管理層發言
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 were provided. 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 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 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 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 eight 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 highlight 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 III development around mid-2027, both approximately six 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, 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, and 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.
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 patient benefit 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 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 least, we look forward to providing updates as our CDK2 molecular glue KT-200, partnered with Gilead, advances towards an expected IND and clinical start next year. Taken together, our progress across all of these programs highlights 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 three 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-0/1 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 atopic dermatitis, asthma, eosinophilic esophagitis, 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 disease on advanced systemic therapies. There is no doubt that this represents a significant 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 many 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 position us—once these two studies are completed—to fully explore the broad potential of KT-621 across our dermatology and respiratory programs in later-stage trials. Now turning to KT-579, the oral IRF5 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, IRF5 is a genetically validated driver of innate immunity dysfunction and inflammation and is implicated across multiple autoimmune diseases such as lupus and IBD. 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 seeking 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 TLR7, 8 and 9 agonists, including type 1 interferons, pro-inflammatory cytokines and inflammatory pathway gene transcripts. We have guided that our expectation is we should see between a 50% and 80% reduction in these biomarkers across the three TLR pathways assessed if we are engaging IRF5 effectively, which would suggest the potential for IRF5 degradation translating into clinical activity in a 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. 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 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 positions at Johnson & Johnson and 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's STAT6 program represents a truly transformational opportunity, not only for the company, but most importantly 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 two to three 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.
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. Research and development expenses for the quarter were $119.5 million, including approximately $10.4 million in noncash stock-based compensation. Excluding stock-based compensation, 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.
General and administrative expenses for the quarter were $21.1 million, including approximately $8.6 million in stock-based compensation. 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.
分析師問答
Operator instructions were provided. 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 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 dupilumab 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 that you had two questions in one. So let's start with the first one. Baseline characteristics—one of our main goals of the study, and as I mentioned earlier, was to prioritize quality of execution over speed. In fact, our initial timelines reflected those expectations. We expected that some of the systems we put in place would direct the speed of execution toward those expected timelines. And despite that, we still saw pretty fast enrollment, which, again, we believe was driven by the excitement around the program, the oral opportunity, the data that we generated, and so on. But going back to your first question, yes, the goal has been to ensure that we had patients with the right severity in the study. As you know, when the first biologics in the space were developed—dupilumab, for example—that Phase II was more than 10 years ago and there wasn't any approved systemic drug at that time for a broader population.
So the baseline severity in those earlier studies was probably higher than what we've seen in more recent studies. We put measures in place to ensure that while it's difficult, if not impossible, to replicate that type of baseline severity, the patients in our study would follow at least what has been seen in the past few years. I'm not going to comment on where we landed specifically, because you'll see that when we release the data, but we feel good about the baseline characteristics. On your second question about the bar for success, there are maybe two ways to answer it. When we started this program, we were very science-focused. We showed for the first time that you can block STAT6 signaling through degradation of STAT6. In our labs, we saw downstream blockade that mimicked what we have seen with dupilumab. Our narrative and the science around the program has continued over the years to demonstrate the effect of STAT6 degradation on IL-4 and IL-13 signaling.
What we've learned interacting with the medical community, including patients, is the strong need for an effective oral therapy; that's the consistent feedback. I've been in every investigator meeting, I've visited sites, I've talked to many KOLs. The main consistent feedback is the need for an effective oral drug. We believe success, both clinically and commercially, is to deliver what patients want—an effective, safe, well-tolerated oral option, which currently does not exist across many of these comorbid indications. Scientifically, over the past six-plus years, degrading STAT6 seems to be as effective as blocking IL-4 and IL-13 with dupilumab. Preclinical and early clinical data show we can block the pathway, affect downstream biomarkers and initial clinical endpoints in a similar way to dupilumab. So our expectation is that this study will be in that ballpark of what dupilumab has shown at week 16 in previous AD studies, understanding that different studies and different populations vary.
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.
Thanks, Tazeen. We're very excited about IRF5. To our knowledge, this is the first drug targeting IRF5 in the clinic. We feel responsible to demonstrate the power of this biology. The underpinning excitement is human genetics showing that IRF5 activation is associated with diseases like lupus, RA and IBD. Preclinical data show IRF5 is a central node for three key pathways: B-cell autoantibody production, inflammatory cytokines such as IL-12 and IL-23 and TNF, and type 1 interferon. When IRF5 is activated, it acts as a master regulator of immunity. In this Phase I healthy volunteer study, the necessary but not sufficient step is first to show we can robustly degrade IRF5—our target is at least 90% degradation—and do so safely. Next, we need to show that blocking IRF5 modulates these three important pathways. The team has developed assays to measure these pathways, and we expect that even in healthy volunteers we can interrogate the relevance of these pathways by blocking IRF5 signaling. That should give us confidence to move into lupus and consider other indications in the near future.
Our next question is from Andy Chen from Wolfe Research.
This is Jason taking for Andy. I just wanted to ask if you guys have any plans around unveiling new degrader molecules maybe in the next year or two? How many molecules should we expect? And are they likely to continue to be in immunology indications or with derisked mechanisms?
We have a productive research engine. We have a general guidance of at least one new molecule entering clinical development every year. We're on track to have development candidates in 2026 that will be entering the clinic in 2027 and beyond. We plan to disclose more programs when appropriate. We have two important clinical readouts in the second half of the year, so we're deciding whether the next clinical program disclosure will be this year or early next year. Approximately 80% of our preclinical effort is in immunology, so it's highly likely the next programs will be in immunology with highly validated targets and oral options.
Our next question is from David Dai from UBS.
Regarding the STAT6 degrader KT-621, given the high placebo response we're seeing in some 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?
Great question, David. We won't go into the detailed specifics, but we understand STAT6 biology well and powered the study within a range of expectations informed by biology and our Phase 1b data. We recognize placebo rates have increased and we accounted for that in our power calculations. There have been some extreme cases of very high placebo rates that no study can reasonably plan for, but otherwise, recent studies that delivered positive data—and the increased placebo rates seen—were accounted for. The enrollment speed did not change our power assumptions. When you have a high enrolling study you sometimes enroll slightly more than planned, but we haven't changed our power assumptions.
Our next question is from Ellie Merle from Barclays.
Can you give more color on how enrollment is going in the Phase 2b asthma trial? With the acceleration of enrollment in AD, how should we think about whether we can see similar speed in asthma? What are the different dynamics playing into AD enrollment versus asthma that could explain the different timelines?
Thanks. What's common between the two studies is excitement around the mechanism and the well-understood pathway. We've done a strong job educating the community about STAT6 and the oral opportunity, creating confidence. For the AD study, there are more AD patients and we are enrolling moderate-to-severe patients broadly. For the asthma study, we have specific entry criteria including FeNO and eosinophilia at baseline, which targets a subset of asthma patients—type 2 or eosinophilic asthma. That reduces the denominator and typically increases screen failure rates. So while asthma enrollment has the opportunity to move at good speed, it may not match AD's pace. We are enrolling well, across more regions than for AD, and remain confident in our ability to deliver high-quality execution within our timeline. We will only change timelines if required and after enrollment completes, not while studies are in flight.
Our next question is from Brian Cheng from JP Morgan.
I wanted to touch on the BROADEN-2 open-label extension. Can you give color on the rollover rate so far? Are patients allowed to dose adjust across the three doses in the OLE?
We're not going to comment on rollover rates at this time. We might offer some insight when we release the BROADEN-2 data by the end of the year, but it's too early to comment on the percentage rolling over. On dosing, patients are all going on to one dose in the OLE, and 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 wanted to ask your latest thoughts on the competitive landscape. Specifically within the STAT6 class—Pfizer confirming activity in Phase II, Nurix and Sanofi dosing programs—and beyond that with bispecific and trispecific approaches. What's your latest view on that landscape?
Good question. STAT6 is of high interest across the industry. Our focus is on execution—high quality and speed—to maintain the advantage we've created in timeline. Regarding Pfizer, from public information, they are trying to understand their molecule's performance in humans; their reported timelines suggest completion in early 2028, which appears long. We don't believe small molecule inhibitors will match degraders because degraders can block the pathway completely at low doses and maintain blockade over 24 hours, which we believe is needed to match upstream pathway blockade. Regarding Nurix and Sanofi, we've seen their programs start—if all goes well, timelines will vary. So far, KT-621 has behaved well and is well tolerated. We're also interested in learning from bispecific and trispecific approaches; they help the field learn where mechanisms can deliver enhanced activity in heterogeneous populations like AD. Our view is KT-621 could be a first-in-line therapy for many moderate-to-severe AD patients who are not well served by topical steroids. We are open to combinations and novel mechanisms, and we're observing developments carefully.
Our next question is from Brad Canino from Guggenheim.
Thanks to Jared for his collaboration over the past years. My question is about moving STAT6 to late-stage development: How are you positioning the company to extend benefit to pediatric AD patients? For dupilumab, it took several years to expand the label from adults to different pediatric cohorts. Are you doing anything now to try to accelerate pediatrics development?
We're focused on accelerating pediatric development. We've incorporated adolescents—12 and up—into our study. Going younger will involve discussions with regulatory agencies. From Kymera's perspective, we are heavily focused and will update when we know more. We expect to know more after the Phase 2b data; you shouldn't expect updates before then.
Our next question is from Judah Frommer from Morgan Stanley.
Congrats to Terence and Jared as well. Could you help us with cash runway guidance remaining into 2029, given the acceleration in timelines for KT-621? Any changes to spend trajectory over the next couple of years as you think about that?
Thanks, Judah. Our runway into 2029 is intact. Even with acceleration in timing, it's not enough to bring the runway in closer; there's a bit of cushion. As we get to year-end and see the data and solidify development plans—including core and other contemplated indications—we will discuss whether an update is warranted. We're in good shape with over ten quarters of cash even with the accelerated timelines. Our runway assumes completion of ongoing Phase II studies, the IRF program proof-of-concept and getting underway with Phase IIIs, and we expect to come pretty close to finishing the AD study within our runway if all goes well.
Our next question is from Geoffrey Meacham from Citi.
On KT-621, as you look to Phase III design in AD and asthma, how important is washout or prior therapy experience? Do you plan to include biologic-experienced patients in Phase III, and how might that affect probability of success?
Washout is critical—regardless of entry criteria, you need to fully wash out prior biologics based on their half-life to preserve data integrity. Regarding biologic-experienced patients, we included biologic-experienced patients in our Phase 2b with caveats—specifically not enrolling previous nonresponders to the same mechanism. For Phase III, this is an active topic of discussion internally and with regulators. We expect biologic-experienced patients to be part of Phase III in some form, with nuance around their prior biologic experience that we'll define as we align with regulators.
Our next question is from Derek Archilla from Wells Fargo.
Jared, good luck in the next chapter. Terence, welcome. Following up on pediatric development: Are there any gating factors to a sprinkle formulation of KT-621? And how would you frame the pediatric opportunity relative to adolescents and adults?
We interacted with families and patients that highlighted the burden of injectables for children, which underscores our responsibility to deliver an easy-to-take, effective and well-tolerated drug for kids. From a formulation perspective, we are in a good place. The timing for studies in younger children will depend on regulatory permissions. Having data from a global placebo-controlled randomized Phase 2 study, especially around efficacy and safety, will be important to initiate those discussions with regulators. From Kymera's perspective, we will be ready to proceed as soon as we have completed this study.
Our next question is from Alex Thompson from Stifel.
Thanks for the progress. Nello, with 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 KT-621 heading into the data later this year?
It's hard for us to comment on ongoing blinded safety in an active study. We'll be able to discuss unblinded safety data when we report the readout in a few months. A little patience is required; we're eager too, but we have to wait until the data are unblinded.
Our next question is from Jeff Jones from Oppenheimer.
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?
We have a translational hypothesis that IRF5 is a master regulator of three pathways: B-cell activity, type 1 interferon and certain inflammatory cytokines. If we do not see a biomarker profile reflecting that biology, we'll have to rethink our clinical strategy beyond the translational hypothesis. I would be surprised if the data are surprising, but we'll see what the biomarker data show.
Our next question is from Biren Amin from Piper Sandler.
In your slide deck, you mentioned that the BROADEN-2 trial data could support trials in GI indications. What data from BROADEN-2 could support development in GI, and is the interest in GI due to STAT6 activation in ulcerative colitis? Also, would you potentially look at IRF5 in IBD given IRF5 expression in IBD and some data with anti-TNF reducing IRF5 in IBD?
Good questions. To clarify, when we mention GI on our slide, we are referring to eosinophilic esophagitis (EoE). We believe the Phase 2 dose we identify from AD could be applicable to other dermatology indications and possibly EoE, but development plans may differ. For EoE we may have a slightly different plan, which we'll disclose after the Phase 2b data. Regarding IRF5, we're definitely interested in IBD and have exciting preclinical data; we'll share more as that program advances.
Our next question is from Brian Abrahams from RBC Capital Markets.
This is Kevin on for Brian. As you think about lupus and the heterogeneity of disease, what are your latest thoughts on the addressable opportunity in lupus? Would the ambition be to have biologic-like efficacy or is the paradigm more nuanced compared with KT-621 in atopic dermatitis?
From my perspective, lupus patients need effective therapies, especially oral options with favorable benefit-risk profiles. There are challenges in lupus drug development, and we recognize unmet need. We believe an effective oral option that provides meaningful disease control would be valuable. Terence, do you want to add?
Thanks, Nello. I would underscore that there remains tremendous unmet need in lupus, including for oral medicines with a favorable benefit-risk profile. Brian flagged the challenges of lupus drug development—patient selection, site selection, careful trial design and oversight are key. That's exactly what we're working through now.
Our next question is from Mark Frahm from TD Cowen.
Congrats, Jared, and best wishes. This is mostly for Terence. The company has talked about interest in combinations across the pipeline, including STAT6 and IRF5. At your prior job, combinations were a big push early on. How do you view the optimal time to start combinations? What do you need to see from earlier trials to start working on combinations?
Thanks, Marc. There's tremendous opportunity in combining established mechanisms to pursue greater efficacy. We're learning from the field; some combinations have shown altered outcomes and some encouragement. The key learning for an oral drug developer is which combinations are rational to pursue in combination with one proven target. It's a topic we're looking at carefully.
To add, it depends on what we're trying to do—biology and market positioning both matter. Our North Star remains advancing oral options for patients. There might be cases where we study combinations with injectables to understand mechanisms, but our primary focus is on oral combinations and oral-first strategies.
Our next question is from Jeet Mukherjee from BTIG.
For the BROADEN-2 data coming by year-end, is there a cap on the number of patients who are on prior biologics? And will you ultimately break out the data by biologic-experienced versus biologic-naive patients?
There is no cap on prior biologics. Regarding breaking out the data by prior biologic experience, we'll analyze the data and determine the appropriate breakdown. Let's wait until the data are ready.
Our next question is from Mayank Mamtani from B. Riley Securities.
Best wishes to Jared and welcome to Terence. For BROADEN-2, can you comment on what proportion of patients come from outside the U.S. or specifically from Eastern Europe sites? Also, what was the screen failure rate and how does that compare to recent biologic trials? Do you expect discontinuation rates to be better for an oral pill versus biologics? Finally, to clarify timing: last patient in was before the end of Q2—can the four-month efficacy data drop ahead of the IRF5 program, or are they tracking in parallel?
We have a global presence—U.S., Canada, Australia, Japan, South Korea and Europe—so the majority of patients will come from outside the U.S., but we will have a significant U.S. presence. We're not going to provide a breakdown of patients or screen failure rates at this time; we may provide details when we release the data. On discontinuations, we'll discuss those metrics with the readout. Regarding timing, it's extremely likely the IRF5 data will be reported first, and then the BROADEN-2 data will follow. We will provide more specifics as we approach the data releases.
Our next question is from David Hoang from Deutsche Bank.
To what extent could we look at the ongoing launch of the oral IL-23 inhibitor icotyde in psoriasis as an analog for how commercialization of KT-621 in atopic dermatitis might go? What lessons can we learn there, and what reasons would that be or not be a good comparison?
There are useful parallels. Icotyde targets a validated mechanism and has shown strong adoption, even in a competitive psoriasis market. Psoriasis is a more mature market with multiple approved drugs, including oral options, and yet icotyde has achieved rapid adoption. AD is a different market—less penetrated by systemic therapies—and there's a bigger unmet need for an oral option. If we can deliver an effective and well-tolerated oral therapy, AD could present an even larger commercial opportunity, given the millions of patients not currently on systemic therapies. Execution will be critical.
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 taking time to ask thoughtful questions even in the middle of the summer. 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 sets in the second half of the year, given these are both first-in-class programs in highly relevant indications. Stay tuned and I look forward to seeing many of you at conferences in September and then at our calls to disclose the data. Thank you.