Kymera Therapeutics, Inc. (KYMR) Q2 2026 Earnings Report, Transcript and Summary

Good day, everyone. My name is Michelle, and I will be your conference operator today. At this time, I would like to welcome you to the Kymera Therapeutics Second Quarter 2026 Results Call. [Operator Instructions] At this time, I would like to turn the call over to Justine Koenigsberg, Vice President, Investor Relations. Justin, please go ahead.

Good morning, and welcome to Kymera Therapeutics Quarterly Update Conference Call. Joining me today with prepared remarks are Nello Mainolfi, our Founder, President and CEO; and Bruce Jacobs, our Chief Financial Officer. We'll also have brief comments from Jared Gollob and Terence Rooney, our new Chief Medical Officer, who will also join us for Q&A. Following our prepared remarks, we will open the call for questions from our covering analysts. To ensure we have time to hear from everyone, we will limit each analyst to question. Before we begin, I would like to remind you that today's discussion will include forward-looking statements subject to risks and uncertainties described in our most recent Form 10-Q filed with the SEC. Please note that any forward-looking statements speak only as of today's date, and we undertake no obligation to update them. With that, I will now turn the call over to Nello.

Thank you, Justine, and good morning, everyone. Before we dive into the quarterly update, as we announced last week, I'd like to take a moment to recognize Jared as he prepares to retire and thank him for his many contributions over the past 8 years. Jared has been instrumental in helping build Kymera and has made a meaningful impact across virtually every aspect of the company. His leadership, dedication and partnership have helped shape where we are today, and we're incredibly grateful for everything he's done. While we certainly miss him, he leaves the organization in a position of great strength. With Terence stepping into the role, I'm confident that we'll have a seamless transition and continue to build on the strong foundation Jared has helped create. You'll hear from Terence later in the call, but I'm very excited to have him join the team and believe that his long and deep experience across all phases of immunology development and commercialization, along with his insights and capabilities will be critical to helping advance our next phase of growth. On behalf of everybody at Kymera, thank you, Jared. We wish him nothing but the very best in this well-deserved next chapter. Before we get started, we wanted to give him the opportunity to share a few words. Jared?

Thank you, Nello. While it's truly bittersweet to say goodbye, I have made the decision to retire after having spent 20 years in academic medicine, followed by 20 years in industry, including the last 8 years at Kymera. This is obviously an exciting time for Kymera, and I cannot be prouder not only of all that we have accomplished, but also of all that the company will accomplish in the future. I am happy to note that I'll be staying on as an adviser through year-end to help with the transition as needed. But I'm ultimately excited for this next chapter and for the opportunity to spend more time with my family. But before I go, I want to say a heartfelt thank you to all of you. It has been an incredible privilege to be part of this organization and to work alongside such talented, dedicated and inspiring people. I have also enjoyed all the interactions I have had with all of the investors and analysts on the call today, which I will miss as well. Looking back, I'm filled with gratitude for everything we've accomplished. I have tremendous confidence in the future of Kymera and can't wait to see all that's still to come. It's been an absolute honor to be part of this journey. Thank you.

Thanks, Jared. Now with that, let's turn to our quarterly update. We entered today's call with strong momentum across the business, driven by progress in our lead programs, advancement of our broader pipeline and continued execution against our long-term strategy. At Kymera, our ambition is not only just to develop new medicines, but to redefine what is possible for patients by changing treatment paradigms. We believe we have the ability by leveraging not only targeted protein degradation, but also our broad small molecule capabilities to fundamentally reshape how diseases are treated. Our focus remains firmly on translating the science into transformative oral medicines that can create meaningful impact for patients. Reflecting on our recent accomplishments, last quarter's highlights was undoubtedly the announcement that we completed enrollment in our Phase 2b AD trial, approximately 6 months ahead of schedule. As a result, we now expect to report top line data by year-end 2026 and to initiate Phase III development around mid-2027, both approximately 6 months earlier than previously planned. We view this rapid enrollment as a reflection of many factors, including the compelling preclinical and Phase 1b AD data generated to date. Our appreciation and confidence from investigators and KOLs in a well-understood pathway, the incredible excitement from investigators and patients for the opportunity of a once-a-day oral therapy, as we have seen in other areas, outstanding execution by our clinical trial operations and medical teams. We completed this trial well ahead of expectations, as I mentioned earlier. I would add that we did that while maintaining our strict focus on quality, which included many measures that we put in place, some of which could be perceived as burdensome to patients and sites. And this approach remains consistent throughout enrollment. In addition to the momentum around our STAT6 program, we continue to demonstrate that our platform can repeatedly generate differentiated investigational medicines against high-value targets, reinforcing our strategy of building a robust pipeline capable of driving high-impact patients and in doing so, delivering long-term value. Our second wholly owned program is also progressing in the clinic with the ongoing Phase I study of KT-579, our oral IRF5 degrader. We believe IRF5 represents a highly compelling target in immune -- in autoimmune diseases with the potential to address multiple high-value indications. We expect to report Phase I healthy volunteer results in the fourth quarter of 2026 and to advance the program into its first proof-of-concept study in lupus patients soon thereafter. In addition, KT-485, our second-generation IRAK4 degrader partnered with Sanofi, recently entered Phase I development, resulting in a $20 million milestone payment to Kymera. The Phase I is designed to evaluate KT-485 in both healthy volunteers and patients with hidradenitis suppurativa, and we look forward to its advancement under Sanofi's leadership. And last but not the least, we look forward to providing updates as our CDK2 molecular glue KT-200, partnered with Gilead, advanced towards an expected IND and clinical start next year. Taken together, our program -- our progress across all of these programs highlight both the power of our discovery and development capabilities and our ability to consistently translate into potentially transformative medicines for patients and meaningful value creation for shareholders. Turning more specifically now to KT-621. As we prepare for the upcoming readout later this year, I wanted to quickly refresh you all on the details of the trial and then touch on how we view the opportunity for KT-621. As a reminder, the study is evaluating 3 doses of KT-621 compared to placebo. The primary endpoint is percent change from baseline in EASI score at week 16. Key secondary endpoints include EASI-50, EASI-75, vIGA-01 and pruritus NRS. When we report top line results later this year, these along with safety are among the key endpoints we expect to share. As we think about the upcoming clinical readouts, our overarching goal is very clear. We are developing KT-621 to deliver what we hear patients want, an active, safe oral therapy in diseases like AD, asthma, EoE, COPD and others that lack such an option. This is not only true in these type 2 indications, but also more broadly. There is an overwhelming demand for oral pills that can help manage debilitating chronic diseases. It comes down to clear preference among patients and physicians for treatments that are better suited to fit their lives. With respect to the market opportunity, we made this point in the past, but it bears repeating. Market data tell us that there are a significant number of patients that are not well served with existing treatments. In fact, there are an estimated 43 million adults in the U.S., EU5 and Japan with atopic dermatitis and only a small percentage of patients, single digits really, with moderate to severe diseases are on advanced systemic therapies. There is no doubt that this represents a significant, if not unprecedented opportunity for KT-621. If we are successful and can deliver an oral therapy that is both clinically efficacious and well tolerated, we have the potential to meaningfully expand the use of systemic treatment and dramatically change the existing treatment landscape. Finally, on the opportunity, I think it's important to highlight that KT-621 has the potential to become not only the first oral therapy with a favorable safety profile for individual type 2 inflammatory diseases such as atopic dermatitis and asthma, but also the first and only oral therapy capable of addressing the full spectrum of type 2 diseases and their associated comorbidities. This would represent a powerful tool for physicians and position KT-621 as a potential first and best option for all patients with type 2 diseases, given more than 50% of the population presents with additional type 2 comorbidities. Now with most of my comments focused on the AD trial, we're similarly excited about the progress we're making in asthma. We continue to hear strong enthusiasm for the potential of an effective oral therapy in type 2 asthma based on our discussions with KOLs, including most recently at the ATS conference. Importantly, we hear consistently from KOLs that a well-tolerated oral therapy delivering clinically meaningful benefit could address a significant unmet need and expand treatment options for a broader population of moderate to severe patients. Enrollment is underway in the BREADTH Phase 2b trial, and we remain on track to report top line data by late 2027. As we continue to advance KT-621 in the Phase 2b trial, we're also focused on generating the long-term data that will be important both for regulatory purposes and ultimately for commercialization. We're pleased to share that we've initiated an open-label extension asthma study, which will allow patients who complete the BREADTH study to continue receiving KT-621 for up to an additional 52 weeks. Taken together, we believe our development strategies across both AD and asthma positions us once these 2 studies are completed to fully explore the broad potential of KT-621 across our dermatology and respiratory diseases in later stage trials. Now turning to KT-579, oral IRF5 degrader. We remain on track to report top line data from ongoing healthy volunteer study in the fourth quarter of 2026. As a reminder, IRF5 is a genetically validated driver of innate immunity dysfunction and inflammation and is implicated across multiple autoimmune diseases such as lupus and IBP. KT-579 seeks to control a challenge that has been elusive among traditional drug development approaches in this space. By selectively degrading IRF5, KT-579 is designed to modulate multiple disease-driving pathways with a single mechanism and therefore, has the potential to be the first novel mechanism with broad utility in diseases where patients are desperately seeing more efficacious and well-tolerated oral therapies. The Phase I healthy volunteer study is designed to evaluate single and multiple ascending doses of KT-579 with the objective of achieving more than 90% IRF5 degradation in blood at doses with a favorable safety profile. We will also assess PD activity using ex vivo stimulation assays to understand the impact of IRF5 degradation on key inflammatory pathway biomarkers upregulated by TLR 7, 8 and 9 agonists, including type 1 interferons, pro-inflammatory cytokines and inflammatory pathway gene transcripts. We have guided that is our expectation that we should see between a 50% and 80% reduction in these biomarkers across the 3 TLR pathways assessed if we are engaging IRF5 effectively, which would suggest the potential for IRF5 degradation translating into clinical activity in subsequent patient study with KT-579. Looking ahead, we plan to advance KT-579 into a study in lupus patients soon after the healthy volunteer study is complete. Despite recent scientific advances, most lupus patients continue to cycle through therapies without achieving sustained disease control, underscoring the need for differentiated treatment approaches. Before I wrap up my remarks, I'd like to briefly highlight a few additional leadership updates. We're pleased to announce that at our recent annual meeting, Felix Baker has assumed the role of Chairman, succeeding Bruce Booth. Felix has been a member of our Board since 2024, and we look forward to his continued leadership and partnership. We are also grateful for Bruce's many contributions since our founding, and we're pleased that he continues to serve on the Board as a Director. We also recently welcomed Penny Carlson to lead our development operations and Liz Laws as global program lead for KT-621. Penny joined Kymera after a long and successful career leading global clinical development, most recently at Takeda. Liz joins us from Sanofi, where she was highly involved in the development of dupilumab. Both Penny and Liz bring extensive experience leading complex clinical development programs with direct relevance to Kymera. And their expertise will be invaluable as we advance our pipeline and continue building the capabilities needed to support a growing late-stage clinical portfolio. And last but not at least, as mentioned earlier in the call and disclosed last week, I could not be more excited to introduce Terence as Kymera's new Chief Medical Officer. Terence joins Kymera with what can only be described as the ideal set of experiences, expertise and knowledge as we continue on this journey to transform the immunology market. He held senior leadership position at J&J, Eli Lilly, where he helped build and advance leading immunology franchises, including Icotyde, Stelara and TREMFYA. His extensive experience across clinical development and portfolio strategy is highly complementary to Kymera and will help guide the continued advancement of our pipeline. I want to allow Terence to share a few thoughts with you, and we will also have him join the Q&A. Terence?

Thank you, Nello. I'm excited to be joining Kymera at such an important time in the company's evolution. With multiple programs advancing across the portfolio and significant opportunities ahead, it's a privilege to be part of the team as we enter this new chapter. By way of background, I've spent some 17 years in the biopharma industry, focused on the development of treatments for immune-mediated inflammatory disease. Most recently, I served as the Head of Portfolio and Asset Management for Immunology at Johnson & Johnson, where I led strategy and asset development for a broad immunology portfolio. Prior to that, I've spent time throughout the pharma R&D value chain, including stints in early and late-stage clinical development, in business development and end-to-end R&D leadership. Before biopharma, I spent 12 years as a physician in academic clinical practice and research, specializing in rheumatology and internal medicine. So I've had the chance to work across academic medicine, translational research and global pharmaceutical R&D, all focused on advancing innovative therapies from concept through clinical development to approval and beyond. What drew me to Kymera is the opportunity to help unlock the potential of targeted protein degradation to transform the treatment of disease. The science is highly compelling. The pipeline is strong, and I'm joining a great team that I'm convinced is well positioned to deliver meaningful innovation for patients. To wrap up then, I'll echo what Nello said earlier about KT-621. Kymera STAT6 program represents a truly transformational opportunity, not only for the company, but most importantly, of course, for human health. And I couldn't be more excited to be joining and to help Kymera fully realize the potential of this and our other assets.

Thank you, Terence. In conclusion, with KT-621 advancing through Phase 2b development and KT-579 expected to enter its first patient study shortly, we're sharply focused on building the team and capabilities needed to execute potentially more than 10 Phase III studies over the next 2 to 3 years. We have also begun building our commercial capabilities to deliver on our vision of becoming the global leader in innovative oral immunology medicines. Importantly, we're doing all of this from a position of financial strength. With a robust balance sheet and cash runway extending into 2029, we're well capitalized to advance our pipeline. Looking back to the first half of the year, we've executed across our portfolio from accelerating the development of KT-621 to advancing KT-579 while also progressing our preclinical pipeline and partner programs. With multiple catalysts ahead, we remain enthusiastic about the opportunities in front of us and look forward to sharing additional data and updates in the months ahead. With that, I will turn it over to Bruce to review the financial results before we open the call for questions. Bruce?

Thanks, Nello. As I walk through the second quarter results, please refer to the tables included in the press release, which was issued earlier this morning. Collaboration revenue for the second quarter of 2026 was $65 million, reflecting a $45 million option exercise fee related to the company's collaboration with Gilead Sciences and a $20 million milestone payment associated with Sanofi starting the Phase I study for KT-485. We have recognized all deferred revenue, so we do not expect additional revenue this year. Any future revenue will be tied to milestones achieved in either the Sanofi or Gilead collaborations in 2027 and/or beyond. Turning quickly to operating expenses. R&D expenses for the quarter were $119.5 million, including approximately $10.4 million in noncash stock-based compensation. Excluding stock-based comp, adjusted cash R&D expense was $109.1 million, an increase of 22% compared to the first quarter of 2026, primarily reflecting continued investment across our advancing clinical portfolio. G&A expenses for the quarter were $21.1 million, including approximately $8.6 million in stock-based comp. Excluding stock-based compensation, adjusted cash G&A expense was $12.5 million, a decrease of 4% compared to the first quarter of 2026. We ended June with cash, cash equivalents and investments of approximately $1.5 billion, providing runway into 2029 and positioning us to execute on a number of important value-driving milestones over the coming years. Our balance sheet supports the completion of the KT-621 Phase 2b trials in AD and asthma and the progression of KT-579 fully through our planned proof-of-concept study in lupus. Within our runway, we also expect to fund the beginning stages of the asthma Phase III study for KT-621 and most of the KT-621 Phase III study in AD. At the same time, we will continue investing in our research pipeline and building the capabilities needed to support our transition into a later-stage development and commercial organization. Overall, we believe we are well positioned financially to execute on our strategic priorities while maintaining a disciplined approach to capital allocation. With that, we'll pause briefly while we make our way to the conference room and assemble the question queue, at which point, we'll open the call for Q&A.

[Operator Instructions] Thank you. Our first question is from Thomas Smith from Leerink Partners.

Congrats on all the progress. And let me add my best wishes to Jared in his retirement. Given the really strong enrollment here in BROADEN-2, I just wanted to come back and ask if there's any color you could provide on sort of the baseline characteristics for these patients that were enrolled into the study. Anything that you can say relative to some of the other large contemporary Phase III biologic studies would be helpful. And then just thinking about the bar for success for BROADEN-2. I know you characterized this as clinically efficacious and well tolerated, but just wondering if you can provide a little bit more specifics with respect to the profile relative to [ Dupi ] and what some of the injectables have shown and what maybe some of your market research is pointing to in terms of a clinically meaningful profile.

Thanks, Tom. I love you had 2 questions in one. So let's start with the first one. So baseline characteristic. Obviously, one of our main goal of the study, and as I mentioned earlier, and we've done it in the past, was to actually prioritize quality of execution over speed. And in fact, our initial time lines were actually reflecting those expectations. We expected that some of the systems we have put in place would kind of direct the speed of execution towards those kind of expected time lines. And obviously, with that, we still saw a pretty fast enrollment, which, again, we can comment, as I commented earlier, driven, we believe, based on -- driven by the excitement around the program, the oral opportunity, the data that we generated, et cetera. But going back to your first question, yes, the goal has been to ensure that we had the patient with the right severity on the study. As you know, when the first biologics in the space was developed, dupilumab at this point, I think Phase II was more than 10 years ago, there wasn't any approved systemic drug at that time for a broader population. So the severity of the baseline of those patients was probably higher than what we've seen in more recent studies. I think, again, all the things that we put in place was to ensure that while we believe it's difficult, if not impossible, to replicate that type of severity at baseline that the patient in our study would follow at least what has been seen in the past few years. So I'm not going to comment on where we landed because I think it's unnecessary, but you'll see when we release the data. But we feel good about where we landed with the baseline characteristics right now. On your second answer, the bar, I think there is maybe 2 ways to answer your question, and I'm sure this is a question from many others. So maybe I can be really good at answering it once. So the -- what we've learned, so when we started this program, obviously, we were very science focused, right? And we were showing for the first time ever that actually you can block STAT6 signaling through degradation of STAT6. And what we saw in our laboratories was basically a downstream blockade that mimic what we have seen with dupilumab. And so our kind of narrative and science around this program has continued over the years to kind of continue to demonstrate the science behind STAT6 degradation and how effective it is how effective it is to block IL-4 and 13. So what we obviously learned along the way by interacting with the medical community, including patients, is the really strong need of an effective oral therapy. That's the feedback we've continued to hear. This is the feedback we've heard. I've been in every investigator meeting. I visited -- I've been in every medical meeting. I've talked to a lot of KOLs myself. And really, the main consistent feedback we've heard is the really, really important need of an effective oral drug. And that's what we want to deliver patients. So we believe success, both clinically and commercially is to deliver what patients want, which is an effective, safe, well-tolerated oral option that right now doesn't exist. Not only it doesn't exist in AD, but actually does not exist across all these comorbidities. So that's, I think, maybe the North Star. Now when we go to the science of it, we've continued to see over the past 6-plus years that degrading STAT6 seems to be just as effective as blocking as I mentioned IL-4 and 13 as dupilumab. And so the data has shown both preclinical and early clinical that we seem to be able to block the pathway and affect the downstream biomarker as well as initial clinical endpoint in a similar way as dupilumab. So our, let's say, data expectation is we will continue to be in this study to be in that ballpark of what dupilumab has shown at week 16 in the previous AD studies, understanding that, obviously, different studies, different populations.

Our next question is from Tazeen Ahmad from Bank of America.

I wanted to ask about 579. I think that's an exciting potential next big drug for you guys. I wanted to understand what you're hoping to learn from the healthy volunteer data that you're expected to show in the fourth quarter, especially since you've already picked lupus to move into Phase 1b there.

Yes. So thanks, Tazeen. So we're very excited about the IRF5. This is, again, we believe, unless we're mistaken, I don't think so. This is the first drug targeting IRF5 that has gone in the clinic. And so as we've done in the past, we feel the responsibility to actually demonstrate the power of this biology. So the underpinning excitement is around the human genetics that tell us that when you have this point mutation or activation of IRF5, you see many of these subjects develop diseases like lupus, RA, IBD, et cetera. But actually, I would say even more importantly, what we've shown, where is this biology coming from, right? And so what we've shown in preclinical species is that actually it comes from the fact that IRF5 is a central node for 3 key pathways. It's B-cell autoantibodies production, it's inflammatory cytokines like 12, 23 TNF, et cetera, and it's type 1 interferon. And obviously, when this pathway is activated, and we believe in some of these diseases, it's extremely relevant, we see IRF5 being this master regulator of immunity. So in this Phase I healthy volunteer study, the kind of the necessary but not sufficient step is first to show that we can degrade IRF5 robustly, we're saying at least 90% or more and safely. And then I guess the next step will be to show that by blocking IRF5, we can modulate these 3 important key pathways. And we have -- the team has developed, we believe, some really good assays to actually measure all these pathways. And so we expect that while this is not a patient study, the fact that even in healthy volunteer, we can interrogate the relevance of these 3 pathways by blocking IRF5 signaling, I think, should give us the confidence to move into, as you say, lupus, but actually we're planning and discussing internally what other indications we could start as well in the relatively immediate future.

Our next question is from Andy Chen from Wolfe Research.

This is Jason taking for Andy. And I just wanted to ask if you guys have any plans around unveiling new degrader molecules maybe in the next year or 2? And how many molecules we should expect? And are they likely to continue to be in immunology indications or with like derisked mechanisms?

Yes. So obviously, we have a very productive research engine. And hopefully, this is also appreciated externally. We have a general goal/guidance of having at least one new molecule entering clinical development every year. And so we continue to be on track to have development candidates in 2026 that will be entering the clinic in 2027 and beyond. So for sure, we obviously want to be able to share more programs. Obviously, we have 2 important clinical readouts in the second half of the year in 4Q. So we're figuring out whether the next clinical program to be disclosed will be either this year or early next, again, based on everything that we're doing, that decision still to be made. Likely, obviously will happen because we're on track with these programs, but we're still deciding exactly what the timing will be. And 80% of our effort preclinically is in immunology. So it's extremely likely, it's not almost 100% sure that at least the next program, next couple of programs will be immunology program with highly validated target without oral options.

Our next question is from David Dai from UBS.

So regarding the STAT6 degrader KT-621, given the high placebo response we're seeing in some of the AD studies, what assumptions were used around placebo response and effect size when powering for the BROADEN-2 Phase 2b study? And have the recent enrollment dynamics changed your confidence around those assumptions?

Yes. I mean -- thanks, David. That's a great question. We're not going to go into the details of your question, although it's a very good one. So we understand the STAT6 biology well. We powered the study within a range of expectation of what this biology can deliver clinically also with the Phase Ib data in hand. We obviously know that the placebo rates have increased and we've accounted for that. Obviously, there has been a couple of cases where at least one where we had some crazy high placebo rate in the 70s. Obviously, no study can plan around such a high placebo rate. But otherwise, if you look at the recent studies that delivered, let's say, positive data in -- and we've seen many in the past few years actually. And we've seen increased placebo rates. Those have been accounted in the power of our study. The enrollment has not really changed. The speed of enrollment has not changed our assumptions. When you have a high enrolling study, you often end up enrolling slightly more than you plan just as the mechanics of the study will kind of force you to do. But we haven't done anything with regards to changing our power assumption.

Our next question is from Ellie Merle from Barclays.

Jasmine on for Ellie. Congratulations on all the progress. Can you give some more color on how enrollment is going in the Phase 2b asthma trial? So with the acceleration of the enrollment in AD, how should we think about whether we can see this in asthma as well? And what are, I guess, some of the different dynamics playing into the AD enrollment versus asthma that could attribute to why the time lines are shaping up to be different?

Thanks for the question. So I would say what is common between these 2 studies is the excitement around this mechanism. I think that, as I said earlier, one thing that might be appreciated or not is the fact that this pathway is really well understood by investigators all around the world, right? This is probably the most drug pathway in immunology, right? We have so many agents targeting IL-4, IL-13, both of them, et cetera. So I think that actually is a common theme of we understand the pathway. We as a team, I should say, have done, I think, an amazing job educating the public about our mechanisms and STAT6. So there is a level of confidence about where STAT6 fits in that pathway. And then you combine, let's say, the sense of, let's call it, comfort with our program and you combine it with, as I mentioned earlier, this really strong need of an oral option. I think what is common when we talk to both dermatology investigator and respiratory and allergist investigator, I think what's common is these kind of 2 aspects. Now the 2 studies are quite different, right? For the AD study, obviously, there are more AD patients, let's start there. And also, we are enrolling all moderate to severe patients. For the asthma study, if you recall, we had some specific criteria with regards to FeNO and eosinophilia at baseline, which is looking at a subset of asthma patients. I like to call them, we call them type 2 patients. Some people call them eosinophilic asthma patients. Anyway, that's maybe for another day. And so that is a subset of the asthma population. So naturally, the denominator is smaller in this case. And because we have this, again, very specific entry criteria, generally, we would see a higher screen failure rate. So while I think we have also in asthma an opportunity to move the program enrollment at a good fast speed, I don't think we can match what we've seen for atopic derm. But anyway, we are enrolling well. There's a lot of excitement. We're even in more regions than we were for the AD study. And so we're confident that we'll be able to deliver a fast but obviously, high-quality execution and within the time line that we set. In terms of changing time lines, as we've done for it, we're only going to do it if and when we complete or I should say, when we complete enrollment, but not before because these are highly variable parameters, and it's really difficult, high priority to start changing expectation time lines while you're [ in flight ] for these studies.

Our next question is from Brian Cheng from JP Morgan.

Just want to touch on the BROADEN2 OLE portion. Can you give us some color on the latest there? How is the rollover rate looking? And are patients allowed to dose adjust across the 3 doses in the OLE?

Yes. Thanks, Brian. Great question. So we're not going to comment on that. We might offer when we release the BROADEN2 data in the -- by the end of the year here in '26, we might maybe offer a bit of an insight on that. But right now, we feel it's too early to comment on how the percentage of patients rolling over into the OLE. So on the dose adjustment, I think we've said this publicly, patients are all going on to 1 dose. And I think I'll leave it at that for now.

Our next question is from Faisal Khurshid from Jefferies.

Congrats to Terence on joining a great team. I just wanted to ask your kind of latest and greatest thoughts on the competitive landscape. And I'm wondering both within the STAT6 class, like yesterday, we had Pfizer confirming that their STAT6 is active in Phase II and Nurix and Sanofi dosing their program. And then beyond that with bi and trispecific as well, we also heard some interesting comments on that yesterday as well. So yes, we would just love to hear your latest and greatest thoughts on that landscape.

Yes. So yes, I can share a few thoughts. So on the STAT6, I mean, as you know, this is a highly interesting targeted pursuit by I think probably at this point, majority of companies that are in immunology for all the reasons that we're all here today. So we -- our focus is obviously on execution and making sure that we execute with high quality and speed in order to maintain our -- the advantage that we've created in terms of time line. We know -- obviously, there is Pfizer in Phase II. We don't know much about their molecules. Obviously, there's been many flow of information from the study about starting and pausing enrollment and then restarting. There are other pilot studies ongoing to study the molecule, the formulations and DDI studies. So really, obviously, Pfizer, from what I can see from macro where I sit is trying to understand more about this molecule, the performance and the behavior in humans. I think they're reporting to complete the study in early '28, which seems like a very long time. So again, I don't know what that means. I can only go by what's publicly disclosed. As you know, we don't believe small molecule inhibitors will be competitive with degraders, driven by our ability with the degrader to block the pathway completely at very low doses and low concentration over 24 hours, which we believe is needed to match this pathway blockade that you see with upstream agents. Then yes, we've seen the Nurix, the Sanofi program starting. Again, I think we'll be in Phase III if everything goes well by the time some of this program might have some Phase I data. So we feel good about 621. I think so far, all I can say amazingly well-behaved molecule, well tolerated and we're focused really on ourselves, but being aware of the overall landscape. With regards to other mechanism, we're all -- we're really excited by our oral options. We're also excited about learning about new biology, right? I think the bispecific and trispecific is an opportunity for everybody to learn where some of these mechanisms can deliver enhanced activity in a still relatively heterogeneous population, which especially AD can be. So we're obviously -- there was some early data from a small company recently with a bispecific. Obviously, Pfizer is going ahead with this trispecific doing a head-to-head study with Dupi, which makes sense. I mean our view is, again, as I said earlier, KT-621 position is, from our perspective, first-in-line drug for the millions of patients that have moderate to severe atopic derm that are not doing well with topical steroids, which is probably the majority of patients given how difficult it is actually to be responding well to topical steroids. It's not even how they work. It's just how complicated it is for patients to use them. So if we think about 621 is the first-in-line drug, then I think many of these trial will probably be later lines once you don't respond to these, I think, single mechanism drug that address most patients, right, for in AD and other indications. So as we said also in the past, we're interested by novel mechanism. We're thinking about combination of STAT6 with other mechanisms. So we're obviously very curiously also observing these new mechanisms out there.

Our next question is from Brad Canino from Guggenheim.

Thanks to Jared for the collaboration over the past 5 years. I definitely learned a lot from our conversations. My question is about moving STAT6 to the late-stage development phase. How are you positioning the company to extend the benefit to pediatric AD patients? I know for Dupi, it took several years to expand the label from adults to different cohorts of pediatrics. Are you doing anything today with a goal to try to accelerate that?

Yes, Brad, thank you. So yes, we're heavily focused on how to accelerate pediatrics development. I mean the one thing that we've done, as you know, is incorporating adolescents in our study, right? We have 12 and up, which actually are pediatric patients. Now going younger in ages is obviously something we're not in full control of. This is a conversation with regulatory agencies. All I can tell you is that we're heavily focused on it, and we will update you all when we know more. For sure, we will know more after this Phase 2b data. You shouldn't expect any update between now and then.

Our next question is from Judah Frommer from Morgan Stanley.

Congrats to Terence and Jared as well on their moves. Just curious if you could help us with cash runway guidance remaining into 2029, given the acceleration in time lines for 621. Any changes to spend or trajectory over the next couple of years as you think about that?

Yes. No, thanks for the question, Judah. I think it's still intact. We had a runway into 2029. Even with the acceleration of timing, it's not enough to pull the runway in closer. So we're still into 2029 with that. So you can assume there has been a bit of cushion there as well. I think clearly, as we get to the end of the year and see the data and I guess, solidify all of our development plans, not only for the core indication, but some of the others that we're contemplating, we'll talk about whether there's an update warranted. But we're in good shape over kind of 10-plus quarters of cash even with the accelerated runway. So we should be able to -- as we said in the past, we -- our runway will incorporate, obviously, all the Phase IIs that we're running -- the Phase II is running today, the full execution of the IRF program and then as well getting underway with both the Phase IIIs, and we should come pretty close to finishing the AD study within our runway if all goes well.

Our next question is from Geoffrey Meacham from Citi.

I just want to say congrats to Jared on the retirement and Terence, welcome to the team. So Nel, on 621, as you guys look to Phase III design in AD and asthma, I guess how important is the washout or prior therapy experience? I know there are multiple pathways that drive type 2 inflammation beyond STAT6, but are some sort of tilted pathways more heavily treated patients or maybe patients have gone for a longer duration or maybe those that have worse baseline. Just trying to think of like the entry criteria and kind of the probability of success as you look to a Phase III.

Yes. No, Geoff, that's a great question. It's actually a topic of discussion. I just want to separate the 2. So obviously, the washout is critical, right? No matter what the entry criteria are, how you parse out whether you're going to allow every previous biologic patients or not. Obviously, based on the half-life of the drug, you need to completely wash out patients to actually retain the integrity of the data of the study. Then maybe the other question in your question was, do we allow a biologics experience patient in the study. And as you know, we've done that in our Phase 2b with a caveat of not aligning the nonresponders, previous nonresponders to this drug. But for Phase III, I think it's a topic that we're still discussing. Obviously, we need regulatory interactions as well. But we expect that in some shape, biologics experienced patients will be part of our Phase III study. There's just some nuance about what was their experience on biologics that we might have some kind of criteria around. But that's still something that we're discussing both internally and we'll have to align with regulatory agencies.

Our next question is from Derek Archilla from Wells Fargo.

Jared, good luck in the next chapter. Terence, welcome. So just actually following up on a prior question on the pediatric development. Are there any gating factors to a sprinkle formulation of 621? And I guess, how would you frame the pediatric opportunity relative to adolescents and adults?

Well, we actually had a 5-year-old child at Kymera a few weeks ago with their parents -- with his parents talking about the life of a child on an injectable biologic. I wouldn't say which one. It's not that difficult to guess. And I think he crystallized for us what it is that these kids have to go through and what is the -- not only the opportunity, but I would say the responsibility to deliver for children an easy to take, effective and hopefully, obviously well-tolerated drug. So we are doing, as I mentioned, all we can. From a formulation perspective, we actually are in a very good place already. Again, I don't want to talk about specifics about what is it that we need to go into younger patients. And then it's really about when we will be allowed to do -- to run those studies. And as I mentioned earlier, obviously, having data from a global placebo-controlled randomized Phase II study, especially with regards to both efficacy and safety, we feel is the important data set to initiate those discussions with regulatory agencies. But all I can tell you is from Kymera perspective, we will be ready to go as soon as we have completed this study.

Our next question is from Alex Thompson from Stifel.

Congrats on all the progress. I appreciate you taking the question. Maybe another one. Nello, I'm not sure you will answer, but I just wanted to ask about -- you've had a lot more experience now dosing patients to 16 weeks plus across AD and asthma. Can you comment at all about blinded safety and your confidence in the continued clean profile of 621 heading into the data later this year?

Yes. No, thanks, Alex. It's a great question. I think you get it right. It's hard for us to comment on ongoing study blinded safety. So it's only actually a few months away where we can actually all look at the unblinded data and then share it with you. So just a little bit of patience. I feel the same way. I like to know everything, but we have to wait.

Our next question is from Jeff Jones from Oppenheimer.

Congrats, Jared, and welcome, Terence. Question on the IRF5 program with KT-579. As you look at those results coming late this year, is there anything that will guide you towards or away from particular indications beyond lupus?

Yes, great question. So we have this translational hypothesis around KT-579 around being this master regulator of 3 pathways when IRF5 is activated. So B-cell type 1 interferon and some of these inflammatory cytokines. I think if we don't see a profile that reflects our understanding of this biology, obviously, we will have to rethink what is our clinical strategy besides the translational one. I would be surprised if we are surprised by the data, but we'll see. I think we'll have to see what the biomarker data looks like.

Our next question is from Biren Amin from Piper Sandler.

It's interesting in your slide deck, you mentioned that the BROADEN2 trial data could support trials in GI indications. So now, I wanted to kind of understand that. What data from BROADEN2 could support development in GI? And also, is the interest in GI due to STAT6 activation in ulcerative colitis? And since I'm talking about GI, would you potentially look at IRF5 and IBD given the expression of IRF5 in IBD. And I think there's some proof-of-concept data with anti-TNF reducing IRF5 in IBD.

Biren wins. He asked 3 questions. So quickly, so what we mean -- so you caught an important point actually that requires a nuance on our slide. So first of all, when we talk about the GI, we talk about EoE, eosinophilic esophagitis, which actually should not even default the eosinophilic, but that's another point. So for that, the question is how is the Phase II study going to help us. So we believe the Phase III dose that we will get from the AD study should be applicable in all the other derm indications. Could be directly be applicable to EoE but maybe or maybe not. And actually, for EoE, we might have a slightly different plan, which we will be disclosing at some point after the Phase 2b data next year. So it will definitely be informed, but the development in EoE might not be the same as we might do for CSU and other derm indication. For IRF5, we're definitely interested in IBD. We have shown some really exciting preclinical data. So stay tuned as we share more information on that.

Our next question is from Brian Abrahams from RBC Capital Markets.

This is Kevin on for Brian. So maybe another one on 579. Just as you think more about lupus, the heterogeneity of the disease and just maybe some of the challenges prior agents have had and novel ones, which could be approved in the next few years. Just what are your latest thoughts on sort of what the addressable opportunity could be in lupus? And would the ambition here also be to have biologic-like efficacy? Or is this paradigm sort of a little bit more complicated or more nuanced than what we typically think about with 621 in atopic derm?

So maybe I'll start and given that Terence is a trained rheumatologist, maybe you can help me on this one. So the quick answer from me who I'm not a trained rheumatologist is that what we're seeing in lupus is what the patients need, which is our effective therapy that are acutely needed in this population. So I think we need different mechanisms. We need different options. The reality is there are no good right now oral options approved. There are some interesting ones in clinical development. So I think we believe that we can, again, continue to serve patients that want effective oral options. Terence, is anything you want to add on this space in general?

Yes. Thanks, Nello, and thank you, Brian. I would just underscore that, yes, there remains tremendous unmet need in lupus, including for oral medicines with a favorable benefit risk profile. Brian, you flagged the challenges of lupus drug development. That's absolutely acknowledged. Key to that is going to be patient selection, site selection, careful trial design and careful oversight. So you can imagine that's exactly what we're working through at the moment.

Our next question is from Mark Frahm from TD Cowen.

Congrats, Jared, on a great career at Kymera and best wishes for the next step. This is mostly for Terence. The company kind of talked in broad strokes about being interested in combinations across the pipeline, but STAT6 and IRF5. But obviously, Terence at your prior job, that was a big push early on. So what do you think -- how do you view the optimal time to start those? What do you need to see from some of these earlier trials to really kind of start working on combinations?

Thanks, Mark, and thanks for the welcome. I think you're right. There's tremendous opportunity combining established mechanisms in particular, in pursuit of greater efficacy. Now I had some remarks earlier on about the field there, and we're learning as we go. In some instances, we have combinations that have altered. And in recent instances, we've seen some encouragement. I think the learning, therefore, for an oral drug developer is which combinations in the future might be rational for somebody like ourselves to developing an asset against one proven target. And I'll probably leave it there in terms of when to decide to combine STAT6 with another oral asset, but safe to say that it's a topic we're looking at carefully.

Does it need to be oral to be interesting? Or would you be interested in novel combinations that maybe aren't all oral?

Maybe I can help there. I mean I think it depends on what we're trying to do, right? I think there is a biological understanding of synergies or additivity and then there is like market positioning. We continue to believe that advancing oral options for patients is where the future needs to go towards. Would there be a case where we try to understand the mechanism with an injectable biologic? That might happen. But I'm not sure that's our North Star right now.

Next question is from Jeet Mukherjee from BTIG.

Just for the BROADEN data that's coming up by year-end, could you comment if there's a cap on the number of patients who are on prior biologics? And will you ultimately break out the data by patients who are on prior biologics versus those who are not?

No cap on prior biologics. With regards to how we break out the data, we'll have to analyze the data. So let's wait on that.

Our next question is from Mayank Mamtani from B. Riley Securities.

Best wishes to Jared and look forward to working -- getting to know Terence. So on the BROADEN2 program, if you could comment on what proportion of patients come from maybe ex U.S. or specifically Eastern Europe sites. And sorry if I missed the screen failure rate. I don't know if you commented on that, Nello, and how that's maybe similar or different than recent biologic trials? And if your expectation as an oral pill would be for discontinuation rates to be actually better than the biologics, if you could comment on that. And then just on timing, just clarifying last patient in was before the end of 2Q. So can the 4-month efficacy data drop maybe ahead of the IRF5 program? Or they're both tracking in parallel? Or how do you plan to have that disclosure?

Yes. Maybe I'll start with the last one. I think it's extremely likely that we'll have IRF5 data first, and then we'll have the BROADEN2 data. With regard to many of the other questions, I'm not going to -- all I can say our sites, as you know, you can look at it now on clinicaltrials.gov, there's a global presence. There is U.S., Canada, Australia, Japan, South Korea, Europe. So the majority of patients will obviously come from outside of the U.S. But we have a big -- obviously, expected big U.S. presence. I'm not going to be able to go into like a breakdown of patients at this point. I don't think we're not going to comment on screen failure rates. We might, when we release the data, be thoughtful to anybody, maybe our competitors. And then we'll talk about some of the other points you made about discontinuations, et cetera, when we release the data.

Could you comment -- sorry, for one follow-up, if I may. Could you comment on when you plan to have an end of Phase II discussion focused on AD? And would that need to wait until the asthma data?

No, we'll have an end of Phase II meeting with the FDA, obviously, as soon as we can after we have Phase 2b data in AD. So yes, no, we will not wait for the asthma data.

Our next question is from David Hoang from Deutsche Bank.

So I just want to ask, to what extent could we look at the ongoing launch of the oral IL-23, which is Icotyde in psoriasis as an analog for how commercialization of KT-621 in atopic derm might go. So what lessons can we learn there? And what reasons would that be or not be a good [ comp ] for KT-621?

Yes. Obviously, we have Terence here that was obviously involved in that program. So he probably will have a lot to say that he can even say. But what I will say is that I think what is in common is the fact that from where I sit, IL-23 peptide is a validated mechanism with a novel way of dragging in that particular target or pathway with a molecule that I believe has actually behaved quite well in terms of efficacy and safety and is showing that even in a saturated market. I guess the difference is the market, right? Psoriasis is a -- I think from a point of view, a much more mature market with several drugs that have been approved over the years, several biologics, several orals. And even with all of that, you're seeing some really impressive adoption of that drug. I think in the first quarter, there are more than 100,000 patients on the drug, if I'm not wrong. So with KT-621, hopefully, right, I think that what we can match is the ability to drive efficacy and safety of an oral drug in a validated pathway. And I think what's different is that AD is a very early immature market with very low penetration overall. And I think our expectation is that we should be able to launch the drug and have even a superior success than Icotyde is seeing if we do a good job and if we obviously retain the profile that we want because there are so many patients that don't have any oral safe options, while for psoriasis, I think there are oral effective and safe drugs that maybe the Icotyde is slightly better, but still there are options there while in AD, there are no options.

There are no more questions at this time. I'd now like to turn the call over to Nello for closing remarks.

Well, I want to thank everybody for attending our call, all the analysts for attending and asking questions even in the -- we're in the middle of the summer. So we appreciate you taking time away from your vacation, if you are. And we continue to be super excited about where we're going. Please stay tuned. We're going to have some of the most interesting data set probably for the industry in the second half of the year, given these are both kind of first-in-class program in highly super relevant indications or population. So stay tuned and look forward to seeing many of you in our conference in September and then after that at our calls to disclose the data. Thank you.