Kymera Therapeutics Q3 2024 Earnings Call Transcript

Quartr
Provided by Quartr
October 31, 2024

There are 16 speakers on the call.

Operator

Good day, and welcome to the Chimera Therapeutics Third Quarter 2024 Results Conference Call. All participants will be in listen only mode. After today's presentation, there will be an opportunity to ask questions. Please note this event is being recorded. I would like now to turn the conference over to Justine Koenigsberg, Head of Investor Relations.

Operator

Please go ahead.

Speaker 1

Thank you. Good morning, and welcome to Chimera's quarterly update call. Joining me this morning are Nelo Manolfi, Founder, President and CEO Jared Golub, our Chief Medical Officer and Bruce Jacobs, our Chief Financial Officer. Please note that during Jared's remarks, we intend to reference data from slides in our corporate presentation, which is available within the IR section of our website at chimeratx.com. Following our prepared remarks, we will open the call to questions.

Speaker 1

We ask that you please limit your questions to 1 and a relevant follow-up to ensure we have enough time to address everyone's questions. 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. 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.

Speaker 1

With that, I will now turn the call over to Nelo.

Speaker 2

Thank you, Justine, and good morning, everybody. We have a lot of important updates today, so let's jump right in. First and foremost, we're extremely excited that we have started the Phase 1 study of KT-six twenty one, a 1st in class oral STAT-six integrator and the 1st STAT-six medicine to ever enter clinical development. It's important to highlight that we were able to accelerate the path to the clinic given our recent increased focus of resources and capital that were directing towards our growing immunology pipeline. I believe this is also an important moment for the whole industry.

Speaker 2

We have shown in preclinical species that a STAT-six degrade or like KT-six twenty one can block IL-four and IL-thirteen similarly or even more importantly than an upstream biologics like dupilumab in both cellular and in vivo models. We've also shown that KT-six twenty one was well tolerated in all safety studies that we have run-in a wide variety of preclinical species. In summary, we have an investigational drug that has the potential to have a dupilumab like profile in a daily oral tale. Many of you know there are more than 150,000,000 patients just in the U. S, Europe and Japan who suffer from diseases associated with Th2 inflammation.

Speaker 2

And according to market data, less than 1,000,000 of those patients received dupilumab. While one could focus on the roughly 1,000,000 of patients currently on dupilumab, Chimera is focused on expanding access across the tens of millions of patients that are waiting for a convenient, safe and effective oral pill. One that doesn't require needles, refrigeration, syringes and frequent trips to the doctor's office. We believe KC-six twenty one is a medicine that has the potential to transform treatment paradigms in many diseases that affect millions of patients, such as atopic dermatitis, asthma, COPD, EOE, just to name a few. In addition, given that TH2 diseases are highly prevalent in children, we believe this has the potential to be a drug that will change quality of life for many families in the future.

Speaker 2

Our next Type 6 update is expected to be upon completion of the healthy volunteer study in the first half of twenty twenty five, at which point we will share the full results. Following the completion of the Phase 1 study, our plan is to move quickly into patients. We have those plans well established and we expect to provide guidance on next stage of 6:1 clinical development next year. Jared will share more details around the ongoing Phase 1 study later in the call. I also wanted to briefly highlight another important update on KT-four seventy four, our 1st in class IREQ-four degrader.

Speaker 2

This is another program where Cannair was first to clinic and the success has influenced the industry with several companies following our lead with other iREC4 directed assets. We're finally able to share more information on the expanded Phase 2 studies that are being run by our partner Sanofi. As I'm sure you have read in our press release earlier today, the program is transitioning from proof of concept like Phase 2 studies to fully powered Phase 2b studies with dose ranging as a mean of accelerating our path to registration of Phase 3 studies right at the conclusion of the ongoing studies. In terms of the specific trial changes, we have basically added 1 dose group to each study who have enough information to being able to select the dose for the subsequent registrational Phase 3 studies. We're thankful to our partner Sanofi for the increased confidence in and commitment to this important program.

Speaker 2

Turning to TYK2, we have exciting progress to report as well. At our R and D day in January of this year, we introduced our TYK2 program in our lead molecule KT-two ninety four. Similar to all of our programs as KT-two ninety four was being advanced through preclinical development, we had parallel work ongoing on other promising compounds. One of the compounds we were evaluating demonstrated an even more compelling profile than KT-two ninety four, highlighted by greater in vivo activity and with a similar selectivity and safety profile. As a result, we have decided to advance the new compound KT-two ninety five as our linked clinical candidate.

Speaker 2

Importantly, we believe we can do that without impacting our previously stated T2 development timelines, which assume the Phase 1 trial start in the first half of twenty twenty five. Finally, I just wanted to provide everyone with a broader strategic update and specifically as it pertains to our oncology programs. As many of you recall, it was around this time last year, we first shared that we had increased our focus in immunology. The rationale was driven by the profoundly impactful profiles we believe we could generate in immunology with oral degraders that could compete with injectable biologics in terms of efficacy and safety. As shown with KT-four seventy four in the clinic and with our STAT6 and TYK2 efforts pre clinically, we think we're positioned to develop a potential best in industry portfolio of oral immunology assets with opportunities to impact millions of patients.

Speaker 2

Even more today with KT-four seventy four in multiple Phase 2b trials, KT-six twenty one in the clinic and KT-two ninety five close to the clinic and other exciting immunology programs that we would be unveiling starting from next year, we believe that now is the time to focus even more of our resources into this space where we believe we can create outsized value. As a result, while we made some encouraging progress with our clinical oncology pipeline demonstrating promising clinical activity in a variety of tumor type, as we have completed Phase 1 enrollment, we have made the decision that we will only advance KT-three thirty three, our STAT3 degrader and KT-two fifty three, our MDM-two degrader beyond Phase 1 with a partner. You can expect that we'll share more on this if and when it makes sense to do so. While there are many considerations that contributed to this decision, ultimately, we believe our internal resources, both capital and people, are best focused on our expanding immunology pipeline. It should be noted that we did not take this decision lightly or made it without thinking about the potential impact on patients.

Speaker 2

We're in fact grateful to patients, families and investigators and the Chimera team who support their studies and these programs. In conclusion, as we approach year end, it is quite exciting to see the trajectory that Chimera has had in 2024, especially within our immunology pipeline. We've advanced in the clinic KT-six twenty one with what could become one of the biggest programs in our industry. We have supported Sanofi to advance KT-four seventy four in expanding the Phase 2 studies. We've developed a TIK2D grader with a compelling profile and are closer to the clinic.

Speaker 2

And we have raised a total of approximately $600,000,000 in just 2024 that has enabled us to have cash into mid-twenty 20 7 and through several inflection points across our pipeline. I will pause here and let Jared share more details on our programs and Bruce will walk you through the Q3 financial results. I'm looking forward to the Q and A session at the end of our prepared remarks. Jared?

Speaker 3

Thanks, Noah. As it relates to immunology, I'd like to first recognize our KT-six twenty one team for the rapid progression to advance this 1st in class program through IND enabling studies, culminating in the IND clearance and the initiation of the Phase 1 healthy volunteer study earlier this month. As we have not shared many details on the trial design, I wanted to take the opportunity now to provide a quick overview of the Phase 1 design. The SAD MAD healthy volunteer trial includes single and multiple ascending dose cohorts evaluating KT-six twenty one as compared to placebo. In the SAD component, each subject receives a single dose of either KT-six twenty one or placebo.

Speaker 3

In the MAD component, each subject receives a daily dose of either KT-six twenty one or placebo over 14 days. In terms of data we plan to share, the main objective of the trial is to demonstrate that we can robustly degrade STAT6 in blood and skin at doses that are safe and well tolerated. Based on our preclinical work, we are targeting STAT6 degradation of 90% or more, which is the level at which we saw strong biologics like activity in our preclinical models. In fact, levels of pathway blockade, in this case measured by STAT6 levels, are the data that we have shown to be translatable to patient efficacy. As we have said, STAT6 degradation and safety and tolerability are the key readouts from this study.

Speaker 3

Additionally, as many of you know, we plan to measure certain Th2 biomarkers, specifically IgE and TARC in the healthy volunteers on our study. We fully expect KT-six twenty one to have an impact on these biomarkers. However, we believe the impact is likely to be much more robust and relevant in patients as was also true for dupilumab. With enrollment underway, we continue to expect to report the full SAD and MAD Phase 1 results for KT-six twenty one in the first half of 2025. At or before that time, we will also share our plans for the next stage of KT61's development.

Speaker 3

I'll now turn to our TIC II program. As Nelo mentioned, we made the decision to advance a new development candidate KT-two ninety five into the clinic, which we believe we can do without impacting our stated timelines of the first half of twenty twenty five for the start of the Phase 1 study. I thought I would take a few minutes to share some details around KT-two ninety five, particularly a comparison to KT-two ninety four that influenced our decision. You can also reference the TIC-two program slides in our corporate presentation, which is available on our website. On Slides 4849 of our corporate deck, you can see that in preclinical testing, PT-two ninety five demonstrated picomolar degradation potency and potent inhibition of the IL-twenty three, IL-twelve and Type 1 interferon pathways, showing its potential to recapitulate the biology of human TIK2 loss of function mutations.

Speaker 3

Like KT-two ninety four, on Slide 50, KT-two ninety five did not impact any of the other JAK proteins and spared IL-ten signaling, a feature important in the treatment of inflammatory bowel disease. Importantly, KT-two ninety five had greater in vivo activity compared to KT-two ninety four as shown back on Slide 48. With this profile, KT NUH95 has the potential to replicate the TIK2 loss of function profile and achieve biologics like activity at lower doses than what was predicted for KT-two ninety four. To round out our INI franchise, I will cover IRAK4. We are pleased that Sanofi has taken steps to accelerate the overall KT-four seventy four development program.

Speaker 3

And as a reminder, the goal of the previously announced decision to expand the Phase 2 program was to structure the hidradenitis suppurativa in atopic dermatitis trials with the necessary regulatory perspective to enable dose selection and advancement directly to pivotal Phase 3 studies, ultimately with a meaningfully shorter timeline. To support this strategy, the size of the studies has increased with additional doses being evaluated in both trials. There are no changes to study endpoints. Specifically, the HS Phase 2 trial has been expanded from 99 to 156 patients and will evaluate 2 doses of KT-four seventy four versus placebo versus just one active dose previously. The AD Phase 2 trial has increased from 115 to 200 patients and will evaluate 3 doses of KT-four seventy four compared to placebo versus just 2 active doses previously.

Speaker 3

These changes drive the primary completion dates to the first half of twenty twenty six and mid-twenty twenty six for HS and AD respectively. While that obviously extends the time before the complete Phase 2 data readout, we expect that it will meaningfully reduce overall development timelines for the KT-four seventy four program by allowing a faster path to pivotal studies. We're energized by the progress and potential impact of our immunology programs, each representing pipeline and product opportunities. And we believe that our oral degraders are uniquely positioned to have both the efficacy and safety of biologics with multiple development opportunities in large high unmet need indications. Finishing up on oncology, I will not add too much more to what Nalo said earlier.

Speaker 3

But I did want to remind everyone that we will be sharing the totality of the Phase 1 data for our STAT3 degrader PT333 at ASH in December. As a reminder, our latest enrollment was focused on Hodgkin's lymphoma patients given the promising responses we observed in that population and those results will be included in the poster presentation. I'll stop here and ask Bruce to review the Q3 financial results. Bruce? Thanks, Jared.

Speaker 3

As we have a lot to cover on this call and I'm sure you all have many questions, I'm going to provide a quicker than normal overview of our financials and then refer you to the financial statements in the press release and our 10 Q, which we filed this morning. In the quarter, we recognized $3,700,000 of revenue that was all attributable to Sanofi and the collaboration. Combined spending of R and D and SG and A excluding cash based non cash stock based compensation was $61,000,000 in the quarter and that's down about 2% sequentially from the June quarter. And then finally, we ended the quarter with $911,000,000 of cash on our balance sheet providing a cash runway to mid-twenty 27. I'll now turn the call back

Speaker 2

to Nelo. Thanks, Bruce and Jared. Before we open the call to questions, I just want to reiterate that we're more enthusiastic than ever about the opportunities in front of us. Advancing KT-six twenty one in the clinic is a significant milestone for Chimera and the industry, and we're doing so with a very exciting drug profile based on our preclinical finding. We're executing on the rest of our immunology pipeline and we look forward to sharing updates on TYK2 and providing more visibility on other pipeline programs, which we have yet to disclose likely next year.

Speaker 2

We're well resourced to advance our best in industry pipeline of degraded therapeutics and look forward to keeping you updated with our progress. The next 6 to 12 months will provide multiple value creating catalysts and we look forward to sharing these with you. Finally, I wanted to thank the Chimera team and our collaborators for continuing to deliver on very ambitious goals and first in industry endeavors. I'll pause here and ask the operator to open the call to questions.

Operator

Thank you. We will now begin the question and answer session. The first question comes from Mark Frahm of TD Cowen.

Speaker 4

Cohen. Thanks for taking my questions. Maybe thinking to the 61 healthy volunteer data, and thanks for the kind of clarity on exactly where the target profile is. But maybe thinking through to the Th2 biomarkers, investors seem to be really trying to comp this to what was seen with DUPI as you alluded to. How reliable do you think those changes, this percent changes in IgE and TARC from the healthy volunteer study almost a decade ago, really are?

Speaker 4

How comparable and how tight of a range do you think you need to get to?

Speaker 2

Yes. Maybe I'll start and Jared please jump in. So first thing is Jared I think explained that the main goal of the Phase 1 study for any program, but especially for us is first to demonstrate that we have predictable PKs and the safety is translating from the amazingly well tolerated profile that we've seen pre clinically. Now with a degrader as we've done in multiple times, we have this unique opportunity to access a direct biomarker. So don't forget lots of other modalities and companies use downstream biomarkers because they're not able to have a proximal biomarker.

Speaker 2

So we have the most proximal biomarker, which is STAT6 protein levels. So we can look at STAT6 protein levels in blood and skin to show that we're able to block IL-four thirteen pathway fully. That's the goal of the study. That is the only biomarker that has been correlated to disease impact. Again, blocking the pathway has been correlated to disease impact.

Speaker 2

In fact, actually there was a recent paper sorry, if I'm digressing a bit, where there actually there were humans where they found partial loss of function variant of STAT6 that was protected against TH2 asthma. So that's actually now for the first time even correlating protein function, protein levels to protection in TH2. So now many companies including Regeneron back in the day and you also saw another other companies with this long acting biologics obviously look at downstream levels again because you can't really measure your direct biomarkers. As you know, people have looked at IG and TARQ. I feel like IG has been mostly detected by the dupilumab data.

Speaker 2

And I think it's from recent publication from other companies, I actually haven't seen IG data out there, but mostly TARC and phosphatistics for other companies. But so it's important to understand that they're modestly elevated in active volunteers, right? You're trying to measure something that is just around the baseline. There is intersubject variability, so it makes it difficult to predict the degree of reduction. So if you look at for example, if you look at the published paper of dupilumab that you were referring to in anti volunteers, you see IG is impacted between 10% 30%.

Speaker 2

Actually, if you look at the subcu dose, actually up to 15% and there is quite a bit of variability and TAR between 15% 35%, which is actually in line with the data also from the long acting IL-thirteen biologics that is being evaluated in Phase 1. So I think that kind of sets the range. I would just discourage people because from trying to understand the exposure to biomarker relationship because this data, at least in other endeavors, are very noisy. So that's why we say what we know is critical is obviously safety PKA, but levels of SAD3 degradation because they tell us ability to suppress pathway signaling. Then again, we have confidence that we'll change the biomarkers and I'm sure they will be in the range of what has been seen for these agents that have been in the clinic.

Speaker 2

Sorry, long answer the

Speaker 4

Long, but very helpful. Then maybe just more on the model with Bruce. Just talk through with the kind of continuing prioritization of the immunology side. Are there kind of any savings of that from the oncology or it's all going to be redeployed into immunology?

Speaker 3

Yes. Thanks, Mark. It's a good question. So, I mean, there are savings, yes, in aggregate because of the fact that obviously some of the clinical development plans that we contemplated, we won't be undertaking on our own. However, we do imagine that a meaningful part of that, if not all, would be invested in our immunology pipeline, both the clinical development of the programs you know about and the ones that we haven't yet disclosed, but will in the future.

Speaker 3

So while there might be a modest change in the ultimate cash runway, not enough to change the guidance. I think most of it you should assume will be reinvested in our immunology programs.

Operator

Our next question comes from kalpit Patel from B. Riley. Please go ahead.

Speaker 5

Yes. Hey, good morning and thanks for taking the question. Maybe just one on the STAT6 program here. I'm curious if you've made comparisons to DUPI preclinically, if you've looked at the change in ear thickness in the atopic derm model, the MC930. And as a follow-up, I think the 32 milligrams per kilogram showed the most reductions in IgE.

Speaker 5

So I'm curious what that dose translates into humans. Thank you.

Speaker 2

Yes. Thanks, Kapit. Great question. So let's start with the second. So if you look at the slides that have been up for now close to 12 months, so in the mouse, to reach 90% degradation, because that's really what we're looking at.

Speaker 2

We use a 30 basically what you said 30, 32 mgs per kilogram. In monkeys or in dogs, you actually need a much lower dose in the single digit milligrams per kilogram. So the reason why mouse you need a larger dose is because actually plasma protein binding in mouse is higher than it is in dogs, in monkeys and in humans. So when you do those projection, you should look at maybe more the dog and the monkey data. I would say the dog will show NOR data than using the mouse.

Speaker 2

So we don't talk about dose projection. What we said in the past is that the doses that we've explored in the AREK4 programs broadly are probably again broadly what we are we would be exploring in this program as well. So it's relatively low doses. With regards to your first question, so when we run these models, we focus on Th2 biomarkers and Th2 driven disease outcomes. And so that's why we looked at again in those models, IG and other TARC and other measures of Th2 inflammation.

Speaker 2

And for disease outcome, we look at more at the asthma model where we can look at both lung and infiltrative cells in the lungs as well as other Th2 biomarker. That model is not only Th2, so ear thickness is not something we kind of monitor either for doopy or for our degraders just because it's a more composite outcome that is non TH2 as well.

Speaker 5

Okay, got it. Thanks for taking the questions.

Speaker 2

Operator, next question.

Operator

Our next question comes from Kripa Devarakhanda from Tuohist Securities. Please go ahead. Hi.

Speaker 6

This is Alex Sanagas on for Kripa. A question on the OTIC-two asset. We've had some conversations with investors about what they would describe as a slow launch for OTIC-two, citing some efficacy, good efficacy in indications like psoriasis and maybe some challenges and others like IBD. Do you think that a degrader could address these issues and provide additional benefit? And when you think about future enrollments for the studies, would you consider enrolling TYK2 inhibitor experienced patients in the trial as an expanded opportunity?

Speaker 6

Thanks.

Speaker 2

Yes. Maybe I'll address the first one and I'll let Jared address the recruitment one. So I mean, you obviously bring the point of the current commercial success of T2 inhibitors. I'm going to answer it a bit differently, but hopefully still addressing your point. So what we have right now in the industry, we have a genetically validated target, TIK2, that has been dragged by multiple molecules from different companies.

Speaker 2

1 has been approved by BMS and there are at least 2 or 3 other companies in different stages of development. We believe strongly at Chimera and I think people that understand T2 biology would tend to agree with us that all these inhibitors are going to be difficult to be differentiated because they don't address they address only partial function of TIP2. TIP2 has a well characterized scaffolding function that actually is important in receptor signaling IL-twenty three, IL-twelve, type 1 interferon. By removing the protein, we are going to completely block the T2 signaling and we're able to near complete block 3 of these pathways. So obviously, if the profile of our degrader look like the inhibitor, we would obviously have failed.

Speaker 2

That's not the type of profile that we're looking for. We're looking for something that can compete with biologics in many of those indications. And I actually believe that if we're able to translate the preclinical profile, we have an even and more active molecule with 295 because again, full target degradation is the name of the game in this particular program. I think that we're going to have a really transformative drug. And I think at this point it's been missed right now because there is a bit of general maybe fatigue in the TIK2 space.

Speaker 2

But Jared, did you comment about recruitment?

Speaker 5

Yes. I think for the initial proof

Speaker 3

of concept study in patients, we would likely not put on patients who had been on prior TYK2 and had progressed. Whereas we might include patients who have been on a prior TYK2 inhibitor, but it come off due to tolerability issues. Further down the road, once we've gone through initial proof of concept, we might be interested in understanding the activity of our drug even in those patients who have progressed after prior TIK2 inhibitors, but we probably wouldn't do that in the first study.

Speaker 2

Next question operator.

Operator

Our next question comes from Brad Canino of Stifel. Please go ahead.

Speaker 7

Hi, good morning. I know you stated in the prepared remarks that the next steps for STAT6 will be shared after the SADMAD results and hitting that 90% plus degradation safely. But dupilumab replication in TH2 patients is the major question. Is there a particular type of TH2 disease where this test is best to conduct? I guess how much duration of testing is likely needed?

Speaker 7

And do you need hard clinical endpoints or will biomarkers in patients be sufficient to accelerate mid to late stage development? Thank you.

Speaker 2

Yes, Brad, great question. So I would kind of say it this way. I think the goal of the Phase 1 study is to demonstrate that you can reach STAT6 degradation levels that we believe are therapeutically relevant, which as you said, actually anywhere between 70% 90% we've shown that is therapeutically relevant, but 90% is where we see maximal activity in a safe manner. I believe that Regeneron and Sanofi have done an excellent job actually doing studies of what does dupilumab do in the blood and skin, especially of AD patients with regards to biomarker signature. And I think there's a really well established dupilumab signature, especially in the skin of AD patients.

Speaker 2

And I think that one could actually very briefly get into that type of context and demonstrate that you're able to have relevant biomarker signature that shows that statics degradation box the pathway at least as well as an IL-four receptor antagonist. So you could imagine a biomarker study in patients to be exceptionally telling of the profile of the drug. And that will probably allow you to move into a large studies in all the important relevant population. So I think that could be an interesting sequence of events. I think we're not quite ready to share what our plans are, but those are important opportunities to validate this mechanism.

Operator

Our next question comes from Vikram Parikh from Morgan Stanley. Please go ahead.

Speaker 8

Good morning, everyone. This is Gaspar on for Perkin. We have one question on KT-two fifty three and KT-three twenty three. What would an ideal partner and partnership look like? And are discussions with potential partners currently underway?

Speaker 8

And should a partnership be something we expect in the near term? Thank you.

Speaker 2

Yes. Great question. So we're not going to comment on the ongoing or hypothetical conversations that obviously happen at any time in the lifetime of companies. But what I will say is we've shown across our oncology pipeline that we've been able to demonstrate a really impeccable translation of our PK, PD and safety into the clinic across the different programs. And we've shown some exciting early clinical activity across different indications.

Speaker 2

And Jared mentioned, we'll have an ASH poster on 333, which I encourage people to look out for. And so these are the activity we've shown has been in many cases in heme indication. So in order to maximize value in those patient populations, I think a partner that is that has I think a partner that is that has franchise both clinical and commercial in those areas, I think we'll be able to create most volumes. And for us, it's really how do we help patients in the most effective way and that's what's going to drive some of our decision making, given that our focus will be again our internal resources in immunology.

Operator

The next question comes from Kelly Hsieh of Jefferies. Please go ahead.

Speaker 9

Congrats on the progress and thank you for taking my questions. I would appreciate your insights. What are the major differentiations of targeting status 6 compared to targeting interleukin-four thirteen or like OX40 from biology perspective? For example, step 6 is also now involved in innate immunity besides L4-thirteen signaling. So what do you see the breadth of indications that the STAT 6 program could pursue based on its MOA?

Speaker 9

Thank you.

Speaker 2

Yes. Jared, I'll take a bit of this, but maybe you can help me. So, yes, great question. So, what we've shown in our studies pre clinically that the activity that we see of STAT6 in immune cells is really almost all, if not all, driven from IL-four receptor signaling, so IL-four and IL-four and IL-fourteen. And we've shown that if you block IL-four thirteen, as others have shown, you reduce phosphostat 6 levels.

Speaker 2

If you reduce that 6, you reduce IL-four receptor level. Again, I don't want to keep quoting this recent paper, but if you read this recent paper on the partial loss of function variant of that 6 actually shows the same that there is reduction of IL-four receptor signaling. If you look at gain of function in humans, again, I'm talking about human people, humans, sorry. Also there is the IF STAT6 gain of functions have severe allergic diseases, Th2 biology. So we kind of expect to be Th2 biology that we're the mechanism we're eliciting.

Speaker 2

So, biology biologically, we feel like it's really on pathway to IL-four receptor. Jared, is there anything you want to add or Ken?

Speaker 3

No, no. I think that covers it. I mean, we expect stat 6 degradation to phenocopy what's been seen with drugs like dupilumab that are resulting in full blockade of IL-four, IL-thirteen. And we've seen that impact both in our in vivo models, where we see efficacy that's comparable to DUPI in the asthma and AD models. And we've seen it in multiple cell types even in a recent EADV presentation where we looked at STAT6 degradation and human sensory neurons, we saw that it was able to block IL-thirteen induced our regulation of transcripts involved in itch and pain, which are key symptoms in AD.

Speaker 3

So we think STAT6 targeting really has an advantage in addition to the unique pharmacology of being able to degrade STAT6 by over 90% sort of 20 fourseven could give us pharmacology that may be unique and differentiated from what can be achieved with the upstream monoclonal antibody biologics.

Speaker 9

Great. Thanks.

Operator

Our next question comes from Jeff Jones of Oppenheimer. Please go ahead.

Speaker 10

Good morning, guys, and thanks for taking the question. I guess I'll stay on 621 and STAT6. Clearly, you guys aren't the only ones targeting STAT6 and your IRAK4 partner Sanofi is working with both RECLUTIX and Nurix. Could you comment on the differentiation between a degrader approach here for STAT6 versus the small molecule approach? And maybe any differentiation between your degrader platform and Neuroxes?

Speaker 10

Thank you.

Speaker 2

Yes. So great question. So first, I would say that we're the only company that has actually generated a wealth of data comparing 621 and stat 6 degradation to approved medicines. And while all the data so far has been preclinical, so there's always the caveat of preclinical, we've shown that STAT6 degradation can phenocopy in a variety of models what dupilumab does, both in that breadth of activity. And some would argue that we've seen even more activity than dupilumab in some of these models.

Speaker 2

But so that's that. I think what we believe is that degrading STAT6 is the only pharmacological way to block this pathway as fully as the saturating dose of an IL-four receptor alpha antibody. You can use a small molecule inhibitor to block STAT6, But blocking the path, we've given a deeper occupancy base that there is the challenge of PK and PD correlation. We believe that the degrader there is both highly potent and catalytic that doesn't require the correlation between PK and PD has a much more profound impact in terms of pathway blockade. I would also encourage you to be patient as well You'll hear more from us on this particular topic in the near future.

Speaker 2

With regards to us and other companies, it's hard for me to have again, I think no other company has shown any data. No other company has a compound even in from what we understand that has made past or at development candidates. So I mean those are the 2 companies you cited are just too out of many that are doing preclinical work in STAT VI. I think since we shared our data, I've heard of many other companies that are attempting to do what we've done. Again, I'll encourage you to continue to follow us.

Speaker 2

You'll hear more about our efforts in STAT6 even beyond 6:1 as we progress this program.

Speaker 5

Appreciate the update guys. Thank you.

Operator

Thanks. The next question comes from Eric Joseph of JPMorgan. Please go ahead.

Speaker 11

Hi, good morning. Just picking up on the Phase 1 trial with 621, could you I'm sorry if I missed it, but can you give us a sense of sort of the number of dose cohorts and patient numbers that you're evaluating in the SAD MAD and whether the readout in the first half would include both STAT and MAD components or maybe a partial readout thereof? Yes, and the extent to which sort of the prior Phase 1 with the IRAK4 is a useful roadmap here?

Speaker 2

On the good side, you didn't miss anything, Eric. So Jared can tell you more about at least what we can at this point about your question.

Speaker 5

Yes. I mean, we can't provide a whole lot of color around

Speaker 3

the actual number of dose cohorts, but I think your comparison to the IRAQ4 Phase 1, SAD, MAD, probably is within the ballpark in terms of how we plan to interrogate both the SAD and MAD portions. And just as a reminder, these are placebo controlled cohorts of healthy volunteers, with the MAD being 14 days of dosing and the set obviously being single doses. So I think we'll generate a very robust data set going across the full range of doses in both SAD and MAD and we plan on doing that efficiently with healthy volunteers. And as we mentioned, the data readout in the first half of next year will include both the SAD and MAD portion. So it will be the full data set from the healthy volunteer SAD MAD that we reveal in the first half of next year.

Speaker 2

Excellent. Sorry, Eric, just to add, because it's going to show up on clinicaltrials.gov in a few days anytime. I think we said there that the total number of patients in Setyma is roughly 120 or up to 120. So that's the additional piece of info we can share today. Go ahead.

Speaker 2

Do you have a follow-up?

Speaker 11

Yes. Thanks for that detail. Yes, we were looking for the trial entry, couldn't find it. But anyway, thank Follow-up, just with the kind of the focus going forward here in I and I, any I guess, we should be anticipate additional targets programs here in that space over the next year or so?

Speaker 2

Yes, I mean, it's for sure. So we've it's been 3 plus years that we have focused our research and now development effort in immunology, we're working on many, many programs. We have multiple development candidates that are being nominated in the past few in the next few months. So we'll be happy to share as again, as we've done in the past, when we're close to the clinic, we're happy to share next targets. I think we've also learned from our previous experiences that maybe we should wait a bit longer before sharing our target and data package for competitive reasons.

Speaker 2

So maybe we'll share when we're a bit closer to the clinic than in the past, but you should expect next year at least one disclosure.

Operator

The next question comes from Ellie Merle of UBS. Please go ahead.

Speaker 12

Hey, it's Sam on for Ellie. I guess can you just touch on a little bit your level of confidence for IRAQ4's efficacy in HS versus atopic derm heading into those Phase 2 readouts in 20 6? And then, second on SOT6, how quickly do you expect to move into patients, following the SAD MAD portion? And, any expectations for timing on that? Thanks.

Speaker 2

So, maybe I'll take the second and then I'll let Jared take the first one. On so as we said, I think we've said it today that we expect to go into patients soon after the Phase 1. To be honest, mostly for competitive reason, we're not sharing those plans yet. We have them, we've had them for months, if not for years. But we would be able to share as we're closer to those studies what the plans are, both in terms of near term development and eventually long term development.

Speaker 2

Gerald, on Ira, Thor? Yes.

Speaker 3

I think in terms of your question around our level of confidence and being active in HS versus AD, I think we have Sanofi as well have a high level of confidence in potentially being active in both of these indications. Mechanistically, for example, HS, we know is driven by IL-thirty six, IL-one, total like receptor activation. AD, we know there's an important component of IL-one, IL-thirty three and total like receptors. And so I think there's a mechanistic basis for believing that IRAK4 targeting should be effective there. And I

Speaker 2

think also if you look

Speaker 3

at our Phase 1 study where we did have experience with both HS and AD patients, we did see impact both on skin lesions and importantly on symptoms in both of those diseases impacting pain significantly in HS and pruritus and AD, these being the number one symptoms that affect quality of life in these patients. And so I think in addition in that Phase 1 study, we showed modulation of pro inflammatory pathways and skin biopsies from both of those patients. So I think we have confidence in both and look forward ultimately to the clinical readouts from the Phase 2b trials, which will ultimately answer that question.

Operator

The next question comes from Michael Schmidt from Guggenheim. Please go ahead.

Speaker 13

Hey, good morning. Thanks for taking my question. Another one on 621, Nelo. So degraders as a modality have obviously been very safe so far. But based on the mechanism and perhaps preclinical data, what are potential on target or perhaps off target AEs that one might expect to see in the study at high-six 21 doses in the clinic?

Speaker 13

And what are learnings from STAT 6 knockout animal models? Thanks so much.

Speaker 2

Yes. Thanks, Mike. So, in terms of what we know is that STAT6 degradation and even 40 fold above the exposure in which we reach the full status degradation. We have not seen in preclinical species any adverse events. Our molecule, as you've seen, 621, is an exceptionally selective molecule in both proteomics as well as any other biological testing that we've done.

Speaker 2

So we do not expect to have any off target activity. So I don't have an answer for you what we expect to see in terms of safety flag. The reality is that so far we haven't seen anything. We hope not to see anything in the clinic also. In terms of what we know from genetics, so we know that knockout mice are normal and fertile.

Speaker 2

We know gain of function STAT6 people have severe atopic diseases, which again tells you that STAT6 is really only signaling through the IL-four receptor alpha pathway. Again, I mentioned already twice, this is also this partial loss of function, humans, which also are protected, they don't have any phenotype. So, I would say that if we look at the totality of our data, it is the perfect target and we hope we're right.

Speaker 13

Great. And just a quick follow-up. So in terms of subsequent studies, how do you think about prioritizing potential indications? Would you move into AD first perhaps? I know there's a lot of work on STAT 6 out there in lung inflammation.

Speaker 13

So asthma is at top of the list. How do you plan on prioritizing potential opportunities?

Speaker 2

Yes. I mean, look, again, as I mentioned earlier, we were not going to disclose our clinical development plan, not because we don't have it. It's just it's premature at this point. But I can say that we believe this is a Th2 drug. This is not an AD drug or an asthma drug.

Speaker 2

This is a Th2 drug. So this drug has the opportunity to work in all these indications that dupilumab has worked in. So we're talking now 7, 8 indications with those of the most recent data. Our approach would be to prioritize the larger indications for obvious reasons. So AD, asthma, COPD would likely be the primary indications, but we are committed to helping all patients of all ages of all severity of diseases.

Speaker 2

That's our mission and vision for this program for this franchise, I should say. And so we are going to do as much as possible to help as many people as possible unlike the biologics that are now on the market or soon to be on the market.

Operator

The next question comes from Faisal Khurshid from Leerink Partners. Please go ahead.

Speaker 14

Hey, guys. Thanks for taking the question. I realize this might be premature, but wanted to ask anyways. So how are you thinking about partnership opportunities on KT-six twenty one? And when do you think the best time for that would be?

Speaker 2

One answer would be we're not thinking about that. But to answer, it is a good question, it's not premature actually, not because we're planning to do so, but it's good to discuss. So we believe we're best positioned to develop KT6 to 1 in our franchise through the next inflection point. We believe it will be except I believe personally, it will be exceptionally premature to have these discussions in the near future. I think we have a great development plan that will take us through some compelling hopefully Phase 2b studies.

Speaker 2

I think as we're nearing commercialization and Phase 3 and commercialization, the questions will be based on our cost of capital, our pipeline, what is the best way to create value and impact patients. One path will be to go all in and become these amazing companies that commercializes this product everywhere. Another path will be to find a partner that helps us commercialize this drug in particular regions. But it's going to be an extremely high bar for us to partner SAD6 and we've been asked multiple times is probably an understatement.

Speaker 3

Great. Thank you.

Operator

The next question comes from Andy Chen from Wolfe Research. Please go ahead.

Speaker 15

Hey guys, it's Chuka here for Andy. Thanks for the clarification on iRx4 trial design changes. So Sanofi is deciding to add an additional dose to both HS and AD, are they adding a dose because they think the previous doses are too safe or too unsafe? Our guess is that the previous doses are very safe. So is it safe for us to assume that these new doses or these new higher doses in both trials

Speaker 11

Can you guys hear me?

Speaker 2

Yes, yes. I think we got to yes, did you have anything else? I think you stopped at some point.

Speaker 15

Okay. Yes, it sounds like you cut off for a second. So let's say first to assume that the new doses are higher in both trials because the efficacy can go higher or are we thinking of this wrong?

Speaker 2

So it's a great question actually. So let's take a step back because actually maybe we because we've talked about this for so many times, we didn't today. So I want to remind everybody that how we got to this point that Sanofi decided elected to do in a safety efficacy IA early in the year to look at the profile of the drug to that point and decided to use that data set to make an investment decision or not actually. And the data and again, early data in both safety and efficacy was supportive of an increased investment to accelerate the overall development timeline. And so what we haven't said publicly whether it's a lower or higher dose, I think you can speculate a 1,000 things.

Speaker 2

I think what we've said though publicly is that the need or the desire to add another dose was driven from regulatory needs to conduct dose ranging studies before selecting the dose for Phase 3. And so it's probably neither of your hypothesis is more they wanted to add another dose so that you've checked that box in order to move into late development into Phase 3 studies and maybe less about was it not safe or too safe. I think the data that we both saw was compelling enough that it was about accelerating the study.

Speaker 15

Got you. Got you. Makes sense. Thank you.

Speaker 2

So I think this was the last question. I wanted to thank everybody for joining our call. As you all know, we're easily reachable if there is any follow-up questions from our stakeholders externally. I want to thank our team again because they continue to do some amazing work and looking forward to an exciting year end and early next year. We've probably never been busier at Chimera.

Speaker 2

And so I think everybody says busy is good. So looking forward to the next update.

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Key Takeaways

  • Chimera initiated dosing in its first‐in‐class oral STAT6 degrader KT-621 under a healthy volunteer SAD/MAD Phase 1 study, targeting ≥90% STAT6 degradation to mirror dupilumab‐like efficacy, with full data expected in H1 2025.
  • Partner Sanofi expanded the Phase 2b studies of the IRAK4 degrader KT-474 in hidradenitis suppurativa and atopic dermatitis by adding dose arms to enable direct advancement into pivotal Phase 3, with primary completions in H1 2026 (HS) and mid-2026 (AD).
  • For its TYK2 program, Chimera selected a more potent degrader candidate KT-295 over KT-294 based on superior in vivo activity and maintained the Phase 1 start timeline for H1 2025.
  • The company refocused internal efforts on immunology, opting to advance only STAT3 and MDM2 degraders in oncology beyond Phase 1 via partnerships, redeploying capital and personnel to its expanding immunology pipeline.
  • Financially, Chimera reported Q3 revenue of $3.7 million (all from Sanofi), combined R&D and SG&A (ex‐stock comp) of $61 million, and ended the quarter with $911 million in cash—funding operations into mid-2027 after raising ~$600 million in 2024.
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Earnings Conference Call
Kymera Therapeutics Q3 2024
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