IDEAYA Biosciences, Inc. (IDYA) Earnings Call Transcript & Summary

Welcome, everyone, to the 42nd Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I am one of the senior biotech analysts here at JPMorgan. I'm joined by my squad, [ Malcolm Kuno, [ Maria Hall ], Priyanka Grover. Our next presenting company is IDEAYA and presenting on behalf of the company, we have CEO, Yujiro Hata. Yujiro?

Well, great. Well, thank you so much, everyone, for attending today's presentation, and thank you also for JPMorgan for the opportunity to present today. So earlier on Sunday, we provided several key program updates, which I'll highlight today. In addition, we did give our 2024 corporate guidance. In 2024, we believe there's going to be a big opportunity for darovasertib, in particular, a significant focus on our Phase II company-sponsored neoadjuvant uveal melanoma trial. In addition, we've given specific guidance of our target to present Phase II clinical efficacy data in the middle of this year. Next, providing regulatory guidance also in 2024 for the neoadjuvant uveal melanoma indication. The daro and crizo first-line metastatic uveal melanoma potential registrational trial enrollment is going as planned. We noted on Sunday that we have achieved double-digit enrollment and international site activation has been achieved. Next, for MTAP deletion, we had several key updates, including continued Phase I/II expansion in MTAP deletion, specifically targeting non-small cell lung cancer and bladder cancer. In addition with our partner, Amgen, for the IDE397 and AMG 193 combination that we have ongoing Phase I enrollment in the dose escalation and the development of a joint Amgen and IDEAYA [ publication ] strategy in 2024. Next, a few weeks ago, we did announce a new partnership with Gilead for the combination of IDE397 with Trodelvy, specifically in the indication of MTAP deletion bladder cancer. And we are guiding towards a target FPI on that trial in the middle of this year. Next, further down our portfolio is IDE161, which is a first-in-class PARG inhibitor targeting HRD solid tumors, where we will be targeting program updates in 2024 as well as enabling specific combinations in 2024. Our fourth first-in-class program in the clinic, GSK101, which is against Pol Theta Helicase, is ongoing in terms of Phase I dose escalation. Next, for Werner Helicase, we continue to be on track for IND submission in 2024. Here, we can say high level. We feel good about where we are on the GLP toxicology studies and everything continues to be on track for what we believe has the opportunity to be a best-in-class molecule for Werner Helicase. And then lastly, we have multiple next-generation programs where we're targeting a development candidate nomination in 2024. We're in a strong financial position, and we're guiding towards a cash runway into 2028. So over the last 8.5 years, IDEAYA has built a leading functional genomic synthetic pathology platform. And through that, we pursued several key patient selection biomarkers, including MTAP deletion, HRD and high microsatellite instability, which has generated several of our key first-in-class programs into the clinic. What underpins this pipeline is a very vast and integrated drug discovery platform, including Target and biomarker discovery, drug discovery as well as translational research. We've built our synthetic lethality target and biomarker discovery platform through several key molecular biology platforms, including Dual CRISPR as well as a paralog gene platform as well, where we integrate both public and proprietary data sets to help us both prioritize our targets as well as validate our potential biomarkers for the clinic. Since the company's founding, one of the key focus areas for us has been to pursue and unlock chemical opportunities where we have the ability to be first-in-class and we've done this in several examples, including MAT2A, which is now in Phase II; PARG, which is in Phase I expansion; Pol Theta, which also recently entered Phase I; and as we noted earlier, Werner Helicase, where we recently selected a development candidate. An area where we're continuing to invest in building our capabilities is around AI/machine learning-enabled computational drug discovery, where we integrate these capabilities where our capabilities in structural biology to specifically advance our time lines to IND for challenging first-in-class targets. Since our founding, we have now built a highly diversified first-in-class portfolio that includes four first-in-class clinical programs in darovasertib where we initiated a registrational trial in first-line metastatic uveal melanoma. Next, IDE397, MAT2A, targeting MTAP deletion, which is now in Phase II expansion. We're in two key combinations, including with Amgen and Gilead. And then third, IDE161, which as noted earlier, in Phase I expansion, targeting several key HRD solid tumors, including CRC, endometrial cancer as well as others. And then as noted earlier as well, Pol Theta Helicase, which is in Phase I with our partner, GSK. And then Werner Helicase, where importantly, we're targeting IND submission this year. And we have retained significant rights, including a 50-50 U.S. profit share. In terms of darovasertib, here, this is targeting specifically a target called PKC and we're targeting a specific activating mutation of GNAQ11. What makes this mutation unique is the predominance of uveal melanoma patients harbor this activating mutation of either GNAQ or GNA11. Darovasertib, has shown to the bottom left, a significant single-agent activity in addition to the ability to demonstrate single-agent regressions here in a specific GNAQ being modeled. The clinical data that we reserved to date in terms of a tolerability profile, we believe darovasertib has an overall favorable tolerability profile. And here, what we're highlighting within the trial data that we've generated, and we'll go through the efficacy data here shortly, which is when you compare our Phase II data, which we'll walk to shortly versus [indiscernible] randomized Phase III data. We have been treating patients that have had much higher disease burden, including based on LDH status, size of the metastatic lesion as well as when you look at single versus multi-site metastasis. Here's a really quick summary of the data that we've shared to date in terms of a waterfall. And as you can see in the first-line setting, we see a very robust confirmed overall response rate of RECIST to 45%. Historical response rate in this indication has been from 0% to 5%. Importantly, we do see activity irrespective of HLA-A2 status, as shown to the left in the HLA-A2 population where we are running our frontline registrational trial and to the right and the HLA-A2 positive setting, as we can see, we see clinical advocacy irrespective of HLA-A2 status. We've also looked at ctDNA molecular response. There has been data published in the indication of metastatic uveal melanoma which demonstrates that ctDNA can be a valuable efficacy tool in particular, for being predictive of survival. And that data was published in the New England Journal of Medicine. As we can see, we see quite a significant response rate as it relates to molecular response of 94%. In addition to the various response rate data that we've shared, we also believe we have a very favorable median progression-free survival. Historical PFS in metastatic uveal melanoma has been 2 to 3 months. Here in the frontline setting, we're seeing a PFS exceeding 7 months. And importantly, in the hepatic only setting, a PFS that's approaching a year. And here, I would highlight [indiscernible] pivotal phase III study, over half of the patients that they treated in the frontline setting had hepatic only disease. Here, we highlight further data that supports the durability that we're observing with this combination in the metastatic uveal melanoma setting. This is a 2-year PFS Kaplan-Meier curve. And as you can see as shown clearly here in the figure, this combination in the any-line [ MU1 ] setting shows a very favorable Kaplan-Meier curve versus [indiscernible] frontline trial as well as versus their control arm. And we would anticipate in our registrational trial, only looking at the frontline setting that this -- we would have the opportunity to further enrich this 2-year Kaplan-Meier curve. So in summary, when you look at overall response rate and progression-free survival and any additional metric that we looked at in our Phase II company sponsored trial, our data does compare very favorably versus the historical data as shown on this table. So as we now noted in the beginning of the presentation, we've launched into a frontline registration trial. That study is well underway. And the key aspects of the design of the trial is that it's a randomized trial against investigators' choice at a 2:1 randomization. The primary endpoint for accelerated approval is medium progression-free survival. This is an integrated Phase II/III design that would enable us to get both accelerated approval and full approval in the same study and the full approval endpoint is overall survival. We have also received Fast Track Designation for this combination in MUM and we've also achieved Orphan Drug Designation for uveal melanoma. A key aspect of darovasertib for 2024 will be the neoadjuvant uveal melanoma opportunity, where we're seeing a clear signal of efficacy as a monotherapy agent and as noted earlier, we're committing to give a Phase II clinical efficacy update middle of this year. There's two cohorts that we're focusing on in the neoadjuvant application. First is the enucleation cohort. Here, we believe one of the key endpoints has the opportunity to be around eye preservation and the second cohort being plaque therapy. Here, looking at decrease in radiation dose as well preservation of vision. In addition to MUM, we've also looked at cutaneous melanoma. And to the right, we have some early data where we're clearly seeing a durable signal. In this case, two patients that have responded as confirmed PRs, patients that have been treated out to almost 600 days. And as you can see here, 3 out of 4 patients, we see tumor shrinkage. Overall, darovasertib, we believe, is a blockbuster potential opportunity with the ability to potentially get approval in the frontline setting across this entire patient journey, including neoadjuvant, adjuvant and metastatic uveal melanoma. Our next program that we'll highlight is MAT2A and the MTAP deletion space. This program is targeting a patient selection biomarker called MTAP deletion, which does represent roughly 15% of all solid tumors. IDE397 preclinically has demonstrated robust single-agent activity, including tumor regressions and models and tumor indications, including lung cancer, as well as bladder cancer. One of the key aspects of the program is the clinical combination that we are advancing with Amgen, with their MT cooperative PRMT5 inhibitor, AMG183. In 2023, we presented with Amgen in a peer-reviewed setting the combination data, which is reflected to the right, where we see tremendous synergy with these two molecules together, importantly, at a fraction of the monotherapy dose, where we see in this model, in this MTAP lung cancer model to the right, complete responses in all animals in both cohorts. In terms of our experience of IDE397 in the clinic and our Phase II monotherapy expansion, we're specifically focused in lung cancer as well as bladder cancer. And as we can see, we both see molecular responses as well as tumor shrinkage greater than 30% based on CT assessment. A month or so ago, we also announced a new collaboration with Gilead to do a combination with Trodelvy, which is a Trop-2 ADC with IDE397, specifically targeting MTAP deletion bladder cancer. And several pieces to highlight here. First, we believe this potential combination from a mechanistic standpoint is unique to MAT2A versus PRMT5. Second point I would highlight is that MTAP deletion prevalence in bladder cancer is over 30%. And we have seen monotherapy efficacy in the clinic with IDE397 in the MTAP deletion bladder cancer setting, including confirmed complete response, as well as robust tumor shrinkage across multiple patients. And as you can see to the right, a very significant activity from a ctDNA molecular response rate perspective. So there are 3 key activities for this program, including our monotherapy expansion, our combination work with Amgen with their MT Cooperative PRMT5, and then lastly, with Gilead with our Trop-2 ADC inhibitor. The next program that we'll go through is PARG IDE161. So several key highlights here. PARG is a target in the PARG pathway, often been referred to as the counterposing mechanism to PARP inhibitors. Here, we are targeting HRT solid tumors, and we also have interest in tumor indications where PARP is not approved, including CRC and endometrial cancer. Here, we just highlight that IDE161 is a first-in-class inhibitor, a very active [ cellularly ] as well as in vivo and we'll show more data on that here on the next slide. One of the key aspects of PARG, which got us excited about this target versus PARP is that we do see differential activity in the HRD setting with a PARG inhibitor versus a PARP inhibitor. In addition, we do see activity, specifically in the ER-positive HER2-negative breast cancer setting and more favorable efficacy preclinically relative to commercially approved PARP inhibitors as shown to the right. We have observed early RECIST responses in the clinic, as noted here. We have 2 patients where we observed a RECIST response out of 5. We are still early in our dose evaluation as well. We have not confirmed to move forward dose at this point yet. In addition, new data that we did share Sunday morning is that we also now have a prostate cancer patient with a greater than 50% PSA reduction. And at this point, we've only treated two prostate cancer patients. So this highlights our current focus. So for monotherapy, as noted earlier, will be a focus on several key tumor types, including endometrial cancer, colorectal, ER-positive HER2-negative breast as well as prostate cancer. In addition, the team is hard at work for enabling several opportunities on the combination front, which we believe are going to be, one in particular, a potential near-term opportunity. Hopefully, we'll share more about in 2024. Our fourth program in the clinic is GSK101. This is the first Pol Theta Helicase inhibitor to enter the clinic. Here, we're very focused on HRD solid tumors. And here, we believe the primary utility of Pol Theta Helicase is going to be in combination with PARP inhibitors, specifically to address what has been a key challenge for PARP inhibitors around PARP acquired resistance, specifically around the mechanism of BRCA reversions, of which we believe the backup repair mechanism of microhomology end joining plays a key role, which we know Pol Theta is a key Achilles heel of microhomology end joining. Beyond our four clinical programs that we just walked through, the next key asset targeting to get in the clinic as Werner Helicase. Here, we're targeting IND submission this year and as noted earlier, we believe we have the opportunity to be first in class. Next, we have multiple development candidates that we're targeting for 2024, including an MTAP deletion space and look for us to continue to bolster our drug discovery platform to future -- our future pipeline. Quickly on Werner Helicase. As noted earlier, a key opportunity, we believe, one of the most exciting targets in precision medicine oncology today. Here the patient's actual selection biomarker is high microsatellite instability. And as you can see to the right, we show exquisite activity in the high MSI setting, and we see no effect on the microsatellite stable setting. We believe here, there should be an opportunity in the clinic, both in terms of as a monotherapy as well as in combination with GSK's PD-1 dostarlimab. And as noted earlier, we do believe we have the opportunity to be best-in-class based on very specific features of our Werner Helicase inhibitor versus the current competition. So this is just a quick summary of what's to come next in our pipeline that we're now targeting to advance for development candidate nomination 2024. As you can see to the middle, we're showing data where we see 8 out of 10 complete responses in the MTAP setting. This target is not in the PRMT5 pathway, and we also believe it has the potential to be combinable both with MAT2A and MAT2A-cooperative PRMT5. So as you can see, 2024, we believe is set up to be a truly transformational year for IDEAYA with 4 first-in-class programs in the clinic, soon to be 5. In addition, we believe we have line of sight opportunities that have 7 or more first-in-class opportunities, all within our cash runway. As noted to the bottom, we have over $650 million of cash on the balance sheet and an extensive runway into 2028. So with that, on a pump, we're done with our presentation and excited to [indiscernible].

Do you want to introduce who is coming up.

Sure. We have Michael White, our Chief Scientific Officer; and Darrin Beaupre, our Chief Medical Officer.

Many of you have been in sessions with me. So just to review. There are three ways to ask a question, right? Old school, raise your hand. I'll call on you. There's like a new school way, which if you have access to the Q&A portal, you can submit it, and I'll get it on this iPad, and I'll ask anonymously on your behalf. I guess there's an intermediate strategy where you can just e-mail me and also ask it anonymously on your behalf. So with that, I kind of wanted to talk a little bit about maybe first, we'll start with Daro. And the language for daro in terms of the metastatic setting said clinical -- I mean, it said clinical update, right? Now that could be data, that could be enrollment progress, that -- you talked about the site activation. Like what does that encompass?

Yes. So we -- the reason why we use that language is for the first-line registrational trial. We do think for that trial -- for that program specifically, it is going to be more about where we are as it relates to the progress of that registrational trial. It's obviously a randomized study. We think there are several key aspects in terms of milestone; in terms of, for example, where we are with enrollment; how we selected one of the two doses as part of the design of the study. So we think there are several opportunities for inflection points. And Anupam, as you're aware, a lot of our analysts have been projecting a late '26 launch. So we have been pegging our enrollment targets to enable that type of outcome. So in terms of the actual clinical efficacy data there, at least our anticipation right now is the predominant focus for this program will be in our Phase II neoadjuvant uveal melanoma study. And that's where we provided the specific guidance for update middle of this year as well as the target to have regulatory guidance update this year as well.

So 2 questions there, right, on the neoadjuvant side. So for your corporate update, what's going to be the size and scope of that neoadjuvant update and what have you learned from some of the IST stuff that might inform how you think about a win scenario?

Sure. I'll have Darrin, our CMO, to answer that.

Yes. So many of you have probably seen some of the data that we have accumulated through our investigator-sponsored trial in Australia. It's actually quite striking in the neoadjuvant setting where we have seen a significant amount of patients have tumor shrinkage and a large number of patients, in fact, of a small sample size, had their eyes saved. And so as part of an extension to that, we're obviously going into the '09 trial, where we will be evaluating two populations of patients. One population of patients is those folks that have a large tumor that are likely to have enucleation and another set of folks that have mid- to small-sized tumors that will likely go on to plaque brachytherapy. The idea here is to accumulate the data necessary to show that we can, in the case of a large tumor, shrink the tumor but also allow eye preservation, and hopefully vision preservation. And then on the brachytherapy side, the idea would be if a patient is destined to get plaque brachytherapy and then ultimately have a high likelihood of being blind thereafter. So saving the eye is nice, but going blind isn't so nice. The idea would be to give neoadjuvant therapy so you could shrink the tumor enough, less radiation. Therefore, allowing eye preservation. So the idea is to produce a data package based on what we've seen in the IST and based on what we've seen in our currently running '09 study, which we believe by midyear, we'll have a significant amount of evidence to have a discussion with the FDA of how we plan to proceed into a registration opportunity that would allow us to achieve an accelerated approval type approach for those folks with large tumors and to get full approval based on a randomized approach, likely with the brachytherapy group. That's sort of where we're sort of heading at the moment, and the data looks outstanding at the moment. Our [ 09 ] study is as expected, and we're really building on a story that we've already seen preliminarily in the IST trial.

Questions from the audience? Yes. Old school way of asking questions.

Peter Tummino from Nimbus Therapeutics. You said with your Werner's Helicase agent that it's an opportunity for you guys to be best-in-class. Can you say a word about what you think the attributes are that are going to distinguish the various Werner inhibitor agents progressing? What's going to be most important?

Yes. Thank you very much for the question. I'll let Mike answer that. And I'll just sort of highlight, we obviously have more information than we can publicly disclose. I think we've been given some pretty specific direction from our partner to keep some of this information confidential. But I think we can high level, try to capture some of the key things.

Yes. And I think some of the key points there is obviously, you're going to want a molecule that is going to deliver the synthetic lethality that is CRs in the MSI high setting, not MSS. So that's really key. We have a really nice efficacy package on the table showing that, especially showing that in very stringent models that represent patient populations, downstream of many lines of treatment, including immunotherapy, which is obviously where we're going to be running our Phase I. So that's quite exciting, that's quite important. You need to have a molecule that is able to stay on this target in the context of MSI high, which is obviously mutagenic. And so we're very excited. We think we have a molecule that can do that, that can withstand that environment with respect to intrinsic and acquired resistance. Also, the genetics is telling you that this should have -- this target in this setting should have a therapeutic window that you can sail an aircraft carrier through. So you should have a molecule that's very, very safe. And we're winding down our preclinical activities to get the IND out and the in-life is behind us for the GLP studies in both species, and we continue to have high conviction in that thesis.