Earnings call transcript: Kymera Therapeutics Q2 2025 results miss forecasts

Kymera Therapeutics reported its Q2 2025 earnings, revealing a larger-than-expected loss with an earnings per share (EPS) of -$0.95, missing the forecast of -$0.83. Revenue for the quarter was $11.5 million, falling short of the $20 million forecast. Following the announcement, Kymera’s stock fell 5.8% in pre-market trading, reflecting investor concerns over the earnings miss and revenue shortfall. According to InvestingPro data, the company’s revenue has declined by 26% over the last twelve months, while maintaining a high revenue valuation multiple.

Key Takeaways

• Kymera’s Q2 2025 EPS was -$0.95, missing the forecast of -$0.83.
• Revenue of $11.5 million was below the expected $20 million.
• Stock dropped 5.8% in pre-market trading following the earnings release.
• R&D expenses were significant, totaling $78.4 million.
• Company maintains a strong cash position, increasing to $1 billion in July.

Company Performance

Kymera Therapeutics experienced a challenging Q2 2025, with revenue derived entirely from its collaboration with Sanofi. Despite significant investments in research and development, the company faced a larger-than-expected quarterly loss. The broader immunology treatment market remains underpenetrated, presenting potential growth opportunities for Kymera’s innovative oral degrader medicines. InvestingPro analysis shows the company maintains a "Fair" overall financial health score, with particularly strong momentum metrics. Get access to 10+ additional exclusive ProTips and comprehensive analysis through InvestingPro’s detailed research reports.

Financial Highlights

• Revenue: $11.5 million, all from Sanofi collaboration.
• EPS: -$0.95, compared to a forecast of -$0.83.
• R&D Expenses: $78.4 million, including $8 million in non-cash stock-based compensation.
• G&A Expenses: $17.6 million, including $7.4 million in non-cash stock-based compensation.
• Cash Balance: $963 million at the end of June, increasing to $1 billion in July.

Earnings vs. Forecast

Kymera reported an EPS of -$0.95, missing the forecast of -$0.83 by 14.46%. Revenue was $11.5 million, significantly below the forecast of $20 million, marking a 42.6% shortfall. This earnings miss highlights challenges in meeting market expectations and underscores the volatility in the biotech sector.

Market Reaction

Following the earnings announcement, Kymera’s stock fell 5.8% in pre-market trading to $38.29, down from the previous close of $40.62. This decline reflects investor disappointment in the earnings miss and revenue shortfall. The stock is trading closer to its 52-week low of $19.45, indicating cautious investor sentiment. Based on InvestingPro Fair Value analysis, the stock appears slightly undervalued at current levels. Notably, analysts maintain a strong buy consensus with price targets ranging from $53 to $70, suggesting significant upside potential.

Outlook & Guidance

Kymera plans to report Phase 1b data for its KT621 program in Q4 2025 and is preparing for Phase 2b trials in atopic dermatitis and asthma. The company aims to advance one new immunology program annually and has extended its cash runway into 2028, supported by a recent $288 million follow-on offering. InvestingPro data confirms the company’s strong liquidity position, with a current ratio of 8.49 and cash holdings exceeding debt obligations. The company’s beta of 2.18 indicates higher volatility compared to the market, typical for clinical-stage biotech companies.

Executive Commentary

Nella Manalthi, CEO of Kymera Therapeutics, emphasized the company’s commitment to developing groundbreaking oral degrader medicines, stating, "We believe our approach has the potential to deliver for the first time in our industry biologics-like efficacy with the ease and convenience of an oral pill." She highlighted the unmet need for advanced systemic therapies in immune inflammatory diseases.

Risks and Challenges

• High R&D Expenses: Significant investment in research may strain financial resources.
• Revenue Concentration: Reliance on Sanofi collaboration for revenue poses a risk.
• Competitive Landscape: The biotech sector is highly competitive, with rapid innovation.
• Regulatory Hurdles: Drug approval processes can be lengthy and uncertain.
• Market Penetration: Achieving significant market share in the underpenetrated immunology market remains a challenge.

Q&A

During the earnings call, analysts queried Kymera’s dose selection strategy for KT621 and the rationale behind the IRAK4 candidate switch. The company plans to report data on itch relief, a key concern for patients with atopic dermatitis, which could influence future market opportunities.

Full transcript - Kymera Therapeutics Inc (KYMR) Q2 2025:

Olivia, Conference Operator: Good day everyone. My name is Olivia and I will be your conference operator today. At this time, I would like to welcome you to the Chimera Therapeutics second quarter twenty twenty five results call. All lines have been placed on mute to prevent any background noise. After the speakers remarks, there will be a question and answer session.

If you would like to ask a question during this time and if you have joined via the webinar, please use the raise hand icon which can be found at the bottom of your webinar application. If you have joined via phone, please dial 9 on your keypad to raise your hand. At this time, I would like to turn the call over to Bruce Jacobs, chief financial officer.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics: Good morning. I’m Bruce Jacobs, and I’m kicking off this in place of Justine Konasberg, our head of IR, who is out today. Joining me this morning are Nella Manalthi, founder, president, and CEO, and Jared Golub, our chief medical officer. Following our prepared remarks, we’ll open the call to questions from our publishing analysts. If you’d like to ask a question, please use the raised hand icon, which can be found at the bottom of your meeting window.

And to help us move efficiently through the Q and A session, we ask that you’re ready to unmute your line when called upon. Ask that you’re through Before we begin, I’d like to remind you that today’s discussion will include forward looking statements about our future expectations, plans and prospects. These statements are subject to risks and uncertainties that may cause actual results to differ materially from those projected. A description of these risks can be found in our most recent 10 Q 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’ll turn the call over to Nello.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Thanks, Bruce, and thank you for joining us this morning. As I mentioned at the beginning of the year, we set ourselves up for a very productive and exciting 2025, and we’re delivering on that promise. The updates we’ve shared in the first half of the year represent a powerful validation of Chimera’s innovative and disciplined approach to drug development within the biopharma industry, while paving the way for our future progress across our high impact immunology pipeline. We’re committed to leveraging the unique capabilities we have developed to unlock disease biology and deliver groundbreaking oral degrader medicines for areas not served well by existing technologies. Today’s immunology treatment landscape still leaves millions of patients without adequate options, forcing difficult trade offs between efficacy, safety, cost, convenience.

Millions of patients with life altering immune inflammatory diseases don’t have access to advanced systemic therapies, mostly injectable biologics. This is true if we look across countries with extremely diverse systems on how they prescribe, reimburse and deliver these highly effective medicines. The issue is really more fundamental than the inefficiencies of the health care ecosystems around the world. Simply put, well tolerated oral drugs that can be as effective as these difficult to access injectable biologics have the potential to transform the treatment landscape and in doing so, impact lives of millions of patients. This is what we’re set to do at Chimera.

It’s an exciting time for the company, and I wanna take a moment to briefly recap some of the key accomplishments of the 2025. Starting with our first in class statics program, we completed the first KT six to one trial in healthy volunteers and reported positive results that exceeded even our high expectations, surpassing our target product profile. Importantly, the data further derisks our path forward and highlights the possibility of KT621’s dupilumab in appeal profile. As potential first in class treatment, we believe KT621 has the ability to be a broadly accessible oral option for many dermatological and respiratory diseases like AD and asthma. In addition, for Japanese regulatory purposes, we recently completed a second small healthy volunteer study in Japanese subjects with results that were consistent with The US study.

You can expect that we’ll present these findings at a future medical meeting. We also wanted to share a few updates regarding KT-six 21 Phase Ib broaden study in moderate to severe AD patients. As noted in the release, the patients’ data we plan to share will include data from two different dose groups. While we initially set out to explore a single dose, the speed at which the trial enrolled allow us to evaluate the translation from healthy volunteers into patients more broadly, which we believe gives us an even richer dataset to inform our phase 2b dose choices, which was an important goal of this study. The phase 1b was designed with a flexible protocol that contemplated this scenario, allowing us to make this choice without impacting timelines and as a result, we’re well positioned to report results in the fourth quarter as planned.

I’m also happy to share that we have selected and finalized the three doses that will be included in the two Phase 2b studies as well as completed long term toxicity studies. These were really the final important pieces of our planning to start these studies beginning later this year. Given we’re moving into data collection and analysis mode soon, we’re going to limit our comments around the study to what we have said previously until we’re able to share the full results in the fourth quarter. But we can certainly say that we’re pleased with the speed at which the trial has enrolled, very excited by the trajectory of the program and we look forward to sharing the full dataset when it’s available. The additional PRISM news to share is that we have select a follow on STAT6 degrader to KT6:one with strong potency, selectivity and safety profile and have advanced it through all required IND enabling studies.

The degrader is IND ready should we decide to further advance it into the clinic in the future. More broadly, we’re building what we believe is the best in industry oral immunology pipeline. And beyond STAT6, we’re also very excited about what’s next. Early this year, we’ve unveiled our oral IRF5 program, which is moving through IND enabling studies. The compelling preclinical data we’ve generated showcases that targeting IRF5 can lead to correcting immune dysregulation across multiple disease pathologies while generally sparing normal cells.

And it remains our goal to progress our early discovery pipeline of novel immunology programs, unveiling one new program per year to expand access to oral systemic advanced therapies for broad patient populations in the space. We hope to share more about this next year. Additionally, we announced two important partnerships updates in June. First, we’re very excited to announce our first oral molecular glue degrader program targeting CDK two will be developed under our collaboration agreement with Gilead. We have a highly innovative research engine and the CDK two program is a great example of this given the challenges of existing technologies to address this highly valued target.

With our focus in immunology, this program was the ideal candidate for partnering. We and Gilead believe that a highly specific, safe and effective CDK2D grader has exciting potential to meaningfully improve treatment for patients living with breast cancer and other solid tumors that are inadequately treated today. Secondly, Sanofi announced that they officially opted in into the IRAK4 program and will assume full responsibility for development activities of KT485, our second generation oral IRAK4 degrader, which we expect to advance into Phase I testing next year. Based on our preclinical results, KT-four eighty five has greater potency, broader distribution and a generally improved overall profile than KT-four seventy four, our first generation degrader. As a result, Sanofi made the decision not to advance four seventy four into further development as KT-four eighty five has the greatest potential benefit for patients.

Both these collaborations have the potential to realize significant milestones for Chimera, which Bruce will cover later in the call, and we’re happy to collaborate with two industry leaders on these novel programs. Finally, to support all we have ahead of us, we’ve extended our cash runway into the 2028. We raised approximately 288,000,000 in the follow on offering that we launched at the June and received the upfront payment from Gilead increasing our cash position to $1,000,000,000 as of the July. Our well capitalized balance sheet should allow us not only to take KT six to one through the planned phase 2b studies in AD and asthma, but also to prepare for and initiate several phase three studies across multiple indications while also progressing an earlier stage pipeline. As you’ve heard me say before, our strategy centers on combining the unique power of targeted protein degradation with carefully selected targets and pathways to create transformative new class of medicines.

By focusing on immunology, we’re not only addressing large patient populations, but also meeting a significant unmet need to create effective save oral therapies. We believe our approach has the potential to deliver for the first time in our industry biologics like efficacy with the ease and convenience of an oral pill. Again, I couldn’t be more excited about the foundation we built and where we’re going. I’m looking forward to the Q and A discussion, but let me pause here for Jared to discuss KT-six twenty one and our pipeline. Jared?

Thanks, Nelo.

Jared Golub, Chief Medical Officer, Chimera Therapeutics: Looking back on the last quarter, we were excited to share the first KT-six twenty one clinical data, which we believe greatly derisks the next stage of development. We identified clear goals for the Phase I healthy volunteer study, and the data not only hit the mark, but in many instances exceeded our expectations with compelling translation from preclinical studies to humans. The primary objective in the healthy volunteer study was to show that we can robustly degrade STAT6 in blood and skin, which we define as a reduction of 90% or more at doses that are safe and well tolerated. As shown here, the results exceeded our expectations across every measure. We showed more than 95% degradation in both skin and blood at very low doses.

The safety profile was undifferentiated from placebo. And we are encouraged by the biomarker profile, which we believe is at least comparable to what dupilumab showed in healthy volunteers or patients and, in some cases, is superior. That said, I’d like to take a few minutes this morning to recap the results and next steps with KT-six twenty one, which we believe has the potential to profoundly alter how PH2 diseases are treated by delivering an oral drug with a biologics like profile. For the full dataset, please reference the slides presented in early June, which are available on our website. As a reminder, we enrolled 118 volunteers in a randomized double blind placebo controlled study to assess single and multiple ascending doses of KT621 across a range of doses from six point two five to eight hundred milligrams in SAD and from one point five to two hundred milligrams in MAD.

In all SAD cohorts, including the lowest dose of six point two five milligrams, KT621 degraded stat six by 90% or more, and at doses of seventy five milligrams or greater achieved complete degradation, with greater than 95% mean stat six reduction and stat six levels below the lower limit of quantitation in multiple subjects after just a single dose. In MAD, where volunteers were dosed daily over two weeks, we were able to completely degrade STAT6 in both blood and skin at doses of fifty milligrams and above. In fact, to establish the lower end of the dose response curve, we had to go back after the initial cohorts and add the one point five milligram MAD cohort, given none of the initially planned doses had less than 90% degradation. The robust degradation of STAT6 led to functional inhibition of the IL-fourthirteen pathway as demonstrated by median reductions of up to 37% for TARC and up to 63% for eotaxin-three at day fourteen, a result that was comparable or superior to what has been observed for dupilumab either in healthy volunteers or in patients with Th2 diseases. Importantly, whether treated at the lowest or highest dose or anywhere in between, the safety profile was undifferentiated from placebo.

There were no serious adverse events, very few treatment related adverse events that were mild, no treatment related discontinuations, and no clinically relevant changes in vital signs, laboratory tests, or ECGs with daily dosing up to two hundred milligrams, which is 16 fold above the lowest MAD dose with greater than 90% degradation. As many of you have asked, we are also happy to share that we recently completed our four month GLP toxicology study. And consistent with our earlier non GLP and GLP tox studies, we did not see any adverse events of any type at all of the doses tested. This study completes the necessary preclinical work to allow us to initiate the Phase IIb trials planned to start later this year and early next. Prior to reporting the healthy volunteer data, we initiated a twenty eight day Phase Ib trial named BROADIN, which was designed to enroll approximately 20 moderate to severe atopic dermatitis patients.

We’ve had a high level of engagement from sites on the trial and are pleased to report that we are on track to share data in the fourth quarter. As a reminder, the key study aim is to show that robust STAT6 degradation in blood and skin lesions by KT621 has a dupilumab like effect on multiple Th2 biomarkers in the blood, TARC being the most relevant in AD patients as well as on the Th2 transcriptome of active AD skin lesions. We will also assess KT621’s effect on clinical endpoints, such as EASI and pruritus NRS. Beyond the phase 1b BROADEN study, which, again, is designed as a streamlined biomarker focused study, we are planning parallel phase 2b dose range finding trials to enable subsequent registrational phase three studies across multiple indications. As Nella mentioned, we have selected the three doses for the studies, and our Statistics team has done a remarkable job keeping this program moving at a rapid pace, including all the necessary work to initiate two global Phase IIb trials.

The AD Phase IIb trial will begin in the fourth quarter this year, and the asthma study is expected to initiate in the 2026. And quickly on the IRAF5 program. Historically, an undrug transcription factor and genetically validated target, IRAF5 is a master regulator of innate and adaptive immune response pathways involving pro inflammatory cytokines, B cell activation and autoantibody production, and type one interferons. We believe IRA5 degradation has the potential to be the first broad anti inflammatory mechanism that effectively addresses immune dysregulation while sparing normal cell function. KT579, our potent selective and oral degrader, has the potential to be the first IRA5 targeted therapy to deliver a completely novel and potentially transformative treatment option, in many cases, superior to pathway biologics, in a range of autoimmune and rheumatic indications such as lupus, RA, Sjogren’s, and others.

This program is progressing in IND enabling studies, and we expect to advance KT579 into phase one testing in early twenty twenty six with what we believe will be the first oral IRA5 degrader to enter the clinic. Across our portfolio, we see strong potential to advance multiple first in class oral degraders that address major market opportunities in immunology. Our STAT6 and IRF5 programs represent significant advancements not only for our pipeline, but for the industry and patients as we look to deliver the first oral therapies with biologics like profiles in immunology. We’re excited about their continued progress and remain focused on our goal of expanding access to transformative treatments for millions of patients. So let me pause here, and Bruce will review our second quarter financial results and provide a collaboration overview.

Bruce?

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics: Thanks, Jared. I will quickly run through our results for the quarter. Also, because this past quarter has been busy with collaboration and financing activity, I wanted to provide a brief summary of our recent news as well. As I walk through the second quarter results, please reference the tables found in today’s press release and 10 Q, which was filed this morning. Revenue in the 2025 was $11,500,000 all of which was attributable to the Sanofi collaboration.

With respect to operating expenses, R and D for the quarter was $78,400,000 Of that, approximately $8,000,000 represented noncash stock based compensation. The adjusted cash R and D spend of $70,400,000 which excludes that stock based comp, reflects a 3% decrease from the comparable amount in the 2025. On the G and A side, our spending for the quarter was $17,600,000 of which $7,400,000 was noncash stock based comp. The adjusted cash G and A spend of $10,200,000 again, excluding that stock based compensation, reflects a 6% increase from the comparable amount in the prior quarter. And overall, adjusted operating expenses in total were down slightly from the prior sequential quarter.

We ended June with a cash balance of $963,000,000 Our quarter end cash balance included the base proceeds from our $250,000,000 follow on offering that closed at the June. The June total does not include either the additional proceeds from the underwriters’ overlapment option, which was fully exercised in July, or the first payment that we received from Gilead as part of our recently signed CDK two partnership, both of which were received in July. As a result, we ended the month of July with a cash balance of approximately $1,000,000,000, providing a cash runway into the 2028. Just a quick reminder that our runway calculations exclude any unearned milestones. And with that in mind, I’d like to take you briefly through the key financial terms of our two collaboration agreements.

Starting with Gilead, under the collaboration, we’re eligible to receive up to 750,000,000 in total payments in addition to tiered royalties on net product sales that range from the high single digits to the mid teens. This 750,000,000 includes $85,000,000 related to the upfront payment, which was received in July, and you can see on our balance sheet shown as deferred revenue, and the potential option exercise. If Gilead chooses to exercise its option for an exclusive license, they will assume global rights to develop, manufacture, and commercialize all products arising from the collaboration. Turning to Sanofi and the development of KT-four eighty five, under the existing collaboration, we could earn up to $975,000,000 in clinical, regulatory, and commercial milestones for KT-four eighty five. We retain the right to opt in to a fifty fifty cost and profit share in The US prior to the first phase three trial in addition to international royalties.

If we decide not to opt in, we would instead be entitled to worldwide royalties ranging from the low double digits up to the high teens. To conclude, as you’ve heard today, there’s a great deal of momentum across our programs. And importantly, we have the resources in place to continue executing on our development strategy and the progression of our earlier stage pipeline. With that, we’ll pause here so we can convene in our main conference room, at which point, we’ll open the call to questions. Thank you.

Olivia, Conference Operator: Thank you. At this time, if you would like to ask a question, please click on the raise hand button, which can be found on the black bar at the bottom of your screen. If you have joined by phone, please dial 9 on your keypad to raise your hand. When it is your turn, you will receive a message on your screen inviting you to join as a panelist. Please accept and wait until you are promoted to panelist.

Please unmute your audio, turn on your camera, and ask your question. As a reminder, we are allowing analysts one question and one related follow-up today. We will now pause a moment to assemble the queue. First question is from Michael Schmidt from Guggenheim. Please unmute yourself and begin with your question.

Paul, Analyst, Guggenheim: Hey, guys. It’s Paul on for Michael. Thanks for taking our question. I had one on the dose levels, that you’re exploring for six two one. Maybe first, could you provide some color on that decision to add the second dose in the phase one b study?

I I think it’s probably safe to assume that both the doses fall within the broad range that achieved complete statics degradation, but just wondering how you’re thinking about exploring both the the high and the low dose versus perhaps two doses in the higher range.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Yeah. Thanks, Michael. Wanna make sure we’re you can hear us. So so as we said today, so the doses both doses are within the range that we that we explore in the phase one anti volunteer study. And as we’ve also said, as you’re aware, we had initially decided to explore one dose thinking that, you know, roughly 20 patients will will be enough to give us the data to speak to what is the profile of that one dose.

And then, obviously, as we were moving along with the enrollment and given how quickly it was going and, you know, given that we were able to assess the performance at one dose, we decided to explore an additional dose so that we’ll get even robust translation from multi volunteer to patients of, you know, stat stat six degradation. I think it’s important to keep in mind that in the healthy volunteer data, we had multiple doses. I would say almost all doses besides one met our target product profile. And so we wanted to confirm that the really, really robust profile could be translated into patients with the same level of fidelity. And so I think we’re happy that we did that.

Obviously, I’m not gonna speak to high, low, medium, etcetera. Rest assured that the main goal was really to refine the phase two b dose selections. And so the the all that happened so quickly that now between the healthy volunteer data and whatever data we have access from this study, we’re able to firm up and select the phase three the phase two b doses even in the absence of of completing the phase one b study.

Paul, Analyst, Guggenheim: Great. And if I kind of quick quick follow-up on that that point, mostly on just what backed into the dose selection for the phase two studies. Was it predominantly the healthy volunteer data you presented? Was there anything emerging from the Japanese studies or GLP tox? Can you say if there’s a different range of doses being explored between the AD and the asthma studies?

Thank you.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Yeah. No. So a great question, actually. So as you saw, it was a very, very busy q two. I I don’t think we’ve had a busier q two in the history of the company given everything that we’ve accomplished.

So I will say that if you look back at the healthy volunteer data, there was a dose selection based on this data. Everything else that we’ve done confirmed was able to confirm our initial instinct. We didn’t learn, to be honest, anything new that made us change the initial instinct, let’s say, on dose selection, but it was highly encouraging that everything that we’d seen in healthy volunteer was supported by, obviously, the four month talks, which we said was completely clean, the Japanese study, which was very much in line with The US study, and the early let’s call it early data for the phase one b.

Paul, Analyst, Guggenheim: Great. Thanks very much.

Olivia, Conference Operator: The next question is from Derek Ochilla at Wells Fargo. Please unmute yourself and begin with your question.

Derek Ochilla, Analyst, Wells Fargo: Hey. Good morning, and, thanks for taking the question. Congrats on the progress here. So just one and a follow-up. So, basically, just wanna understand maybe following up on this this line of questioning just in terms of what you would expect to see, you know, at these, at these additional doses that you’re looking at in the phase two b.

Ultimately, like, we saw very good degradation and and and pretty quick. So I guess,

Analyst: you know, how do you

Derek Ochilla, Analyst, Wells Fargo: think some of the doses will differentiate? And then just a follow-up to that, you know, what do you what do you actually expect to see with the follow on stat six that you’re developing? What sort of optionality are you really looking for with that molecule? Thanks.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Great question, Derek. So the first one, I just wanna confirm we’re talking about the dose for the phase two d. So I think the important thing for a drug, obviously, is to find a a dose that is has the best risk reward profile. And so I think what we wanna ask in a, you know, in in a sixteen let’s say, for AD, a sixteen week study is what is the maximal or we believe close to maximal at that point level of clinical activity that we would see, and what is the safety profile at different levels of degradation. Obviously, we will we’ll explore maximal degradation, which we call complete, which, again, is where, really, we see in most subjects, stat six level be below the lower limit of quantitation.

So we wanna ask that question. What is the clinical profile of maximal degradation? And then, obviously, we wanna ask the question at a couple of lower doses just to, again, at the end of the study, being sure that we’re taking into phase three the profile that we believe has the best risk reward. So it it’s obviously a necessary step that we need to take as a company to fulfill regulatory requirements to do dose ranging study before selecting a phase three dose. You know, I think we have bets in the company on what that phase three dose would be already, but we gotta run the studies and make sure that we do all the right steps to derisk the program.

With regards to the follow on molecule, so that’s something many of you that has followed us for years know that every program, we always have a a next generation molecule. As you saw for IRAK four, Sanofi decided to focus the efforts on the full on, then we we call it the next generation molecule, k t four eight five. For for stat six, to be honest, we didn’t really have a particular goal with the with the next generation compound given how well k t six two one has performed. And this is the reason why, you know, we’ve advanced a very good molecule that in many ways looks, at least in terms of profile, very much like k t six two one. It’s, you know, potent, extremely well tolerated, very active in vivo.

And the principle is, you know, to to support the franchise for one is for the eventual, you know, unlikely scenario that we need another molecule or for a for a strategic choice of eventually advancing another molecule should we choose to do for different severities or different indications. I think given how well k d six two one is doing, we have decided for now to keep this full on molecule IND ready, meaning that we have everything we need to file an IND, but we’re not planning to file an IND in the in the short term. I think another important point in this highly competitive space as statistics is becoming, having a molecule IND ready probably ahead of any other, let’s call it, competitor that that is behind us. So we have two molecules ahead of every other competitor. I think he also sends a message how committed the company is to this franchise and to potential of this franchise.

Derek Ochilla, Analyst, Wells Fargo: Excellent. Thanks, Nelo.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Thanks, Eric.

Olivia, Conference Operator: Question is from Andrea Newkirk at Goldman. Please unmute yourself and begin with your question.

Andrea Newkirk, Analyst, Goldman: Hi, guys. Good morning. Thanks for so much for taking the question. Two for me as well. Maybe the first, recognizing the primary objective of the phase one b data is to show a dupi like profile here on biomarkers.

But I was hoping you might be willing to frame your expectations on what you’d like to see on the clinical efficacy measures, particularly EC75 as well as NRS. And then secondly, just noting the completion of the GLP talk studies that you mentioned, and obviously your phase one healthy volunteer also looked really clean. But, if you could just speak to the potential safety risks of degrading stat six completely, What type of signals are you most looking for in the phase one b to to really feel comfortable here with the safety profile, as you move forward? Thanks so much.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Well, thanks. Great question. Jared, I thought maybe you could take Sure. At least the first one, if not both.

Jared Golub, Chief Medical Officer, Chimera Therapeutics: Yeah. In terms of on the on the clinical expectations, I think, you know, we’ve emphasized always that the primary objective here is to show robust stastic degradation in the blood and in active AD skin lesions and to show that that results in a dupial like biomarker effect both in blood and in skin, where in skin, we’re looking at the t h two transcriptome and and the wanting to see a dupial like effect there. You know, we sort of have set our expectations around biomarkers. I think TARC is the most important blood biomarker probably in AD where, you know, Dupi studies have shown even at twenty eight days about a 70 plus percent reduction in dupilumab. So that’s a general ballpark that we would expect to see in patients who, like in those Dupi AD studies, had greatly elevated TARC levels at baseline.

We’ll be looking at other biomarkers in the blood as well as these, you know, various, you know, transcriptional biomarkers in the skin. In terms of clinical endpoints, again, we’ve always emphasized that in the absence of a placebo control, these are more exploratory. However, we think we do have an opportunity to look at endpoints like EZ and pruritus NRS and IgA because we know from Dupi that you can see impact on those biomarkers as early as twenty eight days. And we’re not really giving specific numbers where that bar would would be set. I think the published data are out there with Dupi, and one can look at those published data at twenty eight days and get a sense for what we mean by sort of being in the ballpark with regard to those clinical endpoints.

In terms of your second question around safety risks, as you noted, you know, we’ve been very pleased with what we’ve seen in our GLP tox studies. We’ve now, you know, completed our four month tox studies as Noah indicated, and we’ve seen no safety signals whatsoever. That’s very in line with our four week GLP tox and our prior non GLP tox studies. We’re very encouraged by the fact that our safety profile was undifferentiated from placebo in healthy volunteers with two weeks of dosing, so that’s very encouraging. And now we’ll be looking at safety with four weeks of dosing, of course, in the in the phase one b.

I think overall, this is in line with our expectations based on our mechanism of action and and based on the fact that it appears that, you know, stat six is highly selective, you know, for the IL four, IL 13 pathways in human genetics have pointed, you know, not just to the phenotype of abnormalities in stat six, but also to the safety of knocking down stat six as have mouse knockout studies. And so this is all in line with what we expected for a transcription factor that is very specific for IL four and IL 13 and for a drug like ours that is highly selective just for stat six.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: I would only thanks, Jared. I wouldn’t say anything differently. I will only add one thing just to be clear. Again, as Jared said, on the clinical endpoints, it’s difficult to compare you know, it’s also difficult to compare placebo controlled randomized study. Like, the industry is full of these these arguments over comparing placebo controlled studies.

So it’s even more difficult to compare noncontrol study. But but I just wanna say our expectations are that we will have a very active drug. I don’t wanna hide behind impossibility to compare. We expect that this mechanism is gonna be in on par with what dupilumab has shown, and that’s the bar for us without talking about numbers.

Andrea Newkirk, Analyst, Goldman: Okay. Understood. Thanks, guys.

Olivia, Conference Operator: The next question is from Faisal Khershid at Leerink. Please unmute yourself and begin with your question.

Analyst: Hey. Good to see you guys. Thanks for taking the question. Just want to ask on the doses for the phase 1b and the phase 2b. Are you able to confirm if the dose that you added to the phase one b is higher or lower than the dose that you originally went in with?

And could you also confirm if, like, either or both of these doses are part of, like, the three that you selected for phase two b?

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: So so so I I don’t wanna get into the higher or lower because I think whatever I say is gonna be viewed one way or the other. What I can say is that both doses have been tested in the healthy volunteer studies. I don’t wanna talk about what what our doses are for the two b because I think we might choose to keep that, as I’ve said, in other venues, to keep that close to the vest for as long as we can only for competitive reasons. All I can say that, you know, we have several doses in the healthy volunteers that performed really well. And so, really, the main driver here, are these doses going to perform as well in patients given that I actually don’t remember the number.

Bruce will know better, but we’re spending tens, if not 100 plus millions of dollars in these two studies. And we’re not gonna optimize over you know, for these studies on, you know, making or thinking that we selected the right doses. These are consequential decisions. And so so given that we had the time to do it, we said, let’s make sure. So that’s really what’s behind this.

And, you know, I think once we’ll share the data, we can add a bit more color to what came first.

Analyst: Got it. Makes sense. And then could you confirm if it’s still 20 patients for the phase one b? And then also, like, between the two doses, would you like to, or do you have to see a dose response between those two doses?

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Great question. So I think what we said that that the the goal of the one b was approximately 20 patients, and that’s still the case. I don’t wanna get into the the dose response. I think we will talk about it once we once we share the data.

Analyst: Sounds good. Thanks for taking the questions.

Olivia, Conference Operator: The next question is from Alex Thompson at Stifel. Please unmute yourself and begin with your question.

Alex Thompson, Analyst, Stifel: Hey. Good morning. Thanks for taking my question. I guess another question on the next gen STAT6. How different is the, scaffold, binding to STAT6 than six twenty one?

Is that a key part of this decision making? And when might you consider potentially splitting indications here? Is that a near term decision, or are you gonna wait, quite a while before that, comes down? Thanks.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Yeah. So what I can say thank that’s a great question, Alex. So we have several scaffolds, let’s call it, across actually all binding moieties, whether it’s e three ligase or it’s stat six. We have plenty of chemistry. Some, you know, patents have published from us.

As many have seen, there is plenty that haven’t yet. So we have a plethora of chemistry in this program that covers everything that you can imagine. So maybe I’ll leave it at that. On the indication splitting, it it it it’s a bit obviously challenging to to think about that particular endgame given kind of the evolving landscape right now in terms of pricing and reimbursement and global versus US. So I think we wanna keep maximal optionality, and that’s kind of the goal behind everything that we’re doing.

But it’s difficult for us right now to at least disclose what’s the latest thinking on that. But, you know, as we get closer to phase three, which, you know, which actually with the the the recent raise, hopefully, was clear from from our remarks earlier. Now with the money we have in hand, we can actually initiate multiple phase three studies. So we I think as we get closer to those, we’ll be able to disclose more about what our indication sequence and strategy would be.

Alex Thompson, Analyst, Stifel: Great. Thank you.

Olivia, Conference Operator: The next question is from Tazeen Ahmad at Bank of America. Please unmute yourself and begin with your question.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics0: Hi, guys. Good morning. Thanks for taking my question. Going back to the data that you’re gonna have by year end, I just wanted to ask, you’ve talked about your expectations for what data you’re going to show, should we assume that you’re also gonna be able to show some level of itch data? I ask because some doctors have indicated that in addition to, let’s say, EC scores, that is something that they feel is important when they’re gonna make a decision in a real world setting about what potential options they might choose?

Thanks.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Yeah. Tazeen, yeah, it’s a great question. And as Jared said, yes, we will show easy pruritus NRS, and so itch is gonna be an important factor. As you know, itch is probably has the biggest impact on quality of life of these patients, and so it’s something that we’re watching very closely. So we will share that data as well.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics0: And will that be for all the patients that you’re gonna show, or it’ll be a subset?

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Well, I mean, if we if we have collected the data, yes, so we will share it. So, yes, it should be all patients.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics1: Okay. Thank you. Yep.

Olivia, Conference Operator: The next question is from Kelly Shee at Jefferies. Please unmute yourself and begin with your question.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics2: Congrats on quarter. So one question on status six. Conjunctivitis is believed to be on target a year for Dupixent. So do you expect to see similar level of conjunctivitis in k t six two one phase one b trial, like in one or two patients? And also, could a daily oral drug differentiate a safety profile versus of versus injectables due to a potential Limablat’s PK curve?

Thanks.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Maybe I’ll I’ll start, and then I’ll pass it to Jared that can speak more to the medical part. I mean, our view at Chimera is that stat six and and hopefully, it’s not just here at Chimera. Stat six is the selected transcription factor of IL4 and 13, and we’ve shown preclinically, early clinically, and hopefully, we’ll show in q four that if you block STAT6, you can phenocopy dupilumab. So if if conjunctivitis, which is actually mostly, if not only seen in atopic dermatitis patients, so it’s really a a feature of the disease and decide for 13 biologics. So, again, if conjunctivitis is a on mechanism event adverse event for I four n 13 biology, then we expect to see.

If it’s to do with the receptor or the cytokines, then we wouldn’t see it. So it’s hard for us to know. Maybe, Jared, you can speak to you know, also, you know, is it seen after only four weeks? I don’t know.

Jared Golub, Chief Medical Officer, Chimera Therapeutics: Yeah. I mean, you know, mechanistically, you know, it’s not really known why some patients, especially AD patients, do develop conjunctivitis. If you look at the dupilumab studies, when you do see conjunctivitis, oftentimes, you’ll see it within the first, say, four to eight weeks or so of treatment, and then over time, it actually tends to diminish. You know, it is a an adverse event that one does see with Dupi. It’s not a dose limiting adverse event, and most of the cases with dupi are sort of in the mild to moderate range.

I think, importantly, you know, we haven’t seen it preclinically in our tox studies. We haven’t seen it in healthy volunteers, and we really wouldn’t expect to see it there in healthy volunteers since this appears to be something unique to AD patients. But as Nello said, you know, we don’t have any reason to believe that we’d see either less or more AD patients compared to what dupilumab has seen.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: But, yeah, we’re we’re watching it because it’s a it’s an interesting, obviously, feature of many of these drugs. Right? It’s not only dupilumab, all the I thirteen drugs have it. So we’re watching that very closely and see if we see it in our four week studies, and we’ll obviously, we’ll share all the data in four q. And then you talked about the safety difference between once oral daily and a and a biologics.

I mean, from from what we have both understood and what we’ve empirically derived in our preclinical studies, dupilumab has a very, very robust pathway blockade. I would compare dupilumab pathway blockade pretty much in line with the level of pathway blockade we see from our fifty hundred mg dose, two hundred, you know, the the complete degradation type of pathway blockade. I would put it on that kind of level of pathway blockade. So if that’s the case, then I don’t see why pathway blockade coming from stat six degradation should look different from pathway blockade from an alpha alpha blockade. So, anyway, I think that’s another feature and another part of the analysis that we will do.

Again, I’ll repeat, in our preclinical study now where I did the four month talks, k t six to one has been exceptionally well tolerated, so we’ll continue to, again, watch everything that happens in the

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics1: clinic. Super helpful. Thanks.

Olivia, Conference Operator: Question is from Judah Frommer at Morgan Stanley. Please unmute yourself and begin with your question.

Jared Golub, Chief Medical Officer, Chimera Therapeutics: Yeah. Hi, guys. Thanks for taking the question. Just one for us. I guess, can you comment a little bit further on enrollment progress and the success you’re having there?

Maybe what feedback is from investigators? Is the oral administration of the drug resonating? And curious if you think you’d have similar success if there were a placebo arm in a

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: trial. Yes. It’s a great question. So the the challenge of a twenty eight day study, remember, is that the patients, you know, are are not gonna be on the drug beyond day twenty eight. We don’t have an extension arm to the study.

So it’s it’s, I would say, before we started the study, we were nervous because, you know, the there there there aren’t huge amount of incentives for patients to come onto the study besides knowing they’ll be on an on an active drug. And that’s part of the reason why we decided not to have placebo. We thought it would have had an impact on our enrollment rate. As we expect part of us or our expectation was that patients do want an oral drug, and so I think we are seeing that in our in our study. And the data has allowed us to, you know, meet our enrollment goal, I would say, even exceed our enrollment role for sure.

And maybe that’s where I’m gonna leave it. I think once we start seeing more differentiation, it’s probably gonna be in the phase two b study where now you’re offering sixteen week potentially OLE. And so that would be interesting to see our enrollment versus biologics and whether it’s telling us also something about what patients are also looking for in the market.

Jared Golub, Chief Medical Officer, Chimera Therapeutics: Right. Thanks.

Olivia, Conference Operator: The next question is from Kripa Devarakonda at Truist. Please unmute yourself and begin with your question.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics1: Hey, guys. Thank you so much for, taking my question, and congrats on the progress through the quarter. So I’ll ask one, nonstatistics question. So, congrats on your, CDK partnership with Gilead. I know this diversifies your pipeline into oncology where you’ve been focused a little bit more on INI in the recent past.

But given the data we’ve seen so far with CDK two inhibitors, can you talk a little bit about how you think the degrader could be differentiated based on the data that you have and what the strategy of development is? And then I have a follow-up.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Yeah. Yes. Thank you. So to just to be clear, our discovery engine has has been, you know, also very focused on immunology. We have programs that we were working on from the earlier days, and one of our program was in CDK two.

And so with our strategy shift to focus on developing immunology drug, we decided that it was best to place a very exciting CDK two program from a development step standpoint in the hand of a partner that was committed to that space. So that’s a bit to the strategy. The reason why we have that program is because we firmly believe that small molecule inhibitors of CDK two are really not able to selectively target CDK two. They all inhibit to a large extent CDK one at pharmacologically active doses to different degrees. And that it leads to clinical doses that are probably not optimally blocking CDK two, again, for the risk of hitting CDK one.

Another important aspect for us to develop this drug was to have a brain penetrant asset so that we would also address potential brain secondary tumor or metastasis from breast cancer. And so our degraded program molecular to degraded program is highly specific CDK two also reaches the CNS. And we believe it’s gonna has the potential to be best in class. If I look at the small molecules out there, it’s by far superior. Obviously, I’m not aware of other programs that are in, you know, early discovery, early development, so I can say, obviously, for sure.

But with regards to the development, that’s a question you have to ask, Gilead. We, you know, we can’t speak for them on that particular front.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics1: Okay. Thank you so much. And just following up on Tazeen’s question about itch relief, and this is something that we’ve heard from KOLs too that it’s really important to see rapid re itch relief. Will we get a sense of that when we see the data, the rapidity of response in fourth quarter?

Jared Golub, Chief Medical Officer, Chimera Therapeutics: Yeah. We will. I mean, you know, as Nelo already mentioned, you know, looking at it pruritus NRS is is a key part of the sort of suite of clinical endpoints, and we’ll be looking at it, you know, fairly regularly as we’ll be looking at EASI. So we’ll have a a good sense of the kinetics of impact on itch as well as on EASI. That will be sort of part of the profile that that we share once we have those data in q four.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Yeah. I think you you’ll see, hopefully, that will be the case. But it would be like you know, we’ll show day seven, day 14, then 21, day 28. So you’ll be able to see the kinetics of all of these parameters.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics1: Okay. Great. Thank you so much.

Olivia, Conference Operator: To note, each questioner can ask one question now. No follow-up questions. The next question is from Mayank Mantani at B. Riley. Please unmute yourself and begin with your question.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics3: Yes. Good morning. Thanks for taking our questions, and congrats on the progress team. Any color you’re able to provide on the baseline EZ scores of the patients you’re enrolling or have enrolled. And and I wonder always about the screen failure rate for the topic dump trial sites.

And maybe just remind us how you’re measuring degradation in skin tissues. There’s obviously a, you know, a couple of ways to do that. And, lastly, any anything you’ve learned on the degradation from the four months GLP talks studies you completed?

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Oh, yes. Four questions in there. So that’s a way to

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics3: keep I will not ask a follow-up. I promise. No follow-up.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Well, you’ve asked four.

Jared Golub, Chief Medical Officer, Chimera Therapeutics: My call.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Let’s see if I remember. So the first one was the easy yeah. We’re not gonna comment on the baseline easy, but I will refer you to entry. So the the baseline criteria for entering the study is easy above sixteen sixteen or above. There is obviously itch as well.

There is PSA more than 10%. So we have strict criteria that really overlap with what has been done with dupilumab. On the, again, on the failure rate, again, Waltman, I don’t know if we’ll speak when we release the data. All I can say is that our team is watching the study very closely, and we we we’ve worked very, very hard to make sure that patients that enter enter our study actually have atopic dermatitis, which would be shock that that that, you know, could be possible if you don’t watch the study closely that, you know, their their their disease is active. And, obviously, that their lab work is, you know, in line with making sure we’re not, you know, taking sick patients on our study.

So I think when you take all of that, that results into, obviously, screen failures that, again, I’m not able to comment on today. On the degradation in the skin, as we’ve done in many of our studies, we are fortunate enough to have patients on our study be willing to take biopsies, which, as you know, it does add an additional layer. That’s why we’re so impressed on how we were able to enroll patients again quickly because we asked patients to undergo biopsy at baseline and day 28 to to to measure stat six with the mass spec. So that’s how we’re gonna measure it.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics3: Anything you learned from the GLP talk study on degradation?

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: I mean, I mean, all we learn in these studies is that we obviously, at this tox doses, there is no stat six anywhere to be found even though we degraded completely. That’s maybe all I can say. Yeah. If the question is, does this stat six degradation wanes off after sometimes? Obviously, the answer is no.

We we see stat six degradation both throughout the study.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics3: It’s great to hear. Thank you.

Olivia, Conference Operator: The next question is from Jeet McCary at BTIG. Please unmute yourself and begin with the question.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics4: Great. Thanks for taking my question. I know we’re a long ways out, but can you speak to payer willingness to cover therapies in the dermatology space that give an alternative administration format, like an oral option with Dupixent like efficacy for k t six two one, or is there bar truly superior efficacy versus standard of care options? Thank you.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Well, no, it’s a great question. We believe that when you make the case for an oral option, first, you will hear from prescribers that actually you don’t even need to have dupilumab like activity for expecting a substantial adoption in the market. It just speaks to the fact that there is a need of flexible, easy to prescribe, reimburse, and take medicines. So the reason why we say dupil like in the pill is because all the data we’ve seen so far speaks to that. And so that’s why our bar has always been there, hopefully, will continue to be there.

Again, I think when you make the case for head having a therapy even even with the same activity, you’re telling actually insurance companies and prescribers and patients that that this drug has a much bigger impact on their quality of life and asking for a lot less, right, in terms of visit to the doctors, testing, you know, needing or lack thereof of, you know, cold storage of the drug, needles, injection site reactions. So I think that’s the the value case that, you know, a a drug like this will have. And especially if you compare it to for example, the the only drug that right now is approved in AD, it’s a drug with a black box, and that drug actually is doing quite well. I think that speaks and then it’s a drug that requires testing before you start that therapy. And so it speaks to the hunger that that this market has for an oral drug.

And I think we you’ve seen in all in all markets, oral drugs and multiple effective therapies are needed to expand access and penetration. Now, you know, the especially atopic dermatitis market is really dominated by a single player, I would say, mostly with dupilumab, but it still has less than fifteen percent penetration. I would say if you look at all moderate to severe, it’s less than ten percent. And so I think we need this option to expand access dramatically in The US and all over the world.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics4: Appreciate it. Thanks, guys.

Olivia, Conference Operator: The next question is from Jeff Jones at OpCo. Please unmute yourself and begin with your question.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics: Good morning, guys, and thanks for taking the question. One question from us on Iraq four. Can you provide any additional detail behind what drove the exchange of $4.07 4 for the $4.08 5 candidate? You know, given the specificity differences, was there something that was being seen with four seven four that was concerning?

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Great question, Jeff. Thanks for asking about this. So just to remind everybody, the the decision was made by Sanofi to focus all the resources of the Eric for collaboration on k t four eight five. Based on preclinical data, k t four eight five seems to be superior to four seven four on both potency distribution, and we demonstrated also lack, complete lack of the subclinical QT finding that we had seen with four seven four in our clinical studies. I will also reiterate that that particular finding was self resolving with continued dosing, meaning that it will go away as you continue to dose.

And we didn’t learn anything even in the ongoing phase two studies that that spoke negatively with regards to the safety of the drug beyond what we’d already shared. So I think it was really focused on the fact that four eight five overall seem to have a better profile, and and we believe both clinically and maybe commercially more competitive. And since you asked me about, actually, IRAK four, I thought it it’s it’s also interesting to see how the landscape is evolving. I don’t know if if you guys have seen AstraZeneca starting about to start a big phase two study in in COPD after they’ve run a small earlier study, which we haven’t seen data for, but they’ve they’ve shared that they’re gonna share their data for their IRAK four inhibitor in HIT COPD. So that’s it.

And that’s another indication that we at Chimera thought IRAK four could be well positioned for. So it’s exciting that a big company is I think it’s a 400 patients. No. It’s more than that. Yeah.

A thousand patient study. So, anyway, just the field continues to learn and evolve, and, you know, we’re excited to have a great asset out there that hopefully could also go towards that that direction. But that’s something that we need to obviously discuss with Sanofi.

Olivia, Conference Operator: The next question is from Andy Chen at Wolfe Research. Please unmute yourself and begin with your question.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics5: Hey. Thank you for taking the question. On IRF five, is there a reason for degradation and cytokine reduction and all that to not translate into humans? It it looks like your stat six degrader has more than translated. Wouldn’t all of that read through to IRF five, or is there still something special about that molecule that makes you think that, you’re still maybe semi concerned and maybe the derisking steps are still ahead of you?

And, also, what are the, top two, three, safety signals that you’ll be watching for in humans? Thank you.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Yeah. Great question. So for IRAF five, I mean, we’re the stage, to be honest, we’ve been here for a while, where all of our programs have translated really well. You can argue whether you like the the target and the biology translate, but all of our programs have translated really well in the clinic. So we expect IRAD five to translate just as well as k d six to one.

Also, for IRAD five, k d five seven nine in non GLP tox, we’ve seen no adverse event of any type, and we went up to 200 fold above the the expected 90% degradation human exposure. We are in the midst of IND enabling studies. I’m confident we’ll continue to see an exceptionally well tolerated drug. So we’re excited about that drug. We’re working already really hard not only to prepare for the healthy volunteer study that would start early next year, but the team has been spending the past few months working on and planning our patient study that will will start soon after the healthy volunteer study.

We’re prioritizing indications. We’re talking to KOLs and refining protocols. So, yeah, we we’re working under the assumption that the translation will be, you know, happening just as well as it did for six to one.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics5: Thank you,

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics: Adam. We’re just about up

Jared Golub, Chief Medical Officer, Chimera Therapeutics: up against time. Operator, we’ll try

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics: to just move really quickly through these last few.

Olivia, Conference Operator: One moment while we wait for questioners.

Jared Golub, Chief Medical Officer, Chimera Therapeutics: The

Olivia, Conference Operator: next question is from Ellie Mel at UBS. Please unmute yourself and begin with your question.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics6: Hey, guys. Thanks so much for taking the question. Just another one on IRAK4. I guess, can you elaborate a little bit on what was seen clinically with the first generation IRAK4? And I guess, what gives you the confidence in the efficacy of this target in AD and HS?

And, I mean, I heard your comments on, AstraZeneca. I mean, difference now in terms of how you might be thinking about the opportunity set across indications now for IRAK4? And then also just follow-up on CDK two. Can you elaborate on some of the learnings on working with molecular glues versus heterobifunctional degraders and your confidence in the selectivity for CDK two with these programs? Thanks.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Yeah. So on on ERAK four quickly, we can’t speak to what we’ve seen or not seen in the in these studies. Unfortunately, that is, you know, Sanofi’s guidance on that. On the indications, again, this is, again, another question for Sanofi, but asthma and COPD have always been on the high priority list for for that biology. Obviously, we’re talking about eosinophilic at COPD, which is a huge patient population.

And with CDK two so we we again, we’ve historically said that these two, the heterobifunctional degree of molecular are two complementary technology, and they’re not one, the next generation of the other. Although many companies seem to go in that direction. We use molecular glues where we believe that binding site and bind ability to bind to the target is either not feasible or not with the selectivity. If you use binding specific binding to CDK two, it’s really difficult to find selectivity against CDK one, and that’s why we built our CDK two degrader, which does not has any any kind of cross binding with CDK one. That’s how we that’s why we went in that direction.

Bruce Jacobs, Chief Financial Officer, Chimera Therapeutics6: Great. Thanks.

Olivia, Conference Operator: There are no more questions at this time. I would now like to turn the call over to Nello Menalofy for closing remarks.

Nella Manalthi, Founder, President, and CEO, Chimera Therapeutics: Well, thanks, everybody. Sorry we went a bit too long today. Another exciting quarter. We’re here for any follow-up questions. You know where to find us, and thanks again for joining.

Have a great day.

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