Conference Transcript - KYMR 2026-06-03

Pastor Krasheed, Analyst — Jefferies

All right. Thanks. All right. Good morning to everyone in the room and on the webcast. My name is Pastor Krasheed. I'm one of the senior biotech analysts here at Jefferies. Really pleased to kick off this first morning of the Jefferies Global Healthcare Conference in New York. We're starting today with Chimera Therapeutics. I have on the stage with me Dr. Nella Minolfi, CEO and co-founder of the company. Nella, could you start by introducing the company as well as the journey that you guys have been on now that you're 10 years into the founding of

Nello Mainolfi, CEO

Well, thanks for the invite. Great to be here. So let me start with a bit about Chimera. So we just celebrated the 10-year anniversary. We started the company with a simple and ambitious idea, using a new technology, targeted protein degradation, to develop a whole new generation of medicines that will go after targets that have been historically undrugged or poorly drugged in pathways with high degree of both genetics and human validation. And you know it's been an amazing journey of build, of learning, of evolution, of refinement of our strategy. I think we're in a very unique spot right now. We have I think one of the most exciting programs in industry. I think the most but obviously I'm biased. So, we have a program like KT621 against STAT6, which has the potential to impact millions of patients around the world that have type 2 inflammation, we're in two global face-to-be We have, I think, one of the most interesting targeting in immunology with IRF5, where we're targeting an undrugged transcription factor that is known driver of disease, lupus, IBD, We have two really productive collaborations with Sanofi and Gilead in both immunology and oncology. And actually, I would say almost more importantly, we continue to innovate, which is a master at Chimera. So, we have a rich preclinical pipeline full of exceptionally interesting programs that we look forward to sharing as they enter usually IND enabling space. So, that's where we are today. and you know the best is ahead of us guys so let's start with broadened to

Pastor Krasheed, Analyst — Jefferies

and I know you guys are not going to give like a play-by-play on the study but in terms of the enrollment period of the study you know we're kind of at the halfway mark given when you started and when you've guided to completing enrollment can you talk to us at all about how it's gone so far and if you

Nello Mainolfi, CEO

feel like you're on track yeah so the broadened to is our face to be studying atopic dermatitis with KT621, just to remind everybody, KT621, as I mentioned, is a STAT6 degrader. We've shown that by degrading STAT6, you're able to block IL-4 and 13 signaling. We believe we've shown, as well as upstream biologics, whether it's Dupixent or others. And so that has put this program in a very unique place, which is, you know, the uncharted territory of oral drugs with biologics-like activity. So the BROADEN-2 study is a global phase-to-B study, dose-ranging studies, where we have two important goals. One is demonstrating in a placebo-controlled, randomized, large study the efficacy and the safety of the drug, as well as, almost as importantly, selecting a dose to proceed into registration of phase 3 study. So we started enrolling the roughly 200 patients that we set out to enroll. We started in late last year, late 25. We expect to complete enrollment by the end of this year with data by the middle of next We're on track, as I said earlier. I think we've said publicly now, I believe a few times, that we are going to give an update when we've completed enrollment. Until then, we probably think it's responsible not to provide other updates.

Pastor Krasheed, Analyst — Jefferies

Got it. And both phase IIb studies brought into and BRATH are dose-ranging studies. Can you talk to us about what went into selecting the doses for the studies? And also, is it the same doses selected for each of the two phase IIb studies?

Nello Mainolfi, CEO

Yeah. So the BRATH study, if you don't mind, I'll just quickly clarify. The BRATH study is a phase IIb global study evaluating KT621 against placebo in eosinophilic asthma patients. And so the two studies use the same three doses plus one placebo. So it's one to one to one to one. And, you know, the beauty of targeted protein degradation, and I think it's one of the most important compelling reason why this technology has disruptive potential, is because you can actually understand the level of targeting engagement at any given time with your drug. So we dosed more than 200 subjects in our healthy volunteer study or generally in the phase one study to actually understand what is the level of degradation that corresponds to the exposure that corresponds to the dose. And then when we selected three doses for the phase 2B studies, we had, you know, simple questions. Basically, based on preclinical data, we know that more than 90% degradation leads to a pathway blockade that is similar to one of upstream biologics. And so we feel like that is the pharmacological dose. And then the question is, what if you go slightly above or slightly below that dose? What is the level of efficacy and safety that you see with that particular paradigm? So this was our dose selection process.

Pastor Krasheed, Analyst — Jefferies

Got it. And from a regulatory perspective, as you think about providing a sufficient evidence base to support phase three dose selection, do you have to show a dose where you have slightly less efficacy to show that you have kind of truly interrogated the correct dose?

Nello Mainolfi, CEO

Yeah, I think ideally, out of the three doses, you would like to show that one dose has less pharmacological and clinical effect so that you've shown that you have interrogated the biology and the clinical response as well.

Pastor Krasheed, Analyst — Jefferies

Got it. And would the goal be to have a single dose to move into phase three? And I guess it's a nuanced question because the question is, would you have the same dose as well in the derm diseases and the respiratory diseases?

Nello Mainolfi, CEO

Yeah, great question. So, maybe the first part first. So, obviously, it will be ideal to select a dose, one dose. It will make the phase three design and also probably timing of enrollment, etc., I think much faster. That does not mean that having two doses is bad, it's just obviously more complex. So ideally it would be one dose, but we'll be data-driven and we'll make a decision with data in hand. And then the answer to your question about will it be the same dose in AD and asthma, so that's a great question and I think it's a question that we'll answer with data. I mean, at high level, we have seen pre-clinically that we see consistent degradation across all relevant issues, and so that has basically allowed us to project that probably the same dose would be as effective across diseases. The answer that we'll only know with data will be, do you require more or less degradation in different diseases? If that is the case, let's say you require more degradation in one disease and less in another, in that event, it's possible that you'll end up with two different doses.

Pastor Krasheed, Analyst — Jefferies

Got it. And then jumping in more deeply on broadened to the phase 2 B and atopic dermatitis, you're telling me that you've been spending a lot of your time, you know, on the operations of the study and visiting the study sites and doing things like that. Could you talk to us about what gives you confidence in the company's execution capabilities for this very important study and what you're doing to avoid some of the common pitfalls in this disease and even what those pitfalls are.

Nello Mainolfi, CEO

Yeah, so, I mean, obviously, this is the, I think it's fair to say that this is the most important study that we run at Chimera, and so everybody's really focused on, you know, excellent execution of the study. And so, there are a few things to keep in mind. So, what are we trying to protect from? Mostly trying to protect from an execution of the study that might lead to higher placebo rates that might obviously eat into the depth of efficacy that you see. And that is because that has been seen with other studies, let's say, in the past five to ten years. Now, the reasons for these increased placebo rates have been mostly driven by one fact, which is the patient population that is enrolled in these studies is a bit less severe than it was in the early days when there were no systemic drugs approved. So naturally, with the less severe population, you have more disease fluctuations and you'll have more placebo rates. I think that's not the only reason. Some of the other reasons are high. It's a highly competitive space, so there is competition for sites, for patients, for attention, and when there is competition, often, sometimes, quality can be impacted. And so, having a process where you can ensure you have the right patient on the study, you have the right oversight on the CRO and on the sites, that you have oversight on the quality of data that you monitor daily is, I think, what's required to ensure highest quality of outcome. And so, that's what we know we've all been focused on. You know, my involvement is mostly to, you know, obviously continue to speak about the opportunities with this program to make sure that there is knowledge, excitement, hopefully, and awareness in the medical community, in the investigator community. And I think it's the responsibility of the company to do so continuously, actually, not just now.

Pastor Krasheed, Analyst — Jefferies

Got it. And then, with respect to other, you know, studies in the atopic dermatitis landscape, There's at least two things that are unique, and I'd love to hear if there's anything else that you would point out as unique as well. One is that, obviously, your drug is an oral drug, so you have oral placebo as well. And then the other is that your study actually allows prior IL-4 and IL-13 targeted drugs as long as patients didn't fail those drugs. Could you describe those features a little bit and also tell us, are those features that are expected to change the placebo rate in either way, up or down?

Nello Mainolfi, CEO

Yeah, I don't expect the way the drug is administered orally versus CEP-Q or IV to have an impact on placebo rates. Again, I think the placebo rates are mostly impacted by the patient's characteristics and baseline, as well as by quality of execution. With regards to prior exposure to biologics, I think what we're doing is the probably most rational thing to do, which is KT621, which is a type 2, I think potentially the best type 2 drug, is targeting IL-4 and 13. We expect that a drug like KT621 should be a first-in-line drug for all patients with type 2 inflammations, not just AD but other diseases and their comorbidities and so we you know we obviously welcome patients that have been on pathway drugs that have had response to them because that obviously will will explore how well patients will do if they go from one injectable to to an oral I don't think it's the time where we need to explore the refractory patients because we don't believe that's where the medicine would be placed in the treatment paradigm. Got it.

Pastor Krasheed, Analyst — Jefferies

And then would it be fair to assume that by allowing those patients, you might actually help mitigate against some of the risk of higher placebo effect?

Nello Mainolfi, CEO

Yeah, that's actually an interesting insight. I think if you have a patient that has responded to a drug of this pathway, that means that that patient is sensitive to anti-type 2 inflammatory drug. I'm not sure, again, that that will necessarily impact the placebo rates because, again, those are impacted by so many other factors. But for sure, I think it has an opportunity to increase the signal-to-noise ratio.

Pastor Krasheed, Analyst — Jefferies

Got it. And now that you're well into the study enrollment time window, can you talk to us about your expectations going into the study for baseline, easy, and if those expectations have changed now that you've seen the profiles of some of the patients coming in?

Nello Mainolfi, CEO

So obviously, I'm not going to comment on what we're seeing, but so our expectation has been, so if you look at our Phase 1B study, I think our mean EASY at baseline across the two doses was around 25. That is somewhat consistent with many studies that have been run. Recently, I think you see any, I mean, I'm talking about good studies. There are studies where baseline EASY is 20, which, you know, probably they're not good studies, but, you know, 24, 25, 26, it's probably generally the norm, and, you know, again, that's our expectation. We'll see where we land. Again, we've deployed some, I think, quite, I would call it quite sophisticated approaches to ensure high patient quality, so I'm actually quite curious to see where that will lead us with regards to patient severity and patient quality. Got it.

Pastor Krasheed, Analyst — Jefferies

And then on the specific things that you're doing from an execution perspective, could you at least maybe hint at, do you believe that what you're doing is substantially different from what other companies in the space have historically done?

Nello Mainolfi, CEO

So I would say it that way. What are the parameters that you can control, or at least you want to try to control? You want to ensure that patients that are enrolled into your study have atopic dermatitis, which, you know, surprisingly is actually not a given. Then you want to ensure that patients on your study are actually moderate to severe, which is also not a given. Then you want to ensure that, you know, that the investigators that rate your patients are consistent and are experts and are trained. and then that sites and CRO and Chimera has close oversight over the study conduct. So those are the parameters, right? The rest, you know, it's biology, drug, luck. And so the things that we can control, I think we are doing everything that we think is humanly possible to do it in a way, obviously, to retain study integrity. And I would be surprised if there is any other company that is doing anything that is more innovative than we are. Got it.

Pastor Krasheed, Analyst — Jefferies

And then on the safety side of things, what are the key safety events that you are just, like, looking out for for this drug class in general?

Nello Mainolfi, CEO

Well, you know, we are at the forefront of this drug class. So I can only go back to what we have experienced so far. So, what we've seen so far, pre-clinically, we've run so many, you know, tox studies, two weeks, four weeks, four months, six to nine months. And so, we've actually run the whole gamut of pre-clinical safety. And in all studies, I've never actually probably seen that ever in my career, we have not seen any adverse findings in any studies. So, then in the phase one studies, we had healthy volunteers with placebo and AD without placebo against placebo-like safety, I would say, probably across the board. So we don't have, actually, based on preclinical data, we don't have anything we're on the lookout for, and based on clinical data, we haven't seen any emerging pattern. So it's hard for me to say that we're on the lookout for anything. I would say we're on the lookout for everything. We're obviously monitoring, the team is monitoring safety very closely, and, you know, we'll see. Got it.

Pastor Krasheed, Analyst — Jefferies

And then one of the features on the safety side that's seen for the IL-4, IL-13 biologics is conjunctivitis. Can you talk to us about how do you see the risk of conjunctivitis for KT621? Is there any biological reason for this to be any better or worse than what we see with IL-4 and IL-13?

Nello Mainolfi, CEO

Yeah, so I think what we know is patients with AD have conjunctivitis, and then what we know is that if they take an IL-4 and 13 drug, they seem to have more conjunctivitis than in the placebo group. I think that's the fact right now. Then the percentage of conjunctivitis that you see across studies varies. I'm personally not convinced that all these drugs in this pathway, whether it's Dupixent, it's Labri and others, have different rates of conjunctivitis. I think there is a very stochastic aspect to this. And generally, I think they're in the same general ballpark. It's my interpretation. I might be wrong. But let's say they're in the general ballpark. And again, it's the phenomenon of having conjunctivitis, and then on top of it, this drug class seems to increase the rates by, let's say, generally 10% or so, 10 to 15%. So what I can say for STAT-6 is so far in the Phase I-B in patients, we have not seen conjunctivitis. But remember, we had 22 patients, those for 28 days. If you look at Dupixent, 28 days, the rates of conjunctivitis were within the 5 percent, so it would be like one patient at worst. So the fact that we haven't seen it yet, I'm not sure tells us that STAT6 targeting does not lead to conjunctivitis. My base case is that we will see it, and then I think if we see, if we don't see it, we see less or more, will be something we'll have to wait for the data.

Pastor Krasheed, Analyst — Jefferies

Got it. And within the atopic germ competitive landscape, what are you paying attention to more or less within the competitive landscape? Oral or in general? Just in general. I know what investors ask me about, but I'd love to hear just as you look into the landscape, as you go to medical conferences, what are the specific drugs or specific mechanism classes that you guys kind of have on the radar and are looking at?

Nello Mainolfi, CEO

You know, so I've been at both EADV in the fall and AAD now in the spring, I guess. And I think KT621 was one of the most exciting drug in the clinical landscape. That's not what I'm saying, but what has been discussed extensively by KOLs and presenters. So that I know I'm paying attention to. I like innovative things. So I like understanding how we can get the AD disease be responsive to a therapy like we've seen psoriasis. Psoriasis is a much more homogeneous disease, and we've learned that if you hit L23-17 biology axis, you can basically cure most patients. AD is nowhere near that. We know it's a type 2 skewed disease, but obviously there is more than that, right? We obviously don't see 100% easy scores, at least not dramatically. And so I'm very curious about novel mechanisms that are asking the question of what's happened to the remaining patients, whether alone or in combination is what I'm interested in. Less interested in, like, incremental changes to existing drugs.

Pastor Krasheed, Analyst — Jefferies

Got it. And then within the STAT-6 landscape, there's another STAT-6 grader that is, I believe, at the stage that you guys were at, we'll call it like 18 months ago. Other than the timing difference, we don't have to name drop on the mic, it's okay.

Nello Mainolfi, CEO

It's all right.

Pastor Krasheed, Analyst — Jefferies

Other than the timing difference, can you comment on how you see that program as similar or different from yours?

Nello Mainolfi, CEO

Because I think 18 months, six to one was still, 18 months ago, still the best molecule. So, 80 months later, we're still better than others. No, besides the choke. So, I know there is a couple of degraded programs that are, as far as I understand, in IND enabling studies. We just don't know enough about these molecules to have an opinion. Again, our data is out there. We've been presenting in conferences. We have a couple of publications that we're writing. So it's very easy for our, let's call it competitors, although many of them are friends, to, you know, being able to demonstrate their activity versus Dupixent and in that way compare to 6 to 1. So I look forward to kind of seeing that data from other companies so we see where these molecules stand. And I think we have a drug that degrades 90 percent at least in any dose above 1.5 milligrams once a day with placebo-like safety. So it's hard to know what you can do to make another drug competitive.

Pastor Krasheed, Analyst — Jefferies

Got it. And then I want to shift gears to talk about asthma a little bit. I think this is a topic that investors are not talking about or thinking about enough. Can you give us just overall high level the pitch on KT621 and asthma?

Nello Mainolfi, CEO

Yeah, I mean, I think the most impactful thing for KT621, I believe strongly that this is a type 2 drug that will impact all the diseases of people with type 2 inflammation. And it's not just an AD drug. For as much as AD is a huge disease. And I think the amenity in asthma, I would argue, is actually even superior. Not because asthma, in asthma they don't have effective drugs. They actually have many more drugs than AD. But all systemic, effective, advanced drugs are reserved for, you know, what is called GINA-5, meaning you have to go through four more steps of treatment, which include bronchodilators, include corticosteroids, either inhaled or systemics, that actually have deleterious effect, especially on children. And it's actually quite difficult to accept that in order to have a drug that treats the underlying inflammation, you have to go through years of being treated with drugs that do not affect the underlying inflammation. So I think the opportunity we have is to change the treatment paradigm. My dream would be that KT621 would be the drug that you're given as soon as you're diagnosed with eosinophilic asthma, meaning you have IEOs, more likely when you have IEOs, you have I-Pheno, but you have a number of EEOs that tells you you have eosinophilic asthma, and you should be on that drug instead of drug that don't treat that disease. That is a huge population.

Pastor Krasheed, Analyst — Jefferies

Got it.

Nello Mainolfi, CEO

And that is not served right now.

Pastor Krasheed, Analyst — Jefferies

So your phase 1B study was an atopic derm. Can you give us an idea for how the extent to which you feel the atopic derm phase 1B de-risk your asthma development program?

Nello Mainolfi, CEO

Well, you know, so we've shown extensively. Do we have five more minutes? We'll go quick in these last five. No, I was just checking because I thought it was almost done. So what we've shown pre-clinically is that we are able to impact type 2 inflammation in lungs, in skin. Actually, we have also other data in other tissues. And in the phase 1b data, not only did we show that based on biomarkers, we block all these type 2 biomarkers that are relevant to AD, asthma, and other diseases. But we also had a few patients with comorbid asthma. We had a few patients with comorbid allergic rhinitis. So we had nine, we had like 14 patients out of 22 with comorbidities, and we showed in all of them that we were able to impact their comorbidities, both asthma and allergic rhinitis, showing that a drug gets into the upper airways or lower airways, block the inflammation, and have initial, again, initial impact on disease presentation. So, I think that is huge for a drug that mechanistically is supposed to do that. The fact that you demonstrate that makes you very confident.

Pastor Krasheed, Analyst — Jefferies

Got it. So, we have four minutes left, so maybe we'll try to, you know, rapid fire go through a few So, you have fast track designation for 621 in both AD and asthma. Can you talk to us about what benefits does that confer, and is a breakthrough designation a possibility for this program?

Nello Mainolfi, CEO

Yeah, so the fast track allows us to actually engage with the FDA more frequently to kind of ask questions and, you know, to talk about plans and strategies that we have in place. And this is something that we're, you know, fully trying to benefit from. The breakthrough designation is a good question. I would like to think so. You know, obviously, Dupixen had breakthrough designation as the first systemic drug in AD. I think we might have an opportunity as an oral drug with the safety and the efficacy that we hope we'll have, but it's not on me to make those decisions. I would like to think that that's possible, but unfortunately I don't make that decision.

Pastor Krasheed, Analyst — Jefferies

Got it. And then just briefly on the IRF-5 program, you're going to have phase one data later this year. Can you set expectations for what would be a positive outcome in that data set?

Nello Mainolfi, CEO

Yeah, no, I'm super excited about IRF-5. This is definitely a program of potential big impact in diseases that don't have good oral drugs. Lupus, almost no good drugs, though some new are being approved now that have exciting efficacy, but not oral good drugs. I think we have opportunities in IBD, potentially array, to go after patients that don't really respond to first-line therapies. and more importantly we have a new axis that we're targeting thanks to protein degradation that is the central node of multiple inflammatory pathways so what we want to show in the second half of the year is strong degradation you know we like to go beyond 90% as we always do we might not need it for that target but we still want to get there we want to be able to show obviously that the safety is consistent with our expectation, and that through this ex vivo assay, we can block pathway cytokines as we've seen pre-clinically so that we can tie the genetics, the biology with the potential clinical translation into patients.

Pastor Krasheed, Analyst — Jefferies

Got it. And then just one final question to wrap us up here, Nelo. So you're going to have meetings for at least part of the rest of the day here. what is one investor question that you wish you didn't get anymore that you hear the question you think oh man I wish I don't have to talk about this anymore and what is one investor question that you feel like people don't ask you and you think oh I wish people were asking me about this no I think

Nello Mainolfi, CEO

one question I think talking about beyond ad like you just did I think you're the first one in a while if ever that you know want to talk about asthma and the asthma opportunities. I think that is a topic that I'd love to talk more. I don't have questions that I don't want to hear. I mean, there are questions that we've been discussing for a while or questions that could have been asked 10 years ago. But we're here to answer questions. And I think it would be really a bad attitude not to want to answer questions. So we're here for that reason.

Pastor Krasheed, Analyst — Jefferies

Did you have a third? No, no, no. That was it. Pretty politically correct answers, very unlike me, actually. I try asking this question, and my hit rate is not good for getting a very candid answer.

Nello Mainolfi, CEO

In this setting, it's hard to answer that question.

Pastor Krasheed, Analyst — Jefferies

Okay, well, thank you so much, Nelo, for joining us. Thank you to everyone who's dialed in and in the room as well. Really appreciate it. Thank you. Thanks for having us.