Kymera at Guggenheim Conference: Strategic Innovations in Healthcare

On Monday, 10 November 2025, Kymera Therapeutics (NASDAQ:KYMR) presented its strategic vision at the Guggenheim Securities 2nd Annual Healthcare Innovation Conference. The company’s focus on advancing its drug pipeline, particularly KT-621, an oral STAT6 degrader, was highlighted. While Kymera aims to become a commercial-stage global company, challenges remain, such as interpreting clinical data without a placebo control. The company’s financial stability was also emphasized, with cash reserves expected to last into the second half of 2028.

Key Takeaways

• Kymera is focused on developing KT-621, aiming for it to replicate the effects of dupilumab.
• The company has financial stability with cash reserves lasting until 2028.
• Kymera plans to maintain its pipeline diversity and avoid being a single-asset entity.
• Current studies on KT-621 target atopic dermatitis and asthma.
• The company is open to partnerships but prioritizes executing Phase 2B studies.

Strategic Priorities

• Kymera is committed to building a commercial-stage global company, not just a single-asset entity.
• The company is advancing a pipeline of products addressing unmet needs in immunology, focusing on oral degrader medicines.
• KT-621 and STAT6 are top priorities, but Kymera continues to invest in other pipeline programs like KT-579.

KT-621 Preclinical and Clinical Data

• Preclinical studies show over 90% STAT6 degradation, effectively blocking IL-4 and IL-13 signaling.
• Healthy volunteer studies demonstrated complete STAT6 degradation in blood and skin with placebo-like safety.
• The impact on TH2 biomarkers was comparable to dupilumab.

Phase 1B Atopic Dermatitis Study

• A 28-day, open-label study involves approximately 20 patients with atopic dermatitis.
• The primary goal is to assess the impact of KT-621 on TH2 biomarkers, particularly TARC.
• The study was amended to include a second dose to better understand the dose-response relationship.

Interpreting Clinical Endpoints

• Kymera emphasizes comprehensive assessments, including PK/PD relationships, biomarker changes, and clinical endpoint correlations.
• Despite the lack of a placebo control, the company believes biomarker data and IL-4/IL-13 pathway biology provide meaningful interpretations.
• Challenges exist in comparing clinical data to historical dupilumab trials due to differences in baseline EASI scores.

Business Development

• Kymera views KT-621 as a once-in-a-generation program, positioning itself ahead of competitors.
• The company has resources to drive KT-621 development through Phase 2B and potentially into Phase 3.
• While open to partnerships, the focus remains on executing Phase 2B studies and maximizing value creation.

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

Full transcript - Guggenheim Securities 2nd Annual Healthcare Innovation Conference:

Chris Cannino, Senior Analyst, Guggenheim: Okay, great. Thanks, everyone, for continuing to join us here at the second annual Healthcare Innovation Conference for Guggenheim. My name is Chris Cannino, Senior Analyst here. Very happy to have a fireside today with Kymera. I’ve got Nello Mainolfi, the founder and CEO. Nello, thank you so much for being here.

Nello Mainolfi, CEO, Kymera: Thanks, Brad. Thanks for having us.

Chris Cannino, Senior Analyst, Guggenheim: I’ve actually had the pleasure of covering Kymera for several years now. I’ve seen a lot of science and innovation and hard questions get pushed into the pipeline. Now we’re sitting here at this juncture where you’ve got KT-621, your oral STAT6 degrader, moving into a period that’s going to potentially demand a lot of investment resources, but you’ve still got a very productive pipeline, again, asking some really interesting questions around degraders. I guess I want to start the conversation before we move more into KT-621, just about how you think today about balancing the investment and the strategy between those two pieces at Kymera.

Nello Mainolfi, CEO, Kymera: Thanks, Brad. Yes, I like how you put it. We ask hard questions. That’s definitely true. Our goal since we founded the company nine and a half years ago is to build a commercial stage global company. Probably this is a concept that is abused in the industry, but in our case, we believe not only do we have an opportunity to do so, but I actually personally feel we have a responsibility to build all the capabilities to take this technology into a commercial stage reality. If you look historically, only biotech companies that were committed to this, to building all the pieces on a new modality, were the ones that were really successful. When I say successful, I say that they have one or more drugs that are approved around the market, which is our goal.

Sorry, going back to your question, we cannot become a single asset, and we will never become, at least as long as I’m there, a single asset binary event company, because in the moment in which you become that, you’re actually on your way to extinction as a company, right? Whether you’re successful, the drug is successful or fails, I think the company probably will unlikely continue to exist as it was. For accomplishing our vision, we need to continue to advance a pipeline of products that are asking the difficult questions that you were talking about before. Especially in immunology, where you can say the space is dominated by excellent injectable biologics that are effective and in most cases safe and well tolerated, but have limited access to millions of patients to advance systemic therapy.

With our degrader medicines, that we can overcome the challenges of traditional small molecules of the direct PK/PD correlation and have a new paradigm of once a day oral drugs that can have biologics-like pathway blockade, we can change the landscape of how doctors treat patients with immune inflammatory diseases. Our commitment is well beyond a number one program like KT-621 that I think is a once in a generation program, but nonetheless, we continue to invest. We have KT-579 right behind it, and we have other really exciting programs in our preclinical pipeline. While we do all of that, we also understand well priorities. Today, KT-621 and STAT6 is the number one priority at the company. Should there ever be a discussion around resource allocation, as there is almost on a daily basis, we have our priorities right.

Chris Cannino, Senior Analyst, Guggenheim: Okay. Now you unveiled this program less than two years ago, and it came out with a very compelling preclinical package. Let’s start there. At certain thresholds of STAT6 degradation, what did you see relative to dupilumab and the impact in certain model systems of inflammation?

Nello Mainolfi, CEO, Kymera: Yeah, so we started this program, I won’t say when for competitive reasons, but a few years ago. Our questions were always the following. On paper, when you look at this pathway, and if you study the literature as we had, if you block STAT6, you block IL-4 and 13 signaling. There is no other target out there, intracellular or extracellular, besides the IL-4 receptor alpha that blocks IL-4 and 13. We had this unique opportunity to block the intracellular node responsible for IL-4 and 13. We had two simple questions. One was, can we replicate with the first in class tool early on that actually degrading STAT6 really blocks IL-4 and 13 only and completely? And what is the safety of degrading STAT6 and blocking IL-4 and 13 intracellularly?

We launched into extensive studies in human cells, in animals, of safety and of efficacy and mechanistic studies. We learned that in every single context that we looked at, and believe me, we tried to prove ourselves wrong because we wanted to learn if we were wrong as early as possible, right? We wanted to be really good stewards of capital. We have been right, meaning that STAT6 replicated IL-4 and 13 blockade from the first experiment to date. I believe that is only because this is what the biology is telling us.

What we learned preclinically is that if you degrade STAT6 90% or above in either human cells or in preclinical models of asthma or atopic dermatitis or even other diseases, you’re able to block IL-4 and 13 as well as a saturating dose of an IL-4 receptor alpha blocker like dupilumab. We have not seen to date any biology outside of that. There was a publication from our team in a recent conference where we showed a transcriptomic analysis in human keratinocytes of IL-4 receptor alpha blockade versus STAT6 degradation. We saw this amazingly one-to-one correlation of the profile. To me, that is probably one of the most elegant ways to show the coherence of biology within this pathway, I should say.

Chris Cannino, Senior Analyst, Guggenheim: Okay. Now you provided the first healthy volunteer update earlier this year. How did you measure success in that study?

Nello Mainolfi, CEO, Kymera: You know, before the study, our goal was to show that we can degrade the target 90% plus in blood and skin. We wanted to show, we wanted to see whether that would be well tolerated. We wanted to show that we had a dupli-like impact on TH2 downstream biomarkers that could be measured even in healthy volunteers. As you know, when we shared the data in early June, even we admitted that the data went beyond our expectations. What I mentioned was success. What we were able to see was that we could degrade STAT6 completely in blood and skin. We were able to dose up to almost 20-fold above the 90% degradation goal with pristine safety, with placebo-like safety. We show that with regards to the TH2 biomarker, we were equal or I would say numerically superior to what dupilumab had shown in healthy volunteers.

The caveat is in healthy volunteers, the baseline levels of these biomarkers are very low, so the dynamic range is very low. It’s really difficult and I would say unscientific to compare and say our drug is equal or better. I think the main message was that we continue to show, as we’ve done preclinically, that STAT6 degradation blocked IL-4 and 13 as well as biologics because we could measure downstream biomarkers that were affected the same way as if you had used an upstream biology.

Chris Cannino, Senior Analyst, Guggenheim: Okay. After the Healthy Volunteer, I guess the question I have is, why did you consider then running a short 28-day atopic dermatitis study without a placebo in about 20 patients as the right and important drug development step to do next?

Nello Mainolfi, CEO, Kymera: Yeah. I just want to take another step back. When we designed the development plan for this program, our goal was to enter, actually our goal was to get to the market as quickly as possible with the potential broader development plan possible that would allow us to go in all the indications that are impacted by type 2 inflammation. In order to do that, we needed to do dose-ranging studies in two, let’s call it sentinel, I would call it also the more important indications in type 2 inflammation. One is atopic dermatitis that is the largest market and the most important derm indication, and asthma, which we believe is the most impactful respiratory indication for type 2 patients.

We believe that running two dose-ranging studies in parallel in those indications were the most important step that probably this company has ever made to date. Our timelines, our plans were really locked onto these phase two B studies. We realized that we had a window of opportunity between the Healthy Volunteer study and the phase two B, the initiation of the phase two B study to run a small proof of concept study. We realized that in order to run a short proof of concept study, in our view, we had to be powered on biomarkers where we could demonstrate in patients with elevated baseline level that we could impact biomarkers in the same way that an upstream biologist could do. If we wanted to run a placebo-controlled study to also power on clinical endpoint, we had to run a larger study.

A larger study would have actually been longer and compete or push out the phase two B studies. Here is the thought process. I’m not saying it’s the only way to do it. For us, it was the way to not impact the phase two B timelines and generate data that will continue to give us reasons to believe that STAT6 degradation happens as effectively in patients that impacts type 2 biomarkers as well as an upstream biologics. Even without placebo, you can see if you look at all the data that you generate, changes on clinical endpoints that can be tied to degradation in a biomarker profile that is in line with upstream biologics.

Chris Cannino, Senior Analyst, Guggenheim: Okay. Maybe some follow-ups there then. Which of the specific TH2 biomarkers are most important to look at in a 28-day AD study? How would you describe the benchmarks for that?

Nello Mainolfi, CEO, Kymera: Yeah. So obviously there are several important biomarkers. If you look at blood and if you look at the studies with dupilumab in atopic dermatitis, you’ll see that TARC seems to be the most sensitive biomarker. If you look at those studies that were run a few years ago, you see a robust effect on TH2, again, on TARC in AD patients, where if you see, if you look at the baseline levels of patients with atopic dermatitis versus baseline level of TARC in healthy volunteers, actually there is an order of magnitude change. That is why you see such a robust effect. They were in the, let’s say, low 70s to high 70s, even low 80s, again, depending on the study and the baseline level.

Again, the reason why we like TARC is because, again, assuming we’ll have TARC levels at baseline in AD patients that is comparable to the dupi baseline, we should be able to see the same impact of, again, low 70s-high 70s, because that’s what the biology has been telling us. That is the expectation.

Chris Cannino, Senior Analyst, Guggenheim: Got it. Maybe on the clinical measures, can you explain a little bit more about why you think those can be interpretable at four weeks with no placebo control?

Nello Mainolfi, CEO, Kymera: Yeah. Look, I think if you run a study of a new agent and all you look at is clinical endpoint, I think you have to be extremely careful with the interpretation. I will start by saying that our study is, every study we’ve ever run, and you’ve been following us for years, Brad, we do a comprehensive assessment of how the molecule is behaving and how the biology is translating. When I say how the molecule is behaving, does it have the right PK? Does it have the right degradation in blood and skin? Then how is biology behaving? Does the degradation affect the biology in the way that we expect? Does the biology impact the clinical endpoint in the way that we expect? This is not a novel pathway. This is the most proven pathway in type 2 inflammation.

If you’re able to show that biomarker impact, that the molecule degrades STAT6, STAT6 degradation leads to a biomarker impact, and this biomarker impact impacts clinical endpoints in the range of what has been shown with an upstream biologic, we believe even the lack of placebo will make this data interpretable. What we should be careful about is not to be over precise on a study that doesn’t have that built in. First, at day 28, and if you look at most drugs in the type 2 space, it’s in the steep part of the efficacy curve. Whatever you see at day 28 is obviously not the full efficacy of the drug. As you know, when you are in a steep area of the curve, a small variation can be over-under interpreted. One.

Second, again, the fact that we have small Ns will always introduce more noise. That is why we like to look at the continuous variable endpoints because those have just more robustness than these categorical endpoints that could be impacted by one or two patients going one way or the other. As we said, we’ll share all the data. Again, the goal is that if you look at a comprehensive data set, it is matching the story of KT-621 and STAT6, which has the potential to be a dupi-like drug in a pill.

Chris Cannino, Senior Analyst, Guggenheim: Yeah. So more of a focus on, you said, change from baseline. I guess one of the questions I’ve gotten from investors is around, we’re comparing now to, for dupi data that are about 10 years old now with patients who came in with much higher EASI baseline scores, so more severe disease. Could that impact the magnitude of effect that you see? I’m wondering, as you’ve looked and scoured the dupi data with your team, do you see differences in the ability to reach that change from baseline and the magnitude of that based on a starting EASI score?

Nello Mainolfi, CEO, Kymera: Yeah. Yeah. Let’s actually talk about two things. Maybe I’m talking too long. My answers are too long if I look at the time that we have left. I’ll do my best to be more concise. If we look historically, I think it’s fair to say if you look at the dupilumab studies of, as you said, 10 years ago or so, the EASI baseline was in the, which is a representation of severity, although usually people like to look at IGA more than EASI, but let’s continue to use EASI, a high 20s, low 30s at baseline. If you look at studies from drugs in development in the past couple of years, I would say even in the past five years, you’re probably in the mid 20s. What is that telling you?

That the sites that everybody uses, these are sites that have obviously access to biologics. So the patient population has shifted to less severe. Obviously, these are all moderate to severe patients. It just, because there are now drugs on the market, there has been a slight shift to the EASI at baseline. If you look at the dupilumab data, I think you will say that there isn’t a material difference between responses if you have, let’s say, EASI 22 at baseline versus EASI 29 or 30 at baseline. I think the difference is non-material. What is the difference is mostly the placebo responses. The milder the disease at baseline, the more fluctuation of disease you will see, and so the higher placebo rates you’ll see. This is why with an EASI in the mid 20s these days, you see higher placebo rates.

I believe that if you look at a drug like Dupixent, again, a STAT6 degrader is the only mechanism that blocks IL-4 and IL-13. We should not be comparing it to other drugs that do other things. Really, the only, in my view, competitor should be dupilumab that blocks IL-4 and IL-13. Again, we do not believe if you look at the data, there are thousands of patients’ worth of data. There is not a material difference between EASI 22 and EASI 29. If you are on dupi, it does change the placebo effect. That is a story, obviously, for our phase two B study. For today, we believe our data should be interpretable. What I always say is we need to think about ballpark numbers and not exact numbers because we do not have the precision in the study design to do so.

Chris Cannino, Senior Analyst, Guggenheim: Very helpful. Would you expect the kinetics of EASI change from baseline to be different between an oral degrader and an injected monoclonal antibody?

Nello Mainolfi, CEO, Kymera: I look at the biology because that’s the only thing we have going that we understand fully. What we’ve shown preclinically extensively is that if you block STAT6, let’s say 90% plus, let’s say completely, and if you compare it to IL-4 receptor alpha blockade completely, the biologies are overlapping. For that reason, I don’t expect that degrading STAT6 is any faster or lower than blocking the receptor. Now, you’re pointing out an obvious part, which is we’re also talking about an extracellular target versus an intracellular target. We’re talking about an injectable biologic versus an oral small molecule. You have the distribution of the drug is likely going to be different. The access to compartments of a biologic versus a receptor of an intracellular degrader versus a transcription factor will be different.

It’s really hard for me, a priori, to say I know exactly how it’s going to play out. I think this is going to be an empirical evaluation. The first data will be next month. Once we go in a 16-week study where I hope and I believe strongly that we’ll understand the full kinetics of the drug, I think that will be probably even more telling where we have more control, multiple doses, placebo, longer duration. We’ll have a 52-week open label extension, so we’ll understand the full behavior of our drug.

Chris Cannino, Senior Analyst, Guggenheim: Got it. Now, you had this dynamic with the trial where after the first 10 patients or so were enrolled, you announced that you were amending to add a second dose to test that. The question is, why did you see adding the second dose to the 1B as the more important strategic decision than confirming what you had seen from the first dose’s signal in that 10 patients?

Nello Mainolfi, CEO, Kymera: Yeah. No, it’s a great question. As I said earlier, I believe I said it earlier, one of the goals of our phase 1B was to refine the phase 2B doses. The phase 2B trials, both of them, are the most important trials in the history of Kymera. Again, to date, we’ll have more important trials in the future. We wanted to make sure that our phase 2B dose selection, based on the healthy volunteer study, was the correct one. After we had data for the first 10 patients and the first dose, we thought we had enough understanding of the translation. Again, we’re talking about translation of degradation into patients. That’s what the decisions on the doses were made on, not on other endpoints. We felt we had enough robust data to kind of feel confident about the translation.

We wanted to understand more the translation of a dose response, which obviously is very different than translating a single dose because translating a single dose is one point into the new graph. If you had two points, now you can start drawing a line or even a curve. That is why we thought, given how consequential the dose selection for the phase 2B was as a decision, we thought, let’s get two points of translation and not one, so that we’re absolutely confident. We’re very happy with the decision we made. Hopefully, once we share the data, it will also be apparent for all of you why that was the right decision to make.

Chris Cannino, Senior Analyst, Guggenheim: Okay. Maybe last question there before we have to wrap up. How do you think about business development for KT-621 and whether it’s required for Kymera to maximize value for the asset?

Nello Mainolfi, CEO, Kymera: Yeah. I mean, part of me wants to say I don’t think about it, but unfortunately, I have to think about business development also. The important point here is we believe this is a generational, once-in-a-generation type of program. We have the fortune and the ability to be ahead of our competitors. We have the company, the team, and the money to drive the development of this drug, at least through the end of phase 2B. Actually, right now, as we have cash into the second half of 2028, we expect that we can fund the beginning of phase three as well. We want to be in control of the most important value creation.

That will mean that we want to go through these phase 2B studies, both of them, evaluate fully the safety, the efficacy, the dose ranging, understanding the real opportunities that we have going forward. If our cost of capital, our ability to scale the team and resources will continue to support Kymera alone developing this drug, we’re prepared, and I would love to do it. If we feel like maximizing value will benefit from a partnership, whether it’s clinical and commercial or commercial only, we would obviously consider that. I think it’s head down now, executing on these phase 2B studies, not being distracted by these conversations that take time and resources. Once we have data, we’ll have plenty of discussions.

Chris Cannino, Senior Analyst, Guggenheim: Okay. Great. Nel, always a pleasure to sit down and discuss the business. Thank you so much. Thank you, everyone, for listening.

Nello Mainolfi, CEO, Kymera: Thank you, Brad.

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