Relay Therapeutics, Inc. (RLAY) Earnings Call Transcript & Summary

Perfect. So welcome to our next session of our Wells Fargo Healthcare Conference. I'm Eva Fortea, one of the biotech analysts here. And we have with us Imogen, Chief Operating Officer; and PETE , Chief Corporate Development Officer of Relay Therapeutics.

Thank you for having us. Yes, great to be here.

Awesome. So maybe we can start with kind of lay of the land, past 12 months, next 12 months, what's up for Relay?

Yes. Yes. And thanks again for having us. Great to be here. Great way to kick off the fall season. So over the next 12 months, coming off a very exciting first 9 months of the year for us, made a number of disclosures across both vascular anomalies and breast cancer. We're able to fortify the balance sheet. And now as we look forward, we're really moving into the next leg of growth here as we start preparing to become a commercial company. And I think a lot of that will be underpinned by additional disclosures and clarity on the regulatory path forward in both breast cancer and [ DAs ]. Specifically, we've guided to regulatory updates for both frontline breast cancer Phase III trial, which we intend to start early next year. And so we'll go have a regulatory interaction before the end of this year and report back out on how that goes. Similarly, with vascular anomalies, that program is going quite well and quite fast from a development perspective. And so we'll have a conversation with the agency on a potential accelerated approval path before the end of the year and report back out on that. And then from a data perspective, we will share additional vascular anomalies data before the end of the year, and we will share additional Phase I/II triplet data in the first half of next year. So it continues to be a very robust set of months for us before we get to the end of the year and then moving our way quickly towards registrational readouts in both breast cancer and vascular anomalies.

So lots of stuff to talk about today. Maybe you can start with the breast cancer side of the story. Maybe you can give us a quick overview of the data we've seen so far for zovegalisib in breast cancer? And what are key differentiators, especially in this very competitive landscape?

Yes. So the sort of -- we'll start with the second line because that's where we've got our current Phase III running. The goal with zovegalisib when we set out was really to try and design a drug that was very specific and did not have the limitations of the generations that came before it, and so avoided some of the off-target toxicity. And so we went after the second-line breast cancer population first because that was the biggest unmet need in the place where it made sense to start. What we were able to show, and PETE alluded to this earlier this year, we showed Fed data, we showed that we had an 11-month PFS, which is really exciting because it avoided some of the off-target toxicity, had a much cleaner profile and it delivered against this promise of if you could have a better tolerability profile, you should be able to extend the efficacy. And so that compares really nicely to capivasertib 5.5 months in a post-CDK4/6 setting. So we're really excited about that, and that's what gave us confidence to launch our second-line Phase III, which we started last year. Then earlier this year, we showed -- we showed data from a median third-line population in the triplet setting also that PETE alluded to. And that looked really compelling, both from an early efficacy perspective. We showed an ORR of 44% there. But more importantly, we wanted to show that from a combinability perspective, it would be a really nice tolerable regimen for patients in the front line and could compete well with the existing standard of care.

Got it. So maybe starting with the REDIScOVER-2 Phase II study, just in terms of enrollment, I mean, is there -- is it tracking in line expectations? And how should we think about time line to read out?

Yes. I mean I think this is probably one of the most important priorities for us as a company right now. It's -- and it's going really well. It's a very compelling study for physicians and patients, given that you are taking Zovega plus fulvestrant versus Capi, the market leader right now versus fulvestrant. It's the enrollment -- people are very excited about it and enrollment is going well. As PETE mentioned, we'll guide at the end of the year -- before the end of the year as to when last patient in will be. But right now, we're feeling really good about it, and we think that we will do very well compared to the benchmarks that we've seen for similarly sized studies.

Got it. Should we expect any impact on this study given the recent focus on the first line?

No, not at all. I think for us, it's one of the key priorities. As I mentioned, it's really important in terms of the patient population. There's a lot of excitement, and we will have a completely separate team working on standing up the frontline study.

And it's kind of nice -- as this study will reach full enrollment and you're then just collecting events, that is in contrast, we'll have the frontline Phase III trial getting up and we can have the team focusing on shifting and focusing on enrollment into that study on a global basis. We will leverage a lot of the same -- we'll use distinct teams internally, but we'll leverage a lot of the global infrastructure we put in place to be able to execute against reDiscovery2.

Got it. You mentioned Capi as the control arm, but we've seen recent data from one of your competitors, gedatolisib that looks very compelling. Do you think this sets a new bar? Or are you still thinking of Capi as the bar to beat?

We still see Capi as the bar to beat. I think we -- gedatolisib came out with an 11-month PFS in their data in PIK3CA mutated patients at ASCO. We think that when you look at the weekly IV, that's just such -- going to be so onerous for patients in this setting. it's going to be a very hard -- it's tough, especially as you think about our own efficacy sitting at 11 months, if you compare a weekly IV versus an oral option, people are going to want to go for the oral option. So I think it's an exciting drug in the wild-type setting where there are limited options. But for PIK3TAmutated patients, I think we can do better.

And I think the dynamic that happened between PIK3CA and TruCap in the setting tell us everything we need to know to that question. You had PIK3CA with about a 6-month median PFS based of the Phase III trial that led to approval but was encumbered by safety and tolerability issues, namely Grade 3 plus hyperglycemia, but also rash, stomatitis, GI toxicities and where TruCap actually had a nominally smaller median progression-free survival of 5.5 months, but just had a slight trading off side effects with numerically lower grade 3 hyperglycemia and has now become the market leader in the space. So I think it really tells you that the safety tolerability profile is paramount for these patients, especially in the second-line setting. And I think that direct comparison between us and really any other regimen that's available today favors VEGA quite a bit here.

Got it. So can you just remind us a little bit on how zovega's tox profile compare? And how are you thinking about the market opportunity in terms of the second line?

Yes. On the tolerability profile, we've seen improvements across the board. We have no stomatitis rash to speak of in our AE table for the second-line patients. Our grade 3 hyperglycemia rate remains in the low single digits across over 100 patients treated at this exposure. And so in the context of whether it's gedatolisib or capivasertib or alpelisib, you see that in the case of Capi, there's a high degree of stomatitis, rash and diarrhea. In the case of gedatolisib, you need 3 or 4 different concomitant therapies just to keep the Grade 3 stomatitis in check and the rash. And so I don't think we're seeing -- one, we don't need concomitant therapies to prophylactically treat these side effects; and two, the overall absolute rates that we're seeing are much more favorable compared to these other agents.

Got it. So maybe talking a little bit about the first-line opportunity. In Earlier this year, you selected Atirmo as the CDK4 of choice for the combination. Where are you at in terms of regulatory conversations? And how do you think about the path forward in the first line?

So as Pete mentioned, we've guided towards coming back with regulatory feedback before the end of the year. That being said, what we're envisioning is a reasonably straightforward design. So our goal is to go after the endocrine-sensitive patient population with a study that largely emulates Pfizer's F4LIGHT-3 study of Atirmociclib in the same patient population. We went after the endocrine-sensitive population because it's the larger portion of the frontline setting. We haven't ruled out going into endocrine-resistant patients. But I think as we thought about what made sense for our initial move, that was the most compelling thing to do. We're still thinking about whether or not to add a small contribution of PAs arm to the study and whether or not we add an [indiscernible] plus AI to help us ex U.S. But inside the U.S., the FDA has been pretty clear that we could reference 4LGHT-3, but I think outside of the U.S., it will be helpful to have at least a small contribution of PAs arm. So our goal is to set that study up to get it designed and approved and then hopefully be ready to launch in the first half of next year, early part of '27.

Got it. And in terms of durability, I mean, follow-up was quite short. from the one that we've seen so far for the triplet, but how should we be thinking about next update? How much data on durability are we going to get?

Yes. The -- I think the biggest thing that we're looking at in the Phase I/II data in the initial update and in subsequent updates will continue to be the safety and tolerability of the regimen. That is going to be the best indicator of eventual durability because we already have good analog data from inavolisib in the front line. So the ANAVL-120 study was inavolisib, a nonselective inhibitor plus palbo plus fulvestrant versus palbo and fulvestrant in endocrine-resistant patients. And in that trial, they had to have a very favorable metabolic profile of the patients in order to keep the hyperglycemia [indiscernible]. But the efficacy was quite profound. You saw a doubling of the PFS in that patient population, which tells you that when you add a pathway inhibitor to these patients in the front line, you're going to get a dramatic prolonging of progression-free survival. And the real key question is when you contemplate the frontline endocrine-sensitive population where you could be treating these patients for upwards of 3 years, can you put together a regimen that is tolerable enough to stay on for 3 years. And so in the Phase I/II data that we continue to generate, of course, we'll continue to report on response rate and eventually, if we get enough data maturity, we can look at progression-free survival in that setting. But the key metric we'll continue to look at is the safety and tolerability of that regimen.

Got it. Are there any safety events that we should expect to accumulate over time versus seeing them at the beginning?

I think when you treat any patient population over the course of 3 years, you're going to -- especially one where the median age, it's a metastatic cancer population and the median age is somewhere in the neighborhood of 60 years old. You're going to see accumulation of certain AEs. I think most of the AEs that we have seen thus far with Zovega do tend to be early on, tend to be low grade. Some of them are reversible. They're all -- they all appear to be exceedingly manageable. I think in the context of combining with a CDK pathway inhibitor, the one addition you're definitely going to see is neutropenia. That is the class AE that we've seen across the CDK class of therapies. It tends to -- it looks like in the previous Atirmociclib data that the grade 3/4 neutropenia tends to be a little bit less than what you see with palbo,beema or rivo and just the general tolerability of the -- of that agent versus the incumbent CDK4/6 seems to be better than what we've seen historically.

Got it. And you also showed in the early data that it seems like there was higher exposure, like a 2.5 increased exposure for Zovega. Is there any risk in dose selection for the Phase III? How should we be thinking about that?

No, we don't think so. We feel pretty confident in the exposure that we've seen and in the dose that we intend to move forward. We know that we do have an exposure of DDI with Atirmociclib, but we don't see dramatic differences in interpatient variability or something like that. So it's a very manageable, predictable exposure increase. So we feel confident moving forward with RRP3D.

Got it. And maybe in terms of control arm, I mean, the landscape is rapidly changing. Do you foresee any unexpected issues with your trial design or anything that could impact what you're thinking?

I mean I think today, as we sit here now, the CDK4/6 plus endocrine therapy is very much the standard of care. And so that's -- this is the best design that we can design from where we sit today. We will see -- there are a number of CDK4s that are in development. We're seeing the rise of some of the oral SERDs. But I think from where we are now, this is the design that makes sense. And this is part of the reason why we wanted to bring a selective PI3K with a selective CDK4 plus the endocrine backbone because we felt that, that was going to be one of the most future-proof designs that we could bring to bear.

And as we think about the 2 main questions you're trying to answer there is, do global -- will global regulators view it as a regulatory standard of care. And I think we can definitively say for the next 5 years or so, that question is going to remain Yes. And then is it a study that physicians on a global basis will want to enroll to? And I think, again, the answer to that question is yes, you're offering CDK4/6 of choice along with the standard aromatase inhibitor backbone in the endocrine-sensitive population. And the option is to randomize into a treatment arm where you're -- as Imogen said, you're offering the selective, selective approach, which based off the data we have in hand today and some of the data we've seen from Atirmociclib Thus far should be a favorable option against the existing standard of care.

Got it. Maybe can you remind us what -- how much data should we expect in the first half of '27 as we get more information about this first-line strategy?

Yes. We continue to enroll in second-line plus patients with Zovega plus Atirmo plus fulvestrant. We've also enrolled smaller arms to look at Zovega plus Atirmo Plus aromatase inhibitor. And we are also trying to enroll or enrolling a smaller portion of patients that are endocrine-resistant with the Zovega plus Atirmo plus fulvestrant regimen. The bulk of the patients we'll see being reported out from the Phase I/II will be this median third plus line of therapies, which is why we continue to focus on the safety and tolerability that we're getting out of this data set.

Got it. Is there any reason to believe this third-line data wouldn't translate well to the first line?