Kymera Therapeutics, Inc.

Good day, everyone. My name is Shell and I will be your conference operator today. At this time, I would like to welcome you to the Chimera Therapeutics second quarter 2026 results call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, and if you have joined via the webinar, please use the raise hand icon, which can be found at the bottom of your webinar application. If you have joined by phone, please press star nine on your keypad to raise your hand. At this time, I would like to turn the call over to Justine Koenigsberg, Vice President, Investor Relations.

Justine, please go ahead. Good morning and welcome to Chimera 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 Gollub and Terrence 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 one 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 eight years. Jared has been instrumental in helping build Chimera 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 there is 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 Chimera, thank you, Jared. We wish you 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 certainly 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 eight years at Chimera. This is obviously an exciting time for Chimera, 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 advisor through year end to help with the transition as needed. But I am 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 Chimera 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 enter 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 a long-term strategy. At Chimera, 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 six months ahead of schedule. As a result, we now expect to report top-line data by year-end 2026 and to initiate Phase 3 development around mid-2027, both approximately six months earlier than previously planned. We view the rapid enrollment as a reflection of many factors, including the compelling preclinical and Phase 1b AD data generated to date, 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 doubt 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 remained 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 one study of KT579, an oral IRF5 degrader. We believe IRF5 represents a highly compelling target in our immune diseases with the potential to address multiple high value indications. We expect to report Phase 1 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, KT485, our second-generation IREC4 degrader partnered with Sanofi, recently entered Phase 1 development, resulting in a $20 million milestone payment to Chimera. The Phase 1 is designed to evaluate KT485 in both healthy volunteers and patients with Hidrotonitis separativa, 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, KT200, partnered with Gilead, advance towards an expected IND and clinical start next year. Taken together, 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 and other shareholders. Turning more specifically now to KT621, 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 KT621. As a reminder, the study is evaluating three doses of KT621 compared to placebo. The primary endpoint is percent change from baseline in EASY score in week 16. Key secondary endpoints include EASY50, EASY75, VIG801, 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're developing KT621 to deliver on 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 US, 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 KT621. 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 KT621 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. These will represent a powerful tool for physicians in position KT621 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 ADS conference. Importantly, we hear consistently from KOLs that a well-tolerated oral therapy delivering clinically meaningful benefit could address a significant need and expand treatment options for a broader population of moderate to severe patients. Enrollment is underway in the BREATH Phase 2b trial, and we remain on track to report top-line data by late 2027. As we continue to advance KT621 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. were 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 KT621 for up to an additional 52 weeks. Taken together, we believe our development strategies across both AD and asthma positions us, once these two studies are completed, to fully explore the broad potential of KT621 across our dermatology and respiratory diseases in later stage trials. Now, turning to KT579, oral RF5 degrader, we remain on track to report top-line data from the ongoing Healthy Volunteer Study in the fourth quarter of 2026. As a reminder, RF5 is a genetically validated driver of innate immunity dysfunction and inflammation and is implicated across multiple autoimmune diseases, such as lupus and IBD. KT579 seeks to control a challenge that has been elusive among traditional drug development approaches in this space. By selectively degrading IRF5, KT579 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. Phase 1 Healthy Volunteer Study is designed to evaluate single and multiple ascending doses of KT579 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 TLR7, 8, and 9 agonists, including type 1 interferons, pro-inflammatory cytokines, and inflammatory pathway gene transcripts. We have gathered that it is our expectation that we should see between a 50% and 80% reduction in these biomarkers across the three TLR pathways assessed if we're engaging IRF5 effectively, which would suggest the potential for IRF5 degradation translating into clinical activity in subsequent patient study with KT579. Looking ahead, we plan to advance KT579 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 welcome Penny Carson to lead our development operations and Liz Laws as global program lead for KT621. Penny joins Chimera 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 Chimera, 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 least, as mentioned earlier in the call and disclosed last week, I could not be more excited to introduce Terence as Chimera's new Chief Medical Officer. Terence joins Chimera 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 and Lilly, where he helped build and advance leading immunology franchises, including Ecotide, Stellar, and Tramphya. His extensive experience across clinical development and portfolio strategy is highly complementary to Chimera and will help guide the continued advancement of our pipeline. I wanted 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 Chimera 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 Chimera 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 KT621. Chimera's 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 Chimera fully realize the potential of this and our other assets.

Thank you, Terence. In conclusion, with KT621 advancing through Phase IIb development and KT579 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 two to three years. We've 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 accelerated the development of KT621 to advancing KT579, 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 Santa Fe starting the phase one study for KT485. We have recognized all deferred revenue, so we do not expect additional revenue this year. Any future revenue would be tied to milestones achieved in either the Santa Fe or 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 non-cash stock-based compensation. Excluding stock-based comp, adjusted cash R&D expense was $109.1 million, an increase of 22% Thank you for joining us today. 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 KT621 phase 2B trials in AD and asthma and the progression of KT579 fully through our plan proof of concept study in lupus. Within our runway, we also expect to fund the beginning stages of the asthma phase 3 study for KT621 and most of the KT621 phase 3 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. Thank you.

Thank you. At this time, if you would like to ask a question, please click on the raise hand button, which can be found on the black bar at the bottom of your screen. If you have joined by phone, please press star nine on your keypad to raise your hand. When it is your turn, you will receive a message on your screen inviting you to join as a panelist. Please accept and wait until you are promoted to panelist. Please unmute your audio, turn on your camera and ask your question. As a reminder, we are allowing analysts one question today. We will pause now a moment to assemble the queue. Our first question is from Thomas Smith from Learing Partners. Please unmute your line.

Hey, guys. Good morning. Thanks for taking our questions. Congrats on all the progress. And let me add my best wishes to Jared in his retirement. Given the really strong enrollment here in De Brogdon II, just wanted to come back and ask if there was 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 Thanks, Tom.

I love you had two questions in one. So let's start with the first one. So baseline characteristic. Obviously, you know, 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 timelines were actually reflecting those expectations. We expected that some of the systems we had put in place would kind of direct the speed of execution towards those kind of expected timelines. 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, the pilumab at this point, I think phase two 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 that's 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 severities at the 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 two 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 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 mimicked what we had seen with Dupiluma. And so our 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've visited, you know, 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 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 six plus years that degrading STAT6 seems to be just as effective at blocking, as I mentioned, A4N13 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 the similar way as dupilumab. So our, let's say, data expectation will continue to be in this study to be in that ballpark of what dupilumab has shown at week 16 in the previous 8D studies. Understanding that, obviously, different studies, different populations. Super helpful. Thanks, Al. Thanks, Al.

Thank you. Our next question is from Tasin Ahmad from Bank of America.

Hi, guys. Good morning. Thanks for taking my question. I wanted to ask about 579. I think that's an exciting potential next big drug for you guys. 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.

Yeah, so thanks, Justine. 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, you know, point mutation or activation of RFI, you see many of these subjects develop diseases like lupus, RA, IPD, etc. 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 three key pathways. It's B-cell autoantibodies production, it's inflammatory cytokines like 12, 23, TNF, et cetera, and it's a type one interferon. and obviously when this pathway is activated and we believe in some of these diseases is extremely relevant, we see RFI being this master regulator of immunity. So in this phase one healthy volunteer study, the kind of the necessary but not sufficient step is first to show that we can degrade RFI robustly, we're saying at least 90% or more and safely. And then I guess the next step would be to show that by blocking IRF5, we can modulate these three 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 three pathways Thank you. Our next question is from Andy Chen from Wolf Research. Please unmute your line and ask your question.

Hi, good morning. Thank you so much for taking my question. This is Jason taking it 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 two, and how many molecules we should expect, and are they likely to continue to be in immunology indications or with the risk mechanisms? Thank you.

Yeah, so obviously we have a very productive research engine and hopefully this is also appreciated externally. We have a general goal slash 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 two 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 There's that decision still could 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 pre-clinically is in immunology. So it's extremely likely if it's not almost 100% sure that at least the next program, next couple of programs would be immunology program with highly validated target without oral options.

Thank you so much. I appreciate it.

Thank you. Our next question is from David Dye from UBS.

Hi, everyone. Thanks for taking my questions. So regarding the STAS6 degrader KT2 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 BRDN2 in a Phase IIb study? And, you know, have the recent enrollment dynamics changed your confidence around those assumptions?

Yeah, 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 1b 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, or 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, you know, 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. You know, when you have a high-enrolling study, you often end up enrolling slightly more than you planned, 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 assumptions.

Thank you so much.

Thank you. Our next question is from Ellie Mill from Barclays. Please go ahead.

Hi, Jasmine on for Ellie. Thank you for taking our question and congratulations on all the progress. Can you give some more color on how enrollment is going in the Phase IIb asthma trials? 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 contribute to why the timelines are shaping up to be different?

Thanks. Thanks for the question. So I would say what is common between these two studies is The excitement around this mechanism. I think, 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. This is probably the most drug pathway in immunology. We have so many agents targeting IL-4, IL-13. Both of them, etc. So I think that actually is a common theme of we understand the pathway. We, the 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, this 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, you know, these two aspects. Now, the two 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 have some specific criteria with regards to Pheno and Eosinophils at baseline, which is looking at a subset of asthma patients. I like to call them, we should all call them type two patients. Some people call them 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 a topic term. 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 timeline that we set. In terms of changing timelines, as we've done for AD, 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 timelines while you're in flight for the studies.

Yeah, helpful. Thank you.

Thank you. Our next question is from Brian Cheng from JP Morgan. Please go ahead.

Hey, guys. Thanks for asking a question this morning. Just want to touch on the BRDN2 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 three doses in the OLE? Thank you.

Yeah, thanks, Brian. Great question. So we're not going to comment on that. We might offer, when we release the BRDN2 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 one dose. And I think I'll leave it at that for now. Great. Thank you.

Thank you. Our next question is from Faisal Khurshid from Jefferies. Please unmute your line and go ahead.

Hey guys, thank you so much for taking the question and congrats to Terrence and 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 two and Nurex and Sanofi dosing their program. And then beyond that with buy and try specifics as well, we also heard some Interesting comments on that yesterday as well. So yeah, we'd just love to hear your latest and greatest thoughts on that landscape.

Yeah, so yeah, I can share a few thoughts. So on the STAT6, I mean, as you know, you know, this is a highly, highly interesting target pursued by, I think probably at this point, you know, majority of companies that are in immunology for all the reasons that we're all here today. Our focus is obviously on execution and making sure that we execute with high quality and speed in order to maintain are the advantage that we've created in terms of timelines. We know, obviously, there is Pfizer in phase two. We don't know much about their molecules. Obviously, there's been many flow of information from their study about starting, then pausing enrollment, and then restarting. There are other parallel studies ongoing to study the molecule, the formulations and DDI studies. So clearly, obviously, Pfizer, from what I can see from 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 a degrader to block the pathway completely at very low doses and low concentration over 24 hours, which we believe is needed to match these pathway blockade that you see with upstream agents. Then, yes, we've seen the Nurex, the Sanofi program starting again. I think we'll be in phase three if everything goes well. by the time some of this program might have some phase one data. So we feel good about six to one. I think so far all I can say is amazingly well-behaved molecule, well-tolerated, and, you know, we're focused really on ourselves, but being aware of the overall landscape. With regards to other mechanisms, we're all, you know, we're really excited by our options. We're also excited about learning about new biology, right? I think the bi-specific and trans-specific is an opportunity for everybody to learn where some of these mechanisms can deliver enhanced activity in a still relatively heterogeneous population, which especially AB can be So, you know, we're obviously, you know, there was some early data from a small company recently with a bispecific, obviously Pfizer is going ahead with this tri-specific, doing a head-to-head study with DUPI, which makes sense. I mean, our view is, again, as I said earlier, KD621 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 6 to 1 as the first in line drug, Then, you know, I think many of these buy and try will probably be later lines once you don't respond to these, you know, I think single mechanism drug that address most patients, right? for NAD and other indications. So we said also in the past, we're interested about novel mechanisms. We're thinking about combination of statistics with other mechanisms. So we're obviously very curiously also observing these new mechanisms out there. Awesome. Thank you so much.

Thank you. Our next question is from Brad Canino from Guggenheim. Please go ahead.

Hey, good morning. Thank you. And thanks to Jared for the collaboration over the past five years. I've 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 Doopie, 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? Thank you.

Yeah, 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 pediatrics 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. Thank you.

Thank you. Our next question is from Judith Frommer from Morgan Stanley. Please go ahead.

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

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 had been a bit of a 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. We're kind of 10 plus quarters of cash, even with the accelerated runway. So we should be able to, as we said in the past, our runway will incorporate obviously all the phase twos that we're running, the phase twos we're running today, the full execution of the IRF program, and then as well, you know, getting underway with both the phase threes and we should come pretty close to finishing the AD study within our runway if all goes well. Great, thanks.

Thank you. Our next question is from Jeff Mecham from Citi. Please go ahead.

Hey, guys. Thanks for the question. I just want to say congrats to Jared on the retirement, and Terrence, welcome to the team. So Nello, on 621, as you guys look to phase 3 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 stat 6, but are some sort of tilted pathways more heavily treated patients, or maybe patients that bond for a longer duration, or maybe those that have worse baseline. I'm just trying to think of the entry criteria and the probability of success as you look to a phase three. Thanks.

Yeah. No, Jeff, that's a great question. It's actually a topic of discussion. I just want to separate the two. So obviously, the washout is critical, no matter what the entry criteria are, how you 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 experienced patient in the study? And as you know, we've done that in our phase two B with the caveat of not allowing the non-responders, previous non-responders to this drug. But for phase three, 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 would be part of our phase three studies. There is just some nuance about what was their experience of 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. Thank you.

Thank you. Our next question is from Derek Akila from Wells Fargo. Please go ahead.

Hey, good morning. Thanks for taking the questions. And Jared, good luck in the next chapter. Terrence, welcome. So just actually following up on a prior questions 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? Thanks.

Well, you know, we actually had a five-year-old child at Chimera a few weeks ago with his parents talking about the life of a child on an injectable biologic. I won't say which one. It's not that difficult to guess. And I think it 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 run those studies. And as I mentioned earlier, obviously having data from a global placebo control randomized phase two 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 Chimera perspective, we will be ready to go as soon as we have completed this study. Great. Thanks, Noah. Thank you.

Thank you. Our next question is from Alec Thompson from Stiefel. Please go ahead.

Hey, great. Congrats on all the progress. Appreciate you taking the question. You know, maybe another one. No, I'm not sure you will answer, but I just wanted to ask about, you know, you've had a lot more experience now dosing patients to 16 weeks plus across AD and asthma. You know, 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? Thanks.

Yeah, no, thanks Alex. It's a great question. I think you get it right. It's hard for us to comment on ongoing study of blinded safety. So, you know, 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. Awesome. Thank you. Thanks, Alex.

Thank you. Our next question is from Jeff Jones from Oppenheimer. Please go ahead.

Good morning, guys, and congrats, Jared, and welcome, Terrence. Question on the IRF5 program with KT579. As you look at those results coming late this year, is there anything that'll guide you towards or away from particular indications beyond lupus?

Yeah, great question. So, you know, we have this translational hypothesis around KT579, around being this master regulator of three 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 Thank you. Our next question is from Birim Amin from Piper Sandler.

Yeah. Hi, guys. Thanks for taking my questions. It's interesting in your slide that you mentioned that the broadened to trial data could support trials in GI indications. So, Nello, I wanted to kind of understand that. What data from BRDN2 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. Thanks.

All right. Byron wins. He asked three questions. So quickly, So what we mean by, 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 esophageitis, which actually should not even be called eosinophilic, but that's another That's another point. So for that, the question is, how is the phase two study going to help us? So we believe the phase three dose that we will get from the AD study should be applicable in all the other term indications. Could be directly be applicable to EOE. Maybe or maybe not. And actually for EOE, Great, thank you.

Thank you. Our next question is from Brian Abrahams from RBC Captain Markets. Please go ahead.

Hi, team. This is Kevin on for Brian. Thank you for taking our questions. 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 and atopic derm? Thank you.

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 What we're seeing in lopals 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. I think we believe that we can, again, continue to serve patients that want effective oral options. Terence, anything you want to add on this space in general?

Yeah, thanks, Nello, and thank you, Brian. I would just underscore that, yeah, 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. Thanks, Aaron.

Thank you. Our next question is from Mark Fram from DD Cowan. Please go ahead.

And thanks for taking my questions and congrats, Jared, on a great career at Chimera and best wishes for the next step. This is mostly for Terrence. Companies kind of talk in broad strokes about being interested in combinations across the pipeline, but STAT6 and IR5. But obviously, Terrence, at your prior shop, 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 and oral drug developers, which combinations in future might be rational for somebody like ourselves who's developing an asset against one proven target. 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. All right. Thanks, Mark.

Next question is from Jeet Mukherjee from VTIG. Please go ahead.

Great, thanks for taking the question. Just for the broad end 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? Thanks.

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.

OK, great. Thank you.

Thanks.

Thank you. Our next question is from Mayank Mamthani from Be Right, Leave Securities. Please go ahead.

Yes, good morning, team. Thanks for taking our questions and best wishes to Jared. I'll be missed and look forward to working, getting to know Terrence. So on the Broaden2 program, you know, if you could comment on what proportion of patients come from maybe ex-US 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 four-month efficacy data drop maybe ahead of the IRF-5 program, or they're both tracking in parallel? Or how do you plan to have that disclosure?

Yeah, maybe I'll start with the last one. I think it's extremely likely that we'll have IRF-5 data first, and then we'll have the broadened-to data. With regard to many of the other questions, you know I'm not gonna all I can say are sites you know as you know you can look at it now on clinicaltry.gov there's a global presence there is US, Canada, Australia, Japan, South Korea, Europe so the majority of patients will obviously come from outside of the US but we have a big obviously as expected big US presence I'm not going to be able to go into like and so on. And then we'll, you know, we'll talk about some of the other points you made about these continuations, 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 two discussion focused on ATD and would that need to wait until the asthma data? Thank you.

Oh no, we'll have an end of phase two meeting with the FDA obviously as soon as we can after we have phase two B data in ATD. So yeah, no, we will not wait for the asthma data.

Thank you. Our next question is from David Hoang from Deutsche Bank. Please unmute your line and go ahead.

Hi there. Good morning. Thanks so much for taking my question. So I just want to ask, to what extent could we look at the ongoing launch of the oral IL-23, which is Icatiid and psoriasis as an analog for how commercialization of KT621 in atopic derm might go? So what, you know, what lessons can we learn there and what reasons, you know, would that be or not be a good comp for KT621? Thanks so much.

Yeah, obviously, we have Terence here that was obviously involved in that program. So he probably will have a lot to say that he can't even say. But what I will say is that I think what is in common is the fact that from where I sit, the R23 peptide is a validated mechanism with a novel way of dragging 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 the first quarter there are more than 100,000 patients on the drug, if I'm not wrong. So with KD621, hopefully, right, I think that what we can match is the ability to drive efficacy and safety of a normal drug in a validated pathway. and I think what's different is that it 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 what Igotype 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 Thank you. Thank you. 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 you know 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 you know 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 programming highly super relevant indications or populations. 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.