Conference Transcript - IDYA 2026-09-08

Mel Fortea, Analyst — Wells Fargo

So thanks so much for joining us in our next session of the Wells Fargo Healthcare Conference. I'm Mel Fortea, one of the biotech analysts, and I'm here joined today by Yujiro, CEO, Stu, CCO, and Josh, CFO of IDEA. Thanks so much for being here today.

Yujiro Hata, CEO

Great. Thank you for having us.

Mel Fortea, Analyst — Wells Fargo

Perfect. So maybe we can start talking about Darovassertib and, you know, regulatory path and kind of like where you're at.

Yujiro Hata, CEO

Yeah, so Daruva Seratib, for those maybe less familiar with the company, has been in a front-line registrational study of metastatic uva melanoma. We did receive our tour, so we've been through the NDA pre-submission module process. The first three modules have been submitted. Our final module is about to be submitted, so everything is on track. All of our commercial preparations continue to be on track. So I think we're in very good shape from that perspective.

Mel Fortea, Analyst — Wells Fargo

Got it. Based on precedent, how should we be thinking about timing here?

Yujiro Hata, CEO

Yeah, so we haven't given more specificity on that exact timing. Ava, as you're aware, most of our analysts are projecting a first half of next year launch. Because we get expedited review through fast track designation, and because we've been going through this rolling process with the NDA under our tour, we are also prepared for a potential earlier date for a potential launch date. So, but I think until we submit the final portion of the NDA, the NDA is accepted, we probably won't be giving more visibility at this time.

Mel Fortea, Analyst — Wells Fargo

Got it. What are the gating steps for submitting this last portion to the FDA?

Yujiro Hata, CEO

Yeah, I would say they are kind of your classic steps within the final submission module process. I'm not sure we'll go into too many more details beyond that, but I would say everything is very much well under control and we do feel very confident in our ability to hit our timeline goal, which is I noted, you know, the first three modules are in, the final module will get submitted here very short.

Mel Fortea, Analyst — Wells Fargo

Got it. Okay. Very helpful. Maybe, you know, one of the big debates has been, you know, whether HLA to positive patients could get included on label, how, you know, what's the latest on your thinking for that, you know, strategy? Sure.

Stuart C. Dorman

Stuart, do you want to talk? Well, I'll say a couple of different things. First, from a regulatory perspective, we've had very positive engagement and collaboration with FDA so far. So while we certainly can't guarantee whether an indication statement would be across all MUM, we remain very hopeful about that. What I would say from a commercial opportunity perspective is that almost regardless of what that label looks like. We've got significant feedback from market research, KOL engagements, that there is a very high degree of expectation of use across both HLA positive as well as HLA A2 negative. So we believe that we have meaningful differentiation in the space, both in the negative setting where nothing is approved, but even in the HLA A2 positive setting where there is an improved agent got it what would be the possible venues can you remind us to you know making sure daryl reaches a2 positive patients yeah so go ahead yeah uh well so i i think from a hla a2 positive perspective if you you look at our data we have meaningful response rate meaningful pfs and and albeit from a phase two study we already have overall survival data that is very very comparable to to the existing therapy in that space. What we've heard from physicians is that there are a significant number of patients even in a frontline setting that are in need of a rapid response. We would be the only regimen in MUM period to offer a meaningful response rate and be able to address patients who have aggressive disease, large tumor burden, those types of things who who need a response immediately even if a patient does start on another therapy and the HLA a2 positive setting what I can say is that physicians feel very confident that there is significant unmet need remaining in the space and that there would absolutely be an opportunity for durova assertive and cruzotinib to play in a second line and beyond setting got it and based on your you know physician feedback how important is the survival data for the phase three for this to a two negative patients for actually for them to prescribe Darrell what I can say is that there there's no question that overall survival is the gold standard in the space with that with that said there is an expectation and a very clear comfort given the given the PFS data and the response rate data that we have so far that there would be no barrier to initial uptake of derovacertib in a MUM population period, regardless of HLA status. I think to ultimately reach peak shares, we want to see how the overall survival data continues to play out from the optimum O2 study.

Mel Fortea, Analyst — Wells Fargo

Got it. In terms of timing, do you have any, have you provided any guidance on when we might see this data?

Yujiro Hata, CEO

Yeah, the only public guidance on this, Eva, we provided as the interim OS analysis is anticipated approximately in the middle of next year.

Mel Fortea, Analyst — Wells Fargo

Got it. And in terms of, I mean, I know it's a little bit early, but in terms of like, you know, pricing and gross to net and the way, how are you guys thinking about those, you know, the different, you know, pushes and pulls off the launch, particularly for the first like year or so?

Stuart C. Dorman

Sure. Yeah. I don't think we're going to comment on specifically on price or our gross to net strategy at this point. But what we can say is that the significant unmet need in this space, the existing price point that has been set with Tabentafosp, as well as the overall value story that we will have to bring with our data, we feel very confident in having the opportunity to have a meaningful price in this space while providing access to patients and physicians that that do need access to the product got it should we be thinking about this more as a rare disease type of launch or more of like your typical oncology launch i i would say it's it's a blend of both it this is rare oncology uh and when you look at the the fact that there are no approved agents in the hla a2 negative space and only one approved agent in in the systemic therapy in the a2 positive space there is very significant unmet need and i think payers have a an understanding of that as well as the fact that look this is a very small patient population so as you think about budget impact to any payer this doesn't really hit their radar screen.

Mel Fortea, Analyst — Wells Fargo

Got it that makes sense maybe just talking a little bit more about the A2 positive patient population we're going to get the phase two or phase two readout right in a few weeks really what should we be expecting here to learn that we haven't already?

Yujiro Hata, CEO

Yeah so this will be the largest data set we're providing that's exclusively HLA-A2 positive. There will be roughly 100 patients with the data, slightly less than that with total valuable patients. We'll have a complete efficacy data set, including response rate, PFS, as well as median overall survival data. That data will be broken out based on treatment-naive frontline patients, as well as all patients combined. We'll also provide a full safety data set that we have. So I think we'll hopefully answer additional questions here. I would say probably the most in focus, although it'll be a subset of the patients, which is, you know, what is the survival we're seeing, at least in that subset frontline patients in A2 positive. So I think just another data point for people to look at. This is largely the data set that we've provided to the FDA as part of the RTOR process, where we've been having this back and forth discussion on all comers or A2 negative. And so, you know, so far as Stu mentioned, you know, the discussions have been going well, but it's a good portion based on this data that will get shared shortly.

Mel Fortea, Analyst — Wells Fargo

Got it. And can you remind us of the split between like first line and second line patients that we should expect? And also kind of like what's the bar for this different patient populations in your view?

Yujiro Hata, CEO

In terms of the split, as it relates to, sorry, you're talking about the ESMO data. Yeah, so it's about 80-20. frontline versus after frontline. So that's the split there. In terms of what you should expect, we know the data as it relates to things like OS, there is quite a drop off from frontline. Typically has been reported about 12 to 13 months in the frontline setting. That number in the second line setting goes down to eight months of OS.

Mel Fortea, Analyst — Wells Fargo

So I think those are your reference benchmarks. benchmarks we do believe including in our randomized phase three study currently we do anticipate a less number in that 12 to 13 month range which is consistent as as we've noted before got it can you just just quick question when you mentioned 80 20 is 80 80 80 percent and later later okay 80 percent yeah later line 20 percent first line okay that makes sense and in terms of you know market size for the MUM patients how are you thinking about peak potential have you shared any numbers there yes we haven't shared specific numbers of what we we believe that we

Stuart C. Dorman

can penetrate but given given the feedback that we have had from physicians that would indicate it's really not a question of if patients are going to to receive our regimen but really a question of when, we feel very confident in achieving very significant share and penetration into this space. With that said, we believe there are, you know, roughly 1,500 patients a year, incident MUM patients in the US. That number is obviously quite a bit larger when you think from a global perspective and that really is representative of our MUM opportunity.

Mel Fortea, Analyst — Wells Fargo

This doesn't get into the the opportunities that we see in the neoadjuvant and adjuvant settings which are obviously quite a bit bigger got it and in terms of x us when should we be expecting you know submissions regulatory submissions and launches yeah so that would be staggered and that would be that that activity would cascade uh post the os uh readout got it okay so you need survival benefit. Correct. Yeah. Got it. Okay. Makes sense. Maybe just, you know, remaining within the ESMO topic, we're going to get some Optimum 09 data. What should we be expecting there? How should we be thinking about that readout? It's always been a little bit more difficult to assess, you know, efficacy in that patient population.

Yujiro Hata, CEO

Yeah. So for the neoadjuvant, we will have just more data, more follow-up on enucleation, eye preservation rate. On the plaque therapy side, I would say similar to before, would be on predicted vision, visual outcomes versus actual visual outcomes. It's still early for that. And my understanding is that we will also likely have some early data in terms of follow-up as relates to EFS or relapse.

Mel Fortea, Analyst — Wells Fargo

Got it. And in terms of metastasis risk, Is this something that we're going to get some insights into and how critical is this for, you know, the doctors that you're engaging with?

Yujiro Hata, CEO

Yeah, look, I think at the end, it is an important question about, you know, how is the neoadjuvant intervention impacting relapse? But just as a reminder, right, the endpoint that we had or we have agreement on with the FDA is a no detriment threshold, which we think is a low bar. and that data is getting collected both in the single arm setting which you could imagine you can also try to compare that ultimately to some world data and we're actually going through that process and then independently of course we're doing a randomized base three but yes we do we do think that's an important endpoint and will be in a consideration got it maybe maybe just moving on to optimum 10 what what triggered the reassessment and kind of like how are you thinking about this strategy from here on? Yeah, so on the optimum 10, so this is our new adjuvant phase three study for the listeners here, and there we've had delays in enrollment, and we believe that's been largely driven by a stricter eligibility criteria that's essentially caused more screen failure rates. And so these are eligibility criteria such as plaque size that we wanted to keep it limited to. And so that has delayed our enrollment. And Ava, as you know, in parallel, as we've been doing market research on sort of the feasibility of potential compendia NCN guideline strategy, I would say some of the feedback we've heard there has been more positive than we had initially anticipated. So I think that's the second component. And then finally, third, is that our phase three adjuvant study is now launching and moving forward. In those patient populations, there is some overlap and potentially even competition for enrollment in those two studies. So that's what we have to sort of evaluate in its totality. On the positive side, if we are successful in an NCN strategy, that would at least have some possible scenario of coming online sooner than any randomized V3 study that's ongoing.

Mel Fortea, Analyst — Wells Fargo

Got it. So how would that scenario, what would it mean in terms of timing and also in terms of like opportunity, depending on whether you pursue a guideline strategy versus an FDA approval strategy?

Yujiro Hata, CEO

Yes. So we are evaluating that now. We haven't specifically said when that ultimately decision will be made, but, you know, I would say we're closely evaluating it. And I would hope we would be in a position to make that decision in the next quarter or so. And I think that that's our concern plan right now. In terms of NCN strategy and feedback, we won't know that until we have approval in the metastatic setting. And then we would initiate that process.

Mel Fortea, Analyst — Wells Fargo

Got it. Is there a potential FDA approval on Optimum 09 or would it be purely NCN strategy?

Yujiro Hata, CEO

Yeah, so that's a single arm data set. So I think that would require us going back to the FDA and having more conversations on how that data set could be utilized. But I think the most likely outcome of that conversation is that we would likely still need to enroll more patients to build a bigger data set. So that's sort of another possible scenario that could be evaluated as well.

Mel Fortea, Analyst — Wells Fargo

Got it. So maybe a question for Josh. Just, you know, if you were to stop the study, how do you invest, you know, the money then? Like, do you have any specific plans? How are you thinking about reinvesting?

Joshua Bleharski, CFO

Yeah, I mean, it sort of depends on the plans, when we exactly make the decision, the number of sites and patients that we already have enrolled. We would have to continue to monitor and follow those patients. But in a lot of scenarios, I mean, it's a pretty significant amount of capital on the order of $100 million that we would then be able to redeploy into some of the earlier pipeline programs. You talk about DLL3, you know, obviously we have a lot going on in our MTAP portfolio, both with our own PRMT5, MAT2A combination, but also in collaboration with Roche, you know, with the two collaborations that we've announced recently. So, you know, I think there's opportunities for us to invest that capital there and really try and accelerate those efforts.

Mel Fortea, Analyst — Wells Fargo

Got it. So maybe this is a perfect segue for the rest of the portfolio, but maybe within the PRMT5, you've provided some qualitative insights on how the study is going. Maybe can you remind us of where you're at there, and when should we expect more data?

Yujiro Hata, CEO

Yeah, so ID892, our MTA-cooperative pure MTA-5 inhibitor, has been in dose escalation. We've cleared multiple dose cohorts. We recently announced that we've initiated the expansion phase, and that was based on a target objective coverage of target EC-90 over 24 hours. And Ava, as you know here, based on the mechanism of action, which is around SDMA suppression, we believe that's historically been a very reliable marker in terms of where we're we're sufficiently hitting that target for 24 hours. So we felt very good about that. That expansion has been going well. I think we can't say at this point, at that initial dose, we've already seen response level activity. So we know that we're sufficiently hitting the target in patients. We've now dose escalated beyond that. And that next cohort is also going well. So we may very well be able to have a second expansion that we'll evaluate. and then we'll see as we continue to dose escalate and define MTD. So we're well positioned on that. In the interim, our PRMT5-MAT2A combination is also advancing. I would say here our primary focus is on MTAP dilution of lung cancer. We continue to have a significant focus on that, as you know, Eva. And then more recently, in the last several months, we announced two collaborations with Roche or Roche slash Genentech with their, both are PanRAS inhibitor, which will be running. And then second, more recently, the KRAS G12D inhibitor, which then Roche will be running. And both of those combinations focus will be in pancreatic cancer. For PanRAS, our hope is that we'll be able to dose our first patient here relatively soon. So Roche has been a great partner with us, very collaborative. It appears at least thus far to date, our clinical strategy seems very, very aligned. So I would hope this is obviously forward-looking, but once we generate that clinical proof of concept, I mean, ultimately, I think where this would hopefully end up is that you would try to then pursue ideally a frontline type trial and PDAC in those subset populations.

Mel Fortea, Analyst — Wells Fargo

Right. Makes sense.

Yujiro Hata, CEO

And in terms of, I mean, it's still early days in a very exciting, you know space but how are you thinking about potential for differentiation yeah so the premise for bringing these two companies together and the molecules together at this phase is a view that we have a potential best in class PRMT5 inhibitor and that's based on three specific parameters so one is highly selective MTA cooperativity versus SAM cooperativity second is around a clean drug drug interaction profile. And then third, our view that brain penetrance is more of a liability than a benefit. And that's based on the specific PRM2-5 biology related to RNA splicing. And as we know, if pancreatic cancer is a priority, we know brain penetration is not going to give you value in the pancreatic cancer setting. So that's on our side. And what we can tell you is before that second collaboration was signed. Roche did do their diligence and saw our most current data to make that evaluation. On the PanRAS KIRAS G12D side in terms of differentiation, they have their perspective on why they believe they have at least an opportunity for a potential best-in-class, both PanRAS and KIRAS G12D. We did see their data to make our own evaluation. We'll let them speak to that ultimately at the end when they hopefully publicly present that data, but we believe their thesis is there. We saw the clinical data. So now you bring these two potential best-in-class assets together with what we think so far is a very aligned vision for what that clinical strategy should look like. And if you can essentially capitulate the type of data that we already saw in terms of the clinical proof of concept when you combine something in MTAP with RAS, where essentially you're hitting the key oncogene and potentially one of the key tumor suppressor loss gene pieces of biology, you can deliver, in this case, a very promising result. If you could do that without the drug-drug interaction potential liabilities, we think there's a clear path of differentiation. So the premise is pretty clear.

Mel Fortea, Analyst — Wells Fargo

Got it. Are there any overlapping toxicities or what's the rationale for combining with a PAN-RAS versus like a G12D? Are there any specific benefits to specific tumor types?

Yujiro Hata, CEO

Yeah, so with pan-RAS, right, I think the plus there is you're going to go after the largest pool of patients in pancreatic cancer. So if you look at the overlap of all the RAS mutations with MTAP, we believe that's about 40% of the population. If you narrow that to G12D and MTAP, we think it's approximately 15%. So still a meaningful population, but a smaller subset. I think where the compare and contrast will be with G12D, at least so far we don't believe you're going to have necessarily that potential skin rash liability. So could that ultimately translate to better dose intensity? And could you then therefore deliver better responses, greater durability, and not have that potential AE concern? So we think there's both parallel paths. Obviously, with PanRAS, if you could deliver an exciting result, we don't anticipate to see overlapping AEs. So, you know, I don't think there's an obvious concern on combining these two mechanisms together at this time.

Mel Fortea, Analyst — Wells Fargo

Got it. And in terms of timing for an update for investors, how should we be thinking? Is that going to be like an R&D day kind of thing? Or how are you thinking about that?

Yujiro Hata, CEO

Yeah, so at R&D Day, I would say the primary thrust of our focus is around our clinical strategy and a lot of the pre-clinical data we have internally around these various combinations, whether it's PRMT5, RAS, CAT67, CDKN2A, which will be hopefully our third molecule in the clinic first half of next year. That's very relevant to the pancreatic space. And really outlining what our broader vision here and the underlying data, in particular preclinical data, to support our hypothesis. We'll also have Dr. Frank McCormick from UCSF, obviously a world leader in RAS, speak on our behalf as well. So we do think it will be an important R&D day. And really big level sort of perspective and objective is to establish our continued leadership in MTAP CDK2A. And now as this next chapter is unfolding at this intersection with KRAS, in particular, and pancreatic cancer. In terms of clinical data, especially for RAS combinations, I think that will more likely be next year. We would need to obviously be in step with our partner Roche on this to make sure we're doing this in coordination with them. And perhaps also the MATS-Wade PRMT5. I think ultimately there's, you know, hopeful disclosures in the PRMT5 monotherapy data. I do think for monotherapy, we would ideally be able to advance something in registrational studies as a monotherapy agent as well. So we haven't specified what indications are of interest there, but I would say that is also a key objective beyond these combinations.

Mel Fortea, Analyst — Wells Fargo

Got it. Very helpful. Maybe, you know, last but not least, the DLL-3, we've seen very exciting data so far. It seems like we're going to get a lot more data this year from both the ex-U.S. study and the U.S. study. So maybe, you know, what should we be expecting here? How should we be thinking about durability and, you know, how should data translate from, you know, ex-U.S. to U.S. patients?

Yujiro Hata, CEO

Yeah, so far, I think big picture, we can say there has been consistency, at least in the preliminary data we've seen in China versus ex-U.S. So I think that's good. Hungary, our partner, has defined their move forward dose as 2.4 mix per kg IV Q3W. We've publicly noted the two doses we shared with the FDA to move forward with is 2.4 and 3.5. We did reach alignment with them on that. So that's good as well. And as you know, we recently confirmed our phase three design through a successful type C meeting in the post-indulterous setting. And I think that timing was fitting. You probably saw the frontline announcement today from Amgen on Indeltra hitting their endpoint in the frontline setting. So it does appear Indeltra is not going to move into the frontline, which enables this study we put in place, hopefully, by default, moving into the second line. In terms of what data to expect, here we'll have a sizable data update at ESMO. We'll be about 100 patients. We'll have a full efficacy data set, including response rate, PFS, 12-month landmark OS data. We'll also be presenting data in our region as well before the end of the year. And really here, pick picture goal is to establish our view that we have a potential best-in-class molecule in DLL3. So a lot of data to come. Both we and Hungary are planning to start our phase three studies by the end of the year.

Mel Fortea, Analyst — Wells Fargo

Got it. You actually pressed release not that long ago, the interactions with the FDA and kind of like the type C meeting. Maybe can you share a little bit, you know, about those interactions and how you're thinking about development from here for the DLL3 franchise?

Yujiro Hata, CEO

Yep. So as, you know, as we know that in terms of our phase three registrational study in the later line setting for our effort to get monotherapy approval, you know, we are a few quarters behind our closest peer. But we believe the study that we're running is fundamentally different. And that's based on some of the discussions we had with the FDA and sort of the perspective that doing a pre- and post-Indeltra population in the study, at least for U.S. approval, would be viewed as a heterogeneous population. So we believe the ability to do a more homogenous population post-Indeltra becomes a cleaner data set. And we think a higher probability success readout, at least as it relates to the actual pairing of the study for U.S. approval. And now, again, with this data coming out from Indelitra on the front line, we think, you know, continues to further validate our clinical trial design that we believe should set us up very well for hopefully our first approval for this program.

Mel Fortea, Analyst — Wells Fargo

Got it. In terms of timing, I mean, how long do these studies tend to take and how are you thinking about the market opportunity in this post-Indelitra population?

Yujiro Hata, CEO

Yeah, so I'll take how long this is going to take. So we have not gotten visibility into how fast we can enroll the trial. But let's just say, based on our projections, we think we can enroll the study fairly rapidly. Also, because of the nature of the endpoints. So here, I should have mentioned, the primary endpoint for accelerated approval is response rate. For full approval is overall survival. Well, for the accelerated approval portion, as you know, we should get that readout quite rapidly. So I think perhaps this is a more near-term, potentially even commercial opportunity than people perhaps appreciate. But we'll start giving more visibility into that once the phase three study is up and running and enrollment has commenced. Now, maybe just on the market side, I don't know, Josh, if you want to make any comments or do on the small-cell NEC side.

Stuart C. Dorman

JOSH SHARFSTEIN- Well, I would say beyond the fast-to-market aspect of things, when you look at a combination of small cell and neuroendocrine, both in a refractory setting, that is a meaningful business opportunity. Obviously, small cell is quite a bit more crowded. So we believe that neuroendocrine, despite having a slightly smaller patient population, may actually be a very meaningful opportunity in and of itself.

Joshua Bleharski, CFO

We believe that, I mean, this asset in general is a blockbuster opportunity. got it very helpful maybe you know with the last minute or so just you know next 12 months for idea main catalyst where do you think you know we should focus as investors and analysts yeah josh yeah i mean i think we covered the three big ones right i think it's all the progress on and on the nda filing and hopefully an approval next year and the launch uh progress and decisions on what we're doing in the neoadjuvant space, the adjuvant trial getting off the ground, starting to enroll. And then in the pipeline, I think you should be focusing on the DLL-3 asset, hopefully getting a registrational study started there by the end of this year. And then in 2027, a lot more data from the MTAP combinations, both with 397, our MAT2A inhibitor, as well as with Roche, hopefully. So with that data, more detail to follow on where we'll take it from there and what our clinical development plan looks like. So lots to look forward to.

Mel Fortea, Analyst — Wells Fargo

Sounds great. Yeah, lots to look forward to. We're out of time. So thank you so much for joining us today.

Yujiro Hata, CEO

Thank you so much for the opportunity.