Relay management team. Next to me, I have Sanjiv Patel, President and CEO, and Peter Rahmer, Chief Corporate Development Officer. Thank you for joining us. To start here, you've reported data from your PI3K alpha inhibitor as a doublet and triplet in breast cancer, as well as in rare disease and vascular anomalies in particular. Could you provide an update on the company's strategy and what you plan to accomplish over the next 12 to 24 months, including further data and updates for zovegalisib in that period? Absolutely. First of all, thank you for the invitation, and thank you for the grand venue that we're in today. It's been a busy time over the last year for our company. Our mutant-selective PI3K inhibitor, zovega, has had multiple data that we've disclosed. The first of it in second-line hormone receptor-positive, HER2-negative breast cancer. We showed data in March of this year at ESMO TAT in Paris to show that we had a very competitive 11 months worth of PFS in these patients, and that's against the five and a half months of capivasertib. We are now busily running a phase III trial there. The goal there over the coming two years would be to, later this year, guide to when we would have full enrollment of that trial. Enrollment's going great at the moment. Obviously, as we come towards the end of this window that we've talked about, we'd like to file and then start our commercialization efforts. We know capivasertib has been very successful in this field at the moment with almost a $1 billion worth of sales there. We think we can meaningfully differentiate from that and hopefully take market share. In the second data that we showed, we showed data concerning our frontline hormone receptor-positive, HER2-negative breast cancer trial. There we showed data from third-line patients and showed a very competitive profile, and we announced that we'll go forward in the frontline with a combination with Pfizer's atirmociclib, their selective CDK4. Over the coming 18, 24 months, obviously, we want to start that trial, and get well through trying to enroll those patients because we see this as a very big opportunity. The third data drop that we made was in Philadelphia, last month now, at the ISSVA meeting, which is the largest global meeting for vascular anomalies, where we showed data for zovega for the first time, where we showed a 60% volumetric response rate, which compares very favorably to the benchmark set by others in the 11%-20% range. We believe we have a truly meaningfully differentiated compound there. Over the next 18, 24 months there, obviously, we will push very strongly towards getting towards an accelerated approval and then commercializing in this field where there are really no good therapies available for these patients. We have had a very productive year, but I think we have a much more productive 18 months ahead of us, too. Starting with zovega and breast cancer, for your phase III study in the second-line plus group, what do you believe is the minimum delta on PFS versus TRUQAP to promote uptake? Based on physician discussions, what is most important to improve upon for tolerability? I think obviously, TRUQAP was launched about 18 months ago now and took significant share from alpelisib, which was the approved non-selective PI3K inhibitor. The share that it took was through a perceived better tolerability profile in that it showed less hyperglycemia but had significant rates of diarrhea. In the real world, I think we've seen that it does have a liability on hyperglycemia as well as diarrhea. I think our hope would be to differentiate on all kind of PI3K wild-type related toxicity, so diarrhea, rash, hyperglycemia, stomatitis. We believe with zovega, we have a very good profile to be able to do that. In terms of the efficacy bar, obviously at five and a half months, we know that from talking to physicians that a three-month delta to that would be clinically meaningful. Obviously, we sit in our data that we showed earlier this year at an 11-month PFS across all mutations. We believe that we should have a meaningfully differentiated profile both on safety and on efficacy. Your triplet achieved about a 44% overall response rate in heavily pre-treated patients. Based on historical translation to earlier-stage patients, how do you believe this ORR could evolve in the frontline patients, and what do you believe will be competitive there on PFS? I think in this profile, what we showed was data in the third-line. Obviously, we know that patients do progressively less well as you go further and further through the lines of therapy. We think it compares very favorably at 44% with what we've seen with other CDK4/6 combinations, which are in the 20s. We have a kind of delta of 20% in the third-line, we think that delta should carry forward into the frontline. The most important thing here in these third-line patients is to look at the tolerability profile. The patients in the frontline will have to be on this triplet for potentially two, three, four years. We know from the Roche INAVO120 trial that adding a PI3K inhibitor in the frontline is additive. They've shown both PFS and overall survival benefit. The challenge in the frontline is all tolerability and stacking three drugs together as they do with a non-selective PI3K inhibitor, then with a CDK4/6 inhibitor, which obviously comes with its own liabilities, can prove a very challenging profile for a patient to take long-term. What we saw in the third-line was very exciting on the efficacy front, but more exciting on the safety front in that we showed a very nice profile combining Pfizer's selective CDK4, dialing out some of the CDK6-related toxicities, then a mutant-selective PI3K inhibitor, obviously dialing out some of the wild-type PI3K toxicities. We believe this selective profile in the frontline should provide a tolerability profile that would allow patients to stay on therapy for multiple years. Do you plan to report PFS in the advanced patients in the first-half update? You can take that one, Pete. That will be dependent on data maturity at that time. From the dose-finding portion of the study, which was what we reported on a month or so ago, it is possible that we could reach a level of maturity in those patients to start to make a point estimate of median PFS. We have also moved into expansion arms at the potential phase III dose of 150 mg of zovega with 300 mg of atirmo. Those arms are enrolling well now, likely wouldn't be mature enough to start to be able to estimate PFS. What do you see as the bar here in advanced patients? We know our doublet in second-line patients is about 11 months median PFS. These patients are a bit more later line than that. I think if we started to see a median PFS in our unoptimized dose finding probably starting to match in and around the doublet, that would be a good sign that as we moved into healthier, earlier-line patients, that this delta that Sanjiv was talking about would continue to play out. Great. Could you speak to your confidence in the dose work with zovega here, noting the concentration increases when you have combined? We're using, in our go-forward work in the frontline, a dose of 150 mg twice a day. That's compared to our second-line dose of 400 mg BID. What we're seeing is a drug that increases the concentration of zovega. That is a relatively flat relationship. At all the doses of atirmo that we've used, we're seeing pretty similar exposure with 150 mg BID of zovega. We feel pretty confident that we can go forward with that dose. How is your use of atirmo a differentiator versus other frontline regimens, especially Eli Lilly's? How do you expect tislelizumab's development to play out, and what gives you confidence in zovega's ability to compete here? I think just on the Lilly compound, it's hard to say. We see our profile as differentiated. They showed data at last week's ASCO meeting. Their doublet response rate still sits in the 30s. As you saw from our disclosure earlier in the year, we're showing response rates in the 40s. Obviously, we've shown PFS at 11 months. We haven't seen the PFS yet reported for that combination from Lilly, even though they have, I think, sufficient follow-up now. In the triplet combinations, obviously, we've shown a response rate in the 40s, and I think they again were in the 20s. I think there's still a lot of unknown. It could be follow-up. It could be dose. We haven't seen the Lilly compound really to be able to get close to us at the moment. On the safety side, I think it's been noted, it does have some what we believe to be drug-specific liabilities around the LFT abnormalities that they've seen at doses. I think unknown yet whether the Lilly compound will be competitive. In terms of the two different approaches to take here, I think as we talked about a little bit earlier, our approach is to use a selective combination. Selective mutant-selective compound as we'll both use, both Lilly and Relay, to also use a selective CDK4 because we believe that that will provide a more tolerable profile. Because these patients are going to be on therapy for multiple years versus Lilly's approach of using the CDK4/6 inhibitors. They are the owners of abemaciclib and have a vested interest in its use. We think a selective combination will be much more competitive in allowing a tolerable profile for multiple years versus the approach that Eli Lilly could take with a CDK4/6 plus a mutant-selective. Great. Is your agreement with Pfizer for PI3K regimens exclusive? Yeah. There is a period of time in which we are exclusive to each other for starting phase III trials with us with another CDK4, with them with another selective PI3K alpha inhibitor. It gives us both time to get the trial up and going and largely make it so that neither party can move into another phase III in the very near term with another selective molecule. Pete, you do plan to initiate the phase III frontline study in early 2027. What are the areas you need to align with on the FDA prior to starting this study? Yeah. It's really just traditional blocking and tackling here. The conversation, as all these do, will revolve around dose. The trial design is pretty straight down the fairway. We're largely mirroring the ongoing FourLight-3 study that Pfizer has ongoing in the frontline endocrinely sensitive population. I don't think there'd be any real questions around that. Because we are going to be doing zovega plus atirmo plus AI versus CDK4/6 of choice plus AI, we will likely need a contribution of components arm. Whether we handle that by adding a small arm of atirmo and AI into the study, or we leverage the FourLight-3 study and do a referencing of that data of the PIK3CA mutant population, I think that'll be another question we iron out with the regulators. Great. We're fresh off a slew of medical meetings here where we saw Celcuity's data, which showed approximately an 11-month PFS for both the doublet and triplet. Notably, just speak to your updated thoughts on zovega's commercial positioning in the context of that. Yeah, I think there'd been a lot of investor interest in the profile that Celcuity would show at ASCO, and its implications on the commercial profile for zovega. As you know, zovega is an oral compound, and the Celcuity compound, gedatolisib, has a weekly IV regimen. This is really going to come down to-- we all know that an oral regimen in this setting, both in the second line and then especially in the frontline, is going to be preferable. The real question was just how much better was the Celcuity data needed to be to justify a weekly IV regimen? Our market research had shown anything above 15-18 months worth of PFS, was what they were going to need to show to get usage in a world where there is an oral therapy with an 11-month PFS. The bar is relatively high. These patients do not want to come in once a week and spend the majority of the day at an IV infusion center. Many health systems across the world are just not set up for it, especially if there's an oral. When they came in with their 11-month PFS, it's a great trial result for patients because obviously the five and a half months worth of alpelisib that they were up against shows a true paradigm shift for patients. I think the conclusion that both us and investors drew was that once there was an oral compound in the market with 11 months worth of PFS, it was going to be tough for an IV regimen to be competitive. No patient is going to want to come in once a week for an IV regimen when they can have an oral therapy, especially if both of them provide exactly the same PFS. I think it's kind of dispelled the competitive threat for us. I think we're just full speed ahead now recruiting the trial and getting this to patients. Why do you think the triplet and doublet performed in line here, and what gives you confidence that the addition of atirmociclib will result in a differentiated triplet for zovega? Yeah, it was a slightly unusual finding. I think the better conclusion here is to say that their triplet performed as expected. It was almost double what the alpelisib arm doublet produced. Their doublet arm, which they put in there, gedatolisib plus fulvestrant, was really there just for a contribution of components. It wasn't adequately powered to show true differentiation. I think if that arm had been slightly more robust, I think we probably would've seen the same separation that we saw in the wild type, where they show, I think, one and a half to two months difference between the doublet and their triplet arm. I think we would've seen the same. I do think we feel that there is a meaningful benefit for adding the atirmociclib. We see it in our own data, where we see in later line patients, our triplet doing very well versus our doublet. We think gedatolisib probably would've shown that if it was adequately powered. From a strategy standpoint, you're sitting with these two verticals, this cancer vertical, particularly with breast cancer here, and the rare disease opportunity. Do you plan to take breast cancer forward independently or partner? I think we plan to take everything forward. I think we sit on three very robust commercial opportunities now. All we believe to be blockbuster in potential. I think we've seen companies like Menarini show that you can commercialize successfully in breast cancer as a relatively small company. On the vascular anomaly side, it lends itself perfectly to a company of our size, given there's only a small number of Vascular Anomaly Centers in each large country. I think we have the ability now to execute. We obviously raised capital a few weeks ago, as we have a robust balance sheet, that should take us well into 2029, executing all of these opportunities well past the top-line data for Vascular Anomalies and the second-line breast cancer trial. We feel pretty confident to go forward and execute. On the Vascular Anomalies front, you reported strong first data there, including 100% Volumetric Response Rate at the 300 mg BID dose, you've selected both the 300 mg BID and 400 mg QD doses for expansion. Could you discuss, I guess, firstly, why you believe you're not leaving efficacy on the table with the 300 mg BID being the highest dose? Given the fact we had 100% response rate at the 300 mg, we do believe that we have maxed out the efficacy. At the 400-mg dose, what we saw was a drop-off in efficacy, where we saw a 57% response rate. That really was because of two reasons. One, we started to see some of the tolerability challenges that come with a little bit of hyperglycemia, diarrhea, some nausea, that doctors were very keen to dose reduce rapidly. The reason why they were trying to do this rapidly is because they could see the 300-mg dose was very effective. We do think that in the end, at 300 mg, we've maxed out the dose. Now, the unknown here is could you max out the efficacy at an even lower dose than 300 mg? That's why in the expansion cohorts, we'll open up the equivalent dose to 200 mg BID, which is a 400 mg once a day, to test the hypothesis that can you even max out efficacy at a lower dose than the 300 mg? Just the further rationale there in taking the 400-mg QD instead of 200 mg BID? We have a very flat PK curve and a long half-life, we have tested a lot of different doses in our oncology work. What we see from that is 400 mg once a day has exactly the same PK profile as 200 mg twice a day. For just the added incremental benefit of having once daily dosing, we'll take forward 400 mg once a day versus the 200 mg twice a day. Mechanistically, why do you believe zovega was able to benefit patients who had failed alpelisib? Yeah. It really comes down to the same logic that ended up showing meaningful differentiation in breast cancer. For the first time, we can actually see what a mutant-selective molecule does in this patient population. We have a meaningful window of selectivity between wild type and mutant, and nearly biologically inert against all the other PI3K family members and the rest of the kinases. I think what you're seeing here is that manifestation coming out in the clinical data and seeing, for the first time, what does this level of mutant selectivity accomplish for these patients? It's really exciting because the treatment goal here is to start treating these patients as early in childhood as you can because these non-cancerous lesions grow with the child. If you can intervene as early in childhood as possible, you're going to hopefully blunt the growth of that lesion and therefore alleviate a lot of the comorbidities that these patients have to deal with throughout their lives. We can't do that today with alpelisib and sirolimus. The way these molecules are being used, because of their toxicity profile, is short bursts of treatment, maybe for 12 to 18 months, then the tolerability profile is such that these patients have to come off those treatments, and they have to try to let their health reconstitute, and maybe they can go back on or switch on and off. Here, we're excited because we think the data that we showed a couple of weeks ago really speak to the potential of treating these patients as a chronic disease and as early in childhood as possible and keep them on drug for their life. Hopefully, the burden of this disease can become as less as we can possibly make it. What does the trial for accelerated approval look like here? Maybe touch on the spend associated with the program as well as the size of the opportunity you're addressing. Yeah. We haven't had a regulatory interaction yet. The FDA will be the ultimate arbiter of what that path looks like. We intend to do that this year and come back before the end of the year to speak about the outcome of that interaction. What we can look at is the precedence here for alpelisib. Alpelisib was approved off of 37 patients of a retrospective chart review of those patients being treated under compassionate use. Really speaks to the unmet medical need here in this patient population. They unfortunately failed their first confirmatory study, EPIK-P2, but their current confirmatory study is a single-arm study that has an N of 104 patients, and that's for full approval. If you think about the spectrum of potential obligations on our side for the N to be able to get to accelerated approval, it's reasonable to think it's somewhere in between those two bookends, 37 and 104 patients. The regulatory endpoint here is in that volumetric response rate to exclude 15% in the lower bound of the confidence interval. Our data today excludes the 15% of the lower bound of the confidence interval. I think when we go to regulators later this year, the nature of that conversation will be, what is the N that they would like to see to give us all confidence that these results can be recapitulated? Also, what's the safety database that would need to be seen to be able to facilitate accelerated approval? Fortunately, we have about 500 patients' worth of cancer data here to help support the understanding of the safety profile of zovega, so that should be a bit of a tailwind for us in those conversations. The size of this opportunity is very large. There's 170,000 of these patients from a prevalence standpoint in the U.S. today with PIK3CA mutations. We don't believe all those patients will ultimately seek chronic systemic therapy. If you get down to the three current subtypes of focus for us, which is PROS, PIK3CA-related overgrowth spectrum, lymphatic malformations, and venous malformations, there's 100,000 of that 170,000 inside of those three subtypes. We believe about 25% of those would seek chronic systemic therapy for the disease. That represents about 25,000 patients, and the simple math shows that at the alpelisib pricing of $400,000 a year, every 2,000 to 3,000 patients would be a billion dollars in peak sales if you can truly provide a therapy in which these patients can stay on chronically. Certainly, if accelerated approval pathway is available to us, which we think it is, the development dollars here are not that large. If you play that forward to a confirmatory study, which if the alpelisib precedent holds, what we likely think would be the solution there is to just expand our current expansions further, enroll more patients, and that can act as the confirmatory study. The total development dollars, in comparison to the opportunity size, are very small. Do you believe you could cover both PROS and lymphatic malformation within the same study and application? That's going to be what we propose. We believe the biology of the disease here is the exact same across these two disease. There's different levels of severity. Obviously, the syndromic presentation brings with it a different level of disease burden than the more severe lymphatic malformation patients only. In our early data sets, it's very encouraging to see that of the four patients that were valuable for efficacy with lymphatic malformations, three out of those four had deep, durable volumetric reductions for a 75% volumetric response rate so far. We need to grow that end a little bit further and see that signal stay consistent. We believe it makes a lot of sense to keep these two subtypes pooled, especially because given the frequency of PIK3CA mutations in these two subtypes, obviously 100% in PROS, 80-plus% in lymphatic malformations, these patients can be diagnosed clinically, and treatment can be directed without a diagnostic test in these two settings. We believe that the consistency of the disease biology, the consistency of our data, and the fact that these patients can be diagnosed clinically is all very good rationale to keep them pooled together. We'll see what the agency says. In pediatric patients, how are you expecting growth inhibition to play out, which has been an issue with alpelisib? We'll measure all the relevant metrics to make sure we track that appropriately. It's too early to tell today, especially because our initial data was in adults and adolescents, 12 years and up, and we just started the 6 to 11-year-old dose escalation earlier this year. It's going to take us some time to really track that signal with zovega, we do believe that that liability is coming from wild-type inhibition. Again, here's where our selectivity profile should play out in our favor to hopefully minimize or not see any of that growth curve inhibition. Just describe to us the treatment pathway, including the numbers of centers of excellence and patients per center and where genetic testing stands today. This is an area where we need to continue to do more work as a field. Have to remember that we've only been using systemic therapies in these patients for about the past 10 years or so, only about the past 15 years have these patients been starting to be diagnosed genetically. There's a lot more to learn and figure out, fortunately, with the data that we are presenting and generating, we'll be able to ask these questions a bit more clearly within the community. Today, we believe that most of the moderate to severe patients are making their way to these centers of excellence or the vascular anomaly centers. They tend to overlap with the children's hospitals in both the U.S. and Europe. Probably the vast majority of them are making their way to these 30 to 40 centers in the U.S., probably similar footprint in Europe. We think that it is a very attractive commercial model from that vantage point, too, to where you can get to a lot of these patients quite efficiently. I think we'll continue to help raise awareness and push more genetic testing, again, the PROS and leiomyosarcomas patients fortunately can just be diagnosed clinically and don't require a genetic test to direct treatment. Can you discuss future directions for the Dynamo platform here in your business development strategy? Yeah. Obviously, we've been very successful over the last decade bringing first-in-class and best-in-class molecules forward. The platform is directed against targets that we don't think others could tackle, it's really simple as that. We see lots of talk around the commoditization of research or the offshoring of research, that really leaves us with a conundrum of what should you focus on? I think what we try to look for is clinically validated targets where the conventional approaches have been futile and that we can deploy our people and platform against trying to solve them. They sit across both rare disease and oncology. There's no point us trying to work on the second in-class molecule. We know that others are just going to be much better and much more efficient than us at doing that. The final question here, there's so much focus on AI development in healthcare, clearly you were one of the first here with using this machine-based- Yeah platform. Is that really the secret sauce that has enabled you to get the products to these stages and to show the efficacy rates that you've shown versus competitors? How do you see leveraging that on the forward with the next targets? Yeah. Obviously, we've been at this 10 years, we're one of the first companies to use computational approaches in the discovery process. I think what we've learned is it's not a kind of silver bullet. The ability to make a new medicine is time-consuming and has many, many thousands of steps in it, and those steps involve machines, people, data, algorithms, and each one of them, the computational approaches can make incrementally better. If you stack the kind of thousand processes together, you make the entire process incrementally better, and I think that's what we've found. Obviously, we see a lot of companies over the last 10 years kind of launch themselves with, "Our platform can use a computational approach to revolutionize the entire process." We haven't seen that. We see it makes everything incrementally better, and then overall the whole thing gets better. You still need humans, you still need labs, and you still need the kind of intuition that goes on with long-term drug discovery. It isn't going to solve all your problems, basically, but it will incrementally solve some of them. Great. Well, with that, thank you so much, Sanjiv. Thank you, Pete. All right. Thank you. Thanks for the invitation