Relay Therapeutics, Inc. Common Stock Morgan Stanley 24th Annual Global Healthcare Conference

First of all, thank you for the invitation. Thank you for all of you attending, both online and in person today. 2026 has been a very eventful year for us, exactly as you said. We have been pushing forward our lead program, zovegalisib, which is a PI3Kα mutant selective inhibitor, across three different indications. The first of those is second-line hormone receptor-positive, HER2-negative breast cancer, where in March this year, we showed data using our pivotal dose of 400 milligrams BID that showed a PFS in this population of 11 months. This compares very favorably with the current standard of care, capivasertib. Our heads down now executing a pivotal trial across the world, and we are very happy with how that is going. Later this year, we will share an update on when we believe the last patient in will be on that trial.

In our first line hormone receptor-positive, HER2-negative breast cancer efforts, we declared in April of this year that we will use a regimen of zovegalisib with Pfizer's selective CDK4. This is a really important mechanism because using a selective approach, we believe we can minimize the side effects and maximize the tolerability of this regimen, which has been the challenge in this field. We know that adding a PI3K pathway inhibitor matters because we have seen that from the INAVO data. The challenge has really been the lack of tolerability and the lack of ability of these patients to take this regimen for up to three to four years. Using this mutant selective and CDK4 selective approach, we feel very comfortable that we will be able to provide the regimen that patients actually need.

In May of this year, we showed data in vascular anomalies where we showed a very robust volumetric response rate of 60% across the doses that we were using. That compares, again, very favorably to the current standard of care, alpelisib. There, we are very much focused on the dose expansion portion of our study, establishing a dose, and later this year, we will do both a data update and a regulatory update on how we believe that we can get this therapy to patients rapidly. It has been a very eventful year, but it is still an eventful year to come.

Yeah. This is a very large market, the second-line hormone receptor-positive, HER2-negative breast cancer market. The standard of care has evolved over the last few years. Alpelisib, which is a non-selective PI3K inhibitor, was approved a few years ago. Unfortunately, commercially was not that successful because although it showed a PFS in the kind of 7-8 month range, the tolerability challenges of hyperglycemia, diarrhea, rash, stomatitis, unfortunately mean that patients just cannot stay on this therapy. Although it's efficacious, it's unfortunately not tolerable. Then we saw the emergence of the AKT inhibitor from AstraZeneca, capivasertib. Again, this showed actually numerically a lower PFS than alpelisib but was perceived to be more tolerable in that it had in its label lower rates of hyperglycemia. But it did have still significant rash.

This has been launched a couple of years ago, and it's been commercially very successful. It's kind of moving towards a billion dollars of run rate in its sales. It shows that if you could have what is perceived to be a more tolerable regimen, you can definitely be commercially successful to the tune of a billion dollars here. The data that we showed earlier this year in this patient population was in second-line, second-line plus patients using our 400 milligram BID dose of Zovega. The premise of this program was if you can have a mutant selective inhibitor in this field, you can dial down the off-target toxicities of diarrhea, rash, hyperglycemia, stomatitis. That's exactly what we showed, which is low rates of all of these.

That means that you can keep patients on therapy with a greater dose intensity, and that should translate into greater efficacy. That is exactly what the data showed. We showed 11 months of PFS in this patient population, and obviously that compares very favorably to the 5 and a half months of capivasertib. We feel pretty confident now as we run this head-to-head pivotal trial against capivasertib that we could be successful in this patient population and create a very commercially meaningful therapy for patients.

Maybe I will hand that one over to Don to talk about the trial design and maybe then Pete can talk about the landscape.

Yeah. It is a 1-to-1 randomized trial of fulvestrant plus zovegalisib versus fulvestrant plus capivasertib. The patients who we are enrolling have all previously been treated with endocrine therapy and a CDK4/6 inhibitor. The criteria for enrollment are a little bit tighter than what we have used in our phase I program to date. For example, we are not allowing patients to have multiple prior CDK4/6 inhibitors or an ADC. We are looking to enroll as close as we can to a true second-line patient population. The trial is powered to show clinically meaningful improvement in PFS. We also have OS as a key secondary endpoint. As Sanjiv mentioned, we opened the trial in the middle of last year, mid-2025. We are very encouraged with the way enrollment is going. Trials of similar size and a similar population have traditionally enrolled over the course of 30 to 36 months.

We just saw for one in second-line patients, this is the oral third trial that enrolled in 33 months. As Sanjiv mentioned, we will have an update at the end of the year on when we think we'll reach full enrollment.

On the landscape in second-line PIK3CA-mutated patients, there are two pathway inhibitors that have full approval. We have mentioned both of them already. Alpelisib, marketed as Piqray, capivasertib, marketed as TRUQAP. The most recent data from both the assets that we have publicly puts their PFS in the same ballpark of about 5.5 months, 6 months. We feel very confident that with the data we have in hand today that Sanjiv has talked through, which is in almost the median third-line patients, that when we move into this phase III trial in more true second-line patients, we will have the ability to see at least close to a maintaining of the PFS we have seen so far in phase I/II now across 120 patients.