Q3 2025 Kymera Therapeutics Inc Earnings Call

Before we begin, I would like to remind you that today's discussion will include forward-looking statements about our future, expectations plans, and Prospects, and statements are subject to risks and uncertainties that may cause actual results to differ materially from those projected, the description of these risks can be found in our most recent 10q filed with the SEC. Any forward-looking statements speak only as of today's date and we assume no obligation to update any forward-looking statements made on today's call.

With that. I would like to turn the call over to nello.

Thank you, Justine and thanks everybody for joining us this morning. Now in the final quarter of the year, as we reflect on 2025, I'm happy to say that our team has executed exceptionally well across all parts of our business and we're very proud of all that we have accomplished this year. We're committed to building a Global by pharmaceutical company and have established a strong Foundation that will serve us. Well, as we scale, an organization and continue to advance our industry-leading oral Immunology pipeline.

As shown on this slide, I'd like to highlight a few of the key achievements this year that position us well for important future milestones.

We initiated our first of 2 Facebook B, trial, rather than 2 in ad, and we're on track to start the breath face to be asthma trial in the first quarter of 2026.

We were also featuring 2 recent late breaking presentations, which have helped us maintain high level of visibility with the medical and scientific communities, where there continues to be strong interest in our own medicines with potential for biologics like activity.

Beyond step 6. We're unveiled. Our Ira 5 program. This spring and presented the robust preclinical data. At the American College of Rheumatology, annual meeting just recently. We've also completed the Katie 579, IND enabling studies, and remain on track to initiate, the first clinical trial in healthy, volunteers early in 2026 in addition to RS5. We continue to advance our earlier stage undisclosed Immunology Pipeline and our goal remains to address many of the major Immunology indications with oral medicines. Importantly, we believe is that synergies across our pipeline provide multiple development opportunities for about for broad patient, populations.

We also entered in into a new partnership. With Gilead outside of Immunology, Gilead is an ideal partner to drive forward, our cdk to oncology molecular glue program, which we believe has brought potential in breast cancer and other solid tumors. In summary, it's been a very busy year and and, and the successful 1 and we look forward to finishing this year strong as we advance our pipeline towards more and more important mind.

Stones.

More broadly. We built. What I believe is 1 of the strongest oral Immunology pipeline in the industry where we're well positioned to deliver novel. Oral treatment options for patients with highly prevalent, immune inflammatory diseases. Several years ago we made a deliberate strategic shift to focus at R&D efforts toward the significant opportunities in immunology and the reason is quite simple within Immunology. Many Pathways have been validated with Upstream biologics, traditional small molecule Inhibitors are not able to block the signaling Pathways as effective as biologics given that direct correlation between PK and PD and the need of high drug exposures, as a result, the power of the power of protein degradation we can now selectively remove disease, causing proteins through a catalytic mechanism that can block Pathways completely which we've consistently demonstrated across all of our programs. This allows us for potential of oral drugs with biologics like activity for the first time in our industry.

And our first in-class pipeline is a testament to this strategy.

if we look specifically at a statistics program, Katie 621 exemplifies this approach there is a tremendous opportunity for a convenient safe and effective oral pill in highly prevalent type 2 diseases, like atopic dermatitis, asthma COPD eoe and others, despite the large size of the patient population, the penetration of other systemic advanced

Therapies like injectable biologics is actually quite low. This creates a significant opportunity for safe and effective oral medicines, which we believe would have potential to change to quality of life, for many patients and family around the world.

We moved our statistics program in a rapid Pace from preclinical to IND to initial clinical proof of concept. And we're not embarked on our first Global phase to be trials. In fact, we filed our end in September 2024, and by the fourth quarter of 2025, we've already launched our first phase of this study. This progress is a strong Testament to the speed, focus and execution of Excellence of our team in driving this program forward.

Looking back at Katie 621 Phase 1 healthy volunteer study, we demonstrated a very low doses. We can degrade statistics, fully and block th2 disease relevant Saito in healthy volunteers as effectively as upstream biologics and in a well, tolerated manner more. We're moving quickly towards completion of the Brazen phase 1B trial, which we initiated in the spring.

To remind you the trial was designed to achieve 3 important goals.

To confirm robust degradation in blood and skin and understand the translation from healthy volunteers to add patients.

To allow us to refine the face to be doses, based on that translation. And to demonstrate that robust statistic, degradation in ad patients, can impact biomarkers and clinical endpoints similar to Upstream biologics, specifically, dupilumab,

Given that the trials fully enrolled and we plan to share the data. Next month, I wanted to use this call 1. Last time to reiterate expectations, were setting into the study across the 4 dimensions were evaluating kt6 to 1 on degradation safety biomarker and clinical activity.

in ad patients, the robust degradation of Statistics in blood and skin that we have seen in the phase 1 healthy volunteer study

The safety profile is Paramount and we hope to continue to see a safety profile in line with what we've seen in both tests, the volunteers as well as our pre-clinical studies.

With respect to biomarkers, we plan to look in both blood and skin.

In blood, we have highlighted targets, the most relevant biomarker at the 4 week time point after achieving up to a medium reduction of 37% uh of TARC in healthy volunteers and given the in a topic dermatitis space. In generally a higher Baseline. T levels are expectation is to show a meaningfully more robust tax reduction.

As a point of reference in published to pilot studies where Baseline T levels were much higher than healthy. Volunteers. The reduction was in the range of 70 to 80% at 4 weeks.

Which is the bar we set for kt6. To1 assuming generally comparable Baseline levels

In skin. We also plan to assess assess kt6 to 1 impact on skin transcriptomics, which we have not assessed in the healthy volunteer studies there. We anticipate changes in Downstream genes that aligns with the expected biological effect of this pathway modulation.

And finally, in terms of clinical endpoints, we went into the study with a robust body of evidence in all of our experiments demonstrating in, Katy, 621 blocks, I4, and 13, as well as dupilumab. And this has resulted in comparable Downstream pathway effects in both in vitro and in Vivo studies. As a result, we entered the broaden study expecting clinical activity of kt6 to 1 to be in the range of what dupy delivered at 4 weeks in its published studies, including on both easycore NH with all the caveats, small ends and the lack of a placebo.

I hope that this is helpful as we approach the data read out next month given that we have quite a bit of investor activities planned this month. Please understand we will refer back to this key objectives and Reserve any additional commentary for the final data presentation in December.

So before I hand the call back to Jared, I wanted to take a moment to welcome Brian Adams. Our new Chief legal officer. At 2 chimira, he's a seasoned life science executive with deep industry experience bringing more than 2 Decades of experience across legal and compliance corporate development, strategic planning and governance. We're thrilled to have him join our team as we enter this next phase of growth and look forward to to his contributions. As we continue, our efforts to building a full integrated commercial Stage Company.

So to wrap up, is I said, on the onset of the call, this has been a year of exceptionally strong execution and we're well positioned to continue advancing. All aspects of our pipeline as we head into 2026. I'm confident that through our expertise, scientific rigor, uh, uh, focused execution. We're building 1 of the most exciting, Immunology, portfolios in this industry. Let me pause here and turn the discussion over to Jared who will provide us an update on the pipeline including additional color on our newly initiated topic dermatitis study Jared,

Thanks, no.

We have made significant progress with Katie, 621 our stat 6 to Greater, and I'm happy to share the advancements. We are making in the clinic with you this morning.

As Melo described, we see this as a transformative opportunity, to develop an oral therapy that delivers biologics, like, efficacy without the limitations of injectables.

It has the potential to positively impact the more than 130 million people around the world living with type 2 diseases, considering all the indications where dupilumab is approved today.

Our first development indication is a topic dermatitis, or add a common, but complex dermatologic condition with a significant unmet medical need.

This is a chronic inflammatory skin disorder. More commonly referred to as eczema that manifests as inflamed itchy and often painful patches on the skin.

These lesions can appear anywhere on the body and range widely in severity from mild irritation to debilitating, full body inflammation.

1 of the most burdensome aspects of this disease is the persistent itch.

it's not just a new sense, it's a Hallmark symptom that can severely impact Quality of Life by disrupting sleep daily activities, and overall well-being,

Antibody based injected therapies like dupilumab. Have made a real difference for many patients providing a well tolerated and safe therapeutic option but it's not a solution for everyone.

For starters, access can be very limited and is a challenge for many patients.

For those who are prescribed, these drugs, it can be inconvenient or a painful route of administration with compliance impacted by lack of Tolerance of injection site reactions or phobia of needles.

And there are also issues with cold storage requirements and imog risk.

In fact, in an industry survey, 75% of patients taking biologics said that they would switch to orals with an equivalent profile.

There are some oral options such as Jak Inhibitors that offer an effective oral alternative.

However, they come with significant, safety, concerns, including box, warnings that limit their use especially in long-term disease management.

Given this important unmet need coupled with the strong pre-clinical and clinical profile of Katie 621 as healthy. Volunteers, we have developed an accelerated clinical development strategy, including conducting, a small phase 1B, biomarker focused, trial in moderate to severe atopic dermatitis patients that we initiated earlier this year,

The key aim of the 28-day, broaden study is to show that robust stats, 6 decreases in blood and skin, lesions by Katie, 621 has a dupilumab like effect on multiple th2 biomarkers in the blood and skin.

It will also assess kt6, to1 effect on clinical endpoints such as easy and parit NRS.

The team has worked very hard to advance this program and in line with expectations we completed enrollment in the study last month and dosing is now complete.

The final patients are completing follow-up and we will collect and evaluate the rest of the data and report results in December.

As we have said, this phase won't be a study was not dating to the start of the parallel phase to the dose range. Binding trials in 80 and Asthma which in turn are designed to enable subsequent phase 3 registrational studies across multiple indications.

This quarter, we initiated broaden 2. Our phase 2B, add study a global randomized. Double blind, Placebo control trial to evaluate kt6, who on in approximately 200 patients with moderate to severe atopic dermatitis.

This study is designed to evaluate 3. Different doses of kt6 211 over a 16-week treatment period compared to placebo.

Patients from the study, have the opportunity to participate in a 52-week. Open label extension period. After completion of the trial, which will contribute to building the long-term safety database. We'll need to support a vual regulatory filings and is also an additional incentive for patient recruitment to the trial.

Eligibility criteria to ensure we're recruiting patients with moderate to severe. ADD include an easy score of at least 16.

At least 10% of body service area, affected and an average weekly price and rest, score of at least 4.

While prior use of biologics is permitted, if treatment was not discontinued for lack of response and following a study to find wash out period. We expect to enroll substantial number of systemic treatment, naive patients, given the attractiveness of the ease and convenience of a once daily oral treatment option.

The primary endpoint is the percent change from Baseline in easycore at week 16.

Secondary end points will evaluate a range of additional safety and efficacy measures including, but not limited. To, the proportion of patients, achieving easy, 50 EZ 75

A validated investigator Global assessment score of 0 to 1 and at least a 4-point Improvement in Peak.

We expect Topline results from the phase. 2B study, will be available by mid 2027.

In addition to atopic dermatitis, we plan to initiate the Breath Phase 2B study in asthma in the first quarter of 2026.

We'll share more information on the trial design, next year, when we get closer to initiation.

Beyond the statistics program we have completed ID enabling studies with Katie 579, our irf5 degrader which we plan to advance into a phase 1, healthy volunteer, study early next year with data expected in 2026 as well.

Last month we shared incremental updates in 2 posters at the ACR meeting in Chicago.

In several preclinical, efficacy models of lupus and Ra, kt5 was generally more efficacious than clinically active or marketed small molecule Inhibitors and injectable biologics feno. Copying irf5, knockout studies.

Have generated showcase that targeting irf5 can lead to correction of immune dysregulation across multiple disease, pathologies while generally sparing normal cells.

We continue to be excited about this opportunity and look forward to moving it into the clinic soon.

All Pause here and turn the discussion to Bruce to review our third quarter Financial results.

First, thanks Jared, as I walk through the third quarter results, please reference the tables Bound in. Today's press release and 10 Q which was filed this morning Revenue in the third quarter of 2025 was 2.8 million all of which was attributable to our collaboration. With Gilead with respect to operating expenses R&D for the quarter was 74.1 million of that approximately 8.4 million represented non-cash stock-based compensation. The adjusted cash R&D spend is 65.7 million, which excludes that stock based cop, reflects a 7%, decrease from the comparable amount in the second quarter of 2025. On the GNA side are spending for the quarter was 17.3 million of which 7.4 million was non-cash stock based comp the adjusted cash GNA, spend of 9.9 million again, excluding that stock based comp reflects a 3%, decrease from the comparable amount in the second quarter and overall adjusted operating expenses were down slightly from the prior sequential quarter. We ended September with the

Cash balance of 978.7 million, providing a cash Runway into the second half of 2028. This Runway allows us to complete. Both Katie 621 phase, 2B trials in ad and Asthma. Cover startup costs in the initial phase reactivities for the stat 6 program Advanced, Katie 579, through initial POC, testing and Advance our research pipeline as we scale and grow. Chimera, just a quick reminder, our Runway collaborations calculations I should say exclude, any honor and Milestones from our collaborations with sanfi and Gilead regarding Santa, Fe we expect that they will advance Katie 485 into phase 1, testing in 2026, which would trigger a development Milestone. Payable to Chimera as for the Gilead collaboration upon exercising, its option for a cdk2 glue. We are entitled to a milestone payment as previously announced at the time of signing the Ghillie collaboration agreement. We are eligible to receive a total of 85 million in upfront and option payments with approximately

Half of this already received as The Upfront payment in the last quarter. We look forward to the continued progress of both the Iraq, 4, and cdk2 partnered programs.

With that, we'll pause here. So we can convene in our main conference room and open the call for your questions. Thank you.

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As a reminder, we are allowing analysts 1 question and 1 follow-up related question today.

We will now pause a moment to allow this queue to assemble.

Question comes from Jeffrey Mitchum City. Please unmute and ask your question.

Okay, great. Uh,

hey guys.

Thank you very much.

I just had a couple questions. Uh, so the first 1 is, you know, when you look at the upcoming data for Katie 621, you know, maybe just highlight know the, the, what are the key characteristics, that could enable it to potentially show. Differential, efficacy versus the pillar map, you know, at relatively early time points. I think that's probably 1 of the bigger uh, points of of uncertainty with investors.

and then the second question is, when you look at the 2 doses of the broaden study,

You know is the expect or the 3 doses, does the expectation that the lower 1 you know, maybe has a lower impact on on degradation and therefore is therapeutic or is it to test the upper ends of where you like to be from a safety tolerability? I'm just trying to get a sense for the selection of the of the doses and kind of how you would frame that out for. What, what would be the ideal kind of result.

Block, I have 4 and 13 signaling as well as an upstream biologics, whether it's an i4 receptor block blocking a drive like the pixel or even an is 13 draw. So generally we're actually the only Aura drive that is able to block is 4 and 13 as well as Upstream biologics in all the studies that we we we've run again, for clinically as I said, few minutes ago, both in Britain. And in Vivo, we've seen comparable activities. And I think this speaks to the biology of the pathway, whether you block the receptor or you block these specific transcription factor for the receptor you see the same biology. So the reason why we say the opportunity here is to have 2 pillow being a pill like profile

It's not because it's actually what we hope to see obviously. We hope to see that, but it's because it's the activity that biology that we've seen so far. So as a data driven company, as we are, we're reporting the observation of so far. We've seen dupy like activity in our Phase 1. Healthy volunteer study where you know, we measured as you remember biomarkers in blood uh in in healthy volunteers. Uh we were able to show also in those biomarkers that we were generally comparable. Some would say even numerically superior to the pillow map. So for me, it's really hard to say. A kt6 to 1 is going to be better than dupilumab, or worse than dupilumab. All we've seen so far. They were generally blocking the path.

With the same way hence that's where the expectations are set. Now, as a data-driven drug development company with, I think a 2 people in the company were very keen to see how the 2 profiles will evolve. And whether they would differentiate, we're talking about obviously an injectable biologic versus a small molecule degraded. So you you will see probably small differences or larger difference here and there, but I priority is very difficult for us to like set the expectation 1 way or the other, I would be in the the probably the happiest CEO in the world if we're able to deliver a duplicate like profile, going to your second question. I think I understand what you're saying and what you were asking but maybe not so you can correct me if I got it wrong. So maybe the way that I'm going to answer, your question is so we selected 2 doses for the phase, 1 bis study because we wanted to really understand well uh what was the translation of healthy volunteer degradation profile?

Into patients to then have high level of confidence in selecting, the 3, doses for the face to be, the only thing I'm going to say right now is that the 2 doses of the phase 1 b, as well as the 3 dosing in the doses that we started in the healthy volunteer study. And generally our approach for the face to be is to uh is to uh um evaluate a range in which we see, you know, maximum pharmacology.

She, uh, and at the top dose, or some would call a super, a pharmacology, and then in the bottom dose of those that reaches, less than the optimal period. And then obviously, it goes in between so that's the general philosophy without going into details.

But thank you. Thank you very much. Yeah.

Thank you.

Your next question comes from the line of Mark Fram. PD Cohen.

Please unmute and ask your question.

Thanks for uh, taking my question. Uh, maybe just on the phase 1, B, you know, your comments, you mentioned the um, kind of Target of 70 to 80% car production. Um, but with that caveat of assuming similar Baseline characteristics. You know, now that you've enrolled the patient, you know, with a group of, you know, 10 per dose levels. There's always some chance that you end up with a little bit of a skewed population relative to the comparators, um, just anything you'd highlight there. You know, based on the patients that have actually enrolled that might be a little bit different than the historical 2 pixel comparators and then I'll probably have to follow up. Yeah, no, it's the mark. Thanks for that. That's a great question. So let me um,

So there are two aspects of this trial. One is the baseline, let's say the baseline ease of patients.

To when when I, when I'm talking about Baseline level of TARC uh, Baseline levels, that was referring to the tarp Baseline levels. And obviously um, you know, I'm not going to comment about what the Baseline of of the study of our study are. But obviously we'll share the data when the time is right, then there is another element which I want to clarify. Then there is the easy Baseline levels. And I think what we've said in the past,

As we've seen generally when duped them up was developed, it worked the first systemic product for a topic dermatologist. And so, if you look at those studies, the Baseline easy where in the high 20s low, 30s, if you look at studies from all companies in the past 5 years or so, you see that the Baseline easy has shifted down in the, let's call it mid 20s and that's mostly because the patient population that were accessing to these trials, um, in the sites that, you know, most companies go to obviously exchange given that this, this size and these countries and these regions have access to the pillow map. So generally the most severe patients are on systemic biologics. Some are not but generally the the the mean number as uh come down a bit. And that's that's what you know, we're observing. And so um that's kind of another elements uh to to the whole study and the outcome of the study. But I just

Just want to separate the point that I was making before where On Target Baseline levels, not necessarily on the easy Baseline level.

Okay. And should we expect that? That same Trend kind of lower, easy scores. Yeah, but it should apply here, but does that have an impact on target level? Likely tarp levels as well? Do you think

I think that, uh, you know, something that will discuss when we release the data, I think we understand really well, uh, obviously the the level of Target Baseline in healthy volunteers right where we see reduction in the, you know, mid to high 30s uh in in many patients on our studies, uh, in the healthy volunteers and we show that also dupilumab. When Baseline levels where in the ratio of anti volunteer at similar reduction. I think again as I've said if you look at other studies to build them up level, you see a correlation between Baseline level and percent reduction of tax. And so I think that's the observation that we're sharing looking at those studies. I don't want to preview our study because you will, as I mentioned in, you know, a few minutes ago, I don't think it would be productive to preview some data here versus December.

Okay, thank you.

Your next question comes from the line of Brian Abrahams. RBC please unmute and ask your question.

Hey guys uh thanks so much for taking my question and congratulations on all the progress. Um, I'm wondering how are you guys thinking? Now that it's been initiated about the powering overall for the phase 2B, add study, just considering the population you expect to enroll the mix of biologics. Uh, and experience the naive patients and your expectations for uh, effect size. Uh, and then just as a follow-up, it sounds like you're thinking about maybe different doses for asthma and respiratory diseases. Uh, versus uh, dermatologic diseases is wondering if you could elaborate a little bit more about uh what you think are the important considerations around that, thanks.

Yeah, do you want to take? Sure? Yeah. I mean we can't um, you know, get specifics around powering. Um, you know, for the phase 2B what we can say is and we have stated that the end of that study, um, you know, you're going to be approximately 200, you know, with their big forearms, 3, drugs, 1 place. So we look very carefully at, you know, what the expectations are with the patterns have been in the past with regard to, uh, easy responses and respirators responses, Etc and that's all gone into calculating. You know, what sort of ends we need to make sure that the study is adequately powered. So you know we've been very careful in the design of the study to make sure that we are powered to show that desired effect relative to placebo.

Another important aim of the study obviously, is to be able to look across the 3 different Doses and to see if we can discern any sort of a dose response. So the study is powered to enable us to do all of those things.

Those is between 18.

Oh, the dose between 80 data so right now. So I think what we've guided is that our plan is to in the phase 2, be to use the same doses, you know, for both, add and Asthma across both Phase 2. These studies

Goes for all studies but that's why we're running different. Those ranging in different diseases with different Target tissues so that we actually understand what the right dose will be.

That's really helpful. Thanks so much.

Thank you, thanks.

Your next question comes from Brian Chen, JP Morgan if you'd like to unmute yourself.

And ask your question.

Hey guys, thanks for taking our questions this morning.

Um, some of the callers you providing here for the December read. Out is pretty much in line with what you already method.

So, I'm just curious, just given the gap between the time, you selected your 3 doses for the face to be.

And when Phase 1 be finished enrollment around early October. What could be added tip to what Jordi know you know, December read out or do you think the data is most likely going to be in line with the data that you had already seen? When you picked the 3 Doses and have a follow-up,

Well, so I I like to maybe clarify. I think what we said before is the same thing that we've been seeing for 9 or 7 months, but but that's maybe just my my small, um, additional color. Uh, so I I just want to clarify when we selected the doses for the face to be uh was actually a few months before uh October. Right, we started to study recently, the face to-face study but in order to submit the protocol and do startup activities, you have

To actually have chosen the doses much earlier. And I think I said this many times, I believe publicly that when we selected the doses, we had visibility into partial data for both doses, for both the first dose in the 1B and less. But still, some do some data from the second dose in the phase 1B. Um, uh, and again, within our access to the totality of the data, but we because we're focused mostly on the translation of degradation, uh, and obviously safety, which is understood. We had enough information to make the right selection for the face to be doses. Thanks hello. Um, in a prepared remarks, um, in the front and 2 trial design, I think you mentioned that you expect a substantial number of patients to be naive to advanced therapy. So I'm just curious what the driver behind that and how should we take that into?

Account. As the investors, think about comparing the bond to a future data against other benchmarks.

Yeah, so I'll start, Jerry, please jump in. So, um, the reason why we believe that would be the case is multi-fold, but I will start with, uh, we believe Katie 621 that I've got 6 program is a whole value proposition to expand patient access to.

To Advanced systemic therapy. The penetration of these Advanced biology to moderate to severe, patients is less than 10%. Some companies claim it to be more than 10%, maybe we align on 10, let's say 10% so we don't have to argue with other companies. So the majority of the patients do not have access to Advanced systemic therapy. That's where uh we're coming from then another part which we discussed as well is uh patients that have gone on to systemic therapies that have failed. Systemic pathway, systemic therapy. How far has 13 Jacks? Will not come onto our study, uh so they will have to have responded to those therapy then decided not to continue and then jump on our 6211 study. Um so for for those 2 main reasons and also I would say for the experience that we had in the phase 1B we believe the majority of patients would be naive and I I would also add hope

Hopefully, I will not be proven wrong that. Um, we don't believe that the issue of their finding naive patients because that those patients are in dire need of an active, uh, systemic oral safe therapy.

Yep. If you're doing it, would add just as a reminder that this is a global study and so we're running the study in North America, Europe, Australia, and Japan, with the majority of sites actually being outside the U.S. So outside the U.S. in particular, there are going to be a number of patients who don't have access to 2B. And so that's another reason why we expect, you know, a substantial proportion of patients on 2B to be naive.

Thanks for the caller. Thank you.

Your next question comes from the line of May mantani B, Riley. If you'd like to unmute yourself and ask your question.

Questions and congrats on the progress. Uh, could you give us a little bit more detail on the asthma? Uh, breath? Uh, I think you're calling a trial considerations in terms of, uh, you know, if you're looking at a 12 or 24 week, if you want endpoint or a longer duration, exacerbation you could be looking at both but just wonder in terms of, uh, you know, which is your primary endpoint and then also curious about the kind of patience you're thinking to enroll there and the allowance of background therapies. And and obviously the uh question is around, you know, timeline

For, uh, data readout for the asthma topic terms. Will they be stacked together in 2027? And then I have a quick follow up.

Yeah, no, thank you for the question. Unfortunately, as we said, we're going to talk more about the phase, 2B bread study when we're in in in the startup mode, when we're close to closing, our first patient. So give us, you know, a few more weeks and then we provide all the callers that that you're asking for. So, why don't you ask the follow-up? So that, at least give me a question and maybe just to talk a little bit beyond, uh, uh, 621 and about your pipeline, uh, beyond that just on the 579. Could you maybe give us some color on what the initial targeted? Uh, indications would be just given, you know, the broader information Cascade that you're targeting. Their thanks for taking your questions. Yeah. And maybe just high level. Uh, so so thanks for asking about the IRS file. This is a program that uh, I think it

as mostly being unparalleled in the industry where you have a highly validated

Genetically validated transcription factor that has been uh, I think the the object of many drug development efforts in the bip Farm industry for a decade or so, but as, as maintained as remained elusive, where Chimera has that solution using targeted protein degradation. So if you look at human genetics, the top 4 places, where 1 would uh would go directly are, you know, generally lupus actually and other subcategories of this disease.

Some other interferon related pathologies um array ipd. Uh so those are where human genetics point to our preclinical data point to. I think 1 work closer to the uh Phase 1 study will be able to share more about our development plans, shared anything you want to ask

Thank you.

Your next question comes from the line of Sudan loans from Stevens. Please unmute and ask your question.

Uh, hi. Good morning. Uh, camera team. Thank you for taking my question. Uh, you looking back at the healthy, volunteer data for Katie 621, I noticed that the median percent change in the serum TARC and the IG e were similar, uh, to that of duplicity volunteer outcomes. Uh, you know, for those same levels went on treatment. Uh, there was a noticeable, you know, rebound, higher, obviously, whenever these on these levels when the patients were off of Katy 621 as, as you showed, um, my question is, how important is the durability for the ad and Asthma patients, quality of life outcomes and will Katie 621, uh, daily oral dose, dosing regimen, uh, make up for any diseases and maybe a durability outcomes that it could have compared to dupy. And uh, does dupilumab motive Administration and systemic effects just inherently lend to a more durable outcome.

It's a great question. So I mean, I will answer back today and then I'll let Jared also speak to part of all of it. Um, so, uh, the beauty about our drug is that it's uh, once a day overall, that allows you to block. I put in 13 continues, um, that steady state

Um, the beauty of our drug is that you can stop and start when you want. If if needed

Uh without you know, long Workshop period, the beauty about it, once a day oral drug is that as long as you continue to take the drug. Once a day orally, you will see profound effects or at least the effect of the biology. The underlying biology will, uh, will have

A couple of days before your next dose, you're not maximizing the pharmacology as much. So you might actually have less pathway blockage, continuous pathway blockade than once a day, all of the greater now. What would that mean? From a therapeutic perspective, obviously, well, time will tell and studies will tell.

Yeah, and maybe coming back to your comment around the phase 1, they just to clarify, you know, um, patients were on a math portion. We're getting 14 daily Doses. And so, when we look at the effect on Target and eotaxin 3 in particular that suppression or inhibition was seen throughout the entire 14-day dosing, period. In fact, if you look at day 7 versus day, 14 levels were actually continuing to go down Target and the effects in 3 between day 7 and 14, which suggested that if we had continued dosing Beyond 14, we might have seen more suppression. So there was no recovery of targeting any attraction 3 until dosing would stop after day 14. And then you see a gradual recovery. So that just speaks to what Nola was referring to in terms of the durability of the effect as evidenced by, we're going to help you volunteers you know our durable effects.

Thank you. Thank you.

Thanks, thank you due to time. Restraints, we are now limiting analysts to 1. Question only

Your next question will come from Andy Chen. Wolfe research if you would like to unmute yourself and ask your question.

Hey, this is Brandon non for Andy. Um and thank you for taking our question uh within broaden to. Are you doing anything to control the rising trend of placebo that we're seeing in a topic dermatitis uh where recent trials have seen a higher Placebo response.

Yeah, thanks for the question. Uh, so I I just want to answer the question and then Jared will address it. So, um, I think that's an important Point. Uh, I think there was speaking earlier, I think with the drifting of uh, patients with the easy. Uh, shifting from, let's say early 30s to mid 20s. I think it's, uh, almost physiological to have seen, uh, an increase of the placebo rate. Um, I think though there are ways in which 1 can minimize the effect and maybe judge you can speak to it. Sure. Yeah. I think, you know, as far as we see it, I think this is based on the general learning from prior studies. There are really 3 main things that 1 can do to try to limit that Placebo rate. 1 is making sure that you have the right protocol design and select selections so that you're making sure you actually have patients with atopic dermatitis. Not other uh, skin diagnosis and that you make sure you have moderate to severe pain.

That you're not somehow also getting mild patients. The milder patient is the more mild patients you have we should not really be enrolled in these studies but if they are enrolled or going to have, you know, a contribution to Placebo rate. A second important thing is to select, you know, very experienced sites because you want the Raiders, the people who are assessing the end points that have the right expertise, the right Derm expertise here for ad and you also want to have the proper training of those Raiders to make sure they're able to, you know, assess easy for example, consistently and accurately. And then finally, it's really important that there be closed sponsor oversight of the sites involved and also the cro that's helping to execute on the study. You know, that oversight is really up study conduct and the sponsor has to really be all over study conduct. So I think all of those elements combined, I think are important in helping to mitigate, uh, we'll see what rate and those are all things that we're addressing in our study.

Thank you. Thank you. Your next question. Comes from creeper. Deborah a tourist if you'd like to unmute yourself and ask a question?

Hey guys, can you hear me?

Yep. Yeah, thank you so much for taking my question. Um, I was actually wondering how you think about the evolution of the competitive landscape for 61, I know, you know, you guys are significantly advanced in terms of the clinical development, there are competitors whether you talk about degraders or some Inhibitors. Uh, but based on what you've seen, how important is the

The fact that, you know, you're ahead in development versus any potential areas of differentiation, and where does the NextGen statistics degrade fit into this context?

Thank you.

Success, right? You're you're ahead of the competition, which is important. But more importantly, you have a drug that is going to be extremely difficult. It's not impossible to do better than, uh, and that's what Katie 621 is. Um, it's a drug that is exceptionally potent. As we've seen, uh, exceptionally well tolerated, uh, with a, with a profile that we believe will allow us to go in any potential indications of patients with kids to diseases. Um, you know, I think others will have to talk about their differentiation versus kt6. To1, I'm not familiar with many of the other programs because they haven't been any Publications on presentations with actual data. What I would say

going on record here is, I believe a small molecule inhibitor statistics, uh, is uh, impossible, uh, to reach the level of pharmacological effect that are degraded will have mostly because will not be able to block this pathway 24/7, almost completely or completely as we do and we believe that that's required to have biological like activity. Um, on the other obviously, the greater programs again, I don't know enough but the important thing here is that we have confidence in our drug where years ahead of competitors. And so our team mandate here, including us around the table is to execute flawlessly.

In the next few years. So that we can accomplish the commercial success that will make 861 uh, a double-digit billion dollar drug uh in the th2 space.

Right, thank you so much.

Thank you.

Your next question comes from Jeff Jones Oppenheimer.

If you'd like, to go ahead and ask your question.

Good morning guys. And thanks for taking the question. Um, we've been talking about TARC eotaxin and some of the other critical biomarkers for the stat 6 program. Um, can you comment on keyar biomarkers? We should be focusing on for the irf5 program when we see that data and should we be expecting healthy, volunteer data in 2026.

Yeah. It's uh, Jeff that you always are very orthogonal question. I love it. So uh yes, we expect to have uh Phase 1 data from 579 in 2026 next year. Um, it's a bit early to speak to the bio markers but as you know, as as you do know as well, uh, we tend to to run Phase 1 head people in future study that are quite rich in terms of information. So as we get closer to the start of the study, we'll share more about our biomarker strategy.

Thanks guys.

Thank you. Your next question comes from the line of Jet, mmmkay, BTIG. If you'd like to ask a question.

Great, thanks for taking my question. Um, you know, you folks have spoken at length about the niche and the opportunity for Katie 621 and the atopic Derm space. But could you just elaborate a bit further on how you see it fitting within the asthma landscape? Thank you.

Yeah, I mean I'll start with actually there's a more fundamental issue. I think in the administration speak to the medical part of it. I just want to talk strategically. Uh so uh th2 as my years in philic asthma, which you obviously we expect this drive to address, right? Um, just to level set is a disease that start very early in life.

Uh, and actually, it turns out that, uh, if uh, you're not able to impact.

the disease uh until um or before your lungs fully developed, you're actually going to have reduced lung function for the rest of your life.

And children, young adults are on, uh, non on therapists that do not address the underlying PH2 information for many years before. They are graduated to systemic biology. I think that is the Paradigm that needs to change because we're actually putting kids lives.

This is a disease of young people, and we need to change how this disease is treated. Let me tell you, you can bring us back to Earth and more medical. Yeah, no, I think. Um, in addition to the, I think important opportunity and and pediatric patients, I think. Also, you know, in, you know, the Adolescent and adult patients, you know, with asthma. I think being able to access a much greater proportion of those patients with moderate to severe disease, right? Who have a significant amount need but just are not going on injectable biologics for all the reasons, around Market access or concerns about being on an injectable or a biologic, to be able to really penetrate the, you know, adult and Adolescent space as well. But, you know, with our drug, for those patients, who monitored disappear. Because now we have an oral drug which hopefully at the Faz if it's comparable to do beat its efficacy and safety, it could really you know transform you know how these adults and Adolescent patients are also treated with asthma.

Thanks guys.

Thank you. Your next question comes from Clara dong with Jeffrey's please unmute and ask your question.

I think it will. We can't hear you.

No.

Yeah, maybe the operator. Do you want to put her back in queue and we go to the next 1 and she can try to sort that out.

Your next question will come from Alex Thompson.

Please bear with us as we invite him to be a panelist.

Thank you, Alex. If you'd like to go ahead and ask a question, greater thanks for, uh, all the updates here. I guess on the the phase 2B, add study again. Uh, you mentioned obviously patients that had experience with biologics. And I think, now, you also mentioned Jack Inhibitors is, is there going to be a cap for how many of those you know, advanced therapy experience patients? You might have in the study and then on uh rescue therapy. How are you doing with that as well? Thank you.

Yeah there will be no cop again as long as you have not failed Advantage semi therapists that block you know these Pathways or as we've seen in England Jax uh there will be no cap for those and I don't think we're discussing rescue therapy. Obviously there is a system on how we're going to deal with it but I don't believe we're. We're going to disclose it at this point. Sounds good, thank you.

Thanks Alex.

Thank you. Our next question comes from FICO care sheet Ling if you'd like, to go ahead and ask your question.

Hey guys, thank you for in the question. Um so I know you've put uh kind of a benchmark out there out there of 70 to 80% on a car production from Baseline. Uh, could you talk to us about what you would, what efficacy endpoint you think, uh, people should focus on given that people are focused on this given that you already showed nice talk and healthy volunteers. Uh, and then if you're not willing to put out a numerical Benchmark and you just clarify for investors, why? That's the case.

No. So uh, thanks, that's a very good question, actually. So we're just basically stating the facts and we've said that this is a biomarker focused study mostly because we, I think, we, we can gather from the data that, um, there is very little, it's almost no, let's call it a placebo effect on biomarkers. So the absence of placebo should not impact the interpretation of biomarkers, right? So we're, we're honestly a bit more comfortable saying, you know, for TARC, assuming the Baseline levels are in the range of what we've seen with the duplicate study, we expect to see the 70%, plus 70 to 80 that's a fact, right? That's what the premium might be seen. Now you would say it's also the fact that the easy reduction in the day 28 there is a number to it. The reason again why we've been shy about the putting a number on that is because as you

You know, clinical endpoint are, you know, much more noisy and much more impacted by uh, by the, you know, potential procedural effects. And so I, I think we, we like to be data driven and signed first company, as, you know, as well. And, you know, I think we, we'll, we'll put out things when we can confidently say that those numbers are something that we can scientifically. Then, you know, follow and adhere to what we said. Again, we're not going to hide behind it. The numbers are out there for 2 people, right? We, I don't have to say what the numbers are. The numbers are up there. The treatment arm numbers are out there. We expect with this study at day, 28 to be in that ballpark because we we know that Tech, 8661 blocks the pathway, as well as cap. So here is the

Exposure. Appreciate it. We'll look forward to the day, the next month.

Thank you. Thank you. Our next question. Comes from Judah, from a

Question, um, maybe just 1. If there's anything you can share on on early recruitment Trends even anecdotally for brought into obviously, you know, the phase 1 B was, was tougher to recruit just given the 28 days dosing here. You know, you can get patients on drug for a a year plus and curious about just awareness of the healthy data and how all that might be helping in recruiting patients. And and what investigator feedback is, thanks,

Yeah, I mean, high level again we just started this study. Uh, we just, you know, activated, a few sides. So we're very, very early into that process. Um, you know, I I think what we believe right now is, um, even on the health people on the phase 1B, there was uh, a lot of excitement, uh, by sites and investigators and eventually patients we believe in accessing an oral option. And obviously, the 28 day study was not set up to get patients excited because it's a short study without an Ole. So the face to be to hold different value proposition and I believe between that and hopefully the day that it will disclose in December. I think it will be. Uh we are confident that this will be a study that we can recruit in a timely manner.

Now uh, recruiting the study as fast as possible is not our goal. Our goal is to recruit the study as fast as possible with the right patient. Going back to what Jared was saying earlier. We have a paranoid, um, oversight of this whole study, uh, because we want to try and control the place of race as much as possible, uh, even if that has to be at the expense of a week or 2 or, or, or, or 4, so that's where we're coming from. But hopefully it will be able to share more uh, about you know, your question as we get deeper into the study.

Thank you.

We would like to invite Clara dong to try 1 more time if you'd like to unmute yourself and ask your question.

Good morning, thank you. Can you hear me now?

We can hear you. We see somebody else. We can, we can hear you. Go ahead.

Thank you for letting me try again. Um, so my question is on the phase, 1, the trial. So this trial has a relatively short follow-up for a week.

So among other key end points like biomarkers uh clinical advocacy and statements, which ones are you in? Your view are relatively less affected by the treatment duration than which end point. Do you think it's more complex to incorporate because of the quality of life? Thank you.

Yeah. So I think very quickly, because we're almost running out of time, if you look at the Zup study, I don't believe—and hopefully I'm not wrong to have to correct me—I don't believe there was any endpoint that reached maximal effect at a week for.

uh so I think uh it's hard for me to say which 1 is going to be less or more impacted by um by this uh 28 day duration, I think well, we'll look at all the data together in December and and until the question better,

Thank you.

Thank you.

Our next question comes from Brad Canino Guggenheim. If you'd like to go ahead and ask a question.

Great to see everyone again. Um, maybe just, uh, close out on a capital, allocation question for now because you're in the most comfortable cast position you've ever been in with the company but also have the highest Capital demands ever faced by the company. So how do you think about deployment of each incremental, investor dollar across kt6 to 1, the name Pipeline and the platform to really maximize value for Chimera at this juncture.

Yeah, great question. So I probably need half an hour for this, but in in 30 seconds is um I think there's never been a biotech company that has developed a program, like kt6 to1 on their own fully. So we appreciate this is uh, a unique both opportunity and responsibility to do Capital. Look.

Spending a lot of money on the other programs and I always believe that we need to earn the rights to invest more. So, our ability to invest more in 6 to 1 will be driven by the success of 6, to 1. Our ability to invest more. Also in other program was depend on. Also our ability to have success with our clinical pipeline. So we don't do resource allocation because we have money, we are locate Capital because we're in the right to do more and that's the strategy since day 1.

Thank you.

Our final question of today comes from Joe Catanzaro Mitsuwa, if you'd like to go ahead and ask your question.

Perfect. Uh, thanks so much. Appreciate you guys taking my question here? Um, maybe a follow-up sort of along the lines of duration of effect wondering. If you could say anything about the level of compliance,

That you observed in the phase 1 B but maybe more importantly, looking towards the phase 2B and 16 weeks of dosing what you guys can do to ensure a a high level of compliance there. Thanks.

Yeah, no, it's a great question. So obviously with an oral drug. Um, you know, industry data will tell you that getting 100% compliance is, you know, it's difficult uh just because we all forget to take 1 being 1 day um uh and with biologics you can assure compliance. Uh, we're asking patients to be injected in the site. So

Obviously, we're aware of it. We're actually using, uh, you know, novel technologies to increase as much as we can, uh, adherence to the study protocol with regard to taking the drug, and we're confident that that will, uh, deliver what we need. I will add one last thing. I know where we're at a time. The beauty about a degraded drug is that you can actually skip a dose and maintain maximum pharmacology, assuming you have the right dose that reaches complete degradation. That you will never see with the traditional occupancy-based small molecule in the video. So we have a bit of a cushion on the endurance question, but obviously, we're not sitting on it. We need to ensure as much as we can, 100% are there because we want to maximize the benefit to patients.

Thank you. Great question. I'd now like to turn the call over janela minolfi for closing remarks.

Okay, thank you. I I'm sorry. We run beyond the 9:30 goal that we had. I want to thank everybody, obviously, lots of questions. We are always available to continue to engage. This has been the most exciting year of chimera and we have 1 and a half more months or so to go. So uh stay close. I think it's going to it's going to be exciting time in the in the next few years. Developing this uh really

Wanting a generation drug and, and the brother pipeline.

So, thank you again today and uh, we'll talk more soon.