Kymera Therapeutics Q1 2024 Earnings Call Transcript

Quartr
Provided by Quartr
May 2, 2024

There are 15 speakers on the call.

Operator

Good day, and welcome to the Chimera Therapeutics First Quarter 2024 Results Conference Call. All participants will be in the listen only mode. Please note that this event is being recorded. I would now like to turn the conference over to Justine Konigsberg. Please go ahead.

Speaker 1

Thank you. Good morning, and welcome to Chimera's quarterly update call. Joining me this morning are Noah Minalffy, 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. To have enough time to address everyone's questions, we ask that you please limit your questions to 1 and a relevant follow-up.

Speaker 1

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

Speaker 2

Thank you, Justine. Good morning, everybody. It's been a very productive beginning of 2024, starting in January with an extensive update at our Immunology R and D Day and a subsequent financing to provide capital that we will invest in our expanding clinical development efforts and growing pipeline. Past quarter has been focused on execution on both our preclinical and clinical pipeline as well as external engagement across a variety of business and medical conferences. Today, our plan is to share a brief update on our programs as well as timelines for news and catalyst we're expecting through the rest of this year and early 2025.

Speaker 2

As we shared earlier this year, we believe we have a significant opportunity to address and expand the existing treatment paradigms within immunology by developing compelling oral small molecule de greater medicines with biologics like activity. Has it been the case all the way back to the founding of the company, we have taken a differentiated approach to target selection and focused on critical molecular pathways that are well validated through human genetics, clinical evidence and or the success of approved drugs. None of these pathways play a key role in immune mediated disease pathology. And while injectable biologics dominate these markets, often due to their strong clinical activity, they are not without limitations, which in many instances can limit penetration. As a result, we believe developing convenient oral options with biologics like activity and a good safety profile represents an enormous opportunity to expand patients' access in many of these markets that are currently dominated by injectable agents.

Speaker 2

Our IRAP-four program, which was our first program to enter clinical development, it simplifies a target and a pathway that has the potential to have broad patient impact. We have talked in the past about our reasons for enthusiasm around RAC4 as a target and our rationale for pursuing it. RAC4 is an obligate node in the IL-one TLR signaling and we believe its degradation is the only approach to fully block the pathway, creating multiple development opportunities in large higher med need indications. In the KT-four seventy four, RF4 Phase 1 trial, we observed deep and well tolerated degradation, early signs of clinical efficacy and high fidelity of translation from preclinical models to patients, which provide key insights for our growing immunology pipeline and position future programs such as our STAT6 and TIK2 degraded programs for success. In March, we had the opportunity to showcase our proprietary immunology programs KT-six twenty one, our STAT-six degree and KT-two ninety four, our STAT-two degree at the American Academy of Dermatology Annual Meeting.

Speaker 2

The poster presentations, which marked the first data from a STAT6 targeted agent and a TIK2 degrader to be shared at a major medical meeting, highlighted robust preclinical passages and support the significant potential of our oral degraders in this pathway. In our KT-six twenty one AAT poster, we highlighted the preclinical efficacy studies comparing KT-six twenty one to dupilumab in a preclinical atopic dermatitis model. Importantly, KT-six twenty one shows robust activity in vivo in this model, equal or superior to dupilumab. KT-six twenty one's degradation of STAT6 was tolerated in multiple preclinical safety studies at doses at a concentration up to 44 above the projected human efficacious concentrations. If we can indeed deliver biologics like activity, a good safety profile and oral once daily dosing, we believe KT-six twenty one could change the treatment paradigm of millions of patients suffering from PH2 driven inflammation.

Speaker 2

In terms of timing, KT-six twenty one is currently in IND enabling studies and is on track to enter Phase 1 testing in the second half of twenty twenty four. It's our intent to conduct a Phase 1 healthy volunteer study to assess single and multiple ascending doses of KT-six twenty one and move quickly from there into patients. We have finalized our clinical development plans and strategy, and we look forward to sharing more details as we move closer into clinical development. Moving to TIC II, we shared a poster AAV that demonstrated picomolar degradation alone atomolar inhibition of the AL23, AL12 and Type 1 interferon pathways, showing KT-two ninety four's potential to repatriculate the biology of human T2 loss of function mutation. The biological differentiation of KT-two ninety four from our steric to small molecule inhibitors was demonstrating through IL-ten sparing compared to Dupra, which is important in the ambulatory bowel syndrome as well as was shown through superior inhibition of Type 1 intracherone pathway compared to Type 279, which is relevant for the treatment of several diseases, including interferon driven diseases.

Speaker 2

Additionally, KT-two ninety four demonstrated deep and sustained TYK2 knockdown in vivo with low daily oral doses. We believe that this data demonstrates that a TYK2 integrator has the potential to deliver best in class TYK2 pathway blockade with productivity across multiple IL-twelve, IL-twenty three and type 1 interferon driven immuno inflammatory diseases. We intend to continue to share updates across our pipeline and medical meetings in 2024. In fact, later this month, we present poster highlighting KP-six twenty one and its potential to treat Th2 allergic diseases at both the American Thoracic Society International Conference in San Diego, as well as at the Digestive Disease Week in DC. These presentations, which built on what was previously shared at R and D Day, will include new exciting additional preclinical data.

Speaker 2

To sum up my intro here, since our funding 8 years ago, a milestone which we will commemorate just in a few days, we have demonstrated consistent and scalable innovation, including strongly clinical to clinical translation of degradation, safety and activity across the whole pipeline. We have also achieved early proof of concept in both immunology and oncology, which we believe is a significant accomplishment for the new modality. As we are transitioning from early to mid late development across our pipeline, we remain committed to building on our early success and expanding our team and capabilities to deliver on the substantial clinical and commercial opportunities that our programs offer to ultimately become a global commercial stage medicine company. In the meantime, we look forward to important near term data readouts in this year in oncology and multiple readouts from our immunology pipeline in 2025. I'll pass here and ask Jared to provide an update on our clinical program.

Speaker 2

Jared? Thanks, Noah. I'll round out

Speaker 3

the immunology discussion this morning with IRAK4 and then give an update on our 2 clinical oncology programs. Our 1st in class oral IRAC-four degrader, KT-four seventy four is progressing in 2 Phase 2 trials in hidradenitis suffortiva and atopic dermatitis. These trials are being conducted by Sanofi under our collaboration and we expect to be in a position to share top line data the first half of twenty twenty five. Recall that Sanofi moved this program into Phase 2 studies based on the early clinical data we generated in HS NAD patients in Phase 1 trial. In that study, not only did we achieve our study objectives in terms of PKPD safety, but we also delivered encouraging signs of clinical activity that we will also evaluate over a longer dosing period in the Phase 2 trials.

Speaker 3

These randomized placebo controlled trials represent an opportunity to demonstrate the potential for IRAK4 degradation generally and KT-four seventy four specifically to transform the treatment of complex inflammatory diseases and to offer HS and AD patients a well tolerated effective and convenient oral medicine. So switching gears now to oncology. I'll start by noting that we recently presented scientific data on our oncology pipeline in both the late breaking poster session and during the major symposium at the AACR Annual Meeting. As we shared in the past, our preclinical and early clinical findings highlighted last month at the meeting support the advantages of degraders over other existing technologies and agents and further validate our differentiated molecular design, target selection and translational strategies to advance the new generation of medicines for patients. KT253, our highly potent degrader of MDM2, KE3 ligase that modulates the most common tumor suppressor p53 is currently in development for the treatment of liquid and solid tumors.

Speaker 3

Preliminary data from the Phase 1 clinical trial showed evidence of target engagement and C53 pathway activation along with initial signs of antitumor activity without dose limiting toxicities including typical hematological toxicity. These findings support our therapeutic hypothesis for MDM2 degraders and the potential to improve the therapeutic index compared to MDM2 small molecule inhibitors.

Operator

As we finish dose escalation

Speaker 3

in the Phase 1 trial this year, we hope to see antitumor activity in a variety of tumor types. And coupled with our biomarker selection strategy, we plan to assess these data collectively to inform next steps. Finally, on MDM2, we are announcing today that we've had an abstract accepted for a poster presentation at ASCO in June, where we will provide a clinical data update. Once the trial is completed, we expect to present the full data set at a medical meeting later in the year. NK333, our highly selective degradator of STAT3, a traditionally undrugged transcription factor recognized as a key component of the JAK STAT signaling pathway with both tumor cell intrinsic and tumor cell extrinsic effects on the tumor microenvironment is currently in development for the treatment of multiple STAT3 dependent pathologies including hematological malignancies and solid tumors.

Speaker 3

Preliminary data from the Phase 1 trial demonstrated 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 some early but encouraging responses in both CTCL and Hodgkin's lymphoma. We also demonstrated stimulation of an interferon gamma response in tumor and blood, which is encouraging given the correlation between interferon gamma and how tumors respond to anti PD-one drugs. Dose escalation in the KT-three thirty three Phase 1 study is ongoing with the goal to further assess safety and antitumor activity in both liquid and solid tumors. We expect to complete the study this year and deliver additional proof of concept data to define KT-three thirty three's path to late stage development.

Speaker 3

We are also announcing that we've had an abstract accepted for presentation at the European Hematology Association or EHA meeting in June, where we will present a clinical update. We plan to present the full data set at a medical meeting later in the year. Now, I'll hand the call over to Bruce to share financials for the quarter. Bruce? Thanks, Jared.

Speaker 3

I'll quickly review our first quarter 2024 financial highlights and you can certainly reference tables down in today's press release. Revenue in the quarter the Q1 of 2024 was $10,300,000 All of that was attributable to our Sanofi collaboration. And just as a quick reminder, we had received or have received $55,000,000 in total milestones as a result of the start of the 2 Phase 2 truck studies in the Q4 of last year. With respect to operating expenses, R and D for the quarter was $48,800,000 about $6,100,000 of that represented non cash stock based comp, resulting in an adjusted cash R and D spend of $42,700,000 a 10% decrease from the comparable amount in the Q4 of 20 23. On the G and A side, our spending for the quarter was $14,400,000 of which $5,900,000 was stock non cash stock based comp.

Speaker 3

The adjusted cash G and A spend of $8,500,000 again excluding the stock based comp reflects a 1% decrease from the comparable quarter sequential quarter. Our cash balance at the end of the Q1 was $745,000,000 In January, as we mentioned, we realized approximately $300,000,000 in net proceeds from our equity offering and our cash balance is expected to provide a runway into the Q1 of 2027 and that will enable us to execute on multiple or should say the first half of twenty twenty seven, that will enable us to execute on multiple data readouts including oncology proof of concept results in 2024, KT-four seventy four Phase 2 data expected in the first half of twenty twenty five and several clinical inflection points for our STAT6 and TYK2 programs also in 2025. So this concludes our prepared remarks. We'd be happy to take your questions. Operator, if you can open the line for questions.

Speaker 3

Thank you.

Operator

Thank you. We will now begin the question and answer session. The first question is from the line of Brad Canino from Stifel. Please go ahead.

Speaker 4

Great. Thanks so much for the question. It looks like we're going to get 2 bites out of the apple for MDM2 this year. And generally, I would assume that the completed 1a and the bio marker data later this year would be most material. So just to not overlook what's coming at ASCO, can I have you talk about the decision to present here?

Speaker 4

What should be the focus and how should investors view it within the broader trial and strategy for the asset? Thank you.

Speaker 2

So thanks, Brad. So just taking a step back, this is a program that we started clinical development in the second half, roughly in the middle of last year. And our first update was in our course to recall in November, if you recall, of last year. And we present a really limited data. As we since then recruited many more patients in the solid tumor lymphoma arm as well as open the AML arm.

Speaker 2

We thought it was important to connect with the medical community and obviously the investor community to give an update on the progress we've made in both arms of the trial that I believe will shine more light on the potentials of MDM2 across the subset of patients and also create more enthusiasm if we can to continue to recruit the right type of patients to our studies. So obviously, when we share data, there are multiple audiences and the investor community being one of them. But the goal is to complete, as we said in the press release, this Phase 1 dose escalation study by the end of the year and then yes, provide a full update as well as plans for further development later in the year. But given the substantial data of patients recruited between November and now, we thought this would be a good update to showcase the progress of the program.

Speaker 4

Okay. Thanks for that. And then Nelo, I know you took part in a targeted protein degradation symposium at AACR. I just love to hear what your general insights were, thoughts were exiting that about the evolution of this therapeutic area? Thank you.

Speaker 2

Yes, that's a great question, Brad. So first, it was a great meeting. I believe I saw you there. It was very well attended, let's call it, symposium with many companies presenting. I actually hadn't been in a TPC focused symposium in probably too long.

Speaker 2

And so it was great to see a huge amount of interest from many stakeholders in the space. I saw many physicians, I saw small and large companies. So I think the level of interest is increasing with the data, especially clinical data that different companies are sharing. I also came home with a great feeling that companies like Chimera are really leading the field here in terms of capability, target selection, sophistication of approach. And so I think generally, there's still a lot of work to do for the field, but I'm glad that we and others are leading and providing hopefully good examples for others to follow.

Operator

Thank you. We move to the next question. The next question is from the line of Ellie Merrell from UBS. Please go ahead.

Speaker 5

Hey, it's Sam on for Ellie. I guess just in line with the previous question, from the MDM-two update at ASCO, measures we should anticipate to look for? And what are you guys looking for from the data as you think about the development path forward?

Speaker 3

Great. Thanks for the question. I mean, this is really planned to be a clinical update for the Phase 1a dose escalation. So really to show the progress that we've made since last November. So the goal here is to share additional information on the types of patients we've enrolled, both solid tumor patients as well as patients with hematologic malignancies, to share the safety that we've been seeing as we've been dose escalating, to share more data on the pharmacodynamic effect of the drug.

Speaker 3

Recall that back in November, we did show an impact on GDS15, which is this key biomarker just downstream of MDM2. So our aim is to show more data that provides that sort of information on pharmacologic engagement and of course to provide whatever response data we have, clinical response data we have for patients with solid tumors and patients with hematologic malignancies.

Speaker 5

Okay, great. Thank you so much. And I guess just a quick follow-up. Just any color on the updates for the biomarker patient selection strategy you guys are pursuing? And how is the progress kind of going there?

Speaker 3

Yes. I think that's an important question. I think Nelo mentioned that earlier, which is an important part of the program for MDM2 in addition to being able to demonstrate that the therapeutic index with our degraders superior, less than seen with MDM2 inhibitors,

Speaker 2

is to be eventually to

Speaker 3

be able to evolve a sort of patient selection strategy or so called sort of biomarker strategy for selecting patients who we think will be most preferably at a medical meeting, we will provide more of those data. Preferably at a medical meeting, we will provide more of those data showing our progress pre clinically and even perhaps some of our clinical data that have been informing our ability to develop a patient selection biomarker strategy focusing on those patients that we think we'll be able to predict would be most sensitive to MTM2 degradation.

Operator

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

Speaker 6

Hey, good morning. This is Yigay on for Michael. We want to get your thoughts on recent RINBOC data that showed superiority over Dupixent As you think about the opportunity for your IRAK4 and STAT6 graders, do the level of results shift the bar for an oral agent in AD and potential other indications? And as a related question, what's your strategy on future head to head studies against biologics for your overall IIN portfolio? Thank you.

Speaker 2

Yes, it's a great question. So I don't think we've learned in today that inhibiting JAK kinases is extremely powerful anti inflammatory mechanism. In fact, I think if you look across several indications, not only in AD, you see jack inhibitors being extremely active. So I don't believe we learned anything new. I think what we are proposing here at Chimera is to use protein degradation to go after targets that provide the best efficacy to safety profile.

Speaker 2

So the opportunity here is to have an oral drug that is well tolerated, that does not require blood or monitor, blood testing or monitoring of patients for severe cardiovascular events. So I don't think this virus moved at all. I think we the field is still looking for oral agents that are active that have a well tolerated profile. And that's really what we're trying to do for both direct 4 and SESD Exentive 2 in different way. Obviously, we can discuss each program individually.

Speaker 2

Next question?

Operator

Thank you. The next question is from the line of Eric Joseph from JPMorgan. Please go ahead.

Speaker 7

Hi, good morning. Just wanted to get a little bit of a better sense of what your internal bar is for moving 253 into 45 later stage development. I wonder whether opportunities in heme malignancy will be strategically attractive enough or do you want something broader that encompasses all tumors as well? And additionally, is the focus more on moving forward with the monotherapy strategy that would you be amenable to combination approaches? Thanks.

Speaker 2

Yes. Thanks, Eric. Maybe I'll start and then pass it to Jared. So first, I would say the reason why we got involved with NBM2, which as we all know is a target that has been pursued by the whole industry in the past 15 years or so. So the reason for us to do so is really unlock a broad variety of tumor types that we have seen are extremely sensitive to removal of MDM2, which is quite different in our view from inhibition of MDM2 PCC3 interaction that small molecule inhibitors do.

Speaker 2

So as Jered was saying, we have developed a sensitivity map, let's say, across tumor types that point to a subset of tumors in which we've seen pre clinically and we'll start sharing some clinical data, but we've seen pre clinically, I can say so far, to be extremely sensitive to these mechanisms. And those go across both hem as well as solid tumors. I think we've shown already pre clinically that AML, especially both as a single agent as well as combo, we've seen some really, really almost best in class activity. And this is an area that we would pursue independently of the opportunity in solid tumors, given the high unmet need and still the relevant commercial opportunity for both first line, but also for refractory AML. So I think I would say that the AML opportunity is in a way independent on solid tumor, but I also would want to say that the impetus to work on MDM2 was to go also beyond hem oncology.

Speaker 2

So we have hopefully exciting plans that we can share with you based on a biomarker strategy that see us expanding in solid as well.

Speaker 7

Great. I appreciate it. Thanks for taking the question.

Operator

Thank you. The next question is from the line of Kalkit Patel from B. Riley. Please go ahead.

Speaker 8

Hi, this is Jay for Kalkit. Thanks for taking my question. Just one on the stat 6 program. The question is, if you have the opportunity to discuss the development of your stat 6 degrader with the Syneurofi. If so, could you share any insights into why perhaps Sanofi opted to collaborate with another statics degree company instead?

Speaker 8

Thank you.

Speaker 2

Yes. So as we said repeatedly in the past, I'll say this again today, we started this program a few b degraders in immunology starting from early days in RF 4, and we have decided that we have no interest in partnering our immunology pipeline in order to at least in the foreseeable future, in order to fulfill our vision to building a global integrated company. I'm not going to obviously share discussions with Sanofi, but I would say generally, this is a program that has been pursued from other parties quite heavily in terms of potential partnership, but our communication has been very clear that we believe this is a program that we want to develop as a standalone independent company for the foreseeable future. I will also remind everybody that we are the 1st company to take a stat 60 grader actually, I would say, statics agent overall in the clinic. We're the 1st company to demonstrate the preclinical activity of such an agent.

Speaker 2

And everybody else is obviously years behind us.

Speaker 8

Okay. Thank you. That's very helpful.

Operator

Thank you. The next question is from the line of Andy Chen from Wolfe Research. Please go ahead.

Speaker 9

Hi, good morning. Thank you for taking the question. Two related questions also on STAT6. Just curious if you can talk about tissue distribution. And so I see deep degradation in the skin in non human primates.

Speaker 9

I'm just curious how well this tissue distribution translates to humans. I'm curious if you can cite several precedents where non human primate distribution is highly correlated to humans. And also in the first half of twenty twenty five, are we going to gain any insight on this exact topic? What kind of metrics will we have when determining whether STAT6 is indeed acting on the skin in humans? Thank you.

Speaker 2

Yes. No, it's a great question. So first, for people that have followed us over the past few years know that we don't discuss preclinical data of PK and distribution besides the degradation data that we show in our presentations. And that's only because we believe those are highly confidential and important data that we want to keep for ourselves at this point. But I will say that if you look at the data we presented, we've shown that KAT-six twenty one degrades STAT6 equally effectively in several tissues in skin, in lung, in blood and I believe in SLEAN II, I'm not sure we've shown that or not.

Speaker 2

But we've shown that our the distribution of the drug allows for, I would say, generally equivalent degradation across all PH2 relevant tissues. And so we our expectation is to see in the clinic the same level of response. And we've seen good translation of preclinical into clinical in terms of distribution across different species. I would say that, yes, in the first half of twenty twenty five, our goal is to share Phase I data as it's been publicly disclosed and the Phase I data will involve both blood and skin biomarkers.

Speaker 10

Thank you.

Operator

Thank you. The next question is from the line of Derek Archila from Wells Fargo. Please go ahead.

Speaker 11

Hey guys, good morning. This is Eva on for Derek. A quick one from us, kind of like following up on the last question. On the STAT6 Phase 1 study, will you be including a cohort of patients to achieve this proof of concept kind

Speaker 12

of like how you did with like

Speaker 11

474 or will this only

Speaker 12

be including like healthy volunteers? Thanks.

Speaker 2

Well, at this point, I think all we said today was that the initial evaluation of the healthy volunteers will share more at a later date.

Speaker 11

Okay, thanks.

Operator

Thank you. The next question is from the line of Divya Rao with C. D. Cohen and Company. Please go ahead.

Speaker 12

Hi, guys. This is Divya on for Mark. Thanks for taking your question. Similar to the earlier question, what is the scope of kind of the disclosure that we should get from KT-three thirty three at EHA? And then as a follow-up, I guess, what do you need to see in this Phase 1 trial, which I guess you're planning on completing at the end of the year and liquid tumors to continue development in both liquid and solid tumors?

Speaker 2

I'll take the second and I'll Jair answer the first part of your question. So the second part was around what do we need to see. So as I said in the past also, our path for continuing investment is having meaningful opportunity with a clear path to a sizable patient population with big clinical and commercial impact. And so the obviously, the more obvious answer to your question is that solid tumor opportunities will would be able to make a much easier case for further investment. As I've said in the past, we don't expect to see single agent activity in solid tumor as we haven't seen pre clinically, but we're evaluating the biomarker, the tumor biomarker effect to then tie with preclinical data that we've already demonstrated in this potential solid tumor combo opportunities.

Speaker 2

So that is 1. And then obviously, having strong anti tumor activity at a single agent in lipid tumor is important for two reasons. 1, because there are potentials liquid tumor opportunities that are sizable enough to be interesting, but also to confirm that the drug is active and it's worthwhile further investment in expanding the opportunity. Jared, do you want to comment a bit on the expectations for EHA?

Speaker 3

Sure. We call that at ASH this past December, we presented data on 29 patients that we had enrolled so far and we showed very encouraging safety data, which was allowing us to continue to dose escalate. We showed very strong pharmacodynamic data, including strong statuary knockdown in blood and tumor, as well as strong immunomodulatory effects in blood and tumor, such as that interferon gamma response that was predictive of potential combination with anti PD-one. And we also showed these promising clinical responses in CTCL as well as in Hodgkin's lymphoma. So the aim for the EHA presentation is really to build on that as we continue to dose escalate to provide further data around safety as we've been dose escalating to provide additional pharmacologic data on target knockdown and immunomodulation in blood and whatever we may have in tumor and to provide additional clinical response data.

Speaker 3

Again, as we said, this is meant to be a clinical update and then the plan will be then later in the year, once we anticipate completing dose escalation to provide a final data set at a medical meeting later in 2024.

Speaker 1

Thank you.

Operator

Thank you. The next question is from the line of Thomas Smith from Leerink Partners. Please go ahead.

Speaker 13

Good morning. This is Nat Shulan Suk on for Thomas Smith. Thanks for taking the question. We have 2, both in I and I. So The first one is what's the getting factor to initiate a Phase I trial for KT-six twenty one?

Speaker 13

And what state I can expect from the readout, you stated in first half twenty twenty five and how to prioritize indications for the subsequent development in IND indications?

Speaker 2

Okay, great. So as we said on the call today and in the press release that we're in IND enabling studies and we're going to leave it at that. We don't usually provide a specific update on where exactly we are on the process. So obviously completing that Phase, filing IND and initiating Phase 1 is what's between us and that. In terms of indication prioritization for STAT6, I think the only thing I would say is, as we've said in the past also, we are focused on getting this drug to as many patients as possible, starting with large indications where we've seen injectables can really have low penetration for many, many reasons.

Speaker 2

So I would say we're prioritizing the larger indications, but that doesn't mean we will not pursue others. I think that will happen, but just in a probably different stage in the manner.

Speaker 13

Got it. And for the IO 4 program with data expected in the first half as well of next year, so no fee will make a decision of going forward or not, but you also have an opt in decision, how are you approaching the opt in

Speaker 2

and what do you need to see to make a decision? Yes. So after Phase II, but before Phase III, so the Phase III needs to be in a planning stage when we will have the opportunity to decide to opt in or not. And the decision will be based on obvious reasons, the excitement we have around the opportunity with the drug, the investment that we have across our pipeline, the cash needs that will be needed across the investments, across our pipeline. I would say, maybe say naively, the best case is if the drug is active as we expected it will be, it would be value accretive for us to obtain.

Speaker 2

And so it would be probably an easy decision to make. But as you know, it's hard to make decisions in a vacuum. So when we're there, we will make the decisions based on all the other parameters I mentioned.

Operator

Thank you. The next question is from the line of Vikram Purohit from Morgan Stanley. Please go ahead.

Speaker 10

Hi, good morning. Thanks for taking our questions. So we also had a couple of questions on 474. Apologies if you mentioned this in your prior Q and A and we missed it, but we were just curious on how you and Sanofi are currently thinking about indication expansion 474 beyond HS and AD and when some of those decisions could be made and how you're thinking about them for the time being ahead of the HS and AD data sets coming in the first half of next year? And then secondly, on a more logistical point, should we hold the expectation that the HS and AD data sets would come together or is that not necessarily the case?

Speaker 10

And if you have any visibility at this point on which venues or which forms might be appropriate to showcase those datasets? That would be helpful color to get from your perspective. Thanks.

Speaker 2

Thanks Vikram. You got 3 questions in. Well done. So let's start with the last one. It's hard for us to know as you both the timing and where.

Speaker 2

As the program's timelines have been presented in clinicaltrials dot gov or disclosures from both Sanofi and us, we're seeing that both studies should be able to read out in the first half of twenty twenty five. I still feel we're too early to know whether they'll be disclosed together or separately. And so give us more time. I think when we're closer, we might be able to answer that question. In terms of the indication expansion, as I also have said, in the past, we've signed the Enkimer work diligently on evaluating many other opportunities.

Speaker 2

Many of these are obvious other indications that this biology has been validated in or known to be relevant. I think there is sensitivity about disclosing what they are just because I think the team right now is focused on executing on these studies. I believe Sanofi will be the one maybe disclosing other indications first and then we'll be happy to provide more color. In terms of timing, again, I can't speak for them, but let's say for now we're focused on executing on these studies. And I believe this is a personal opinion.

Speaker 2

As we get through some of these inflection points, we'll be able to share more.

Speaker 10

Got it. Thank you.

Operator

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

Speaker 11

Hey, thank you. So I guess I have a quick question on given capital constraints, do you think there's a scenario where you guys might partner out some of your oncology assets? Like what factors would you take into consideration when evaluating the potential for a partnership?

Speaker 2

Yes. So thanks for the question. So generally, as we've said, we believe partnering is an option to continue to grow the company and needs to serve a purpose. Rarely, not always, but rarely I would say that financials drive partnerships, but it has to be really financials only, right? They will have to be a win win opportunity.

Speaker 2

I think it's partnering in oncology is something that we've discussed in the past. It might be something that we'd be open to do for some of our oncology programs. I just can't speak to specifics given that we're still in the midst of generating important data that would, 1st of all, tell us the level of commitment that can air on its own once we invest in this program. I think after that, we'll be able to have a clear view of what's the best path for value creation for our oncology pipeline. Okay.

Speaker 2

Great. As always partnership is a tool that any company should use to think about long term value creation as we can't reinvent the wheel in every single program. Go ahead.

Speaker 11

Okay, great. And then what are your BD priorities for this year?

Speaker 2

Sorry, say that again? BD?

Speaker 11

Yes, business development.

Speaker 2

Yes, I mean, I think I've answered that question already. Next question?

Operator

Thank you. The next question is from the line of Kelly Shi from Jefferies. Please go ahead.

Speaker 12

Thank you for taking my questions. I also have a question on Iraq4 program. We see the clinical development is expanding in this space and oral agents like JAK inhibitor and BTK inhibitor socially interesting advocacy signal. I'm curious how should ILADS4 degrade or be positioned to other oral therapeutic candidates? What would be the differentiated clinical features to be anticipated based on targeting strategy and also the MOA of the greater design?

Speaker 2

So it was a bit the sound was not great, but maybe if I understood correctly, you were talking about how is the direct for compared to like other small molecule like JAK or PTK inhibitor in immunology. Jared, do you want to take some of that?

Speaker 3

Yes. I mean, I think certainly the differentiation is there potentially both for efficacy based on the mechanism as well as on safety. We know that 474, iRAC4 to greater because it's impacting the IL-one receptor path way as well as the toll like receptor pathway has the ability to impact multiple different pro inflammatory cytokines essentially with a single compound whereas many other agents in the INI space, targeted agents in particular, have a more restricted effect on all of these pro inflammatory cytokines. And so the broader effect on multiple different cytokines we think can give us broader development opportunities within autoimmune and auto inflammatory diseases. I think that is one important differentiating factor.

Speaker 3

I think safety factor is something which also can't be overlooked. We've presented before or summarized before the fact that there are adult human Iraq for genetic knockouts who in adults who do not have any phenotype or any susceptibility to infection. And so I think being able to potentially maximize knockdown of IRAK4 chronically to essentially optimize efficacy without compromising safety, I think is a real central game changer and differentiating factor from other drugs like JAK inhibitors, for example. The JAK inhibitors do have broad anti inflammatory effects, but they have significant safety liabilities in terms of risk of infection, risk of cytopenias, risk of malignancies. That is not something that has been seen in either human IRAC-four knockout individuals or even in preclinical studies.

Speaker 3

And so I think this ability to potentially really strongly degrade and knock down iRx4 chronically to maximize efficacy, while not having any safety issues could really allow this drug to be broadly developed across multiple different indications, also not just in moderate to severe patients, but also in milder patients. And I think this really provides an optionality that really can't be seen or challenged by other modalities. And so we think that this is one of the real value propositions of 474, both the differentiation potentially efficacy standpoint as well as on the safety standpoint.

Speaker 11

Terrific. Thank you.

Speaker 2

Next question. Thank you.

Operator

The next question is from the line of Jeff Jones from Oppenheimer. Please go ahead.

Speaker 2

Good

Speaker 14

morning guys and thanks for taking the question. Just two quick ones from us. There's some evidence of improved efficacy in targeting IL-17A and F versus just IL-17A BimI versus secukinumab? And could you comment on whether targeting IRAC-four would be expected to impact the pathway for both forms? Just a technical question.

Speaker 14

And then on the financial side, how should we be thinking about the Sanofi collaboration revenues going forward versus milestone payments? Thanks.

Speaker 2

All right. So Jasmine will take the first and then

Speaker 3

Yes. I think the question around the activity of say IL-seventeen AS targeting A, especially in like diseases like HS where there may be an advantage. I think sort of broadly speaking further, I think speaks to the advantage of having a broader anti inflammatory effect versus a more restricted one. I mean here it's still restricted to IL-seventeen, but being able to hit the A and F isoforms rather than just A is already showing you that as you broaden out the impact, we potentially can increase efficacy. Now even though IRAK4 does not specifically target the IL-seventeen pathway, we know that by impacting the IL-one family static ion pathways well as the Toll interceptor pathways, we do impact IL-seventeen production.

Speaker 3

And while we haven't looked specifically at A versus F isoform, we would assume that that fact is probably broad across multiple different IL-seventeen isoforms. And so I think it comes back to the point I was making earlier, which is that having a drug that has a broader anti inflammatory effect within these autoimmune diseases that have very pleiotropic inflammation that includes both HF and AD and many others is an advantage. And I think the 17AF versus A is just another way to sort of highlight the advantage of going broader and having more efficacy versus being more restricted and narrow. And Jeff, just to answer your question on revenues, while we don't obviously guide to collaboration revenues, you can see in our balance sheet the deferred revenue number, it's just over $46,000,000 That's the amount of revenue we expect to recognize over the near term as we fulfill our performance obligation. The inclusion though of additional milestones, there's no additional milestones are included in that number.

Speaker 3

So anything that is achieved with respect to future milestones, those would be largely recognized at that point in time. So that's what I can tell you on that. Great. Appreciate it guys. Thank you.

Operator

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

Speaker 1

Okay. Thank you. We'd like to thank everyone for joining us this morning and look forward to keeping you updated on our progress. Later this month, we'll be participating at the BofA conference and hope to see many of you there. In the meantime, please don't hesitate reach out if there are additional questions following today's call.

Speaker 1

Thank you. This concludes today's call.

Operator

Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

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Key Takeaways

  • Chimera’s IRAK4 degrader KT-474 is in two Phase 2 trials for hidradenitis suppurativa and atopic dermatitis under the Sanofi collaboration, with topline data expected in the first half of 2025.
  • The STAT6 degrader KT-621 has shown robust preclinical efficacy equal or superior to dupilumab and is on track to enter Phase 1 studies in the second half of 2024.
  • The TYK2 degrader KT-294 demonstrated picomolar potency and superior pathway blockade in preclinical models, and Chimera plans to share further updates at medical conferences later this year.
  • In oncology, the Phase 1 MDM2 degrader KT253 showed evidence of target engagement, p53 pathway activation, and initial antitumor activity without dose-limiting toxicities, with an ASCO update slated for June.
  • Chimera ended Q1 2024 with $745 million in cash following a $300 million equity financing, providing runway into early 2027 and support for multiple upcoming data readouts.
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Earnings Conference Call
Kymera Therapeutics Q1 2024
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