Kymera Therapeutics Q4 2023 Earnings Call Transcript

Quartr
Provided by Quartr
February 22, 2024

There are 11 speakers on the call.

Operator

Good morning, and welcome to the Chimera Therapeutics 4th Quarter 2023 Results Call. All participant lines will be in the listen only mode. Please note this event is being recorded. I now turn the conference over to Justine Koenigsberg. Thank you.

Operator

Please go ahead.

Speaker 1

Good morning, and welcome to Chimera's Investor Update. Joining me this morning are Nelo Manolfi, President and CEO Jared Golub, our Chief Medical Officer and Bruce Jacobs, our Chief Financial Officer. Following our prepared remarks, we will open the call to questions. Before we begin, 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.

Speaker 1

A description of these risks can be found in our most recent 10 ks 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 will now turn the call over to Nello.

Speaker 2

Thank you, Justine. As always, we appreciate everyone joining us for our quarterly call today. This is a particularly exciting call for us in that we're reporting from our new corporate headquarters in Watertown, Massachusetts, just down the road from our previous office. Our new building provides added space for our growing team, enabling us to maintain a strong on-site presence as we enhance and scale critical capabilities for our R and D organization, especially in areas like C and C as well as other development functions. We look forward to the opportunity to welcome those of you who would like to visit us at our offices in the future.

Speaker 2

As many of you know, we're on-site 5 days a week. During our prepared remarks, we'll cover 3 main topics today. First, I'll provide an update on our strategy to build the best in industry oral immunology pipeline. Next, Jared will provide an update on our clinical and newly disclosed immunology programs as well as our 2 clinical oncology programs. And before we open the call for questions, Bruce will review our financial results.

Speaker 2

At our Immunology R and D Day in early January, you heard us discuss our strategy for building a best in industry oral immunology pipeline of 1st in class highly valuable programs. We believe we're uniquely positioned to change existing treatment paradigms for immune mediated diseases with our innovative and differentiated oral degradative medicines. As we reported this morning with $745,000,000 in cash and the runway into the first half of twenty twenty seven, we're well capitalized to continue to support these very ambitious goals. I thought I'd start with a few comments reflecting on what has led Chimera to our current strategic positioning with an innovative immunology pipeline of oral degraders with biologic like activity potential. Those of you that have been following us for a long time now, we have been driven by our unique target selection strategy.

Speaker 2

We're focused on 1st or best in class opportunities and in particular undragged or fully drugged targets for which protein degradation is either the best or the only solution. We're also dedicated to pathways that have been that have strong clinical and genetic validation, where there is a clear path to early clinical differentiation. And of course, our focus is on those indications that represent large clinical and commercial opportunities that create significant value for patients and shareholders. As you all know, we pioneered the 1st protein degrader program in immunology with our RF4 program, which in addition to STAT3 where the initial targets at Chimera when it was funded in 2016. And it was the early clinical results with the ARAC4 program with KT-four seventy four, the deep and well tolerated degradation, the early signs of clinical efficacy, which helped us inspire to increase our focus in immunology.

Speaker 2

Additionally, we believe the activity and fidelity of translation of our TPD platform in the KT-four seventy four Phase 1 trial serves as an important read through and informs the probability of success of our new SAD6 and TYK2 oral immunology program. One aspect of the current landscape in immunology that is particularly notable and creates a significant opportunity for kinaris, the dominance in the market of injectable biologics. These antibody based therapies have transformed and revolutionized the treatment of immune to amyloid diseases. We've brought in many cases have been great clinical outcomes for patients. At the same time monoclonal antibodies as you know are injected, they can be costly to manufacture and can be inconvenient for patients.

Speaker 2

To put this in context in a recent industry survey, 75% of patients taking biologics said that they would switch to orals with an equivalent profile. We believe this creates a significant opportunity for effective and well tolerated oral medicines and in particular for protein degraders. In fact, while traditional small molecules offer convenience benefits, they frequently cannot match the powerful pharmacology of biologics as they don't have the ability to block these pathways at the same level. We believe and have shown with preclinical and early clinical data that protein integrators have the potential to provide a unique solution with biologics like specificity and activity, but with the flexibility of oral small molecules. Importantly, because of this profile, we believe that they can potentially reach much broader patient populations, creating significant opportunities for the modalities broadly and for Kynaira specifically.

Speaker 2

So as you think about our immunology pipeline, if we can build a portfolio of molecules that provide comparable pathway inhibition to biologics as we believe we can, but one with the convenience in oral dosing, we believe the potential is enormous. We have a lot happening across our pipeline, including plenty of activities in our early pipeline that we haven't yet disclosed. We're really at the cutting edge of protein degradation and using this technology to address fundamental clinical, commercial needs and opportunities. I believe our unique approach has resulted in one of the most robust high value pipeline in the industry. I'm very proud of in more detail our clinical and soon to be clinical pipeline.

Speaker 2

Jared?

Speaker 3

Thanks, Nilo. Starting with our IRAK4 program. In the Q4, our partner Sanofi initiated 2 KT-four seventy four Phase 2 trials, 1 in hidradenitis suppurativa and 1 in atopic dermatitis. Enrollment in both trials is ongoing with top line data expected to be reported in the first half of twenty twenty five. Importantly, with the start of these trials and the dosing of the first HS and AD patients that we disclosed late last year, we collectively earned $55,000,000 in development milestones from Sanofi, which we have already received.

Speaker 3

We and Sanofi are enthusiastic about the potential for this program. In addition to the 2 initial indications, we continue to discuss and explore additional potential indications and we will plan to share more details as we are able in the future. Moving now to our 2 recently announced preclinical immunology programs. KT-six twenty one, our once daily oral stat 6degradery is slated to enter the clinic later this year. What makes this program particularly exciting is that IL-four, IL-thirteen pathway has been exceptionally well validated.

Speaker 3

CT-six twenty one targets STAT6, which is an essential transcription factor to the IL-four, IL-thirteen signaling pathway and the central driver of Type-two inflammation in allergic diseases. By degrading STAT 6, we believe we can selectively block this pathway fully and importantly this pathway only, potentially phenotyping upstream biologics such as dupilumab. At our R and D day, we shared what we believe is a very compelling set of preclinical data that supports the high level of enthusiasm and confidence we have in this program. Specifically, in our preclinical studies, we have demonstrated full inhibition of the IL-four, IL-thirteen pathway in all relevant human cell context with pikomolar potency superior to dupilumab and exquisite selectivity. We also demonstrated very high levels of activity in multiple well established preclinical models that gives us confidence in the potential of KT-six twenty one to deliver biologic like activity as we advance this program into clinical trials later this year.

Speaker 3

If we are able to replicate our strong preclinical data in the clinical setting, which is something we have accomplished with our clinical stage programs, we believe KT-six twenty one would be poised to be a best in class therapeutic option for multiple indications, representing a multi $1,000,000,000 opportunity. We are currently in the midst of IND enabling studies and expect to advance KT-six twenty one into Phase 1 testing in the second half of twenty twenty four with data from that study in 2025. We also recently unveiled KT-two ninety four, our potential 1st in class oral tick 2degrader. We believe KT-two ninety four also has a potential biologics like profile creating an opportunity to treat a range of autoimmune and inflammatory diseases. Believe degradation of TYK2 has the potential to overcome the challenges of small molecule TYK2 inhibitors, which have limitations due to lack of selectivity, limited target engagement and or lack of potent activity against Type 1 interferon.

Speaker 3

Importantly, we believe TIK2 degradation could allow us to recapitulate the human loss of function biology of near full pathway inhibition of type 1 interferon, IL-twelve and IL-twenty three, while also sparing IL-ten, representing a best in class TIK2 agent. Our plan is to move this program into 1st in human studies in 2025. Across our immunology portfolio, we intend to present preclinical data from the STAT6 and TYK2 programs at multiple scientific and medical meetings this year, starting with the American Academy of Dermatology Annual Meeting next month. We also expect multiple clinical data readouts from these programs next year. To summarize, in the first half of twenty twenty five, we plan to share top line data from the KT-four seventy four Phase 2 trials as well as data from the KT-six twenty one Phase 1 study, which as mentioned is planned to start later in 2024.

Speaker 3

So switching gears to our oncology portfolio, we expect additional proof of concept data readouts for both KT-three thirty three and KT-two fifty three this year. Both programs have demonstrated initial encouraging antitumor activity in liquid and solid tumors and are progressing through dose escalation in line with our expectations. For KT-three thirty three, our STAT3degrader, we shared data at ASH in December demonstrating early signs of antitumor activity at doses that were generally well tolerated and associated with substantial STAT3 knockdown in blood and tumor. Our preclinical to clinical translation showed strong objective responses in both CTCL and in Hodgkin's lymphoma as well as induction of an interferon gamma response in tumor and blood that preclinically was shown to enhance the response of solid tumors to anti PD-one drugs. We believe this supports KT-three thirty three's potential to address both hematological malignancies as a single agent and solid tumors as a potential novel combination therapy with anti PD-one or other targeted therapies.

Speaker 3

Our intent is to complete dose escalation in the Phase 1a study in 2024, at which point we will share the trial results and disclose our plans for the next phase of development for the program. And lastly, KT253, our MDM2 integrator. This is another really exciting program. Arm A of the Phase 1a in solid tumors and lymphomas is ongoing and in November we reported clinical data demonstrating evidence of target engagement in p53 pathway activation as well as initial antitumor activity and a lack of the traditional hematological toxicity seen with small molecule inhibitors. We also announced that we commenced enrollment in arm B for patients with high grade myeloid malignancies including AML.

Speaker 3

For both arms of the study, enrollment is progressing in line with our expectations. Like with STAT3, we expect to complete dose escalation in 2024, at which point we will disclose our plans for the next phase of development for the program. As part of our development plans, later this year, we also expect to present comprehensive preclinical and clinical translational data across liquid and solid tumors that will inform a patient selection strategy for KT253 and ongoing and future clinical studies. I'll now turn the presentation over to Bruce for a review of the Q4 financials. Bruce?

Speaker 3

Thanks, Jared. I'll quickly review the Q4 financial results and you can certainly reference the tables in the back of the press release today. As Noah mentioned, with the advancement of 474 into the Phase 2 trials in HS and AD, we earned $55,000,000 in milestones from Sanofi. We received $40,000,000 of that in the 4th quarter, the other $15,000,000 which was recorded as receivable at year end, that payment was received in the early part of 2020 4. These milestones were added to the total consideration received under the Sanofi collaboration, but the portion recognized as revenue in the 4th quarter and the remaining in deferred revenue.

Speaker 3

At the end of the quarter, our deferred revenue balance total on the balance sheet was approximately 54,700,000 dollars That reflects partnership revenue that we expect to receive over the next several years, excluding the receipt of any potential future milestones. And then quickly with respect to operating expenses, R and D for the quarter totaled $53,000,000 of that about $5,300,000 was non cash stock based compensation. The adjusted cash R and D spend of $47,700,000 excluding that stock based comp was up 13% from the comparable quarter a year ago. On the G and A side, our spending for the quarter was $14,200,000 of which $5,600,000 was non cash stock based comp and that adjusted G and A spend of $8,600,000 again excluding stock based comp is a 5% increase year over year. And then finishing up with our cash balances stated earlier, at the end of 2023, it was $436,000,000 including the $300,000,000 of net proceeds from our equity offering last month and the $15,000,000 that I referenced from Sanofi that was received early this year that brought our unaudited cash and equivalent balance as of January 9 to approximately $745,000,000 That is expected to provide a runway into the first half of twenty twenty seven and it will enable us to deliver the next stage of growth and data readouts including as Jared mentioned the KT-four seventy four Phase 2 data, our oncology proof of concept results this year and then several critical and clinical inflection points for our STAT6 and TYK2 programs.

Speaker 3

So that's what we had for you today in terms of our prepared remarks and now we'd be happy to answer any questions. Operator?

Operator

Thank you. We will now begin the question and answer The first question comes from Vikram Piyush from Morgan Stanley. Please go ahead.

Speaker 4

Hi, good morning. Thanks for taking our questions. We had 2 both on immunology. First, so you alluded to in your prepared remarks potential pipeline expansion for 474. To extent possible, I was wondering if you could speak a bit about what's going to feed into that decision and how the data sets we get in the first half of next year for HS and AD might be related to how you think about with Sanofi where to go next with this molecule?

Speaker 4

And then a similar question for 621294, what will you be assessing from the initial clinical data we're going to be getting next year to help prioritize indications for subsequent development in I and I indications? Thank you.

Speaker 2

Thanks Vikram. So maybe I'll start. So with 474, it's just a bit more challenging because this as you know, this is in collaboration with Sanofi. So we're not in the liberty to disclose several things around decision making and timing. But as we said in the past, the reason why we built this program several years ago, actually we said today that AREK4-five-three were the first programs in 2016, 2017.

Speaker 2

So the idea around AREK4 degradation is the opportunity to generate and develop a broad anti inflammatory drug with a clear tolerability profile. So in our goal, there's always been the possibility and high probability to move beyond skin indications. And we've disclosed some of the other potential indications that one could go after, it could be respiratory, it could be rheumatology, it could be GI. So I think it's I think when we're ready with our partner Sanofi to disclose the path forward, we'll be happy to do so. Obviously, I personally, I don't believe that a skin indication will inform necessarily the probability of success of this drug in other types of diseases.

Speaker 2

But obviously, confirming the safety and activity in longer term Phase 2 studies will bolster confidence to then move into other indication. Maybe that's high level how I would characterize it today. For STAT6 and TYK2, I think it's early for us to comment on decision making beyond early clinical studies. I mean, these are we could spend hours talking about your question, maybe just high level with STAT VI that we've been seeing now for a few months, it feels like 2 months, few months, but it's actually 2 months. It's the value proposition is the oral degrader that can match the biologics like activity of upstream monoclonal antibodies such as dupilumab.

Speaker 2

We've shown with our preclinical data that we can match that type of phenotype. Some would argue are more potent than it in some context, but maybe we don't have to go there. So we have a pretty exciting blueprint of development plans in front of us. I think we as we've done with all the other programs, for us it's imperative that we go into humans and demonstrate this beautiful translation that we've seen with other programs of target knockdown, predictable safety, predictable PKPD. And then we have this, I think, very elegant biomarker strategy that we'll be talking about later in the year that I think will allow us to validate the ability to match the type of pathway inhibition that up stream biologics do.

Speaker 2

And for TIK2 briefly, again, this is a well characterized mechanism. We know what other TIK2 inhibitors are which I would say are several things. Some are selectivity, all our target engagement that and some are ability to block all the other scaffolding functions. And so what good looks like for us is lots of function like phenotype and we know what that looks like based on human genetics and that's what we want to confirm in Phase 1. And then once we're there, Jared and his team will be happy, I'm sure to share more details about the late development plan.

Speaker 4

Got it. Thank you.

Operator

Thank you. The next question is from the line of Michael Schmidt from Guggenheim. Please go ahead.

Speaker 5

This is Paul on for Michael. Thanks for taking our questions. Mine are on KT-three thirty three. So the first one is on your bar for pursuing a development in solid tumors. I believe that the ASH data had about a third of the patients with stable disease.

Speaker 5

So would higher rates of stable disease and biomarker data be sufficient to advance the program into combinations or would you really need to see some objective responses to sort of commit to evaluation in solid tumors? And then second is just how does your thinking now for STAT3 and autoimmune put into your current pipeline? And are you waiting for 333 data to evolve further before making further commitments? Thank you.

Speaker 2

So maybe, Jerry, you want to take the first one and then I'll make comments on the second one.

Speaker 3

Sure. I think with regarding your question on the bar for solid tumors, as you noted, we have had some patients who have had prolonged stable disease and that of course is of interest to us and we continue as we enroll patients onto the study, continue to dose escalate and look for opportunities for bringing on solid tumor patients that can give us a better idea as to what our activity will be as a monotherapy in solid tumors. I think all along, we've been guiding that we expect that ultimately if we move this into solid tumors, it would be as a combination approach, especially anti PD-one combination is something we're very interested in based on our promising preclinical data and based on what we've shown with our biomarkers that can induce this interferon gamma response in tumor and blood, which can actually facilitate responses to anti PD-one. We're also looking at additional targeted agent combinations preclinically. So I think what will inform moving forward with solid tumors will be a combination of what we continue to learn preclinically with combination studies and whether we do see continued signals of some sort of activity as a monotherapy either stable disease or even preferably major responses.

Speaker 3

With regard to major responses, we are seeing those in hematologic malignancies including Hodgkin's lymphoma and cutaneous T cell lymphoma and that continues to be of interest

Speaker 2

to us and we'll continue

Speaker 3

to bring on patients onto the ongoing Phase 1a study to further explore activity there as well.

Speaker 2

Yes. Thanks, Jerry. That's great. And on the SAD3 and I, maybe I just want to go back to our strategy, which is something that we've talked about at the R and D Day. We believe we exist to bring together the power of the technology and unmet needs that are both clinical, commercial and I would say also the opportunity to do with this technology things that cannot be done with other technologies.

Speaker 2

So I guess another type of unmet need, the technological one. And only I think when we marry those 3 together, we're going to go all in. And as you've seen with Ira4, with STAT6 and TIK2, I think we have a very, very easy to articulate value proposition. I hope you guys also feel that way. And these are complete degradation of targets that lead to exceptional anti inflammatory profiles that are well tolerated, at least in our end so far.

Speaker 2

And so with STAT3, it's obviously a program that we know, I would argue better than anybody at this point. We've been working on this target for several years. And the reason why you haven't seen us disclosing more details on Slide 3 INIs because we feel that at this point, we don't have all the information in hand to being able to say that we'll fit the profile of the type of programs that we've articulated so far. When we do, when it does, we'll be able to do so, we'll disclose more. Okay.

Speaker 2

Thank you.

Operator

Thank you. The next question comes from Ellie Moll from UBS.

Speaker 2

Please go ahead.

Speaker 6

Hi, this is Jasmine on for Ellie. Thanks so much for taking our question. Hi, this is Jasmine on for Ellie. Thanks so much for taking our question. What's your latest thinking on whether you would take both STAT3 and MDM2 into Phase 2?

Speaker 6

Or is the thinking that you'll prioritize one over the other given your focus on immunology? And what would your threshold for success be for each program in thinking about the go and no go decision?

Speaker 2

Thank you. I think I felt that there were 2 people, but anyway, I think we got the question. I'm sure there were similar questions. So, great question. So maybe I would start with saying that everything that we've done at Chimera for the past almost 8 years, all our decisions are going to be data driven.

Speaker 2

So and for example, decisions even that we've made for programs that we discontinued, for example, 413, even though the molecule was behaving well and was well tolerated was driven by plethora of data, obviously clinical, commercial, landscape and to a large extent also NPV analysis that we did. So we'll apply the same rigor to all programs in our pipeline, whether these are in immunology or in oncology. As we've said, in order for us to invest in, let's say, in these 2 oncology programs, we need to be able to see in front of us opportunities to impact broad patient populations. So I think our goal criteria for both programs will be driven by opportunities that are both in hem and solid tumors generally at this level. And I think we should probably wait for when we disclose more data later in the year on what exactly the strategy will be.

Speaker 2

What I will say is that for STAT3, we've shown something that has not been shown before, which is this is an active target and we have an active drug. We've shown a small data set in December at ASH. We'll show more later in the year. And in MDM2, we also have an active drug. We've showed really few patients data.

Speaker 2

In November, we'll show much more later in the year. So I think only when we're able together to look at the totality of the data, it'll be much clearer what the decision making process is going to look like.

Speaker 6

Great. Thanks so much.

Operator

Thank you. The next question is from the line of Geoff Meacham from Bank of America. Please go ahead.

Speaker 7

Hi, good morning. This is Susan on for Jeff. Thanks for taking our question. Can you walk us through what strategy is for indication selection for the immunology program, the septics and the sorry,

Speaker 6

the tick

Speaker 7

2 and the IL-four? And just commenting specifically on maybe competitive landscape or maybe what kind of data you're going to look at prior to initiating 1st in human studies?

Speaker 2

Okay. So I'm going to take this really high level just because I want to be consistent with our message, which has been that as we get into the clinic in our healthy volunteer studies, at least for septic and for TYK2, I think at that point, we will feel more comfortable talking about later development for several reasons. We don't have to talk about it now. And 2, the landscape, as you said, is competitive and I don't believe at this point it's necessary to disclose information that are not needed. So just so at the high level, what I want to say is, is high level for STAT VI, I don't believe that there are well tolerated oral drugs in indications in which tupilumab has been approved, that as I say, the well tolerated strong activity.

Speaker 2

So we have a huge potential in a variety of indication. I don't have to name them because they're all well established from AD, asthma, hopefully soon COPD, chronic rhinosinusitis and others, COE. There is actually white space in that area for oral drugs with a good safety profile. So while obviously all of those indications are going to get more and more competitive given large investments that biopharma is putting into immunology, we're actually in a really unique position right now going forward. And once we disclose our development plans, you'll see how actually we would be able, we believe, to be really competitive in terms of timing of our trials as well as the design of our trials.

Speaker 2

With regards to TYK2, it's obviously a different landscape. But I would say that there, while there are several TYK2 small molecule inhibitors, we've seen also recently data from an IL-twenty three peptide from a protagonistJ and J. There is still room to match IL-twenty three type 1 interferon biologics, especially in a single oral molecule that is well tolerated and active. And so I think that is the gap that we're going to fill with our programs. So just patients on the design, but they will come as we get into the Phase 1 study.

Operator

Thank you. The next question comes from Thomas Smith from Leerink. Please go ahead.

Speaker 8

Hi, this is Will on for Thomas. Thanks for taking our questions. A couple on the ZEN and ADVANTAGE trials. If you could give us a sense of how enrollment is progressing thus far and any color on what the patient enthusiasm and willingness to enroll has looked like? And when enrollment is complete for those trials, are you planning to share that information or just wait until the data release?

Speaker 8

And then I have a follow-up.

Speaker 3

Great. Thanks for the question, Pete. As you know, Sanofi is running both of those Phase II trials. If you look on clinicaltrials dot gov, you can see the publicly stated timelines for estimated primary completion for both of those studies, which is in the first half of next year. And to our knowledge, both studies are still on track to meet those timelines.

Speaker 3

That's pretty much all we can really say right now with regard to how those are staying on track. Our understanding is that there is significant enthusiasm on behalf of the various sites who are being engaged. These are both global studies. And so I think that's been very encouraging in terms of what we've heard from Sanofi in terms of site engagement. And so I think, again, we're still expecting that both of those studies would read out on the publicly stated timelines.

Speaker 3

In terms of sharing data, I think that will be something that Sanofi and Chimera will need to sort of work out in terms of exactly how that will look next year, in the first half of next year when those readouts are expected to occur.

Speaker 8

A follow-up as well.

Speaker 3

Thanks, Shane.

Operator

The next question comes from Kelly Shih from Jefferies. Please go ahead.

Speaker 9

Hi, good morning. This is Yun for Kelly. Thanks very much for taking the questions. Are you able to share the status of dose escalation in STAT3 and also the NVM2 program? And also, are you able to disclose, have you reached the targeted 90% degradation that you thought could be required for clinical efficacy?

Speaker 9

And also for INI indications, is there a specific threshold like the 90% in oncology indication that you think you will have to achieve? And based on your experience with oncology indications, how confident are you that preclinical degradation data will translate into human data? Thank you.

Speaker 2

These were I think three questions. I think we'll stop track of them. So let's start with the oncology program. So we generally do not provide updates in this quarterly calls on how recruitment is going. We provide updates when we disclose data obviously and we try to target medical meetings.

Speaker 2

So you should just look out for meetings later in the year where a full update on each of those two programs will be provided. We love to share our plans, but because as you know, there is abstract commission and we need to hear from the conferences, we're not able to now confidently say exactly where, but just know that there is a plan in place and we believe this will be both presented at high impact medical meetings within 2024. If you look at what we disclosed so far, obviously, we have reached for STAT 3, the targeted degradation. And really here, we continue those escalation because we're getting through we're targeting to reach an MTD, which as we've seen pre clinically seems to be above our targeted degradation and that's really a testament to the design of the molecule, the design of the study that the translation has happened in a very predictable and positive manner. For MDM2, it's early.

Speaker 2

I think it's hard for us to comment based on 3, 4 patients worth of data that we shared in November. So just say to for our next update where it'd be clearer where we are with regards to target engagement. I think if you look at all our programs, if you look at our R and D data or actually on our corporate deck today, you will see that each one of our programs, whether in college or immunology, we have reached targeted degradation in the clinic with a good safety profile. With ARRX004, we've reached complete degradation in blood. With STAT-three, we've reached more than 90% around 90% or more depending on patients in both blood and tumors.

Speaker 2

With even 413, we reached that targeted degradation. So we know really well how to design our molecule and translate those profiles in the clinic. So we expect that for SAD6 and T2, that should happen just the same way. Like that is one thing that we're not concerned about here at Chimera. With regards to what is the profile in immunology, the profile in immunology is what you've seen in our preclinical data.

Speaker 2

You've seen that if you degrade, for example, STAT6, anywhere between 80% 90%, you can match dupilumab activity in those preclinical, for example, asthma models or even AD models. So it doesn't look like you need complete target removal, but we will, as we've done in the past, target complete statics degradation and then know that we can obviously do dose exploration in the clinic, similarly with T2. So once we generate data, we can talk more about what is our late stage design. But the Phase 1 design will look a lot like the IREK4 program for immuno.

Operator

Thank you very much. Thank you. The next question comes from Adam Vogel with Wells Fargo. Please go ahead.

Speaker 3

Hey, thank you for taking my call today. I'm on for Derik. So maybe just a few quick questions from us on oncology pipeline. Can you walk us through further what data you expect to share from KT-two fifty three? Will you be reading out data from both arms A and B?

Speaker 3

And then perhaps given your deepening focus efforts in I and I, will you be looking to partner either a 333 or 253 in the future? Thank you.

Speaker 2

All right. So Jared, maybe you take the first one. I just want to take the second one first. So I think we need to think about for us, our decision to invest in programs is driven by a philosophy of the opportunities and return on investment and in patient impact. It turns out that based on our analysis, if you look at our current immunology pipeline, we believe that these are all extremely valuable programs at the outset.

Speaker 2

I think for our oncology pipeline, we believe that if the program translate in the way that we hope based on preclinical data, those could be also really valuable programs. MDM2, if we can unlock it, that biology, that is going to be another really large program. For STAT3, if we're able to also unlock the solid tumor opportunity, I think that will be the case too. So I think the partnering discussion comes with the conversation around what type of expertise we want to build in terms of late stage clinical and commercial, given that we're still an early company. I think at some point, hopefully, we won't be asked anymore.

Speaker 2

You can only do one versus the other because we're trying to build a large commercial stage company. And as you've seen all the successful one can navigate multiple disease areas. But we also are not naive. And so we understand that at this stage, in terms of late stage capabilities, it probably makes much more sense to invest in one area. We've said all right clearly that we're committed heavily in immunology.

Speaker 2

And so I think with oncology, the question is, what are the key value drivers that Chimera wants to drive this program through? And then if we feel that these programs are best positioned in a collaboration for maximum value creation, we can do that, but we also reserve the right to being able to advance this program or one of these programs on our own if we believe that the value proposition fits the philosophy of the company right now. Jared, maybe you can comment on the type of data on 253.

Speaker 3

Sure. So our plan for this year is to complete dose escalation across both studies, the 333 and 253 Phase 1a trials and to establish an MTD and then to present those data at a medical meeting later in the year. That would include, of course, update on enrollment, the types of patients that we're including. And for 253, as you mentioned, yes, we're enrolling in both the solid tumor lymphoma arm A as well as in high grade myeloid malignancy AML arm B. So to show what types of patients have we enrolled, what does the safety profile look like and what is PD and what kind of a clinical efficacy are we seeing to start to give us insights into where we want to go in terms of the next stage of development for both of these programs.

Speaker 3

As I mentioned earlier, in the presentation upfront, for 253, we've also been doing a lot of work on preclinical work and clinical work to really understand patient selection, both for the remainder of Phase Ia, but also for the next steps in development. And so I think we're also looking for an opportunity potentially at a medical meeting to present those data sometime this year as well to give further insights into how we think about patient selection for either liquid and or solid tumors with 253. Great. Thank you.

Operator

Thank you. The next question comes from Mark Frahm from TD Cowen. Please go ahead.

Speaker 10

Hi, thanks for taking my questions. Maybe, Nelo, with IRAC4, when we get the data next year and Sanofi will make their own decision of going forward or not, but you guys will also have well, if Sanofi chooses to move forward, you guys will have an opt in decision. So how are you kind of approaching the opt in? What do you want to see that you would commit Chimera's resources early on? And how important is kind of the Phase 1 data from STAT6 and TIK2 and seeing kind of the exposures you want to making that decision for IRAP-four?

Speaker 2

That's a great question and probably requires a very nuanced answer. So I'll try and do my best in the short time we have. So first, as I just said earlier, we are extremely bullish on IREX-four. Our value proposition has only grown with more data. This has the potential to be one of the largest drug in inflammatory diseases.

Speaker 2

We have early positive data, but I think we are all here recognizing that we just don't know how active this drug is until we run a well powered randomized study, which is what we're doing with Sanofi. Actually, we're doing 2 of them. The value proposition for this drug in our view is, as I said earlier, it's an active oral drug with a good safety profile. In indications that, to be honest, go well beyond HS and AD. I think these are obviously intriguing, exciting early indications, but by no means, our view is that this is where the drug should go only.

Speaker 2

I think if the drug fulfill that profile and we believe that the company is positioned to support the growth of the company the way we see it today, for us would be a no brainer to opt in when the time is right. Again, if the drug fulfill that profile. And the reasons are very not only the value that can be created downstream, but the way that our collaboration is built, we've done all sorts of analysis and all the analysis that we've done financially, even though it might be a bit more expensive early on in the opt in phase while we're doing co development, the value creation at the back end is so vast that the that decision will be so easy. Yes, if we have successful programs with Phase 1, which we believe we will, for statics and tick 2, I mean, I suppose that our cost of capital will be different that we can continue to sustain the growth of this company to support the pipeline. So hopefully that answers the question, but that's how we're viewing it at this point.

Speaker 3

Okay, thanks. Very helpful.

Operator

Thank you. The next question comes from Brad Canino from Stifel. Please go ahead.

Speaker 8

Good morning. This is Brad. Perhaps an expansion of the prior questions really for MDM2 and the data this year, it'd be great to get just more of a scope of the disclosure that you expect to present in terms of patients, disease types? And would you flag any key data elements to watch? And just maybe to be clear on the decision making process at this disclosure, will you be in a position to outline the broader development thesis?

Speaker 8

Thank you.

Speaker 2

So maybe just high level and then I'll let Jerry comment on some more specifics if we're willing to do so. But I think the totality of our data, of our disclosure plans, which hopefully was clear enough from our press release and from comments from Jared earlier. So what is the totality of the data? The totality of the data is a large hopefully close to complete data set from the dose escalation in both solid lymphomas and leukemias, married with the patient stratification work that we're doing that should enable us to build the development program extremely differentiated from others in the space. I think if those things come together and we believe we should be able for those things to come together in 2024 and if all of those are suggesting that we both have activity and also we have a, let's call it, a smart way to develop this drug, I think that decision of continuing investment will be a no brainer.

Speaker 2

Obviously, then depending on nuances there, the decisions could be different. But I think that's high level of the expectation. I think this year, while I hear obviously a lot of excitement around immunology programs and we share those, but those would be 2025 datasets, many datasets, impactful datasets. But I also want to make sure we're also paying attention to 24 data releases around these programs, because we believe there is an opportunity here to change how we think about this target. Jaron, what about patients?

Speaker 2

I don't know what we can say.

Speaker 3

Yes. I mean, I think maybe just to briefly elaborate, I mean, obviously for this program, we do plan on providing a pretty comprehensive update later in the year. As I mentioned earlier, our hope is to be through dose escalation in both arms, the solid tumor lymphoma arm and the hemalignancy arm to really provide a comprehensive update on safety, PD and efficacy. Keeping in mind again that one of the important premises here is that this is going to be very differentiated from MDM2 small molecule inhibitors. We want to show that we have a therapeutic index that is superior to MDM2 small molecule inhibitors that into account both superior safety as well as potentially superior efficacy.

Speaker 3

And so I think our aim

Speaker 4

is to be able to

Speaker 3

show the data set that will hopefully establish that we are well differentiated from MDM2 small molecule inhibitors and show what the real potential is for this drug in both solid tumors and in liquid tumors. And to marry that sort of presentation potentially with a separate presentation on our patient selection strategy, which is also going to be a very important part of what we do moving forward after Phase 1.

Operator

Thank you. The next question comes from R. Patel with B. Riley Securities. Please go ahead.

Speaker 3

Yes. Hey, good morning and thanks for taking the question. One for the STAT6 and TIK2 program. You've shown data from the proteome study to confirm the selectivity and maybe rule out the off target effects. Can you share how many proteins were identified in those studies and what the coverage rate was in those proteome studies?

Speaker 3

Thank you.

Speaker 2

So we run so we're not going to share any more data today on that program and we're going to be to be honest, quite sensitive about what else we're going to share just based on we want to maintain our competitive advantage here. But that doesn't mean I'm not going to answer your question. So we have high proteome coverage in these studies. We usually can detect north of 11,000 proteins in every proteomic study. And what we do at Chimera, we actually look across several cell types.

Speaker 2

So what we've shown, I believe, were PBMCs, because we believe are one of the more relevant for the diseases we're going after. But in order for us to actually cover the whole proteome, which as you know, it's in the 20,000 proteins roughly, hopefully, I didn't get a wrong number here. So we actually go across many cell types, so that we actually cover 100% of the protein. And the picture that you've seen in our slide is consistent. We only really degrade STAT6 and I would say we are really, really bind to STAT6.

Speaker 2

And that's true also for the TIP2 program and for the RF4 program and for the study.

Speaker 3

Okay. Thank you.

Speaker 2

All right. I can keep going. Yes, thanks, Kapiti. Thank you.

Operator

Thank

Speaker 2

you. The next question

Operator

comes from Andy Chen with Wolfe Research. Please go ahead.

Speaker 6

Hi, this is Emma on for Andy. Thanks for taking our question. I guess just focusing on TYK2, we're curious where you see weaknesses with current TIK2 inhibitors on the market and just how much headroom there is for improvement with a potential degrader entrant like KT-two ninety four into the market? Thank you.

Speaker 3

I did not speak here. Differentiation is obvious.

Speaker 2

The weakness, sorry, I didn't hear it well. So I mean, as we said before, there are several layers of differentiation. So there is first that small molecule inhibitors. These are allosteric inhibitors that actually block also the kinase function and some of the scaffold function, but not the full scaffolding function. And so the actual phenotype of small molecule, even allosteric inhibitor is closer to kinase inhibitor than to the loss of function profile.

Speaker 2

We have a slide in our deck that shows you with the pluses and shows where is the kinase that versus lots of function, the business wild type. And only a degrader matches the lots of function profile, which basically means we block IL-twenty three, IL-twelve, type 1 interferon and spare IL-ten. So the compound that is approved, the drug that is approved right now, which is an allosteric inhibitor that actually is not as selective, it actually impacts also JAK1 and so also impacts IL-ten, which is a big detriment for GI indications. It's also not very selective, As Other molecules in the clinic have more, I would say, maybe a higher selectivity profile, but they're not able to block all of the scaffolding function and match the loss of function profile. And we believe that by blocking the pathway fully, we should be able, again, as we've shown with STAT6, we've shown with ERIC4, once you find the mode of full pathway blockade, you should be able to match the upstream biologics.

Speaker 2

So the IL-twenty three biologics, the Type 1 interferon biologics in a single oral molecule. So what is that going to translate in the clinic? We don't have a number, right. So if you look at biologics in psoriasis, they reach close to 90% of PYT75, for example. Small molecules don't get there.

Speaker 2

They get into the 60s, 70s, maybe pushing into the mid-70s. So maybe that is a

Speaker 3

gap that we can fill.

Speaker 2

But I think that the actual extent of gap that we're going to be filling with our degrader, we have a goal of biologics, but we actually don't know. It might be even superior or maybe slightly inferior. I think that is a clinical experiment that we have to run. All we're saying here is that biologically, we have a differentiated profile and we have confidence that that will clinically result in a meaningfully differentiated drug.

Speaker 6

Thank you.

Operator

Thank you. This concludes our question and answer session. I would like to turn the conference back over to Justine Koenigsberg for any closing remarks.

Speaker 1

Thank you. And on behalf of the Chimera team, we'd like to thank everyone for joining us this morning and look forward to keeping you updated on our progress. In the meantime, please don't hesitate to reach out if there are any additional questions following today's call. Thank you.

Operator

Thank you. The conference has now concluded.

Powered by Quartr
Earnings Conference Call
Kymera Therapeutics Q4 2023
00:00 / 00:00