IDEAYA Biosciences, Inc. ($IDYA)

Hello everybody. Welcome back to the Bank of America Healthcare Conference. I'm Tazeen Ahmad. I'm one of the senior biotech analysts here at the bank. Our next presenting company is IDEAYA Biosciences. And sitting up here on stage with me are two members from the management team. We've got Yujiro Hata, who is Chief Executive Officer; and Josh Bleharski, who is, of course, CFO. Gentlemen, thank you for making the trip to see us today.

Tazeen, thank you.

Thanks so much for hosting us. Tazeen, really pleasure to have us. And Josh and I are looking forward to the discussion today. Thank you.

Okay. So really quickly, for those who may not be as familiar with the company, can you just give us an overview of IDEAYA sort of the platform, where you are in terms of developing some key data catalysts and we can go from there.

Sure. So IDEAYA Biosciences, we're a leading precision medicine oncology company. Our lead program is darovasertib. We just recently had top line results in first-line metastatic uveal melanoma. We also recently just received Fast Track designation. So we'll be submitting our first pre-submission for the NDA next week. And so that's all going as planned. We also have two additional Phase III registrational studies that are ongoing beyond metastatic uveal melanoma, including in a neoadjuvant setting as well as in the adjuvant setting outside of the U.S. We have a global partner in Servier, which we're very excited about as well. Beyond that, Tazeen as you know, we have a very deep pipeline precision medicine oncology. We're very excited about what's coming ahead as well in our next assets. And here, I will probably next focus on DLL3, our Topo-ADC IDE849. We are targeting to start a registrational study by the end of the year. Our partner Hengrui in China as well is planning to start registrational study by the end of the year. Here, the key indications are in small cell lung cancer as well as neuroendocrine carcinoma. We have 2 clinical data updates we're guiding towards as well in the second half. Beyond that, we have a deep clinical pipeline and MTAP deletion, both what we believe is a first-in-class PRMT5 inhibitor as well as a potential first-in-class MAT2A inhibitor. Here, we have a significant focus on MTAP deletion PDAC as well as in non-small cell lung cancer. We are also evaluating opportunities to enter into the RAS, KRAS space in terms of combinations, so more to come on that front, which we're quite excited about. Beyond that, I would say probably the next program I would mention is a Phase I KAT6 dual inhibitor. There are only 2 clinical assets here. It's us and Pfizer. We have key focus here in breast cancer, prostate cancer, CRC and so a lot of excitement and enthusiasm. So as you can see, a very deep pipeline going after very large solid tumor indications.

Okay. Yes, you've got a lot going on. Let's try to do some of these in order of near-term events. So for the top line that you reported for the OptimUM-2 study, can you give us a little bit of detail on that? And what the next steps are in that program?

Yes. So here, for folks that may be less familiar with this study. So this is a combined accelerated approval and full approval study that we designed. The primary endpoint for accelerated approval is median progression-free survival and for full approval is OS. What we reported was a PFS of 6.9 months in the treatment arm and 3.1 months in the control arm, which led to a hazard ratio of 0.42 with a p value of less than 0.0001. So great result really puts us on track for that NDA submission. So that's really been the focus. You may also know that last fall, we also reported OS data. This was single-arm OS data just over 21 months. We think a historical OS here is going to come in roughly in that 12- to 13-month range. So we feel also good about OS. We did note as part of the top line results, a preliminary trend, a favorable OS trend as well. We will have an ASCO late-breaker oral presentation on Monday, June 1. So that's exciting. Here, we'll just provide a more fulsome update. So in addition to the PFS Kaplan-Meier curve, which we showed, we'll have a full CT scan waterfall, both treatment control arm, both by central review as well as investigator scoring, including just a full safety data set as well.

Okay. And can you just talk to us about what the competitive landscape looks like here?

Sure. Josh, do you want to take that?

[indiscernible] There really isn't any improvement. Current standard of care is checkpoint inhibitors and chemotherapy. And that was what we had in our control arm in the study that we just reported out. On the A2 side, there is an approved agent. So we'll also explore the efficacy of the [indiscernible] combo in that setting as well nature of the authorities with the FDA on that as well.

And what do you think is the total addressable market opportunity for your product once approved?

Yes. Look, we think this could be a very significant opportunity, obviously, within the A2 negative setting which is where we're primarily focused with A2. We think there's roughly what -- 1,500 patients in the U.S., the majority of which are A2 negative. Again, it kind of comes down to where we land on pricing and duration. Those would be 2 of the major drivers that dictate kind of market opportunity. But we think it's quite significant and you start to factor in a potential uptake in the A2 setting as well as in the primary setting in neoadjuvant and adjuvant setting, those opportunities start to add up.

Okay. For the A2 negative population, how easily are they found?

Yes. I mean so a lot of those patients are treated in concentrated centers [indiscernible] Fortunately, through the work we know where patients are, but there is a long tail of patients that are treated in the community setting. So we're working hard to identify them so that we can reach as many as quickly and efficiently as possible if and when we get approved. And that will rely on sort of a grassroots kind of feet on the ground strategy as well as data and analytical strategy that will complement our sales effort.

Okay. And so given that this is an ultra-rare indication, what's the range of pricing that we could use as comps. Obviously, you're not going to announce price to us today. But as people try to think about range, what do you think would be good comps here?

Yes. I mean that's work that's underway right now. As you said, I don't think we're ready to comment much specifically around pricing. Look, I think what we want to do is look at the totality of our data and price the drug appropriately based on the benefit that we deliver. There's obviously an approved analog out there that I think many people point to. That's not a bad place to start. Again, I think it will have to -- we'll have to see how our data matures, both on the PFS and then overall survival side. But we feel pretty good about the profile and the benefit that we've delivered.

Okay. And so in terms of investments in setting up for a commercial organization, how big of a footprint do you think you'll need for this indication?

Yes, that's a great question. So we think it's a pretty modestly sized sales force based on some of our peers in the industry and the model that they have employed, we think this would be a pretty conservatively sized sales force, and we will be able to effectively target this opportunity in the U.S. And that work is all underway right now.

Okay. And how long do you think it will take over time to expand into those larger populations that you just mentioned?

Yes. So I mean, I think, again, we'll -- we have those registrational studies up and running in the neoadjuvant setting. In the adjuvant setting, we will start that trial imminently with our partner, Servier. That data is going to take a little bit longer to develop and mature. So those are likely several years out on the metastatic launch. However, we will look at ways to accelerate getting into those patients, particularly in the neoadjuvant setting using some of the data we've already generated in the 09 study. So we're going to be looking to publish that data and look for ways to maybe accelerate that potentially through a compendia guideline strategy.

Okay. Go ahead.

And I think just on the other -- on the adjuvant side, we'll be launching that study here shortly, 450 patients. We think enrollment should go quite rapidly for that just based on the demand. There's nothing approved in the adjuvant setting. We will be HLA agnostic. And then also because we'll be focusing on the high to high medium metastatic risk population, also that RFS readout, hopefully will be expedited based on that as well.

Okay. In the few minutes that we have left, maybe we can talk a little bit about some of the pipeline programs, Yujiro, that you mentioned. Maybe let's talk about 849. You mentioned DLL3 positive tumors. How should we be thinking about the opportunities there?

Yes. Look, it's a very sizable patient population. So in terms of the indications of focus for DLL3, I would say first is small cell lung cancer, right? You're talking about an annual incidence globally that's at least 100,000 patients or more. Here, DLL3 is broadly expressed in small cell lung cancer. So we don't anticipate we're going to need to patient select. In neuroendocrine carcinoma as well, also a very sizable population. U.S. alone, you're talking 20,000, 30,000 patients a year. So I think a lot of significant interest there, very high unmet need, as you know, in the neuroendocrine carcinoma space, response rates are even in the teens range, typically, when utilizing chemotherapy. The last indication, we do have quite a bit of interest in is also in melanoma. We know DLL3 upregulation has been high there as well. We have not evaluated patients there yet, but that's also another area that we'll be focused on.

Okay. So how do you prioritize which indications you want to focus on first?

So I would say that right now, our primary focus is in small cell lung cancer and in neuroendocrine carcinoma. I would say the first registrational study we want to launch will be a monotherapy registrational study. We're evaluating both later-line small cell as well as neuroendocrine carcinoma. We're also considering sort of a basket type approach as well to see if we can pool all those populations together. In terms of frontline strategy there, I think that's going to be mainly focused on small cell lung cancer. And for that, you will likely need to do that in combinations, looking at assets like PD-L1. You may know we've recently put a relationship in place with AstraZeneca. We're also doing a proprietary combination with our PARG inhibitor. That could also potentially enable a chemo-free regimen as well. So I think a lot of opportunity there. That will likely be more focused on for next year.

Okay. So in terms of data catalysts for this program, are you going to have -- it seems like you'll have a few next year.

So on DLL3?

Yes.

Yes. So actually, by the end of this year, we'll have 2. One will be our partner, Hengrui's update from their Phase I China study. So that will be over 100 patients. It will be a pretty robust data set both small cell and neuroendocrine carcinomas. And I'd expect that to be a pretty fulsome update from what they showed last year at the World Lung Conference, including potentially an OS cut, so landmark OS data for the first time. So that's exciting. And then in parallel, we'll look to provide an update on our Phase I, IDEAYA sponsored trial with DLL3. And that will be obviously in small cell and neuroendocrine carcinomas. We'd be hoping to show response rates in different tumor types and just probably get a sense of initial activity. It will be probably too early for PFS data, but hopefully, we'll get to see safety and some preliminary signs of activity.

And how many patients' worth of data would that be?

Hopefully, it's 30 to 40. That's what we're hoping for.

Okay. So it's basically a basket study.

Correct. Yes.

Okay. And sorry, Yujiro, you were going to say something.

And Hengrui's data is going to be over 100 patients. So in aggregate, it's going to be a large data set. And I think the other piece we can mention, even based on the early data, the data has been very, very consistent in China and outside of China.

Yes. How derisking is that Hengrui's data going to be for your own study?

We think it's going to be very derisking. And look, we think a lot of the key questions around the DLL3 Topo-ADC space is around durability and we did share some preliminary PFS data at the World Cancer Lung Conference last year, but there wasn't a lot of follow-up. Now there's a year more follow-up, a much larger denominator. We're seeing consistency with the China and non-China data. And now for the first time, we'll also have some landmark OS data. So we're going to answer a lot of questions. In our view, based on what we've seen is we believe we've got a potential best-in-class asset here. So definitely want to pay attention to it.

Okay. And are there other companies looking at the same mechanism?

So in terms of DLL3 Topo-ADC, there's us, there's another biotech company, Roche is also in Phase I with their asset. On the T cell engager side, there's Amgen and Delta. There are several other pharmaceutical companies. So a lot of activity here. I think our view is we have the opportunity to have a best-in-class DLL3 Topo-ADC, but also potentially have a backbone type therapy broad across all of DLL3 and small cell lung cancer.

Okay. And then last question is how do you think about the toxicity profile?

So, so far, it's been very, very solid. I mean I think here, it's been mainly around myelosuppression, I would say consistent with what you've seen with Topo-ADC. I think the advantage we may have with the DLL3 antigen versus, let's say, B7-H3 is I do think we are seeing less ILD in particular, and which we think makes it potentially the preferred antigen target for small cell lung cancer and that could become important as you start thinking about other combinations, whether that's with PD-L1 or with T-cell engagers.

Okay. Perfect. With that, our 15 minutes is up, but thank you guys for making the trip over here. And we appreciate you taking the time, and thanks, everybody, for listening.

Great. Thanks so much.

Thanks, Tazeen.