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

And how do you think about the opportunity here for you? And obviously, there are like Tango is also in this space. But how do you think about the opportunity here for you and IDEAYA? And also maybe around your partnership with Amgen going forward?

Our view here is, we believe IDEAYA is extremely well positioned in the field of tabulation relative to our peers. We believe strongly that the way we're going to drive the greatest patient benefit, irrespective of MAT2A, PRMT5 is through a rational combination. That is our perspective based on extensive preclinical analysis that we have done, and we believe we are strategically aligned with Amgen in our view on that as well. I would say bigger picture, I do think this is an extraordinary opportunity for all of the companies in the area. And I think at the [indiscernible] it's going to be about how to ensure in terms of having the highest probability of success in clinical trial that you're in the right tumor setting and you're enabling the most optimal combinations. And at least our view today with our work that we're doing with Amgen, we have quite a head start.

And it really makes a lot of sense from the complementary nature of MAT2 and PRMT5. But now how do you think about the potential monotherapy opportunity?

So I think we've been very consistent on our communication on this topic. Our view is based on all of the data we've seen preclinically in this path, we have MTAP lead that the way we're going to deliver the most maximum benefit of patients will be through a rational combination we've done extensive evaluation here. We've looked at over 100 different unique combinations. And clearly, what comes to the top is the MAT2A, MT-cooperative, PRMT5. And also, when you look at the various resistant mechanisms, compensatory pathways in MTAP deletion, we believe not only to deliver a better response rate or a broader response rate, ultimately, this is going to be the best opportunity to deliver durability as well.

Now maybe you can tell us a little bit more around 161 and the part opportunity, including today's update.

So I think today's update is quite significant, not just for IDEAYA, but we believe for the broader field of synthetic lethality and damage repair. Today's update this morning is the first time anyone's ever presented clinical -- preliminary clinical proof of concept as it relates to efficacy on PAR. And as you know, we're very early in dose escalation. We've only had a handful of scans. We have also only had first scans on patients. And even within that, we noted publicly today is that we've seen multiple patients with tumor shrinkage. We specifically highlighted this BRCA1, BRCA2 endometrial cancer patient. We're at the first scan, we saw a partial response in the target lesion. We saw a complete response in the nontarget lesion. And the CA-125 tumor marker, we saw reduced by almost 90% in 6 weeks. And we know that in ovarian cancer, where that market has been most well studied, a deep and rapid response of that marker has been correlated with ultimately OS. So we think all of those pieces together, at least our key takeaway here is, it does appear we have quite an active molecule as a single agent.

And obviously, dose optimization efforts are ongoing. What are some of the clinical updates that we could potentially expect from the 161 program?

So we did, based on this update today, and now provide you guidance that this half, we are providing -- planning to provide clinical program updates. We did not specify whether that would include a clinical efficacy update, but we wanted to note that it could include clinical efficacy update, but we want to be able to sort of reserve that right. And obviously, if we did provide that update that we did provide investors and analysts that had [indiscernible] that may be coming.

Now are you giving kind of a lot of good progress that you've made in identifying rational combination approaches. Have you thought about potential combination approaches that may be sensible for PARG.

I'm really happy to ask that question. In fact, I would say this has probably been one of the most important strategic priorities for the company. Hopefully, as our investors and analysts have seen, we do have a capability here. We enabled the first MT-cooperative PRMT5, MAT combination with Amgen. And we believe there are similar opportunities for PARG. Here, I would just highlight 2 pieces. First, our combination strategy is focused on getting us outside of the area of HRD. And then second, we believe these market opportunities if successful has the opportunity to be, frankly, really significant commercial market opportunities. So I would say stay tuned, more news to come there. But obviously, first, great to demonstrate early POC as a monotherapy. I think should just give us more combination as we pursue some of these combination strategies.

You have a new update every -- almost every month or every other month. So a lot could cover. Now also, congratulations on the pull data IND clearance. Do you have any color on potential endpoints that will demonstrate signs of efficacy? And also, as you think about the different indications, are there any specific tumors that you plan on targeting?

So we haven't until the protocol publishes on clinical trials, which hopefully should be published in so I can't share that at this point. But maybe taking one step back. Really, the strategic premise of PARG data is to specifically address the issue around PARP resistance. And we know that a large predominance of those patients has what's called BRCA reversions which has been associated with the genetic signature related to micro homology and joining. And we know that PARG data specifically is the Achilles heel of microhomology and joining. So here, I think ultimately Europe, I think the hope is with this combination, we can really enhance the efficacy of PARG with the hope to really hit these more long-term time-to-event endpoints like OS, which as we know, has been somewhat of a challenge in that area as we've seen in the last year.

Now maybe, Paul, could you maybe talk -- obviously, good to have all these updates coming out in kind of like a bolus every couple of months. But as you think about the capital intensity and maybe also talk a little bit about the business model in terms of how -- you have so many programs to prosecute and push through the clinic. How are you thinking about the capital strategy for IDEAYA?

Yes, I think we've been since [Technical Difficulty] early on in the company had an integrated strategy across business and the science to enable multiple programs advancing into the clinic while we continue to invest in research. And as you know, we've been relatively capital efficient since day 1, including even our lead program, darovasertib, the MAT2A program, IDE397 and the PARG program, 161, where you've noted that each of these are wholly owned by the company, and [indiscernible]. But we've still been able to leverage partnerships to help the capital efficiencies with darovasertib. We have a partnership with Pfizer. We're getting drug supply in crizotinib essentially for free throughout the program and now and have that supply lined up for the registrational trial. So that's really important. And while it may not cost too much, it does save us tens of millions of dollars and 37, as is noted, we have a -- what we believe will be the definitive clinical study in the combination with AMG 193. This is a 50-50 cost share with Amgen, even though they're the sponsor of the trial. We do co-own all the data. We co-own an intellectual property rights. We have a joint operating committee with them where it's a very much integrated clinical effort, but we don't have to pay any of their internal costs. It is sharing external costs. So again, it's capital efficient on that program. But, we are hold of this program. We've not partnered at all yet, but we are thinking about combinations. So we don't have too much about those structure could look then you can add in something like Amgen, for example. Beyond that, we're well positioned from a cash perspective. We have $510 million of cash. We've indicated in our operating time that does enable us to fund our operations into 2027 with long cash runway. Importantly that supports darovasertib the registrational clinical effort as well as early potential commercialization activities there. Other program just comes through meaningful data catalysts. So as we continue to provide these updates and generate momentum on some of these earlier programs, I think in the success scenario, we will need to raise more money, but we have a good balance sheet to work from for now.

In terms of some of the key milestones, I think we've kind of talked about most of those earlier, but maybe just to summarize, what are some of the key updates that investors should pay attention to from your perspective in the next 6 to 12 months?

So I think start with darovasertib. We've launched in the registrational trial. The sites are up and running. We're expanding the number of sites. We've talked about the enrollment there. I think we've noted based on the publication of the ESMO titles that there will be an oral presentation at ESMO presented by one of our investigators that's going to talk around CTDNA data from our Phase II clinical trial, and we'll likely correlate that with the already reported clinical efficacy. So I think that's important because CPA is an area where it can help you to identify patients earlier, happy to see responses earlier or potential responses are. So I think it's just a really important update. Beyond the CTA data, that's all we can associate with ESMO because we're limited by the rules. But we have guided towards some other program updates before the end of this year, including an important metric, which is the prevalence with in metastatic uveal melanoma, the prevalence of HLA negative relative to actually positive. And we have our own data set. I don't think that a broad data set has yet been published that is metastatic uveal melanoma specific. So that will be important to one. We said publicly, it's not just the majority, but we think it's the vast majority, but we're going to provide the underpinnings for that. Then we may also share a subset of data from our Phase II trial, showing the breakout of HLA 0201 negative versus HLA-0201 positive in terms of efficacy. So that's around registrational. On the new agent setting, after [indiscernible] got a Phase II myotherapy, that's a company-sponsored initiative. We recently announced the first patient in. We've been guiding that in parallel, we also have an investigator-sponsored trial that has been running in Australia. So we've been guiding before the end of this year to provide an update from that IST clinical efficacy update that's important. And then moving on between -- after that IDE397 and the combination with Amgen. Amgen has guided that they'll present their myotherapy data on AMG-193 in medical setting this year. That will be an important update for the space generally. Obviously, we'll continue to inform our combination efforts. But then I think we just talked about par having potential program updates before the end of the year. And then on kind of our fourth program, the first patient in would be the sort of next expected update on palate just recently noted with GSK that we cleared the IND. So that would be an update that could be coming seen in order organic towards development candidates. So nomination before the end of the year. So a number of important updates coming still before the end of this year.

I think we have about a minute left. Can you talk about your vision for the company? I think you have been able to succeed in improving out the synthetic lethal narrative where others have struggled. But now I think what you're turning into is really a broad oncology precision platform with some of your own, not only chemistry work but also there's -- now that there's a machine learning component as well fast-forward, what's your ambition and vision for IDEAYA?

I think, first and foremost, Rick, I mean, I do think we have a real opportunity to build the next leading precision medicine oncology company. We have a very strong foundation to do that with 5 potential first-in-class programs in all of which we believe have blockbuster potential. And I think the foundation here is, from our perspective, we have a phenomenal organization. We are doing cutting-edge science. In many cases, we are breaking the ground in new pathways and biology and biomarkers. And that's what you're going to see us continue to do. We've successfully leveraged farmer relationships from Pfizer to GSK to Amgen. And I would say the interest there has never been higher. So although I founded this company over 8 years ago, I think we're just at the start of the journey.

And yes, I think we're about time. But thank you again for making time to come check your way to New York for the conference. Your assets, each asset, I think, are really strong and solid enough to create a company so you effectively have 5 companies and the platform behind it. Good luck with your meetings today, and we'll stay in touch. Thank you.

Great. Thank you so much for the opportunity.

Thank you.