IDEAYA Biosciences, Inc. (IDYA) September 2026 Conference Transcript

Good morning.

Thank you for coming this morning to the Morgan Stanley Healthcare Conference. My name is Ruck Byan. I'm the head of West Coast Healthcare Investment Banking at Morgan Stanley. I have the pleasure of hosting the management team from IDEA Biosciences, Yujira Hata and Josh Blaharsky.

I'll just ask a couple of questions to get the conversation started. so Yuzhara and Josh for somebody that's encountering IDEA for the first time what is maybe the simplest way to understand where the company is today yeah so Rook thank you for the introduction and thank you to Morgan Stanley for the invitation at this year's conference so IDEA Biosciences I think may be 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 Daruva Serotib. We are in the process of submitting the final NDA submission under RTOR. Most of our analysts are projecting a launch time frame in the first half of next year. In addition to frontline metastatic uva 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 melanin patient journey. Beyond that, Rook, 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 three 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 Rook, as you know, we announced two collaborations with Roche in the last several months, both with our PANRAS inhibitor, second with our KRSG-12 CD 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 DARO 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?

Yeah, there's not much remaining as part of the NDA submission under our tour. 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 specificating. I would probably say the primary question that's open is what will be our label strategy. As you're aware, the randomized phase three study was done in HLA-A2 negative. So KimTrack was approved and positive. We believe the negative population is the majority, approximately in that 60-40 to two-thirds, one-third split. Based on additional discussions with the FDA under our tour, we do believe there's receptivity to an all-comers approach. So we are still communicating base case as A2 negative with NCN guidelines as base case, but I would say we're feeling more confident, at least around that FDA receptivity piece.

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

Yeah, look, we think that Derova Serotib 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 seven months. On both of those measures, We believe we're significantly above what's available, including ChemTrack or Epinevo. 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 weak live 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 front line as well as pre-treated setting of HLA-A2 positive.

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

Yeah, 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 Darrow-Cris combo, educating people about the data set, the value proposition. So that's work that's been ongoing for 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, we can get to those patients as efficiently as possible.

Great. Now, maybe think about DARO 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?

Yeah, so I think the good news here, Rook, 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 relates to relapse or recurrence. In addition, I would just highlight we just launched our phase three randomized adjuvant study that is randomized against observation, right? So we're 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 a much larger opportunity to treat patients across the disease continuum?

Yeah, so look, the transition between neoadjuvant and adjuvant, Rick, 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 eunucleation patients, and then around eye preservation as well. There's a secondary endpoint around no detriment for vent-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. The 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 three- to five-year time frame. Got it.

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 A4-9, what do you believe will ultimately define a best-in-class DLL-3 ADC?

Yeah, so, Rook, we believe that DLL-3, as you mentioned, is a highly validated target, obviously with a lot of the success with Amgen and Indeltra. And as you know, the small cell lung cancer space is getting crowded. And within that, we do believe DLL-3 is the most compelling target. So, for us, you know, to your question on, you know, what does success look like and best-in-class look like, you know, it's going to be a balance between efficacy and safety. So, for safety, ideally, we see confirmed response rates in the 60s. Obviously, we'll 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 Indelstra'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 six or six and a half months. And then OS, as we know, in their approval readout, they saw about a 12 and a half month OS. So at ESMO, we will be presenting about 100 patients' worth of data, both response rate PFS and 12-month landmark OS. So based on that Indeltra benchmark, ideally you see a 12-month OS percentage of greater than 50%. In terms of safety, ideally grade 3 or higher SAE rates that are reasonable. So I think here you're probably talking that 20% to 30% range. SAE is ideally in that single-digit percent range. and hopefully very little ILD. So I think relative to some of these other classes like B73, 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 Deltra. We're pursuing a combination with PARG, so we believe hopefully that will give us more flexibility. The last piece I should have mentioned as well as a neuroendocrin 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 DL3 because of its specific antigen expression.

Got it. Thank you. And how should investors think about upcoming catalyst timing and your trial plans for DL3 specifically?

Yeah, so we have several initiatives that we're focused on for the program. So first, you know, as we mentioned earlier, is around the phase three study and extensive state small cell lung cancer. I would say one of the key different points of differentiation versus a peer company that's launched a study here is that we will be exclusively focused on the post-indulteral population. We believe that's the more attractive study design and that it will be more of a homogenous population versus having pre- and post-indulteral patients. And, Rook, as you know, 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 neuroendocrinoma. 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 novel PARC combination with ID.161. PD-L1 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, you know, 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?

Yeah, and so for the listeners that may be less familiar with PARG ID.161, really the strategy here, Rook, is around, as we know, the payload of top-wise summaries 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, Rook, 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. You know, can we have a well-tolerated combination effect while we see extended durability versus monotherapy? If we can achieve that, you know, 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 that may not be available to others, including in areas such as frontline small cell lung cancer.

Thank you. So, the PRMT5 field is obviously getting increasingly competitive. What characteristics of 892 do you think matter most clinically? Selectivity, therapeutic index, PK, the depth of PRMT5 inhibition or combinability? And where do you think ultimately your competitors may run into limitations?

Yeah, so I think for a cure, you know, I would say not too dissimilar to what we're seeing or what we have been seeing over the last decade in the KRAS, RAS field, which is with multiple iterations, you know, these molecules are getting better, right? And we feel in the PRM-25 area, there's three core parameters that are critical for what a best-in-class molecule could look like. So first is around a biophysics question around MT cooperativity versus SAM cooperativity. Rook, as you're aware, the first-generation pre-MT5 inhibitors were either SAM cooperative or SAM competitive, and due to that, we saw myelosuppression, and ultimately there was not a path forward. The second-generation inhibitors are intended to be selectively MT cooperative. However, we believe there's multiple compounds in the clinic that are not just MT-cooperative, they're also SAM-cooperative, which would impact therapeutic window. So that's the first. The second is around this question of do you want a brain penetrant molecule or not? One of our significant focuses is in the area of pancreatic cancer, and in that indication, we believe there is not a benefit to have brain penetrants, and we do believe that that That is more of a liability than a benefit based on the biology of both PRMT5 and MATSUA, specifically as it relates to RNA splicing that we believe could manifest as it relates to CNS tox. Finally, third is around drug-drug interactions. So I would say similar to the RAS field, that is a question because of a lot of the chemistry scaffolds that are being worked on, that drug-drug interactions is not necessarily easy nut to crack. And that's a property that we were extremely focused on for ID892. And CYP3-4 in particular, I would say is a key enzyme you have to really think about based on how some of these other molecules were metabolized, including RAS, G12D, MAT2A, and specific chemotherapies.

Thank you. On the G12D point, the G12D collaboration is an interesting example of intersecting a tumor suppressor vulnerability with an oncogenic driver. Why should simultaneous PRMT5 and KRAS inhibition be better than either approach alone? And which patient populations do you think offer the clearest proof of concept?

Yeah, so here for the KRSG-12D MTAP deletion population here, Rook, our focus with Roche Genentech will be specifically in the area of pancreatic cancer. If you look at the overlap of those two genetic alterations, we believe it's approximately 15% of all of pancreatic cancer. So essentially what we believe we're doing is we are targeting the key driver oncogene in those patients, in that case G12D, with one of the key areas around tumor suppressor loss, in this case MTAP. And, Rick, as you know, there was some recent data, at least both on the G12D PRMT5 side and RAS PRMT5, where we saw quite exciting activities. So, I think here, ultimately, you want to place that into the frontline setting, ideally, and hopefully be able to enable a frontline registrational strategy. So I think that would be quite exciting. So clearly one of the pieces we believe some of the early data early this year provided is in those pancreatic cancer patients that have KRAS. We believe MTAP is clearly playing a role.

Great. I think I already know the answer to this. But if we fast forward two to three years, you potentially have multiple registrational and combination opportunities across ADCs, MTAP, and your pipeline is going to be maturing. Outside of DARA, which program has the greatest potential to change how investors think about IDEA?

Yeah, it's a great question, Rook. I know the answer was limited to one, but I'll provide two here. Look, I would say that the MTAP and KRAS, we do think, is something that is fundamentally important, not just for us as a company, but for the area of precision oncology, really advancing this concept that we just talked about of targeting the key driver oncogene and tumor suppressor loss biology. I think conceptually we're on to something there, and we believe IDEA is uniquely positioned to prosecute on that, Not just with MAT2A and PM2-5 and MTAP, but also, as you know, we have an earlier program in CDKIN2A that we hope will be in the clinic in the first half of next year. The second is around this topo-ADC PARG mechanism that we mentioned, because I think that's really one of the greatest areas of Unmendeed, is how do you extend the durability of topo-ADCs? So this idea around DDR combinations with Tobiasomrace is a very sensible one and we think can make tremendous impact for patients.

Thank you. As your portfolio broadens, how do you allocate capital across advancing wholly-owned programs, forming partnerships, investing in new discovery opportunities, and also, more importantly, thinking about not deprioritizing assets? What is your decision-making process internally? How are you thinking about that?

Yeah, so, you know, I would say at a high level, all of the things that you just talked about will be done from a perspective of having data. So we want to take a data-driven approach to the way we evaluate our programs, the way we prioritize our programs, the trials that we ungate and decide to pursue. and that is obviously the way we've approached building the pipeline thus far and how we've proceeded. I think obviously there's a lot in the pipeline. It's there for a reason. It's done with intent, but as you know, biotech is fraught and, you know, we have to make these decisions based on what we see in the clinic. I think the good news is we're well capitalized in order to take these programs to a point where we generate that data and from there make the decisions around what the appropriate next steps could be, and those could be continuing to fund them on their own or seeking partners or deprioritizing, again, depending on what we see. But, you know, I think we've intentionally tried to capitalize this company and align ourselves with the kinds of people that can help us make those informed decisions. We certainly talk to a lot of the larger players out there, keep them abreast of our progress. So it's the kind of thing that will take shape as we have that data to evaluate, and in the meantime, what we want to do is remain really focused on executing on the things that we've talked about and the things in our pipeline that we are taking forward. Great.

Thank you. So you mentioned up the upcoming R&D Day. What should investors expect to hear at your R&D Day in November in terms of key updates, guidance, et cetera?

Yeah, so for R&D Day, we're going to have a significant focus on some of the areas we covered in terms of our broader clinical strategy and R&D strategy, Rook, in this area of MTAP, CDK2A, and KRAS. And we believe this very critical intersection between those two genetically defined populations, in particular in the indication of pancreatic cancer. There's a lot of data, including preclinical data we're sitting on, that I would say has been informing our strategy and what people should expect to us, not just through the end of this year, but into next year and beyond. We'll also have Dr. Frank McCormick from UCSF with us, who obviously is a world expert in the KRS area. So I think it's going to be a great event. It will be that first Monday in London in that second week of November.

I guess maybe a wrapping question. Looking ahead over the next one to two years, what are some of the key milestones investors should be thinking about, looking at forward that we haven't talked about?

Yeah, so, you know, I know we covered quite a lot from derovaciratib, DLO3, and MTAP KRAS. I would say probably what I would then dig into next is around, you know, the rest of our portfolio. I would say in particular programs like CAT67, which is a lysine acetyltransferase area, or also known as chromatin remodeling. Here we have a significant focus on several key indications, including breast cancer, colorectal cancer, and lung cancer. In addition, our dose escalation is going well. We've cleared multiple dose cohorts. We believe we're now entering into a clinical efficacious dose range. Based on the preclinical data, we do believe at least we have the opportunity to drive monotherapy activity. We're with CAT6 selective molecules. as you know, Rook has been a challenge unless they've combined it with Fulvestrin. So I would say there we also have two combination focuses. One is with CERD inhibitors, specifically in breast cancer, potentially in the setting of ASR1 mutant. And then I would say some interesting data we've generated with PanRAS and KRAS-CRC where we have demonstrated preclinical synergy. So we're having several conversations on both of those fronts. So I think, you know, very exciting program, definitely one that's not, that's a bit under the radar, but hopefully we'll have, you know, a decent amount of data to look at by the end of the year.

And maybe since you brought it up on the CAT 6, what were some of the learnings from kind of folks like Pfizer that have, you know, are slightly ahead? What are some of the relevant learnings? And as you're thinking about the, you know, maybe if you can expand on kind of the competitive landscape and why you think you're differentiated.

Yeah, look, I think we've learned a tremendous amount from Pfizer. So for those that may be less familiar, so Pfizer's now initiated a randomized, a phase three study with their CAT6 selective inhibitor, specifically in combination with Fulvestrin and breast cancer. So I would say, you know, for us, we've, through those learnings with Pfizer, I think we've clearly, you know, come to understand what is a ideal target TPP for CAT6-7. So one, you know, as I noted earlier, due to the dual mechanism, we do believe six and seven is a critical bypass mechanism, which, A, if we can demonstrate more significant monotherapy activity than CAT6, especially in breast cancer, we think that's a significant it win. Second, if you look at what Pfizer is doing with their 6-7 inhibitor, which is they just started dosing this year, they're clearly focused on colorectal cancer, which is truly distinct than what they're doing in CAT 6. And we think that's due to the underlying biology of CAT 7. So I think that's also would be very exciting if we can have a path forward in CRC beyond just breast cancer, and then we talked about seeing the single Asian activity. In terms of competitive landscape, the CAT6 field is getting more crowded, but the 6-7 area, there's only two companies that are in the clinic. It's us and Pfizer, and we believe we're neck-to-neck with them. So I think that's a great position to be in. From a total addressable population, I think this program may be the largest program in terms of TAM that we're working on across our entire pipeline, which is saying a lot because we're working on some big opportunities.

Well, I'll pause here to see if there are any questions from the audience. All right. Thank you very much for getting here early. Good luck with the rest of your conference. I hope your travel is smooth. Great. Thank you, Mark.