Kymera at Jefferies Global Healthcare Conference: Strategic Pipeline Progress

On Thursday, 05 June 2025, Kymera Therapeutics (NASDAQ:KYMR) presented at the Jefferies Global Healthcare Conference 2025, outlining its strategic advancements in targeted protein degradation. The company highlighted both promising clinical developments and financial stability, while acknowledging challenges in competitive positioning.

Key Takeaways

• Kymera’s STAT6 degrader program (KT-621) showed potent target degradation and a favorable safety profile.
• The company plans to advance KT-621 into Phase 1b and Phase 2b trials for atopic dermatitis and asthma.
• Kymera holds $775 million in cash, sufficient to fund operations through the first half of 2028.
• Collaboration with Sanofi on the IRAK4 program is progressing, with Phase 2 data expected next year.
• New IRF5 program targeting lupus and other diseases is set to enter clinical trials early next year.

Financial Results

• Cash Position: Kymera reported $775 million in cash reserves, ensuring operational funding until the first half of 2028.
• Sanofi Milestone: The company received an undisclosed preclinical milestone payment related to its IRAK4 program.

Operational Updates

• STAT6 Program (KT-621):

- Healthy Volunteer Data: Demonstrated over 90% STAT6 degradation at most doses, with a safety profile similar to placebo.

- Phase 1b Trial: Ongoing in atopic dermatitis, with data expected in Q4.

- Phase 2b Trials: Planned for atopic dermatitis and asthma, starting late this year and early next year, respectively.

• IRAK4 Program:

- Partnership with Sanofi: Phase 2/2b studies are underway, with data readouts anticipated next year.

• IRF5 Program (KT-579):

- New Initiative: Targeting lupus and other interferonopathies, with a Phase 1 trial scheduled to begin early next year.

Future Outlook

• Data Catalysts and Milestones:

- STAT6 Phase 1b data release in Q4.

- Initiation of STAT6 Phase 2b studies in atopic dermatitis and asthma.

- Launch of IRF5 Phase 1 study, with data expected next year.

- IRAK4 Phase 2 data in collaboration with Sanofi.

Q&A Highlights

• STAT6 Degraders vs. Inhibitors:

- Degraders achieve robust target degradation, potentially matching Dupixent’s efficacy.

• STAT6 vs. IL-4/IL-13 Targeting:

- STAT6 degradation offers similar efficacy to IL-4 and IL-13 blockade, with potential advantages in safety.

• Positioning KT-621:

- Kymera aims to establish KT-621 as a first-line oral treatment for Th2 diseases, rather than focusing on patients who have failed Dupixent.

For further details, please refer to the full transcript of the conference call.

Full transcript - Jefferies Global Healthcare Conference 2025:

Kelly Xu, Senior Biotech Analyst, Jefferies: morning, everyone. Thank you for attending Jefferies Global Healthcare Conference. My name is Kelly Xu, senior biotech analyst here. We are very pleased to have doctor Nello Manalfi, chief executive officer, and doctor Gollop, chief medical officer from Chimera Therapeutics for this fireside chat session. Welcome both.

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: Thank you. Thanks for having us.

Kelly Xu, Senior Biotech Analyst, Jefferies: Before we dive into individual clinical program, could you discuss technology platform and how it differs from your peers on targeted protein degradation enabling Chimera to achieve maybe others might not be?

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: Thank you. Thanks for the question. So we founded Chimera about nine years ago with the goal of using targeted protein degradation, which is a technology that uses small molecule to remove disease causing protein. So we wanted to use this technology to go after protein targets that have never been drugged before or drugged well. And what evolved along the way is I think the unique ability to marry the power of the technology with the right target to develop really unique profiles.

In the past, let’s say five years or so where we dedicated our efforts mostly or only in immunology, we’ve been able to demonstrate both pre clinically and as well as early clinically that we can develop oral drugs that can block pathways as effectively as biologics and hopefully for the first time develop orals with a biologics like profile. And so that has been the underlying investment thesis at Chimera and that has then evolved into building a pipeline of oral drugs that I believe is one of, if not the best, immunology pipeline in industry with going after, again, targets that have not been drugged or drugged well before. You can think about stat six, for example, that is a undrugged transcription factor in a highly validated pathway like the IL-four and IL-thirteen that has never again, as I said, never been drugged before with strong human genetics data. IRAK4, again, another poorly drugged target in the IL-one TLR pathway. IRF5 and other drug transcription factor in the let’s say TLR cytokine pathways.

So these are all targets that again needed the right unlocking technology and we’ve been able to do that at Chimera. The other important aspect of the company is the capabilities that we built along the way. Our ability again to go after these really difficult to drug targets come from large investments we made in identifying small molecules that can bind selectively and specifically to these difficult to drug protein. Our structural biology capabilities, chemistry capabilities, screening capabilities allowed us to again develop drugs like KT-six twenty one that now we have clinical validation of the unique specificity that translates into this unique safety profile.

Kelly Xu, Senior Biotech Analyst, Jefferies: Fantastic. And now you have a strong focus in inflammatory and immunology diseases and continue to expand the pipeline. We are curious when you screen and select each target for each program, what are the strategic thinking behind?

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: Yeah, so as I was trying to say earlier, we have kind of four key pillars that we parameters, I should say, that we use to select targets. And I would say that those have not changed materially over the past nine years. So one has to be, again, a target that has not been drugged or drugged well before, has to be in a pathway that has been clinically validated. And again, we can use stat six and the IL-four 13 pathway. A target that has strong human genetics, so ideally we’ll like to see both loss of function and gain of function genetics on the target.

So we know what happens if the target is activated and then what is the safety if the target is removed. And then the ability upon us developing a drug for that target to address large patient populations, which is something that we believe is critical in in today’s evolving landscape of, you know, how drugs are prescribed, reimbursed in the in The US or all around the world.

Kelly Xu, Senior Biotech Analyst, Jefferies: Great. Maybe dig a little bit deeper into stat six program. The healthy volunteer data released on Monday clearly exceeded investor expectations and congrats on the big milestone. To start, could you walk us through the developmental timeline for this program? And at a high level, why you view this program as one of the most important programs in the I and I space?

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: Yeah, thank you. So at the high level, maybe just to do a very, very quick recap. I mean, as I mentioned, I think there are very, very few targets across all, I would say across all disease areas where you have a one to one relationship between a receptor and a transcription factor. And so the ability to use all the validation of the drug that targets the receptor, in this case, Dupixent, dupilumab, which is one of the most successful drugs in history. So you know the diseases in which it works in.

You know how it works. You know that it’s actually one of the few, if not I wouldn’t say probably the only, but one of the few drugs that is used for immune inflammatory diseases that is not immune suppressed, that is not considered immune suppressed. So you have an amazing drug that works through targeting the receptor. And now you have a transcription factor that is selective for that receptor. So if you’re able to drug that transcription factor, you should be able to replicate what has been done with the receptor blockade.

So that’s the thesis that we’ve had from the beginning. And so why is it one of the most important program, at least we believe, is because again, for all the reasons I’ve said, you know, Dupixent is going to be probably a $25,000,000,000 drug in the next three to five years, has a potential patient population of more than 100,000,000 patients, at least this pathway in the seven major market. It’s really only been dosed to roughly a million patients. So we have a huge opportunity not only to enter that market, but to actually build that market. If we just think about atopic derm, which is where 80% of the revenues from Dupixent come from, that is a very immature market.

There is really only one really safe and effective drug that dominates that market. That is Dupixent. There are some other biologics that are coming to market. And then there is an oral drug with a challenging safety profile. So I would say this is where probably psoriasis was fifteen years ago or so.

So we need to build that market and a safe and effective oral drug is going to transform that space. That’s really what we’re talking about here. And that goes beyond AD, asthma, COPD and others.

Kelly Xu, Senior Biotech Analyst, Jefferies: Great. We would like to take a closer look for this healthy volunteer data. So, before the data release, we were actually trying to figure out how to interpret when we got the data sets and how much of a read through to patient trial given not too much prior studies we can actually leverage. So, maybe Nello, at this moment, from the the whole datasets, what data point you would highlight the most meaningful and exciting? And also, from this like beating expectation dataset, would you still say like there’s limited risk to a patient trial?

We would like to hear your thoughts.

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: Yeah. Maybe I’ll address the first part and Jared can address the second part. So the first part is, so we’ve always said for the past nine months that the most critical data for the study had to be degradation and safety because again we built a package pre clinically that if you degrade the target, you can have a doopy like effect if you degrade it 90% plus. So the real question was can we degrade it? We had high confidence of being able to degrade targets.

We’ve done it over and over again. But nobody had drug stat six in humans. So we had confidence, but obviously the question, what is the safety profile going to be? And I think what really surpassed our expectations are two things. First, we were able to degrade 90% or more at all doses besides one.

The only one that was less than 90% was the 1.5. And I will say that that dose was selected at the end of the study where we decided we need to figure out when what is the dose that degrades less than 90%. So we had to go all the way down to one point five. We were not planning to actually even dose that that low. But we the drug outperformed our potency expectations in humans.

And then we were able to fully degrade the target in blood and skin. Remember, that is a very, very high bar to being able to degrade in blood and skin. And we were able to do it completely at doses of fifty mgs and above where most subjects were below the lower limit of quantitation. So that also exceeded our expectation. And the last thing was safety.

I personally have been doing this in small molecule drug development my whole career and I’ve never seen a safety profile that we’ve seen in this healthy volunteer study where the lowest dose, one point five mgs, and the highest dose, two hundred mgs. Or if you look at the study, eight hundred mgs, there was no difference in safety. They were all, again, placebo like safety. And that was a compelling data set that actually is pretty much in line with what we had seen pre clinically, but obviously you want to see that translate in humans. Maybe, Gerard, do you want to speak to how any of these will translate into Read through,

Gerard, Chief Medical Officer, Chimera Therapeutics: Yeah, I think, you know, in terms of read through, I think there we think about, you know, how will what we saw with regard to degradation of the target and impact on the pathway ultimately de risk or affect the probability of success of seeing clinical proof of concept in phase 1b. And if you harken back to our preclinical data in our house dust mite asthma model, for example, where we showed that 90% degradation of STAT6 gave dupi like activity, activity actually comparable or even superior to dupi, a full saturating dose of dupi in that model system. That’s why we set that bar at 90% going into the phase one study. The fact that now we’ve exceeded that bar showing complete degradation where we have 95% or greater reduction with majority of subjects going below the lower limit of quantitation at doses of fifty milligrams or greater in the MAD study, I think gives us a lot of confidence in addition to the fact that we could see effects that were either DUPI like or even superior to DUPI on TARC and on Eotaxin three, which is telling us that profound degradation leads to substantial pathway blockade that is on a par with the sort of pathway blockade that you see with DUPI, IL-four thirteen pathway blockade.

So we think that now that heightens, we believe, the probability of success in phase 1b of being able to show, hopefully in phase 1b, the same degree of statics degradation in blood and now inactive skin lesions in these patients to be able to show a dupie like effect on Th2 biomarkers in blood and inactive skin lesions and to also be able to start to show some impact on clinical endpoints realizing that that 1b is a four week, twenty eight day study. But we know that even with DUPI in randomized placebo controlled studies at twenty eight days you can see significant impact on biomarkers like TARC in the blood, on skin biomarkers and on clinical endpoints. So what we want to see in phase 1b is sort of internal consistency. We want to see that statics degradation comparable to what we saw in healthies. We want to see evidence of pathway blockade with even more ability to look at that Th2 pathway blockade by looking at multiple Th2 biomarkers in phase 1b, and then start to look at clinical endpoints.

You know, even though this is a single arm, non placebo controlled study, we can look for internal consistency between degradation, biomarker effect, and clinical endpoints. And I think all of that will hopefully provide a substantial proof of concept in that study and that would then be the sort of read through that we expect.

Kelly Xu, Senior Biotech Analyst, Jefferies: Fantastic. And maybe a follow-up question here is for phase one b, we probably can expect a similar extent on protein degradation for status six, but for biomarkers where we should pay special attention. And also on safety, healthy volunteer data seems like a very clean. But after we extended treatment, any anything like my on your mind on safety profile?

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: So I mean, Jerry just said, I think the great opportunity in patients is that at least some of these biomarkers like TARC, for example, is elevated at baseline. But actually more importantly, the pathway IL4N13, given that AD is a Th2 disease, will be driving the majority of the TARC that we see. And that’s why in the dupilumab study, you see between seventy and eighty plus percent inhibition of TARC even around four weeks. And that’s because the TARC is generated by the pathway and with a strong drug like dupilumab, you’re able to block it. So that will be a good bar to set for us.

So that’s the kind of numbers we’re going to be looking at. And then I think what has been shown also that there is a very well established signature in the skin lesions, as Jared said, of AD patients of a set of genes that are modulated by IL-four and IL-thirteen. And so being able to show that having a signature that is robust in the skin lesions of AD patients would be important. On safety, know, as we’ve said, in preclinical study we actually have not seen any adverse events in the clinic. Again, undifferentiated from placebo, we’re going to expect, we continue to expect a very good safety profile even when we go from two weeks to four weeks.

Kelly Xu, Senior Biotech Analyst, Jefferies: Great. It’s still early days, but curious as a potential oral option next to DUBI in AD, how would you position the status six program and how do you integrate the thoughts into the future phase 2b, phase three trial design? For example, would you actually include the patients had Dupi experience? And also, like basically commercially, how should we think where this is actually placed among other AD options?

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: So I think Gerald should speak to the high level, maybe phase two trial. But just commercially, again, I said, there are no approved drugs with a good kind of risk profile, risk reward profile in terms of safety and efficacy. We believe strongly that an oral is going to transform the landscape. Are kind of right now going into assumption based on all we’ve seen so far is that we should be able to have a doopy like effect. Obviously, we’ve done market research that says to us that you don’t even have to have a doopy like effect to be a successful commercial drug.

But nonetheless, I think biology so far is telling us that, so we’ll continue to have that as a bar. And I think that that will be a drug that has the opportunity to transform how we think about treating patients. And I believe it will be it should be the first in line drugs for all these Th2 diseases. I am not sure that we need to get over creative in the development to demonstrate differentiation over dupilumab, but maybe I’ll let Jarrod comment on at least our thinking high level in the phase 2b.

Gerard, Chief Medical Officer, Chimera Therapeutics: Yeah, I think as Nelo was saying earlier, the AD population is so large and only a very small fraction of that population is actually currently being treated with dupilumab that our aim is not to really feel like we need to go after dupi failures or people who have progressed after dupi. There’s a very large population where we could be the first therapy. So when we’re thinking about eligibility, if you look at our current phase 1B, we allow patients who are dupi naive and we also do allow patients who have had prior systemic biologics including dupi provided they have not progressed on that biologic. So they can’t be refractory to it because again the aim is not to try to position this drug as a drug that’s going to salvage patients who have had progression on DUPI. In fact, in reality there are very few patients who do progress on DUPI.

And I think likewise when we think about Phase 2b, this will be an important dose range finding study both in AD and in asthma. We’ve guided that the AD study, the Phase 2b AD will be later this year in Q4 and then the asthma study in Q1 of next year. But the dose range finding study again will enroll patients with moderate to severe AD just as the Phase Ib is enrolling those patients and will allow both biologics naive patients and patients who have had prior biologics. But again, patients who have not progressed on If somebody was on DUPI and they came off just because they could no longer get coverage or they came off because, in the rare instance where they’re not tolerating it, those patients would be allowed to be on the study.

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: Thanks.

Kelly Xu, Senior Biotech Analyst, Jefferies: Great. And we saw another approach tackling status six next to degrader. And actually, for the, from the last year, we have seen a couple of deals on status six inhibitors. Maybe share your thoughts with us. What are the advantages for to design a degrader versus inhibitor?

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: Yeah. So, I mean, there have been a few deals on inhibitors and degraders. Obviously, we didn’t invent stat six, right? I think this target has been in the public domain for a while. It’s been on the top list of several large companies for the past at least ten years.

We were the first to actually show you can actually drag this target selectively, specifically and potently. Together with the already interest, I think there has been now, let’s early for us a preclinical validation, now a clinical validation. So it’s not surprising that if you have a drug that could be a mega blockbuster, there’s going to be an effect of the industry trying to follow and trying to find other assets given that our strategy has been clear from the beginning that we’re not partnering this program. So to now answer your question about inhibitors versus degrader. So what we’ve learned so far is that you need to degrade the target really robustly.

Again, as we’ve said pre clinically ninety percent plus to see a pathway blockade that can match dupilumab’s pathway blockade. If you talk to the dupilumab’s team, they will tell you that you probably need to hit the target for sure more than 90%, I’m talking about the receptor now, to see the effect that they see in the clinic. So our view is with a catalytic degrader like KT621 that does not require high exposures to be occupying the target 20 fourseven, but it only requires exposure to degrade the target and then relies on this low resynthesis rate of stat six. We can do that, as we show now clinically, very efficiently with low doses as a once a day oral drug. I think, and that’s based on the data we’ve generated, I believe it’s almost impossible with the occupancy based modality like small molecule inhibitor to have the exposures that are going to block this pathway as effectively as a degrader or as a biologic.

So I think you can block stat six with a small molecule inhibitor, but I believe you’re not going to be nowhere near the efficacy that you’ve seen with Dupi or hopefully with R Degrader once we’re in patients.

Kelly Xu, Senior Biotech Analyst, Jefferies: Great. And we would love to learn the nuance of differences targeting status six versus targeting L4 and L13 given that the commercial drug mostly build on the L4 and the L13 pathway. So, in theory, what kind of implication on efficacy and safety from targeting statics versus other Yeah.

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: So first, I mean, the reason why we keep talking about dupilumab as the bar for us is because dupilumab is the only drug in this pathway that blocks IL-four and 13. The important thing about blocking IL-four and 13, you actually block all Th2 inflammation. If you block IL-thirteen only, you will block only part of Th2 inflammation. That’s why dupilumab is the only drug that is approved in all these indications, unlike, let’s say, the IL-thirteen families. And stat six degradation is the only approach that can phenocopy IL-four and IL-thirteen blockade.

And the reason why we believe, based on all the data we’ve generated so far, both preclinical and clinical, that the safety and efficacy should be the same is because if you activate the alpha receptor, you recruit stat six to the receptor to then propagate the signal intracellularly. So there is no data that we’ve been able to uncover that shows that IL-four or IL-thirteen signal through any other transcription factor. Now, I’m not saying it’s impossible because science is obviously very complex, but we haven’t been able to see it. And all the studies that we’ve run so far, including the clinical data, confirms our hypothesis. And so that’s why we believe and obviously we want to continue to generate data to substantiate these kind of statements.

Kelly Xu, Senior Biotech Analyst, Jefferies: Okay. We have spent a good amount of time on status six and a very insightful discussion. Maybe Iraq Four, we also have two data readout from Phase II in HS and AD next year and the trial is running by our partner Sanofi. Maybe tell us where we are and how should we set an expectation?

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: Yeah, so I mean, as many of you know, IRAK4 was the first program that we actually started at Chimera many years ago now. Four seventy four was our first development candidate. So we at Chimera run an excellent phase one study in healthy volunteers with really robust degradation and also impact on biomarkers. Then we also run a phase one, let’s call it B study in HSNAD with some really promising early data. And then the program has transitioned with TUSANOFI and they’ve been running initially a phase two study and then later announced the desire to expand into a 2b study.

So obviously, we’re in contact with them as far as obviously the latest, we were still on track with what has been shared externally. And you know, the expectations around those studies is being able to show an activity that is differentiated from placebo. We don’t have necessarily a target there because also again in those indications I just talked about AD and HS, there are no small molecule oral drugs with a efficacy and safety profile that is balanced. So I think there is still opportunities there.

Kelly Xu, Senior Biotech Analyst, Jefferies: Great. And you recently announced a new I and I program in the making targeting target name IRF five. How much we know on biology and what does the preclinical information telling you which indications we should prioritize?

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: Yeah, maybe Jared, do you want to take this one?

Gerard, Chief Medical Officer, Chimera Therapeutics: Yeah, I mean we know, you know, quite a bit about the biology and the genetics of IRF five. It’s a key transcription factor that’s very important to mediating signaling through many different toll like receptors, especially toll like receptors that are involved in driving interferon production, type one interferon production, pro inflammatory cytokine production and autoantibody production. Know, it signals not just through toll like receptors but through other receptors through which various so called damps and pamps also are ligands. So this is really a very important protein within the innate immune response pathway that also even dovetails into adaptive immune responses. And there’s a lot of strong genetic validation for the role of this transcription factor, this master regulator of innate immunity in diseases like lupus, for example, and other interferonopathies including Sjogren’s Syndrome, systemic sclerosis and others, and even genetic validation for its role in diseases like inflammatory bowel disease as well as rheumatoid arthritis.

So there’s been a lot of interest in this particular target. It’s just been very difficult to drug as you can imagine because it’s a transcription factor. We now have a very potent selective degrader of IRAF5. We’ve shown I think very compelling data in various preclinical models. You know, just recently in a a company presentation showing that we’re quite active in models of lupus as well as in models of rheumatoid arthritis.

So we’re very excited about the potential of a degrader in being able to go after this target and provide real opportunities for addressing unmet need in these diseases like lupus, other interferonopathies, and as I mentioned, other diseases like RA and IBD.

Kelly Xu, Senior Biotech Analyst, Jefferies: Maybe timing on IND?

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: Yeah, so I think we’ve said we’ll be in the clinic early next year.

Kelly Xu, Senior Biotech Analyst, Jefferies: Okay, great. Lastly, would you like to reiterate the data catalyst and milestones in the next twelve months from Chimera?

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: Yeah, so maybe with that, we, you know, as of the last Q, we’ve said that we have $775,000,000 that allows us to fund all the things that we’ve talked about here today through the first half of twenty twenty eight. So we’ll be able to read out several catalysts, including the phase 2b studies for six to one, actually well before this the cash run out date. So the important catalysts obviously for us are the phase 1b study with KT six to one in the fourth quarter, initiating two phase 2b studies, one in AD, one in asthma late this year, early next. Initiating our Phase one study with KT-five 79 or R5 degree early next year with data, Phase one data ready next year. And obviously, the IRAK4 Phase two data with Sanofi.

We also announced in the last quarter that we received a milestone from Sanofi on a preclinical development milestone on a full on molecule for IRAK4. So that’s also an important other program within our pipeline that unfortunately we can’t disclose much of, but another one to keep track of. So lots going on in the company. Likely, we will share a new program next year as well. So that’s going to be another fascinating story, I believe.

Kelly Xu, Senior Biotech Analyst, Jefferies: Fantastic. I’m looking forward to it. And lastly, thanks again, Nalo and Jared for a great discussion.

Nello Manalfi, Chief Executive Officer, Chimera Therapeutics: Thank you. Thank you, Kelly.

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