All right, good morning, everyone. Thank you so much for attending. My name is Zaki Molvi. I'm an associate on Akash Tewari's team, and I'm here with the Relay Therapeutics team. We've got Sanjiv and Pete. I'll let them give some opening remarks, and then we'll get into Q&A. Thanks, Zaki. Thanks to Jefferies for the invite, and thanks to all of you for attending this morning. I think, as we've been doing all year, we're in execution mode. We are heads down now executing phase III with our asset RLY-2608, which is a PI3K alpha mutant selective inhibitor we believe to be the first in the clinic. We're excited about the progress that we're making there. Behind that, we're doing all the work to look at the various triplet regimens that we could potentially use in earlier lines of treatment in breast cancer. We have commenced dosing patients with PI3K alpha-driven vascular malformations. Behind that, we have an NRAS selective asset as well as a Fabry asset. We have close to $600 million on our balance sheet, and we're excited to generate value over the coming years. Awesome. Thank you so much. I guess, you know, I think at ASCO we saw your updated data. We've got a 39% ORR that continues to mature from the last cut, 10.3 month PFS, 11 month in pure second line. We're also seeing the other PI3K alphas, the SERDs, the CDK4/6s, looks like five to seven and a half months. I think just to level set, I think what people want to understand is what's going to be the right competitive bar in second line plus setting and how confident you are that that 10 months will, understanding that it may degrade, may not, in a larger phase III, will that still land in a place that's competitive relative to those? Yeah, it's a question that's really been circulating over the last year, year and a half, because there's so many different mechanisms of action that have read out. Obviously, the hope of all these different mechanisms, CAT6, oral SERDs, CDK4/6 retreatment, some of the non-selective pathway inhibitors, was that you could improve that five and a half to seven months' worth of PFS. Unfortunately, what we've seen is nobody's been able to move that bar. Even more interestingly, the bar could have actually been lowered. Capivasertib was approved a couple of years ago now with actually a lower PFS than Alpelisib, the current that was approved prior to that. Capivasertib has taken significant market share and is on a run right now of $800 million annually just because it has a perceived better safety profile than Alpelisib. We have not seen the bar move from 5.5-7 months. We actually may have seen it actually decline. We feel pretty confident sitting on a 10-month PFS, even with some degradation, that we will be successful in the second line. Got it. I mean, for that second line study for ReDiscover-2, you're going head to head versus CAPI, which I think is a great mix, a lot of sense. I think just looking at the way you've powered the study, I feel like you are kind of powered for at least maybe 2, 2.5 months delta over CAPI. I mean, is that kind of a fair assumption that you're making internally? Look, I think we want to make sure that we have a successful trial against Capivasertib, but we want to make sure that it's also going to be commercially viable. Yes, we think somewhere between two and three months is the minimum that you'd want. As we sit today, it's 10 months PFS across all lines. It's a pretty robust data set now, over 60 patients, over 12 months' worth of follow-up. In second line only, patients were at 11 months. We believe that, as many people point out, there could be some degradation in the real-world trial that we run across multiple geographies. We still feel pretty confident that we'll be able to clear the hurdle. Got it. In terms of, I think, the dose, you announced earlier that you'd be going with a 400-mg BID Fed dose, whereas the previous data that we saw was 600-mg fasted. I think you've shown pretty nicely that it looks like the PK coverage is relatively similar, if not even maybe a little bit better, just with the Fed dose. One thing is, when I looked at the CAPItello study, we know TRU-CAP on the label, it doesn't have a particular restriction. When I looked at the CAPItello study, I think at that time, it was a recommendation of fasting before the dose. I mean, how do you think this kind of compares? How will this data set be comparable if you're now going to Fed? Yeah, so you're correct. We did notice a food effect with 2608, moved to 400-mg BID Fed, very similar exposures. These are exposures that get us, on average, about IC90 target coverage throughout the dosing interval. The interesting thing with CAPI, because of the tolerability profile, they had to move to intermittent dosing, so dose four days on, three days off. The label is agnostic to food. I don't think we don't anticipate that being a challenge at all in the study that we will be asking patients to eat. It can be anything, low-fat diet, high-fat. It doesn't really matter what it is, just getting some food into the system. It is very convenient because it's a BID dosing. Take it with breakfast, take it with dinner, and it shouldn't be an issue. Got it. Actually, on kind of the diet part, in terms of the hyperglycemia, you guys have shown, I think, generally lower hyperglycemia rates than the other PI3K alphas, but definitely it's still a class effect with hyperglycemia. What can you tell us about for ReDiscover-2? There will be monitoring of fasting glucose. I mean, how will patients be monitored? With the Fed regimen, will that have any kind of effect or artifact on the hyperglycemia? We do not anticipate the Fed dosing having any impact on the amount of hyperglycemia we will see with 2608. In the study itself, we do not require at-home glucose monitoring for 2608. CAPI will be administered per label in the study. They recently had, I guess, about nine months ago now, they have updated their label to require at-home glucose monitoring. Those patients will need to, per protocol, be asked to monitor their glucose because that is what the label requirement is for CAPI. The reason why that is, in the clinical study in CAPItello, you saw a numerically lower hyperglycemia grade 3 rate. Like I said, CAPI is dosed four days on, three days off. They were measuring glucose at the end of the three-day drug holiday. We believe that artificially lowered the perceived hyperglycemia rate. I think you're seeing that come to bear in the real world where they're now having a label update to require glucose monitoring. Right. Got it. Makes sense. In terms of, there's another PI3K alpha in the room with the Scorpion molecule. It's funny, at ESMO, we saw, I think even before ESMO, last time we talked, you mentioned that you've actually looked at that Scorpion molecule yourself and done kind of the in vitro coverage tests. It seemed like their 100 mg dose was just starting to touch the coverage that you were getting with your 400 mg go- forward dose. Now we have some 100 mg data from ESMO, where it actually looks like their doublet data, numerically, very similar, 40% ORR. The triplet, it looks like there's like four patients at that dose, like three out of four is 75%. Who knows, really, until the data matures. I mean, do you feel like that thesis is, I mean, how should we look at the Scorpion data now that we have some idea of them at kind of comparable doses? I mean, I think it's the thing that we've all looked forward to. I mean, there's a lot of speculation around the profile and how it could be significantly better than the current standard of care, including 2608. I think the data that came out was still very difficult to interpret. It was early. I think that's the key thing, which is, yes, I mean, the numbers you stated were true. If you really look at the confirmed responses, they were zero in the triplet. I think most of the doublet responses are also unconfirmed. I think the only thing that we could really go away with on the efficacy side is still early. Maybe it could get close to 2608, but we've set a pretty high bar at 39% ORR and 10 months of PFS. I think the one thing that you can tell for certain from the data from ESMO is there are some unknowns around the toxicity profile. In their monotherapy that they showed back in 2024, there was an LFT signal, clearly. They showed grade three LFTs. At that point, it was really only kind of less than two months' worth of follow-up. I think the narrative then, it was only at high doses. Now, in this latest data set, they took out the high doses above 100 mg, and that LFT signal doubled. We're seeing in the doublet, 37% all grade LFTs increasing, and then over 10% grade three. That's close to now at four months' worth of follow-up. They didn't break it out by dose. You imagine that if you follow their narrative from the year before, that those were higher at the 100 mg. I think the real key question on the efficacy is they could potentially get close to us at the 100 mg. The real question is, is it tolerable? We'll find out over time. The signals that we saw on the LFTs are definitely concerning. Right. To be clear, for your molecule, so far in LFTs, we're out of the weeds there. I want to talk a little bit about triplet setting as well, because you partnered with Pfizer to kind of run the triplet study with RLY-2608. We've already gotten a little taste of the PI3K alpha mutant selective triplet data from Inavolisib. They have good, I'd list, triplet data. Looks like 14.6-month PFS in mutant. I mean, are you kind of looking at that as a potential preview of what this mechanism can do in the triplet setting? How are you viewing that other than the efficacy, the other profile otherwise in terms of the IV dosing compared to you? I think we were all thrilled to see the Selpercatinib data readout in the wild type. It was a positive trial. There's just so few options for wild type patients that I think it is definitely a win. I think the question is unknown on the mutant side. It's a small number of patients that they showed the 14 months in. Again, back to the question of how will that read out in a large multicenter phase III, we'll find out, I think, in 2026. The real question is just going to be, again, how tolerable is this profile going to be? I think in the data that we've seen, you need multiple drugs here in the triplet to support it. You need dexamethasone mouthwash. You may need medications for the rash. It is just potentially a four to five drug regimen, and it's an IV administration. Obviously, these are chronic therapies in a predominantly oral market. I do think there are some questions, even if it does hit on the mutants, to the commercial potential of this product versus an oral and the profile of 2608. Got it. Yeah, that makes sense. We also have the Roche triplet data as well. Looks like coming in at a very similar PFS with the 15-month PFS. I think you guys also have the ability to differentiate on safety. I mean, should we be thinking about triplet as the bar for efficacy is going to be a 15-month PFS with generally cleaner hyperglycemia rates? I mean, help us frame that. Yeah. I mean, you hit the nail on the head, and that is very mechanism validating data. They ran a very elegant study in frontline endocrine resistant patients. It was a bit of a contrived patient population in that they had to go into very metabolically fit patients to mediate the hyperglycemia risk. Nonetheless, they proved that if you can thread a therapeutic needle and actually get patients to stay on that study and hit the target, you can have a pretty profound benefit. We now see that they have an OS benefit. That was very confirming to us on the commercial potential that we should think about for ourselves in the frontline setting. Yeah, our goal is to move forward with a triplet in a frontline study. There are two open questions there: which triplet to move forward with and which study to run. We feel very confident that once we get there, there's probably very high POS on that trial. Right. I think one of the things that, as we talk about hyperglycemia, one of the things that you've done, and you're doing it in ReDiscover-2, is the A1C criteria, the under 7%, the fasting glucose, also upper threshold 140. I think the discussions at SABCS had kind of talked about this as one way that you'd kind of potentially limited the risk of seeing events. How should we think about if the study is going to be run in that population, how is it going to look on the label? How might the risk be managed for a broader population that does include people with higher A1Cs? Yeah, I think over time, you'll see us test the hypothesis of going into higher A1C patients. Because we know that the data we generate, both in our current ongoing second-line trial and eventually the frontline trial we run, we know it's likely going to be compared against the different trials that Roche is running with Inavolisib, which has very restricted metabolic criteria. The place to test that hypothesis is probably not inside these phase III studies. We still, by the entry criteria we have, these are prediabetic patients. Anything over six is going to be considered prediabetic. In our phase I/II experience, we had a third of our patients either with a BMI greater than 30 or in the prediabetic range as it concerns HbA1c and fasting plasma glucose. I think we could eventually run that experiment over time. I don't think it's the proper one to run inside of these studies, given the cross-trial comparisons that folks will make in the future. Right. Right. That makes a lot of sense. Right. The idea is you want to keep things consistent. We've seen these encouraging signals so far. I think the idea is you want to be as best positioned as possible to kind of replicate these early signals that we've seen. To that point, I think one of the things that we were talking about as we discussed this 10-month PFS signal in the second-line plus and then kind of replicating higher than that in first line, is there anything that you're doing kind of in recruiting for the phase IIIs in terms of using repeat centers? Anything to kind of ensure reasonable limitations on how much PFS might degrade? The key thing is in the ReDiscover study of the phase I/II, we had about 50% of our patients were third-line plus. Over half of them had seen prior either oral SERD or fulvestrant. A third of the patients had prior chemotherapy. Just by definition, as we move into this phase III, where we're putting a bit more restrictions on the number of prior therapies, we're likely going to see healthier patients, more predominantly second-line patients. I think completely agree with you that historically, going from phase I/II single-arm studies into large phase IIIs, you should anticipate a bit of a degradation in the PFS you've seen. We probably get a little bit of balance in the other direction in that regard because we will control a bit more the amount of pretreatment that these patients have seen. Right. Got it. Makes sense. In terms of, I think in your data, I wonder if there's, we've talked about these kind of other experiments to kind of run. You've seen in your kinase mutation cohorts that like an 18-month PFS in the second-line setting, which I think is kind of an intriguing signal. Do you think there's room to kind of say potentially running a trial to confirm that signal? I mean, is there an opportunity there? I think we believe that we have a pan-mutant inhibitor on our hands in 2608. The data that we showed was 18 months, I think we think a high watermark. We think it's going to be over 12 months. We also think that we have a molecule that covers the helical. We are running the trial to try and get the approval across all mutations. Got it. Now I want to talk a little bit about the vascular malformations opportunity. You're running an interesting trial there. We've already had the EPIK-P1, EPIK-P2 data from Novartis. It's funny, the EPIK-P1 data, right, they showed kind of like a 38% ORR, which kind of in the EPIK-P2, they did half that dose, and they saw pretty much half the ORR, but also half the grade three AEs. I mean, and also some KOL work that we did suggest EPIK-P2 is a little bit less severe patients, maybe not the ideal patient population. I know you are running a study where you're doing kind of an interesting three plus three dose escalation. It looks like you can kind of get to more effective doses more quickly. I mean, tell me a little bit more about how you're taking the learnings from those Alpelisib trials that Novartis ran and incorporating them into your vascular malformation study. Maybe I'll start and you can finish off. Those of you not familiar, vascular malformations is a significant opportunity driven by PI3K alpha mutations. The only approved agent at the moment with accelerated approval is Novartis' Alpelisib. The studies that you cited here, one was the accelerated approval that got the approval, and then the confirmatory trial unfortunately failed. There is plenty of precedent here for us to kind of work through as we figure out what the best pathway for us is. Maybe you can just talk about the design. Yeah. Because of the experience we have of 2608 in oncology, you're right. We can, instead of going through the traditional dose escalation, actually do dose randomization across three doses simultaneously. Each of those doses, each of those arms could be up to 15 patients each. It is a bit more efficient development. The highest dose in that randomization will be the oncology phase III dose. The open question here is what level of target coverage do we need to really affect maximum efficacy in these patients while maintaining a good tolerability profile? We get a little bit of an understanding of that relationship between target coverage and efficacy, as you point out from Alpelisib. They use 250 mg in the label dose, which is about the strangest approval you'll ever see. It was based off of retrospective chart review of patients treated under compassionate use across seven centers. There is no dose finding or justification done there. That is why investigators in the confirmatory study required them to go to half the dose. I think it's difficult to really understand the safety profile of Alpelisib at that 250 dose because that safety data was collected through retrospective chart review of compassionate use patients. It wasn't in the rigor of a clinical study. The confounding factor of the EPIK-P2, like you said, it's done at half the dose. It's probably barely touching the PI3K alpha pathway, the mutants from a target coverage standpoint. I think it'll be interesting to see the profile over time. The clear goal here is better efficacy, better tolerability, get to these patients as early as we can in their disease progression. This is a somatic mutation that happens in utero. The goal would be to treat patients as early in development as we can chronically. I think that's the profile we'll be looking for as we continue to test this clinically. Right. In terms of, I think one of the concerns investors want to know is how quickly will we eventually get data on this? Because these are smaller trials, take longer to enroll than the oncology trials. I mean, when are we really going to be able to see some proof of concept efficacy there? It's a great question. One of the things that frustrates folks is we are not giving guidance on any of our programs at the moment. It's really out of interest for shareholders to make sure that when we do give guidance, it's with a really solid understanding that we'll have robust and interpretable data in hand. We're very happy with how the conduct of the study is going, the excitement amongst investigators, the pace of enrollment. We're just not quite there yet to feel comfortable giving guidance to when we could share that data. Rest assured, when we do, it'll be the data set that we view to be interpretable and really informative for the ultimate next steps that we would pursue here. Yeah. The cash window that we have of close to $600 million in cash runway into 2029 allows us just to go out and execute. As you see in this window, we will have the phase III that we're about running, Rediscover II. We'll have the triplet data that we've talked about. We will obviously have this VM vascular malformations data, as well as bringing the Fabry and NRAS program into the clinic. There are plenty of catalysts ahead. I think that the key at the moment is we're just not guiding to when. Right. I think having that data eventually is something that investors should wait for because it's 170,000 patients across all of the types of vascular malformations. I think one thing I want to hit on is, are there going to be subsets that you think might be the optimal responders? You look in the literature, you see, okay, there's different mutational burdens. Some patients whose disease relies more so on PI3K alpha mutations than others, genetic mosaicism. I mean, do you think the trial program, when you do have that data, will be able to elucidate how big the opportunity is going to be? I think the initial data will start to answer that question. It won't be the complete answer. Our view is that any of these patients with PIK3CA mutated disease should be responsive to a PI3K alpha mutant selective inhibitor. You're correct. There's other biologically, there's other things happening inside of these lesions. We do think that in the mutated patients, that is happening in an otherwise very quiet genome. It's not like cancer where you have polyclonal disease. We do believe the PIK3CA mutation is driving this disease. There are some other mutations that we believe do happen in these patients. TY2, for instance, is one of them. We think that's mutually exclusive to the PIK3CA mutant patients. Right. One thing we notice is there's only a few centers where there are specialists for vascular malformations. When you think about this 170,000 number, I guess, is it commonplace to get PI3K alpha testing? I mean, will those patients know that they are eligible for an inhibitor? I mean, I think in the PROs and the lymphatic malformations is a clinical diagnosis because 100% of patients with PROs have a PI3K alpha mutation and close to 80% in lymphatic malformations. I do think that that allows these patients to be treated much more rapidly. There is a significant amount of testing that goes on here in both populations. Got it. With that, we're at time. Thank you all so much for attending.