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

Thank you. We'll be right back. Thank you for coming this morning to the Morgan Stanley Healthcare Conference. My name is Ruck Byun. I'm the Head of West Coast Healthcare Investment Banking at Morgan Stanley. I have the pleasure of hosting the management team from IDEAYA Biosciences, Yujiro Hata and Josh Bleharski. I'll just ask a couple of questions to get the conversation started. So, Yujiro and Josh, for somebody that's encountering IDEAYA for the first time, what is maybe the simplest way to understand where the company is today?

Yes, so Ruck, thank you for the introduction, and thank you to Morgan Stanley for the invitation at the J.P. Morgan Healthcare Conference. So IDEAYA Biosciences, I think maybe the best way to summarize it, we are a leading precision medicine oncology company. We have a very deep and diversified pipeline in the area of precision medicine oncology in particular. Our lead program is an agent called Darovasertib. We are in the process of submitting the final NDA submission under RTOR. Most of our analysts are projecting a launch timeframe in the first half of next year. In addition to frontline metastatic uveal melanoma, we have several additional Phase 3 studies ongoing, including in the neoadjuvant and adjuvant setting. So here, our view is this molecule has the opportunity to be hopefully standard of care across the uveal melanoma patient journey. Beyond that, Ruck, as you know, we believe we have one of the deepest clinical pipelines in precision medicine oncology today. I would say next program to focus is on DLL3. This is a topo-ADC. We recently announced a successful Type C meeting with the FDA with our intent to start a randomized Phase 3 study and later-stage small cell lung cancer. We do also believe there's an opportunity in neuroendocrine carcinoma. Beyond that, we have an exciting set of assets in MTAP deletion. This is a key tumor suppressor loss gene. It represents about 15% of all solid tumors, including about 40% of pancreatic cancer. And Ruck, as you know, we announced two collaborations with Roche in the last several months, both with our PanRAS inhibitor, second with our KRAS G12C and D inhibitor, all in pancreatic cancer. We have multiple assets beyond that, but I think that's a good high-level summary.

Great. Maybe talking a little bit about Darovasertib and the regulatory path forward. You know, obviously showed a clear PFS and response rate benefit. And, you know, OS is still maturing. Between now and potential approval, what's the most important remaining question for regulators or physicians or investors?

There's not much remaining as part of the NDA submission under RTOR. It's primarily been QC related to clinical summaries of both safety, efficacy, and the broader clinical overview for the program. So there's nothing specific gating. I would probably say the primary question that's open is what will be our label strategy. RECIST, as you're aware, the randomized Phase 3 study was done in HLA-A2 negative. So Kimmtrak was approved in positive. We believe the negative population is the majority, approximately in that 60-40 to 2/3, 1/3 split. Based on additional discussions with the FDA under RTOR, we do believe there is receptivity to an all-comers approach. So we are still communicating base case as A2 negative with NCCN guidelines as base case, but I would say we're feeling more confident at least around that FDA receptivity.

Activity piece. Got it. So in terms of how investors should be thinking about the A2 positive population, where could you fit in in terms of sequencing or even patient selection?

Yes, look, we think that the Darovasertib has several components that are quite attractive relative to the peer agent that you mentioned. So first, we have a confirmed response rate that's approaching 40%. We have a progression-free survival that's approximately 7 months. Those measures. We believe we're significantly above what's available, including Kimmtrak or Ipi/Nivo. In addition, Ruck, as you're aware, we have presented single-arm OS data, and we've reported just over 21 months at the Society of Melanoma Research last fall. We believe the control arm will come in 12 to 13 months. In addition, it is an oral available therapy versus a weekly IV infusion. So I do think we're going to have a lot of benefit, and at least our perspective is we should get robust uptake, both in the frontline as well as pretreated setting of HLA-A2 positive.

Got it. Thank you. How are you thinking about, you know, getting gearing up for your commercialization efforts in terms of physician education, patient identification, so on and so forth?

Yes, that's a big emphasis for us right now, Ruck. So our senior leadership has been hired and is in place for the commercial launch. You know, we're in the process of doing a lot of that market research, you know, meeting with KOLs, talking to payers, you know, really to the point you made, trying to raise awareness for the Darovasertib combo, educating people about the data set, the value proposition. So that's work that's been ongoing for, I mean, many, many quarters and will continue. I think the other piece of this is really trying to understand how patients are seen and where they are. And so that's going to be a combination of some of the KOL networks that we've built and established over the years, as well as some technological tools that we're using to help identify patients, understand treatment paradigms, and make sure that we, if we're approved, can do that. We can get to those patients as efficiently as possible.

Great. So when you think about Darovasertib beyond metastatic disease, what gives you confidence that the activity in the metastatic disease will translate into preventing or delaying recurrence in the adjuvant setting?

Yes, so I think the good news here, Ruck, is that we do, as you know, we have a lot of confidence in the activity we're seeing in the metastatic setting. I think that hopefully bodes well in the pre-metastatic setting, as you mentioned, specifically as it relates to relapse or recurrence. In addition, I would just highlight, we just launched our Phase 3 randomized adjuvant study that is randomized against observation. So we were essentially randomizing against nothing there. So we think that's a very low benchmark. In addition, you know, we've well-powered this study. It's about 450 patients. So we feel good about the target hazard ratio, and what that benchmark looks like.

Got it. Now... Could successful use in earlier stage disease reduce future metastatic population, and how do you balance that possibility against the much larger opportunity to treat patients across the disease continuum? Thank you.

Yes, so look, you know, for the transition between neoadjuvant and adjuvant, Ruck, as you're aware, the primary endpoints for neoadjuvant are quite different. So they're more ocular-related, including preservation of the organ, in this case the eye, for the enucleation patients, and then around eye preservation as well. There's a secondary endpoint around no detriment for event-free survival, which would have some parallels to the relapse-free survival in the adjuvant setting. So that's the first, is that the endpoints and what we're trying to achieve are not exactly the same. Last part, I will say there is precedence and indications like breast cancer as well as others about re-challenging in the metastatic setting. So there is going to be a fairly long duration from when patients are going from pre-metastatic to metastatic. And in many cases, you're talking 3 to 5-year timeframe.

And thank you. Now, maybe shifting gears a little bit. In terms of DLL3, it's really become increasingly validated target in small cell lung cancer. As you think about IDE849, what do you believe will ultimately define a best-in-class DLL3 ADC?

Yes, so, Ruck, we believe that DLL3, as you mentioned, is a highly validated target, obviously with a lot of the success with Amgen and Imdelltra. And as you know, the small cell lung cancer space is getting crowded. And within that, we do believe DLL3 is the most compelling target. So for us, to your question on what does success look like and best-in-class look like, it's going to be a balance between efficacy and safety. So for safety, ideally we see confirmed response rates in the 60s. Obviously, it will depend on what line you're in. We do see, you know, differences between second versus third line plus patients. On the progression-free survival side, and there I should have mentioned, and then Imdelltra's response rate in their '24 approval was roughly in the mid-30s. For progression-free survival, they saw, I believe it was 4.2 median progression-free survival. So we think their success would look like a PFS ideally with a 6 or 6.5 months. And then OS, as we know, so in their approval readout, they saw about a 12.5-month OS. So at ESMO, we will be presenting about 100 patients worth of data, both for sponsor APFS and 12-month landmark OS. So based on that Imdelltra benchmark, ideally you see a 12-month OS percentage of greater than 50%. Safety, ideally Grade 3 or higher SAE rates that are reasonable. So I think here you're probably talking that 20% to 30% range. SAEs ideally in that single digit percent range and hopefully very little ILD. So I think relative to some of these other classes like BTK, we do believe, directionally, you're seeing better safety with either similar or even potentially better efficacy. And that will become important when you think about combinations, whether that's checkpoint inhibitors and Imdelltra. We're pursuing a combination on PARP, so we believe hopefully that will give us more flexibility. The last piece I should have mentioned, as well as in neuroendocrine carcinoma. That's, I would say, more white space. We're clearly seeing monotherapy activity there. So we do think that could be a unique opportunity that's more distinct to DLL3 because of its specific antigen expression.

Got it. Thank you. And how should investors think about upcoming catalyst timing and your trial plans for DLL3 specifically?

Yes, so we have several initiatives that we're focused on for the program. So first, as we mentioned earlier, is around the Phase 3 study in extensive stage small cell lung cancer. I would say one of the key points of differentiation versus a peer company that's launched a study here is that we will be exclusively focused on the post-relapsed population. We believe that's the more attractive study design and that it will be more of a homogeneous population versus having pre- and post-relapsed patients. And, Ruck, Amgen had a recent readout in frontline maintenance in small cell lung cancer, which I think further punctuates that point. Second, so that's the first we'd like to get going. We do have a meeting upcoming in the fourth quarter with the FDA around a potential registrational study for monotherapy approval in neuroendocrine carcinoma. So we're hopeful that that discussion goes well. Once we have that, if there's a path forward, we'll communicate that externally. And then I would say lastly is around a frontline small cell lung cancer study. So there, you know, I think we're still working through what that study design looks like. I would say several components of that. One, we're evaluating this monotherapy PARP combination with IDE161. PDL1 we think is table stakes. So, you know, those are, I would say, the variable pieces that we'd like to lock down ideally by the end of next year to make a go-no-go decision on that.

Got it. Thank you. I guess on that note, in terms of, you know, combination with 161, I think it's one of the more differentiated pieces of your strategy. I think scientifically and mechanistically, I think the rationale is compelling, but clinically, what type of signal would convince you that PARG is actually improving on the durability piece?

Yes, and so for the listeners that may be less familiar with PARP IDE161, really the strategy here, Ruck, is around, as we know, the payload of topoisomerase in terms of mechanism is in the area of DNA damage repair. So if you're thinking about how do you enhance the efficacy, in particular here to your question, Ruck, it's really going to be about can we extend the durability. You'd want to think about what synergizes with the DNA damage repair mechanism of topoisomerase. And here there's been interest in targets like PARP1. We believe PARG is compelling, and that specific enzyme is directly involved in the repair of the DNA damage that's elicited with topoisomerase. So here the objective is really simple. Can we have a well-tolerated combination effect, while we see extended durability versus monotherapy. If we can achieve that, A, this becomes a plug-and-play opportunity across the class of topo-ADCs. But then we also believe it will open up multiple opportunities, I may not be available to others, including in areas such as frontline small cell lung cancer.