Kymera at Stifel Forum: Strategic Moves in Immunology

On Monday, 15 September 2025, Kymera Therapeutics (NASDAQ:KYMR) presented at the Stifel Virtual Immunology and Inflammation Forum, unveiling significant advancements in its drug development pipeline. The company discussed promising results from its STAT6 degrader program, KT-621, and outlined a robust financial strategy. While the company is optimistic about its innovative approach, challenges remain in translating early-stage success to later phases.

Key Takeaways

• Kymera’s STAT6 degrader, KT-621, shows potential to mimic biologics like DUPIXENT in treating allergic diseases.
• The company has a strong financial position with a cash runway extending into the second half of 2028.
• Positive results from Phase 1 studies bolster confidence, with Phase 2B studies set to begin soon.
• Partnership with Sanofi on the IRAK4 program progresses, with Phase 1 trials expected in 2026.
• Focus on mitigating placebo effects in upcoming trials through stringent criteria and strategic planning.

Financial Results

Kymera Therapeutics exited July with approximately $1 billion on its balance sheet, ensuring a cash runway into the second half of 2028. This funding covers both disclosed and undisclosed programs, including the pivotal Phase 2B studies for STAT6 and initial work for the IRF5 program. Notably, potential milestone payments from partners Sanofi and Gilead, totaling nearly $1.75 billion, are not included in this forecast.

Operational Updates

STAT6 Program (KT-621):

• Phase 1 Healthy Volunteer Study: Completed with over 90% degradation of STAT6 in blood and skin.
• Phase 1B Study: Enrollment nearing completion, with data expected in Q4. A second dose was added to enhance translation between volunteers and patients.
• Phase 2B Studies: Set to commence for atopic dermatitis, evaluating three doses of KT-621.

IRF5 Program:

• Clinical trials planned for early 2026, targeting autoimmune diseases like lupus and RA.

IRAK4 Program (Partnered with Sanofi):

• Sanofi to advance KT-485 into Phase 1 trials by 2026.

KT-579:

• IND-enabling studies underway, with clinical trials expected to start next year.

Future Outlook

Kymera aims to rapidly progress its programs into Phase 2B dose-ranging studies and ultimately registrational studies. The company is exploring potential combination therapies and continues to seek attractive targets with commercial opportunities.

Q&A Highlights

STAT6 Degradation vs. Inhibition: Degradation offers a catalytic mechanism for full pathway blockade with once-daily dosing.

Phase 1B Dose Selection: A second dose was added to strengthen translation, not to demonstrate dose-response.

Mitigating Placebo Effects: Strategies include stringent eligibility criteria, site selection, and rater training.

For further details, readers are encouraged to refer to the full transcript below.

Full transcript - Stifel Virtual Immunology and Inflammation Forum:

Alex, Interviewer: Hey everyone, good afternoon. We’re back. Happy to have Kymera Therapeutics here, CMO Jared Gollob and CFO Bruce Jacobs. Maybe I’ll kick it over to Bruce for a brief overview of the company, and then we’ll jump into the Q&A. Bruce, over to you.

Jared Gollob, CMO, Kymera Therapeutics: Great, thanks Alex. Thanks everyone for joining. We’re happy to be here. It’s been a busy year at Kymera Therapeutics, a busy few months as well, and I’m sure the end of the year will be the same. We are focused on pushing forward our STAT6 program. That’s obviously the focus of a lot of investor attention. I’m sure it’ll be the focus of Alex’s questions today. As you all know, by this point, we completed the Healthy Volunteer Study in the early part of June, or shared the results, I should say, in the early part of June. Very pleased with the outcome there on really every metric. It’s with the strength of that data that we headed into the Phase 1B study, which actually started before we shared those full results. It started in April.

We’re at the kind of tail end of that, finishing up enrollment as we speak, and positioned well to share the data with you all in the fourth quarter. I’m sure Alex will have questions about that as well. Just like the 1B started before we shared the full data on the Healthy Volunteers, we are getting ready to start the Phase 2B, the first of the two Phase 2B studies, which will be in atopic dermatitis. It’s likely, if not probable, that you’ll hear that we started that trial just a bit before we’re in position to share all of the data from the 1B. We’ll have a busy end of the year with both data and trial initiations, and we will be spending the bulk of 2026 obviously moving through that 2B study. I’ll save the details for questions, which I’m sure Alex will have.

Otherwise, the company continues to execute across our oral small molecule pipeline in immunology. The IRF5 program is tracking with all of our expectations. We’re finishing up all of our work to get that trial started in the beginning part of 2026, and to be in a position to share data that year as well. We have as a goal, as we always have, to share at least one new program per year. We’re hoping to do that in 2026 as well, a program that we’ve not yet disclosed, and we’ll be excited to share with everyone. The company’s in a great place from a capitalization standpoint. We exited July of this year with about $1 billion on our balance sheet. That takes us through, or into, I should say, the second half of 2028, so runway into the second half of 2028.

It funds all of the programs that we’ve disclosed and those that we haven’t as well, including the 2Bs for STAT6 and also the Phase 1, and also some proof of concept work for IRF5. In a good place, excited about where we are, and looking forward to taking your questions, Alex. Hopefully that gives you a sense of things.

Alex, Interviewer: Awesome, yeah, definitely. We’ll definitely dig in more. Maybe to kick things off, I just wanted to ask kind of a high-level question here, which is sort of, you know, why is degradation, you know, maybe better than classical small molecule inhibition in your view and sort of based on your platform results today?

Jared Gollob, CMO, Kymera Therapeutics: Yeah, so maybe it’s best to answer that question in the context of what we’re trying to do in immunology. Because, you know, within immunology, there have clearly been a number of cytokine pathways that drive diseases like psoriasis, atopic dermatitis, et cetera, that have been strongly clinically validated with injectable biologics, right, that are monoclonal antibodies that are hitting these targets upstream and leading to full pathway blockade. These highly selective antibodies giving full pathway blockade are the reason why you can have such incredible levels of efficacy with such clean safety profiles. In order to try to phenocopy these injectable biologics, we believe that only degraders can accomplish that. The downside of small molecule inhibitors is that small molecule inhibitors tend to have selectivity issues. Most importantly, small molecule inhibitors require a binding event to the protein of interest and inhibition, and that’s sort of a one-to-one stoichiometry.

The activity of small molecule inhibitors is going to wax and wane with the peripheral exposure, the plasma exposure. It’s very difficult for a small molecule inhibitor to block a protein within a pathway 100% 24/7 around the clock. That’s the reason why to even come close to that with a small molecule inhibitor, you probably have to dose it at very high doses or more than once daily, which leads to off-targets and toxicity. It’s hard to match the activity and safety of a biologic with a small molecule inhibitor. A degrader, on the other hand, because the mechanism, the co-opting of the ubiquitin proteasome system, it’s a catalytic mechanism. One molecule of a degrader can degrade thousands of copies of that protein. Degraders are also highly selective and highly potent.

This is the reason why you can use a low dose of an oral degrader, be sure that you’re only hitting that target. Because of this catalytic mechanism, you can keep that target suppressed 95% to 100% round the clock with a single daily dose. That’s why we believe that only an oral degrader can give you that sort of similar biologic safety and efficacy profile with once daily dosing.

Alex, Interviewer: Yep. Maybe pivoting to STAT6 specifically in KT-621, which will be the bulk of this Q&A, I’m sure. You know, STAT6, why is that such a compelling target here for both degraders and then sort of broadly in immunology?

Jared Gollob, CMO, Kymera Therapeutics: Yeah, the reason why this has been a really target of high interest really for the past 10 years is largely because of what DUPIXENT has been able to accomplish, right? The fact that DUPIXENT, by blocking the IL-4/13 pathway, has been so successful across multiple TH2 allergic diseases. STAT6 is really unique as a transcription factor and as a STAT in that it only controls signaling through those two pathways, IL-4 and IL-13. It is highly selective and specific for IL-4 and IL-13 as the obligate transcription factor. Here you have an opportunity to block one protein intracellularly and achieve full pathway blockade to the same extent as IL-4 and IL-13. That’s why it’s such a compelling target because it offers that ability to phenocopy DUPIXENT if you can successfully target STAT6 with a degrader.

Alex, Interviewer: Yep. Maybe some high-level overviews of the Phase 1 Healthy Volunteer Study. I guess to ask the question specifically, what from the Phase 1 really validated your indwelling hypothesis? What are the key takeaways that you want to highlight coming out of that Phase 1?

Jared Gollob, CMO, Kymera Therapeutics: Yeah, you know, I think before we went into the Phase 1 Healthy Volunteer Study, we had a very strong preclinical package, not just around the potency and selectivity of KT-621 or STAT6 degrader and the ability of STAT6 degradation to fully block the IL-4/13 pathway to the same extent, if not even stronger than DUPIXENT. We had very compelling preclinical disease models in asthma and atopic dermatitis that showed us that achieving 90% or greater degradation of STAT6 gave us activity that was comparable or superior to dupilumab in those models. Our main objective in that Phase 1 Healthy Volunteer Study was to show whether we could achieve 90% or greater degradation of STAT6 in blood and skin at doses that were safe and well tolerated. That was really what it was all about, safety and target degradation.

In addition, there was an important question, arguably a more exploratory question, about whether degradation of STAT6 could result in impact on TH2 biomarkers like TARC, eotaxins, and/or IgE that would give us information about whether we were blocking the IL-4/13 pathway to the same extent as dupilumab.

Alex, Interviewer: Yep. On some of those downstream biomarkers, like I think one of the questions there was how interpretable are those biomarkers beyond STAT6 degradation when you look at the historical, you know, Phase 1 experience from DUPIXENT, for instance?

Jared Gollob, CMO, Kymera Therapeutics: Yeah, I think, coming back to the premise of the Healthy Volunteer Study, we know that DUPIXENT had shown in healthy volunteers that they could achieve about median 35% inhibition of TARK in healthy volunteers, recalling that in healthy volunteers, TARK levels are either low or normal to begin with. That 35% decrease in TARK is different from the 70 to 80% decrease in TARK with DUPIXENT that you see in patients who have very high levels of TARK to begin with. If your TARK levels are very high to begin with, you’re going to see a greater % reduction. We knew we benchmarked from the healthy volunteers that 35% median reduction with DUPIXENT, we wanted to be in that range for KT-621 in healthy volunteers. We also added in EOTAXIN-3, which is a really important biomarker.

It’s involved in eosinophil chemotaxis that is a direct downstream target of IL-4, IL-13. We added that into the healthy volunteer study, even though that had not been looked at by DUPIXENT in healthy. DUPIXENT had looked at EOTAXIN-3 in asthma patients and shown strong reductions there.

Alex, Interviewer: Yes. You started the Phase 1B before this was complete. You achieved greater than 90% STAT6 knockdown across multiple doses. I guess, how confident heading into the Phase 1B were you that you picked the right proof of concept dose?

Jared Gollob, CMO, Kymera Therapeutics: Yeah, I mean, we had a very robust Phase 1A data set. In Phase 1A, just as a reminder, we showed that we could completely degrade STAT6 in blood and skin at doses ranging between 50 and 200 milligrams. We actually saw greater than 90% degradation at doses as low as 6.25 milligrams. It was hard for us not to achieve 90% degradation even at very low doses in that healthy volunteer study. Seeing the complete degradation of STAT6 at relatively low doses, 50 to 200 milligrams, and that at those doses also seeing with 14 days of dosing that we could essentially lower eotaxin a median of 63% and TARC by a median of 37% gave us a lot of confidence that STAT6 degradation that was deep and sustained was going to give us a DUPIXENT-like impact on IL-4 or IL-13 path blockade through those biomarkers.

Alex, Interviewer: Yeah, I think the premise of this question of the Phase 1B dose selection is obviously related to your recent disclosure of adding a second dose, right? I think the question folks are struggling with is, did you pick the 50 milligram dose to do in Phase 1B and then maybe decided that that wasn’t high enough and go to something higher? How should we interpret the decision to add a second dose in the Phase 1B?

Jared Gollob, CMO, Kymera Therapeutics: Yeah, so maybe focusing on what the main objectives were for Phase 1B. Phase 1B, again, reminder that this was an open label study, 28 days of dosing with KT-621. For us, the primary objectives were, number one, to show that we could translate from healthy volunteers to AD patients degradation of STAT6 in blood and now in skin, including in skin lesions in AD. We wanted to use that information to confirm our selection of doses for Phase 2B, which we had based largely on our robust Phase 1A data set. Additional important objectives were to be able to show that we had a DUPIXENT-like effect on TH2 biomarkers in blood and skin. Lastly, even in the absence of a placebo control, that we could show a DUPIXENT-like effect or in that ballpark on clinical endpoints like EASI and pruritus.

In terms of dose selection for Phase 1B, between doses of 50, 100, and 200 milligrams within the Phase 1A healthy study, it was difficult for us to distinguish differences in activity. We saw complete degradation there. We knew we wanted to bring a highly active dose into Phase 1B. We have not said what that dose is, but a highly active dose to show a clinical proof of concept and translation. Our enrollment went faster than expected, actually. The aim was to enroll approximately 20 patients onto that Phase 1B. Once we had enrolled 10 patients on the initial dose and saw what we needed to see and actually did that even faster than expected, we had the opportunity to look at another dose.

Without revealing what that other dose was, we wanted to bring in another dose because we felt that showing translation for two different doses between healthies and patients would just be that much stronger and give us that much more confidence in the doses that we chose for Phase 2B.

Alex, Interviewer: I guess, you know, with that context, you know, what does good look like then in the Phase 1B coming later this fall?

Jared Gollob, CMO, Kymera Therapeutics: Yeah, I think for Phase 1B, it’s important to emphasize that even though we have two different dose levels, the aim was not to somehow show a dose response. The aim was again to show strong translation of degradation from healthies to patients and to confirm those doses that we needed to select and to show an impact on biomarkers. For us, what good looks like is hopefully to be able to see similar levels of degradation in blood and in AD skin lesions that we saw in the healthy volunteers, to be able to show, you know, at 28 days a sort of DUPI-like effect on biomarkers such as TARK in the blood and multiple different TH2 transcriptomic biomarkers in the skin.

If you look at the DUPI publications and what they saw at 28 days, you can sort of see where that benchmark is set for being in the ballpark. On clinical endpoints, the same thing. If you look at Phase 2 or Phase 3 studies like the SOLO-1 DUPI studies, which were 16-week studies, if you look at what they saw at four weeks for EZ and pruritus, you know, we want to be in that ballpark, you know, after 28 days of treatment on our study. That’s what good would look like in addition to, of course, showing the same level of pristine safety that we saw in the Phase 1A healthy volunteer trial.

Alex, Interviewer: You’ve also said that, you know, at least some of the early Phase 1B data helped at least confirm your Phase 2B dose selection. Can you sort of elaborate on what that might mean or how we should think about that?

Jared Gollob, CMO, Kymera Therapeutics: Sure, yeah, I mean, the whole aim of Phase 2B, and this goes for both the AD and asthma studies, is to do dose range finding. That’s what the regulatory authorities want us to do, and that’s what we as drug developers want to do. We’re planning on bringing, you know, having, we have three different dose levels of KT-621 in both the AD and asthma studies, and you can think of those three different dose levels as being, you know, one dose level which is a therapeutic dose, one which is a super therapeutic, and one which is somewhat subtherapeutic, plus placebo. Four arms per study, the same doses across both studies. That is really the whole goal of dose selection, right?

To be able to feel confident that you’ve picked doses that will translate in a way that should give you that range of activity within your Phase 2B trial.

Alex, Interviewer: Yep. I think in the field, you know, EADB coming up later this week, much has been made of placebo responses in the atopic dermatitis Phase 2 landscape. I guess as you’re about to start a Phase 2B study, what are your key takeaways from some contemporary studies, and what are you going to do to kind of not make that a factor in your Phase 2B study?

Jared Gollob, CMO, Kymera Therapeutics: Yeah, I think that really is a very important point, right? Because that placebo effect can determine your overall treatment effect. What’s happened over time since DUPIXENT was tested and approved and other drugs that have come onto the market is that even moderate to severe patients who we’re looking at in our studies and ultimately in our registration studies, their overall severity has sort of migrated down a bit over time. In the early days when DUPIXENT was being developed, those trials had patients with baseline EASI scores in the low to mid 30s. If you look at some of the more recent studies that have been out there and published and presented, the baseline EASIs are more in the mid 20s, right? The lower the EASI score, the greater the opportunity for there being a placebo effect.

Number one, it’s very important in terms of mitigating against high placebo rates to make sure you have the right stringent eligibility criteria for moderate to severe and that your sites and investigators are selected so that they adhere to those criteria. I think that’s very important. I think it’s important, obviously, that there is adequate oversight from the sponsor, both for the CRO running the study and for the sites as well, to make sure you’re truly putting on atopic dermatitis patients and that those atopic dermatitis patients truly are moderate to severe and that you have raters who preferably are dermatologists who are able to know how to measure EASI and do it accurately and consistently and reproducibly. That’s also very important, as well as making sure patients are adhering to the treatment and are not taking any prohibited drugs.

Alex, Interviewer: Yep. In terms of, you know, maybe the last, I have more questions about STAT6 on top of the rest of the pipeline too, but maybe what keeps you up at night with the STAT6 program? What are you most focused on to kind of make sure, you know, things completely continue to go smoothly from here?

Jared Gollob, CMO, Kymera Therapeutics: Maybe I’ll let Bruce chime in on that one.

Bruce Jacobs, CFO, Kymera Therapeutics: Yeah, I mean, look, the molecule has performed to our highest expectations. I think we always said from the beginning that one fear is just unexpected. I think with each passing trial, we feel like the unexpected hasn’t occurred and hopefully won’t occur. I think we’re really focused on execution and we talk about, you asked about placebo effect. I think running a strong, effective Phase 2B so we can truly elucidate the activity of this compound is what our focus is. I’d say that we’ve felt really good about how the molecule has performed and are hopeful that that indeed continues.

Alex, Interviewer: Should we totally exclude getting any Phase 2B data next year based on timeline expectations?

Bruce Jacobs, CFO, Kymera Therapeutics: I think it’d be really difficult for that to occur largely because if you think about a 4Q start and the typical enrollment times of these studies, which, I won’t say what our expectations are, but typically they’re in the range of a year or so and we’ve got obviously 16 weeks of follow-ups for the patients. I think we’ve said it’d be pretty difficult to have data in 2026, but obviously, we operate at a high level of rapid speed here at Kymera, so we’ll do our best, but I think that’s probably an unlikely expectation.

Alex, Interviewer: I want to touch on IRF5 too. How does IRF5 kind of fit synergistically as a target into how you’re thinking about the world of immunology with KT-621 as well?

Jared Gollob, CMO, Kymera Therapeutics: Yeah, I mean, I think IRF5 by itself is really a standalone target, whereas KT-621, we think, is the ultimate target for treating TH2 diseases. I think IRF5 is really for a different basket of diseases. The strong genetic association between IRF5, given its role in type 1 interferon responses in autoantibody production and pro-inflammatory cytokine production and the really strong genetic association with lupus, RA, IBD, that’s where we see IRF5 being applied and really also sort of like STAT6 being a first-in-class and best-in-class here. We have a very potent, selective degrader of IRF5. It is an oral compound. We have very compelling preclinical data, both from the safety side of knocking down IRF5, but efficacy as well, including in multiple different lupus models, and we’re generating data now also in RA and IBD and other interferonopathies. We’re really very excited about this target.

Big pharma as well as biotech is very excited by this target. We see it having a separate path from KT-621, but if you think about our pipeline in general, having oral immunology drugs that are safe and quite active, we always do think about possibilities for combinations, whether it be these targets or other targets down the road, it gives us even more optionality.

Alex, Interviewer: Obviously, you haven’t really talked necessarily about your first set of indications, but maybe a higher-level question is, should we view the STAT6 development path as sort of an analog that you would apply to IRF5 from just sort of phase 1 to early POC to a larger phase 2 study? Is that kind of how we should think about it?

Jared Gollob, CMO, Kymera Therapeutics: In very broad brush strokes, yes, I think the aim for both of these studies is to move rapidly to phase 2B dose range finding studies and ultimately to the pivotal registrational studies. I think there are definitely parallels from that perspective in terms of how we think about the initial healthy volunteer effort, what we want to learn from patients, and then really trying to get quickly to those critical phase 2B dose range finding studies.

Alex, Interviewer: What’s left before getting to the clinic at this point?

Jared Gollob, CMO, Kymera Therapeutics: I think it’s really, you know, we’re in the midst of our IND enabling studies for KT-579, and the aim is for us to be, you know, in the clinic, you know, early next year in healthy volunteers and to have data in the second half of next year.

Alex, Interviewer: Would you be in a position to start a proof of concept study, or would you want to do something bigger, a Phase 2B or Phase 2A type study?

Jared Gollob, CMO, Kymera Therapeutics: Yeah, we haven’t provided details yet on sort of the clinical development plan beyond the initial healthy volunteer study, but I do think that, you know, there would be a good chance that we could be initiating our first, you know, patient study with KT-579 toward the end of next year.

Alex, Interviewer: I think one of the things that’s exciting about this is that we have a slide in our corporate deck on our website that looks at the indications, potential indications for STAT6, for IRF5, and also for IRAK4 partnered with Sanofi, and there’s a great degree of complementarity, they’re very complementary, I should say, and it kind of speaks to what our objective here is to find these attractive targets that have interesting commercial opportunities, but have so far generally been undrugged or poorly drugged, and this one fits in nicely.

Jared Gollob, CMO, Kymera Therapeutics: Yep, it makes sense. Maybe briefly, you know, can you touch a little bit on sort of the decision making behind the IRAK4 change on the Sanofi side and what that means for your collaboration?

Bruce Jacobs, CFO, Kymera Therapeutics: Yeah, sure, I can take that. We announced, I guess, earlier this year, mid-year, that Sanofi was going to move to our second generation degrader KT-485 and not continue development of 474. They made a resource allocation decision that felt like they would move forward with what they thought was the best molecule. That program is positioned to enter Phase 1 with that new compound in 2026, and we look forward to Sanofi sharing more guidance on the specific timing of that. We’re excited about the molecule. It’s highly selective, as most of, if not all of our molecules are, greater potency and also broader tissue distribution. I know one of the issues that we were working to solve was the modest QTC impact from 474, and this solves that. We’re excited about the prospects. Sanofi is advancing that.

We still have meaningful milestones in front of us as that progresses through clinical development and hopefully eventually commercialization.

Alex, Interviewer: Great. Maybe last question, I know, Bruce, you talked about cash runway into 2028 timeframe. What does that include sort of post Phase 2B for 621? Is there any kind of Phase 3 prep, et cetera?

Bruce Jacobs, CFO, Kymera Therapeutics: Yeah, absolutely. We’re, I won’t give you everything you want there, because we haven’t shared the specific details on when those studies will start and in what sequence. Suffice it to say, we have included in that runway into the second half of 2028 all of the startup expenses and then beginning those phase three studies in 2028. That’s all covered. It’s at least a year beyond our phase 2B results. We have a good opportunity to make a decision on how we’re going to capitalize the program and the company, what degree partnerships fit in with that runway.

Alex, Interviewer: What’s not included in your runway? You obviously don’t include milestones, but what sorts of milestones are on the table between now and then?

Bruce Jacobs, CFO, Kymera Therapeutics: Yeah, so there’s not quite $2 billion, but around just under $1 billion from Sanofi and $750 million from Gilead. Obviously, some of those are commercial milestones that wouldn’t be within that runway, but there are meaningful milestones that, upon achievement of different accomplishments, if you will, along the way. We never include those, but we have said that there is a milestone from Sanofi at the start of the Phase 1 study for KT-485. There’s also a milestone once Gilead selects a development candidate, opts into the CDK2 program. We don’t include any of those in our runway, and anything we achieve there would be incremental.

Alex, Interviewer: Great. Jared and Bruce, always a pleasure. Thanks for joining us.

Bruce Jacobs, CFO, Kymera Therapeutics: Thanks, Alex.

Jared Gollob, CMO, Kymera Therapeutics: Thanks, Alex.

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