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

Hello everyone. We're on day 2 in the afternoon session of Citi's Biopharma Back to School Summit here in New York City. I'm Yigal Nochomovitz, senior biotech analyst at Citi. We have our next company, which is IDEAYA, great platform, great pipeline and been covering them for a number of years, and it's really been a great journey and a lot more to come. So I'm pleased to introduce Yujiro Hata, who's the CEO, founder of the company. And then also we have Joshua Bleharski, who's the CFO; and Daniel Simon, the Chief Business Officer. So welcome all of you. So Yujiro, a lot is going to happen in the next several months with regard to readouts. But before we get to all that, for those a little bit less familiar, just kind of identify the key programs that you're focused on and the key opportunities in the different market segments that you guys are pursuing.

Yes. First, thank you, Yigal, for the introduction, and thank you to Citi for the invitation to participate again this year. So IDEAYA Biosciences, we're a leading precision medicine oncology company. I think where we're unique is we have a very late-stage asset in darovasertib. The lead indication there is metastatic uveal melanoma. We are in the process of submitting the NDA under our RTOR -- the first 3 modules have been submitted, and we have the final module to submit here very soon. Most of our analysts are projecting a first half of next year commercial launch. So again, a very late-stage asset. In addition to that, we have two additional indications we're pursuing, Phase III studies, both in the neoadjuvant setting as well as in the adjuvant setting. So a very broad set of clinical activities to also expand the opportunity into the earlier line settings. In addition, we have an IDE849, a DLL3 Topo-ADC. We announced recently that we had a successful Type C with the FDA to advance into Phase III registrational study for monotherapy approval in extensive stage small cell lung cancer. Here, the primary endpoint for accelerated approval will be overall response rate for full approval, median overall survival. Beyond that, Yigal, as you know, we have a very broad set of assets in the area of MTAP deletion and CDKN2A. We have announced two recent collaborations with Roche with their -- both our pan-RAS inhibitor and their KRAS G12D inhibitor, and that will be exclusively focused on the area of pancreatic cancer. So for those that may or may not be familiar, the overlap between all of the KRAS mutations with MTAP deletion, we believe, is about 40% of that population. So a very significant population, and we announced those relationships in the last few months. We have more in the pipeline, but I think if we cover that, we would have done very well.

Okay. All right. All right. So let's go to the first thing. So you said you did 3 out of the 4 modules and potential launch in the first half of next year. So what's left to do with this -- what is the last module? What's left to do? And seems like you would need a PDUFA date assigned pretty soon in order to bank to do the 1 half '27 launch. So -- but you have the RTOR and you have the rolling submission, so you have some leverage there.

Yes, that's correct. We have Fast Track designation. So we'll have expedited review through that. And as you noted, our RTOR in terms of the rolling review. So we have -- there's no specific gating item at this point. It's largely QC that's been ongoing related to summaries of both clinical safety and clinical efficacy, as well as the clinical overview section. So that's the good news. We're getting very close. There's no specific gating item that's right now in front of us. It's mainly QC process that's ongoing.

Okay. But the stated guidance of submission is this year.

Correct.

Okay. All right. Now related to that, obviously, there's an important data set in the HLA-A2 positive group. So can you speak to that? I believe you're going to be showing some of that data relatively soon, and there's a potential for getting that sort of into the marketplace through the compendia potentially as a strategy. So just -- can you kind of elaborate on that?

Yes. So we have two fairly sizable updates that's going to be upcoming at ESMO. So first, Yigal, as you noted, we have about 100 patients with the data in metastatic uveal melanoma and HLA-A2 positive. So this is where KIMMTRAK is approved. We will share response rate, PFS, and median overall survival data. We will break that out into first line and then all patients, which is consistent with how we've presented in the past. Our sense is that the biggest investor focus is even though it's going to be in the subset of patients, which is, what does the frontline OS data look like, as you can appreciate, that will be the second time we'll share OS data in the first-line setting. And just as a reminder, at SMR last fall, we did share OS, which was just over 21 months. Here, we think the control arm will likely be in that 12- to 13-month range. For neoadjuvant, we'll also have about 100 patient data set that's presented at ESMO. This will include both the enucleation and plaque therapy patients, consistent with prior disclosures related to preservation rate predicted visual acuity. We -- the actual visual acuity will be still too early. And my understanding is we'll have some commentary related to relapse. So I think that should be helpful as well. And we will utilize this data with a strategy towards a NCCN guideline usage in the neoadjuvant setting with the anticipation of commercial launch in the metastatic setting.

Okay. And then as far as the -- so for the HLA positives, that would be also with this compendia strategy or that could potentially work its way into the label. Do you fold that into the rolling submission? Is that a plan of action or you may not need to say need to do that?

Sure, Josh?

Okay. Yes. So we've had a lot of good dialogue with the FDA and through the RTOR designation, have had the chance to share some of the data that we'll be having at ESMO, and they've seen that data now. And I think -- our sense from the interaction is that they're actually -- they're encouraging us to try and seek a broader label. I think they understand the unmet need there. I think the data sets are remarkably consistent. And I think our intention is to have that dialogue with them and see if we can get an HLA-agnostic label and approval. So that's a little bit of an evolution from where we started, but I think it's really a testament to the drug benefit and the unmet need, and I think the FDA has been very aligned with us and trying to move this forward as quickly as possible so we can get.

So that sounds like a relatively new development.

Yes, yes. I mean it is.

I haven't heard it quite like that before. So that sounds good.

Yes. And maybe part of that, Yigal, is we did have the pre-NDA meeting, and that was largely the focus of the recent meeting topics. And that's why now we had that meeting, we got that feedback. And so you're seeing our communication evolve from that feedback.

Which as recent data?

Correct. Yes, it was recent.

Okay. And then -- so then for neoadjuvant, as you pointed out, compendia listing, but does this mean you may take another thing as far as what to do with OptimUM-10.

Yes. I think in any scenario, we'll submit for compendia for guideline inclusion based on the data we've generated already. What we're thinking about now is just whether that's enough and whether in light of some of the enrollment delays we've had with the 10 study that we've talked about, would it be better for us to sort of pivot rely exclusively on the compendia strategy for the neoadjuvant subset and reallocate some of the funds we'd set aside to run that registrational study towards other high-priority programs in the pipeline. And so -- we have not yet made a determination there, but we are actively kind of thinking through the options and trying to do the analysis to support the decision, which we'd expect would be before the end of the year.

Okay. And what -- so the gating factors there are just showing the data at ESMO getting more KOL buy-in on that data, I gather?

Yes. I mean, so we've had -- I mean the combination of our own market research and some of the work we've done with KOLs and people who have sat on the NCCN panel our take of that is that there's a reasonable likelihood that we would get included in the compendia. So if that were the case, it's a question of what would that mean commercially? So we're doing some of those -- some of that work to try and understand that a little bit better. But suffice to say, we think -- that may be a viable route in light of some of the other challenges I highlighted and could allow us to invest in other things in the pipeline, we'll have to do.

All right. So related to all that, can we talk a bit about just the commercial setup, the build and you're getting very, very close, obviously, to a launch, which would be great, the first launch. So where are you with the commercial build? Who have you hired all the market intelligence work to set yourself up to launch?

Yes. So I think Josh and I could tag team on this. I mean I think it's a fairly straightforward build-out. We're just focused on the U.S. launch. As you know, Servier is handling ex U.S. for us. The sales force is, we believe, approximately 25 individuals, very similar to what Immunocore has done with KIMMTRAK. The base commercial leadership team has been hired. So that's all set. Everything on the supply chain side is also very much on track. So we do have an early scenario commercial readiness and preparation that we'll be prepared for, but everything is all systems go right now.

And anything early that you can communicate in terms of how you see the early launch progressing relative to the obvious competitor, KIMMTRAK?

Do you mean specifically in the A2 population -- sorry, the positives?

Yes.

So -- look, we have seen and heard a lot of enthusiasm from the people that we've talked to about the profile of the drug. Obviously, when we were at ESMO presenting this, the discussion after our presentation, noted that this is a big advance for the field where there's a lot of unmet need still. So we feel pretty good about the uptake, particularly in the A2 negatives where there are no approved therapies, but certainly in A2-positives, where there still remains a lot of unmet need. So time will tell, but we continue to believe that the drug delivers a lot of benefit. And for patients where there's quick progression or even in the post KIMMTRAK setting, we think that this is a nice viable alternative should it be approved for those patients, and we'd expect to see reasonably quick uptake.

Okay? So that sounds good. Well, let's move over to talking about DLL3 and -- so first of all, in terms of the Type C meeting and the alignment on the Phase III design, is that sort of square with your goals for what you wanted to get agreement on there in terms of the end points you mentioned obviously, ORR and OS?

Yes. It was Yigal. I think the biggest question for us when we had the Type C meeting was around how do we think about pre-IMDELLTRA versus post IMDELLTRA patients. And that was really the key question for us. And the feedback was very clear that if we did do a pre and post IMDELLTRA study that it would be viewed as more of a heterogeneous population. And so at least for the U.S. approval portion. So we just felt that it was a cleaner study to do it as purely a post IMDELLTRA study population. In addition, we also did it this way with the mindset that you always want to do a study that's going to be somewhat relevant as you -- at the time of hopefully potential approval. And we did anticipate that IMDELLTRA would hit their endpoint for frontline approval. And as you probably know earlier this week, they announced that they did hit their OS endpoint for frontline maintenance. So that exactly I think further just reinforces the trial design that we're pursuing. I think the main questions we've been getting is, are we seeing responses post IMDELLTRA? Are you -- is there any concern that you might have DLL3 down regulation post IMDELLTRA? And I think there, we can confidently say at least what we know of that that's not a concern. And then second, we are clearly seeing responses in the post IMDELLTRA setting, which gives us confidence in the study design. The last two parts I'll mention is we are interested in neuroendocrine carcinoma. So we are -- we believe we're clearly seeing monotherapy activity there. So we do have another meeting with the FDA set up in the fall, to get more clarity on what a registrational path will look like there for monotherapy, both accelerated and full approval. Here, it's a lot less crowded an area, a lot less activity with antibody drug conjugates. We don't have really IMDELLTRA here as well. So there's a lot more white space. And then lastly, is around frontline small cell lung cancer. And there, I think we can maybe talk about it more, but we think we have more work to do and thinking through what the right strategy is for frontline.

What are the factors that need to be weighed on the front line that you're weighing?

Yes. So first is the landscape is evolving rapidly, right? So as we just saw IMDELLTRA hit their endpoint in frontline maintenance. They have another randomized DLL3 study that has not read out yet in frontline induction. So those type of things, it would be nice to get some sense of where that's all coming out, just so we know we have the right things in the comparator arm, so that's one. I think second, when you think about what you combine it with, at least our view is PD-L1 is fairly table stakes. I think there has been some questions around plus or minus chemo. Obviously, our antibody drug conjugate. And then, of course, as you know, Yigal, we're quite interested in the PARP combination that we're doing, which is a novel combination. And if that does enhance durability, that would clearly provide us a differentiated path forward than others. So if we did do a PD-L1 plus ADC versus PD-L1 plus chemo and now would possibly indulge in the control arm, that may be a high bar study, right? So I think that's what we want to think through before we just sort of launch into the trial that we have just a better sense of all of these various parameters.

Have the KOLs suggested like even combining 849 with IMDELLTRA? Or has that come up or not really?

Yes, it has. Yes. And that's -- that would be another piece of the story, right? But once you do that, you have to think about a lot of other considerations from costs, logistics. I think there's a lot of things that you would have to think through there. So that's why, I think, as we mentioned, versus sort of rushing into a frontline study just making sure we have clarity on what is the highest POS study. And then in the interim, making sure that we get these monotherapy later line accelerated approval studies off the ground, first in small cell. And then next, we'll evaluate if there's a viable path forward for neuroendocrine carcinoma as we collect more information on this question on the front line because yes, you could consider it.

Because some other companies are combining, as you know, right?

That work has just begun. It doesn't look like it's going to be in the first wave of those front lines just because that dosing just began. But yes, those are the questions. But we know in the past, right, Amgen had done B7-H3 ADC combinations, those were halted, right? So why were they halted? So I think those are the type of questions I think are going to be important to have answers to.