as we said, very atypical non-dose-responsive, [indiscernible] QT prolongation that, again, we believe has no impact, in our view, no impact on clinical development of this drug, assuming it stays within the range that we've seen in healthy volunteers. We've also said in the past that we've been able to replicate this change of currents in cardiomyocytes, I believe Jared said it even earlier today and we've also shared that in that particular assay we demonstrated that we can take another IRAK4 degrader and show that we don't change current. So we know it's a molecule-specific event. Going back to the infrequent dosing and safety, I mean, all we will say is that if there is anything out of the study that is worth sharing, we will share. I guess, as I've said it in the past, the reason why we've never discussed this study is because we had almost little or no expectation that it will have an impact on the development of KT-474. It will be informative, again, for the drug. It will be informative for the platform. Again, if there is data from the study that is worth sharing, we will share it in December. But I continue to advise, guide on low expectations there. And then on HS and AD, Jared, if you want to comment on the biology.

Sure. In terms of the biology, even though HS is classically thought of as a Th1/Th17 disease and AD is as a Th2 disease, in reality, there have been very interesting sort of gene expression analyses of skin lesions showing that the inflammation is actually quite mixed in both of these diseases. Even in AD, in addition to Th2, you see Th1 and Th17 elements. And in HS, you can also see some Th2 elements. In reality, both of these diseases, importantly, are driven by toll-like receptor activation. Bacterial colonization of the skin which activates toll-like receptors, is important in both diseases. And both diseases have also been shown to be driven by multiple different IL-1 family cytokine members. And so there's probably more in common pathophysiologically between those diseases than one might suspect. And therefore, we think both of these diseases are really prime indications for targeting with an IRAK4 degrader.

Great. Thanks, Jared. So maybe just to conclude, thanks, everybody, for joining today. I want to say from myself and the whole team we appreciate the engagement from the community, from our analysts and investors. We've had, I don't know, hundreds of meetings this year. So we appreciate that there is interest in what we're doing. As you know, we're always available to follow up with many of you that are interested in understanding the facts and designs at Kymera. We're excited about what we're doing. I think that the sky is the limit for the technology and it's really our responsibility to develop drugs and to build the company that can really capitalize on the power of it. So we look forward to seeing you, hopefully, all of you, in December and some of you maybe at conferences where we'll be present in the next few weeks.

This concludes today's conference call. You may now disconnect.