Kymera at TD Cowen Conference: Focus on Clinical Advancements

On Wednesday, 05 March 2025, Kymera Therapeutics (NASDAQ: KYMR) presented at the TD Cowen 45th Annual Healthcare Conference, where the company shared significant updates on its clinical programs. Led by CEO Nello and CMO Jared, the discussion highlighted both promising advancements and strategic challenges. The company is advancing its KT-61 and TIC2 programs, with a novel program disclosure expected soon.

Key Takeaways

• Kymera plans to disclose healthy volunteer data for KT-61 in June and initiate a Phase 1b study in atopic dermatitis (AD) in Q2.
• The company is on track to file an IND for TIC2 in Q2, with a Phase 1 study readout anticipated in Q4.
• The novel program is set for an early May disclosure, currently in IND-enabling studies.
• Kymera aims to demonstrate biologics-like activity with its oral STAT6 degrader, KT-61, and differentiate its TIC2 program through targeted protein degradation.
• Collaboration with Sanofi on the IRAK4 franchise continues, with updates expected in 2026 for HS and AD.

Operational Updates

KT-61 Program:

• Healthy volunteer data disclosure is planned for June.
• Phase 1b study in atopic dermatitis (AD) is set to start in Q2.
• Phase 2b studies in AD and asthma are scheduled for Q4 and Q1 of next year, respectively.

TIC2 Program:

• IND filing and Phase 1 initiation are on track for Q2.
• A Phase 1 study readout is expected in Q4.
• The program aims to demonstrate a loss-of-function phenotype through targeted protein degradation.

IRAK4 Franchise:

• Collaboration with Sanofi remains on track, with updates in HS and AD expected in 2026.

Novel Program:

• An early May disclosure is planned, with the program currently in IND-enabling studies.

Future Outlook

KT-61:

• The goal is to identify doses for Phase 3 trials through Phase 2b studies in AD and asthma.
• There is potential for expansion into multiple indications based on Phase 2b results.

TIC2:

• Kymera focuses on demonstrating differentiated pharmacology and biologics-like activity in a proof-of-concept study in psoriasis.
• The company plans to advance to late-stage development following Phase 1 and proof-of-concept study results.

Q&A Highlights

KT-61 Data Timing:

• The dosing of the SADIMAD study is expected to be completed by the end of March.
• Biomarker data generation and unblinding will take about a month after the day 38 follow-up, with data sharing in June.

KT-61 Dose Selection:

• Phase 1b dose selection will be based on achieving 90% degradation in blood and skin, ensuring good safety and tolerability.
• Phase 2b dose selection will focus on degradation levels to identify an effective dose across multiple indications.

TIC2 Differentiation:

• The company believes targeted protein degradation will offer a loss-of-function phenotype, setting it apart from existing inhibitors.
• The Phase 1 study will aim to demonstrate TIC2 degradation of more than 95% round the clock and full pathway blockade.

Readers are encouraged to refer to the full transcript for more detailed insights.

Full transcript - TD Cowen 45th Annual Healthcare Conference:

Mark Fram, TD Cowen Biotech Team, TD Cowen: Welcome back to the forty fifth Annual TD Cowen Healthcare Conference. I’m Mark Fram from the TD Cowen Biotech team.

We’re really pleased to have with us for the next session, Chimera, where we have Nello and Jared Nello’s CEO, Jared, CMO, to join us for a discussion. I’ve had a whole list of questions, but anybody in the audience, feel free to raise your hand if you have your own questions. We do want get those answered as well. But maybe to start off with, Nel, you wanna just kind of give a high level overview and maybe the key takeaways from your your earnings update the other day and and some of the updates you provided on clinical programs there.

Nello, CEO, Chimera: Well, thanks, Mark. Welcome to Boston. At least we have a conference in Boston. So we had a call last week where we highlighted a few updates. Maybe if we go program by program.

So we talked about KT 61, which is our you know, first in class stat 60 grader. This is a program that we’re excited about for for many reasons. But maybe the unique feature of this program is that for the first time in I would say in the history of immunology, you can have an oral drug with, potentially biologics like activity for, potentially tens of millions of patients around the world. So this is a drug that has shown preclinically, to have dupilumab like activity in vitro and in vivo systems. And in our hands, pre clinically, has had a really, really compelling safety profile.

So what we said, a couple of things. First is that we will share our healthy volunteer, the totality of the SAD AMAL healthy volunteer data in June. And maybe later I can explain why in June. We’ve also talked a bit about our Phase 1b study, which actually we expect to start ahead of our Phase one health disclosure in Q2. This is going to be a single arm twenty eight day study in atopic dermatitis patient focused on powered four, hopefully, showing a compelling biomarker profile in blood and skin that will be able to compare to upstream biologics.

In that study, we’ll also measure clinical endpoint, but but clearly a biomarker focused study. So we talked about these two, again, new new concept, the phase one b trial design, which again we can go deeper in the next few minutes. And we’ve talked about the disclosure of the healthy volunteer data in June. For TIC2, we said we’re on track with filing an IND and initiating Phase one in Q2 of this year. So the team has done an impressive job keeping on track with the same timeline since January of last year when we first introduced this program.

We also talked about four seventy four in our Iraq Four franchise with Sanofi that is on track to update in both HS and AD in ’26. And then we’re excited to finally being able to disclose our novel pro our new program. So this is going to be an early May disclosure, made because we wanted to obviously make sure we had a clear line of sight to IND. So the program is now in IND and blaming studies having gone through non GLP talks. So we’ve checked all those boxes And we wanted to do it in a time that would not would not overlap with the six to one anti volunteer data.

So we’ll do that in early May. And we hope many of you will attend because it’s a novel program against an untracked transcription factor that has plenty of human genetics data tying that target to many diseases that I believe are not addressed by, for sure, by effective and safe small oral small molecule. So excited about that. So maybe this is the the the main update. So I’ll pause here and see if we can go into any other details.

Mark Fram, TD Cowen Biotech Team, TD Cowen: Okay. Sorry to touch on some of those comments on 06/21. I think that’s a question we feel that some is trying to figure out why that data is in June. Because I think maybe there was a sense that you might be able to finish that trial a little bit faster, particularly given that you’re going to start that AD trial this quarter. Can you maybe explain some of that, like what follow-up do you need before you fully know a dose?

Nello, CEO, Chimera: Yes. I think we’re today maybe in the position to add a bit more granularity into where we are with the study and why June. So we expect that we’ll complete dosing of the SADIMAD study by the end of this month, by the March. I I wanna remind everybody that, when you complete dosing, we’re talking about day fourteen, we actually follow-up patients through day thirty eight. After that, it takes us about a month to generate all the biomarker data.

As you know, we go very deep with biomarker, blood, skin, statistics degradation, other other biomarkers. So it takes a month to do that after day 38. And then, obviously, we need to unblind the study and collate and generate all the data. So you can see if you do the math how we end up being in that March. But the the again, the study has moved exceptionally quickly, and this is a testament to both our team at Chimera that has done an impressive job as well as our partner that is conducting the study.

But anyway, we’ll leave the celebration to later.

Mark Fram, TD Cowen Biotech Team, TD Cowen: And so obviously, if you start that AD trial a bit before June, that means you’re starting it with maybe not all of that biomarker data fully analyzed. Is that accurate? And then and then Yeah. What what what do you need to select a dose to go into the phase 1b versus

Nello, CEO, Chimera: Yeah. I just want to be careful with how I answer this question, which is totally pertinent. So the dose that we’re planning to take into our Phase 1b study is we expect that those that hits our target product profile, which we said in the past, a dose that would be able to achieve 90% degradation, a 9% reduction plus in blood and skin, and those that we believe has a good safety and tolerability profile. So, you know, you should expect that once that profile is reached, we would be able to initiate all the activities to initiate a Phase 1b study, while completing all the analysis of all the doses and unblinding all all the data to report the totality of SADIMAD might take longer.

Mark Fram, TD Cowen Biotech Team, TD Cowen: Okay. And then as you get that all that biomarker data in, you can kind of walk through how you will evaluate dose and that you’re seeing the type of PD activity you expect.

Nello, CEO, Chimera: Yeah. I mean, I think what’s really important is to appreciate that how we’re thinking about the development of KT61. I think this is, for us, a potential once in a generation type of opportunity with this type of program. So we wanna be really thoughtful about what questions we ask in each study and what information we use from each study. So as you know, we’re we’re doing a healthy volunteer study that was main goal is really to demonstrate degradation, safety, and obviously PK to support that.

Yes, we’re looking at TH2 biomarker, but really the weight of the evidence would be on degradation and safety. The Phase 1b, which again we’ll read out this year too, will be heavily focused on biomarkers and heavily focused on comparing the biomarker to upstream biologics in blood and skin. We will also measure clinical endpoints. And then the really critical path study is our phase to b are our phase two b studies. AD that will start before the end of the year and asthma that will start early next year.

And so, the important data that we’ll actually get from the healthy volunteer study are the doses that we’re going to select to initiate our phase two b. So you can imagine if we select multiple doses, for sake of argument, let’s say, three doses, although we haven’t decided yet. We want to be able to have doses that explore different levels of degradation. And so that’s really where the team will spend time both generating the data and evaluating the data because this is probably one of the most important decisions we’ll ever make on this program. The doses that we will use in Phase 2b, especially given that we plan that this Phase IIb is be the only Phase II study that will run, and that out of this Phase II studies, we’ll be able to select the Phase III dose that we will use for all the indications that we’re going to be trying to take this drug into for registration.

So and then just to be maybe even more clear, it is really the degradation in blood and skin that is the only assay that has the depth, the sensitivity to look at pathway biology to the level of precision that we need to make a selection. If you’ve seen, for example, this blood TH2 biomarker in healthy volunteers, they’re not really able to discern the dose response for dupilumab. So if you actually looked at that, you probably wouldn’t pick the dose that dupilumab has been approved with. So they will be informative. They will be helpful.

They will, you know, I think they will be good data to collect, but the degradation is where we’re gonna make a dose selection decision.

Mark Fram, TD Cowen Biotech Team, TD Cowen: And where are those as you get some of those TH2 biomarker data, where’s the thresholds where you you say the biology is kind of is working, like you would expect? And is there a threshold on the high end where you would say maybe some of these hints preclinically, that this mechanism might be slightly more potent than a dupilumab or is

Jared, CMO, Chimera: going to

Mark Fram, TD Cowen Biotech Team, TD Cowen: play out?

Nello, CEO, Chimera: I want to be totally clear on this. And I know that people speculate on this comment that I make. But the impact on healthy volunteer biomarker for dupilumab has had no correlation to the impact of dupilumab in patients if you look at those as well as depth. So this, I feel to me, given that it’s been shown by also other mechanism like the IL-thirteen from another company, I mean, you do see a change of these biomarkers. So I think this is a yes or no.

But by no means, I think we’ll be able to compare drugs based on a 10% reduction or 5% reduction of IG at day fourteen that dupilumab has shown or a 35 versus 30 versus 25. I don’t think that’s scientific. I think we want to collect the data, we’ll generate the data. We expect the data to be looking like dupilumab because we have no reason to believe that this mechanism should have less impact on those biomarkers than dupilumab. But I also don’t want us to get spend time talking about cross trial comparison on baseline levels of healthy volunteers.

It’s just not scientific.

Mark Fram, TD Cowen Biotech Team, TD Cowen: And what about when we get to the late in the year when we get

Nello, CEO, Chimera: to these twenty twenty data? Yeah. That’s for sure. I think there, I can say today, we haven’t even generated any patients’ data. So I can say even more strongly that if we don’t show the depth of TARC and IG and the perioste neotoxin and transcriptomic that dupilumab has shown, then our claims, I think would not be as substance with it, that this is a a do pin appeal type of mechanism.

Mark Fram, TD Cowen Biotech Team, TD Cowen: Okay. I think that that that cover anybody. Anything else on phase one before we get to okay. Phase so now you’ve already kind of started to lay out that phase two plan. Maybe it’s more of a Jared question.

You wanna you wanna run through what you’ve disclosed there around trials, and then we can get into some of the

Nello, CEO, Chimera: You mean the one b?

Mark Fram, TD Cowen Biotech Team, TD Cowen: Yeah. For the, well, I guess 1B. Yes.

Jared, CMO, Chimera: So maybe starting with the Phase 1B, we’ve said it will be in patients. So in moderate to severe AD patients, we’ll take a optimal dose from the Phase 1A study that’s giving us maximal degradation, it’s likely that that dose that we bring into Phase 1b would also ultimately be probably the top dose in our Phase 2b. So we want to make sure that it’s obviously highly active. It’ll be twenty eight days of dosing and fourteen additional days of follow-up. We anticipate enrolling approximately 20 patients with moderate to severe AD onto that Phase 1b study, which we mentioned is starting in Q2.

The primary objective, Nelo already laid this out of that study, really the primary focus objective is impact on biomarkers. And so we’re looking at multiple biomarkers in blood. We’re looking at the TH2 transcriptome in the skin, in these active skin lesions in AD. And we want to be able to show a doobie like effect. And we feel that the study, even as a single arm study, it’s a single arm study with no placebo control, but that the study is powered to be able to show, a doobie like impact on those blood and on those skin biomarkers.

So I think that’s a very important, you know, part of the study. The study will also be obviously looking at STAT six again, you know, in blood and skin. We expect to see a similar effect as we saw in the healthy volunteers, and we will be including clinical endpoints. We actually know that if you look at the dupi placebo controlled studies, even, you know, at four weeks, you can see obviously a very strong effect on th two biomarkers in blood as well as in skin. And you can start to see some impact on clinical endpoints like, EASI, for example, or pruritus NRS.

So we expect that in our phase one b study, even though the primary objective is looking at those biomarker changes at four weeks and wanting to see a doobie like effect on those biomarkers, we will have an opportunity to look at clinical endpoints and to see if those are somewhat comparable to what has been seen. You know, we do be, albeit an understanding that this is not a placebo controlled study. So the true test of the impact on clinical biomarker clinical endpoints will come in phase two b. But I think we will be able to ultimately connect the dots between impact on biomarkers, TH2 biomarkers, where, you know, you very rarely see a real impact on biomarkers in AD patients who are on placebo. So that should be a very robust signal that we hope to be able to see in, phase one b and make the connection between that and the impact we see on clinical endpoints like EZ and pruritus and impact on stat six.

Mark Fram, TD Cowen Biotech Team, TD Cowen: Maybe back to some of the preclinical data. What are the kinetics of pathway inhibition of getting that degradation look like relative to when you use an antibody to hit this pathway? And should we think of I mean, should we truly think of day 14 with an antibody as the same as day 14 with a degree?

Nello, CEO, Chimera: Yes. I think it’s very different actually because I think if you look at I don’t know that we’ve actually shared the data, but we verbally discussed that, which is we have rapid in preclinical species, we have seen rapid degradation of the target in a matter of hours, single digit hours. And when then we can reach steady state, once we reach, you know, let’s say, in preclinical species, 90% degradation, even at, you know, again, after four hours, then we maintain that degradation for the for the whole study duration. Obviously, once we stop those in, in preclinical species, the target comes back and the biology comes back. With the biologics, as you know, it it does take a while, in fact, I think, to beat them up as a loading dose concept.

And so it does take a while to reach saturation. That saturation is maintained for quite a long time. And then, obviously, before the next dose, you might see less saturation. So you still have a PK dependent PD effect for degraders. We don’t have a PK dependent PD effect.

But once you give, let’s say, a dose of dupilumab because of the long half life, you do see the biology be there for quite a while. While, and again, for a degrader, it will it will go you know, it will return back to baseline soon after, you know, we’ll see in the clinic, but preclinically a couple days after we stop dosing. So, I think the kinetics to effect for a degrader preclinically seem faster, and we’ll have to see if that translates into the clinic.

Mark Fram, TD Cowen Biotech Team, TD Cowen: As you mentioned, kind of biomarkers in that phase one b. But with the clinical endpoints, how will you, you know, how will you interpret the clinical endpoints given that it’s not a placebo controlled trial? Yeah.

Jared, CMO, Chimera: I think it’s a good question. I mean, I think we’re still gonna have to understand what the kinetics of response of those endpoints are to our degrader to KT six to one. I think the best, way to really understand that will be in the longer studies that will be in the phase two b dose range finding studies. Here, we’re looking at twenty eight days of dosing. You know, however, as I mentioned, you know, obviously with even with dupilumab after four weeks, you know, you do see clear impacts on easy, and there are benchmarks.

You can look at the public literature and say, okay, this is what do we saw after four weeks in terms of impact on easy. This is what they saw in terms of impact on pruritus. Whether we have to match that or not is another story, but I think our expectation is that we should be able to see, you know, some impact. Now to your point in the lack of a placebo control, you know, you have to take, you know, those data with a grain of salt. That’s why our focus is really on the biomarker data, the TH2 biomarker data and STAT6 for the initial proof of concept.

But I think when you look in the totality of the data, if the clinical endpoints like EASI and pruritus are tracking together with the impact on biomarkers, which the study is powered to show an impact on STAT6 in blood and skin, I think that’ll be a very compelling, you know, package to give us even more confidence in what we expected and see in phase 2b when we will have a placebo controlled study. And And obviously, we’ll have a longer study. It’s it’s a longer study where you can really you know, it’s it’s more relevant to then look, you know, at placebo as a control. You know, for example, the typical AD studies are sixteen weeks. And that’s a better vehicle for really understanding activity versus placebo in benchmarking it.

Mark Fram, TD Cowen Biotech Team, TD Cowen: And how much will this phase 1b really inform your phase 2b trials? Because, you know, if you’re starting you have this isn’t gonna read out until almost year end and you’re starting a phase two b Yeah. Or year end, like, is there really much opportunity for this to even inform, or is that all driven by healthy volunteers?

Nello, CEO, Chimera: Yeah. I mean, I think our our plans for phase two b is driven off the healthy volunteers, but the phase 1b data are an important important validation of our strategy. Right? We we selected those based on the degradation profile in healthy volunteers. We want to demonstrate that the degradation profile is maintained.

We also want to show that our expectation in terms of impact on biomarkers and to be honest also on clinical endpoints is in line with expectation because we also want to generate data to support the study enrollment. And I think showing that this is a drug that actually has an impact on TH2 inflammation in patients. And we’ll have I I don’t wanna go into the details of all the biomarkers at some point we’ll share, but we have a plethora of things that we’re gonna look at. Some are quite creative, that I think will be highly, highly informative and supportive of the existing strategy. So, and importantly, I think for PIs and for patients that will hopefully, you know, also see the data and be excited by it.

Because this will be the first TH two oral drug that is gonna be evaluated in the clinical setting from this pathway. So I think everybody that we’ve talked to is comfortable with the biology of saying, alright, we understand how this biology works. And so I think we have we feel like we have the attention of, you know, investigators and and KOLs. And and, obviously, these are the the sites that are gonna help us also enroll, but, obviously, showing data increases their reason to believe. So it’s an important study.

Mark Fram, TD Cowen Biotech Team, TD Cowen: Jared, do you want to describe the Phase IIBs that have been disclosed? Sure.

Jared, CMO, Chimera: To the extent that I can because I think there’s only there’s limited information we put out there. But in broad brushstrokes, I think Nelo alluded this earlier. Our aim is really to have two Phase 2b studies. We would call them sentinel Phase 2b studies that will then determine dose for registrational Phase three studies across multiple different indications. So the sentinel Phase 2b is one is going to be a moderate to severe AD that will kick off, you know, in Q4 of this year.

That’s what we’ve guided. And the other one will be a moderate to severe asthma that will kick off in Q1 of next year. So we envision that those two Phase two b’s, will be placebo controlled dose range finding studies will allow us to select the dose for phase three registrational studies across multiple indications. So for example, that AD study will inform dose for other derm indications and probably even for GI indications like EOE, whereas the asthma phase two b will inform dose for, COPD, for example, or chronic rhinosinusitis or other sort of respiratory indications. So that we see is a very efficient way to get to the doses that we need for phase three and then enable multiple potentially multiple parallel phase three is across multiple different indications where, you know, in the past two b has been either approved or shown to be effective.

So I think that’s really the most we can say, you know, in terms of dose rate finding studies, placebo controlled, you know, again, in in very rough brushstrokes. If you look at phase two b studies in general, they tend to be two hundred to two fifty patient studies, but we haven’t determined that exactly yet or the number of doses that we’re gonna bring into it yet. And the duration will depend on the endpoints. You know, a typical AD study, for example, will be a sixteen week dosing duration.

Mark Fram, TD Cowen Biotech Team, TD Cowen: And if GP does have a handful of different dosing paradigms across diseases, but those kind of correct dose, sometimes there’s also loading dose. How much of that type of stuff do you think you need to explore? And do you

Jared, CMO, Chimera: or is

Mark Fram, TD Cowen Biotech Team, TD Cowen: it as an oral molecule, the distribution is much more standard and you can just have likely end up with one dose across everybody?

Nello, CEO, Chimera: Yeah. So I think there’s kind of two questions in there. One is, do we foresee different dosing paradigm, meaning more frequently than once a day or less frequently than once a day? The answer is no. This is gonna be a once a day oral drug.

And we believe that thanks to these mechanisms, we should be able, based on the preclinical data, to suppress this target to levels that we’ve seen to be therapeutically relevant, again, preclinically. So then the question is will we see different pharmacology in different disease types? Let’s say derm, which I’m sure will have a skin exposure and degradation component. We don’t know. Personally, I don’t know how big is that component.

But we’ll let’s assume there is a skin degradation and exposure component. And then in, let’s say, in in in asthma, there will be or in, let’s say, in respiratory indication, there is a systemic and, let’s say, a lung component of exposure and degradation. So it is possible that you might end up having two doses because the distribution profile of the drug in in lungs and in skin is different. Based on our preclinical studies, we don’t have any indications that that will happen. So to be honest, we expect that likely this will be a dose for everything, but that’s the beauty of drug development.

We will run the phase two b studies with that goal in mind, right, evaluate which dose, which means which p k, which exposure and degradation profile is benefiting AD patients versus which dose is benefiting asthma patients. And and then we’ll hopefully then select the phase three. I like biologics. So we don’t need a load in those. We don’t need a frequency change.

And so it’s much simpler in a way in a way, it’s a much simpler development path.

Mark Fram, TD Cowen Biotech Team, TD Cowen: Okay. And just yeah. You’ve got a handful of different trials you’re starting up this year, you know, between them. What’s the kind of disclosure strategy? Or do you plan on informing investment community when you start dosing in the phase have actually started dosing the phase 1b or is no news good news?

Just

Nello, CEO, Chimera: Yeah. No. I think, you know, as we’ve as we’ve done often, or almost always, we like to see when the study starts. So it’s likely that it’s not going to have to be the day off. But once we start the dosing of Phase 1b, we’ll share that.

Once, obviously, once we are closer to data readout, we’ll obviously, we’ll communicate when the general expectation of data release will be. When we start our Phase II b’s, I’m sure we will share when those will start. So, yeah, I think, you know, this is an important program and these are important milestones in a way. So, yes, we’ll share them.

Mark Fram, TD Cowen Biotech Team, TD Cowen: Maybe turning to another program that’s about to enter the clinic, the TIC2. I think many in the investment community have soured on that as a target. What do you think they’re missing?

Nello, CEO, Chimera: Well, they’re missing the power of targeted protein degradation. I mean, I totally appreciate the sentiment. There has been lots of undifferentiated TIK2 inhibitors. I’m not saying they’re bad molecules. They’re just highly undifferentiated.

And so, like, if you say, we’re gonna have another TIC two agent, the first answer is what why, right, some would say. But I think we’re talking about a totally different pharmacology. I think for the first time, we are pursuing a tick to loss of function phenotype, which is definitely not what small molecule inhibitors can do. They can even inhibit the the pathway fully twenty four seven. So I think we have to give ourself, or you should give us the benefit of the doubt that this is totally different pharmacology, and we’ve shown this for for ARAC four already.

And, in this case, with with with a proof of a clinically proven target, I think the opportunity of having a clinically differentiated asset is higher even than what we’ve done before with Iraq four. So, I think it’s learning about human genetics. We have a slide on our deck that shows the human genetic loss of function versus the kinase dead profile, and obviously, they’re very different. And the allosteric inhibitors are not, you know, they’re not replicating necessarily only the kinase dead, but they’re not also blocking all the scaffolding functions of TIP2. So we believe that this is going to be a program that will surprise all the skeptics, which seem to be ninety nine percent of people these days, but that’s okay.

Mark Fram, TD Cowen Biotech Team, TD Cowen: It might be over a hundred percent. That’s possible. The

Nello, CEO, Chimera: Well, if

Mark Fram, TD Cowen Biotech Team, TD Cowen: you do early plant the phase one and how quickly we might know that that’s really that, you know, what Melo just described is playing out and and and starting to drive different clinical outcomes.

Jared, CMO, Chimera: Yeah. Yeah. So so the phase one study will start in Q2, should have a beat out in Q4. I think really as a healthy volunteer SAD MAD study, that phase one trial is going to be key in showing that loss of function phenotype biology by looking at the pharmacodynamics. So we think that within that SAD MAD study, by looking closely at tick two levels, you know, in blood and skin, we’re gonna be able to hopefully show, you know, that differentiated pharmacology that we can degrade tick two by more than 95% round the clock to twenty four seven.

So allow us to have that full round the clock pathway blockade that would mimic tick two loss of function. And We’ll also have other pharmacodynamic assays that will help to show that we’re fully blocking IL12, IL23 type one interferon pathways while sparing IL10. Again, that’s by removing both scaffolding and kinase activity. That’s something that we think is gonna be unique to a degrader relative to what this small molecule inhibitors can show. I think if we demonstrate that in phase one, that will be key in showing that differentiated pharmacology.

And then the next step for us, you know, next year, and we provided some color around this, would be to have a single control sort of proof of concept study, you know, in a indication where tick two inhibitors have been active, for example, in psoriasis. And that would be a vehicle to then be able to show importantly that, you know, a tick two degrader has biologics like activity in a disease like psoriasis, you know, comparing it to placebo, which would differentiate it obviously from the small molecule inhibitors that all come up short of biologics like activity. And that would be the package that would compel us to wanna move forward then with further late stage.

Mark Fram, TD Cowen Biotech Team, TD Cowen: I mean, biologics in psoriasis have their own range.

Jared, CMO, Chimera: Exactly. Do

Mark Fram, TD Cowen Biotech Team, TD Cowen: you just need to be in that range or do you need to be at the you know, I’ll you know, do you need to be at the top? In the range.

Nello, CEO, Chimera: In the range would be a huge win.

Mark Fram, TD Cowen Biotech Team, TD Cowen: Okay. Unfortunately, that’s all the time we have, so we’re going to have to cut it off there. But thanks very much Noah and Jared for joining and everyone in the room. Thanks Mark.

Nello, CEO, Chimera: Thank you.

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