My name is Cory Kasimov, one of the senior biotech analysts here at Evercore, and it's my pleasure to host our next discussion with BridgeBio Oncology. Fortunate to have both CEO Eli Wallace and CFO Uneek Mehra here with us today, so thank you both for joining us. Thank you. I guess to start, you know, I've been starting all these conversations with a little bit of shock that we're here in December already, and so asking companies kind of look back over the course of 2025 and kind of highlight what you think are BridgeBio Oncology's biggest accomplishments this year. It's obviously been a pretty big year for you guys. Yeah, and I think we could level set that with a couple of slides we have. Oh, perfect. That will just help the stage. Yeah, I mean, 2025 has been a big year for us. Again, I can't believe it's almost over. We were able to progress all three of our programs in the clinic. All of these were discovered in-house. They're highlighted on this slide, and really all three were designed to drive to high levels inhibition targeting the two most mutated oncogenes, RAS and PI3K alpha. We do that with our KRAS inhibitors, our G12C inhibitor 8520, and our pan-KRAS inhibitor 818 by binding with high affinity directly to KRAS to inhibit both the on and off state. And then we do inhibit the PI3K alpha signaling in a unique way by inhibiting it where it's only activated by RAS. That last example of the RAS PI3K alpha breaker, that's able to inhibit tumorigenic signaling but avoid the effects of hyperglycemia because RAS is important in driving tumors, but RAS doesn't play a role in hyperglycemia. I think, you know, I mean, we just highlight maybe two things, Cory, real quick. One is, you know, we are heads-down execution, and that means clinical execution. For 818, for example, we filed the IND in the middle of January, and we dosed our first patient in March. Really high quality, rapid execution. Of course, we also went public through the de-SPAC process. We announced our intent to merge with Helix II, a Cormorant SPAC, at the very end of February, and we closed that de-SPAC in August, raised $380 million roughly with only 39% redemptions, giving us the runway to take these programs forward. And during that window from February to August, there wasn't a single biotech IPO, so it was definitely the right thing for us. And then if we go just quickly to the next slide, Cory, if you don't mind, let's just highlight what's coming up next year. So 2025 was an important year for us. We set the foundation for 2026, where all three of our programs will have data readout. Our on-off G12C inhibitor 8520 will have a readout in the first quarter. Our PI3K alpha breaker, BBO-10203, will have a readout in the first half, and then the second half will have a readout on our on-off direct pan-KRAS inhibitor, BBO-11818. Perfect. So not only did you answer my first question, you answered my last two as well, so I appreciate that. We want to be official. Yes, this is fantastic. You know, I want to start kind of like big picture and why RAS, like why the company was founded and going after RAS. Obviously a hot area. There's a lot of companies who are working on it. Why RAS and why do you think you can be the best? Yeah, so I've known Professor Frank McCormick for years. When I left Peloton Therapeutics, where we did the HIF2 antagonist, where I was CSO, Frank reached out to me and said, you know, let's come to BridgeBio, let's work on RAS. You know, he's in a way Mr. RAS, discovered NF1 and other functions that, and he said, I think we can really make a difference here. Again, the thesis here is small molecules that can drive to high levels of inhibition. RAS obviously has been the holy grail for about 40 years. About 30% of human tumors have mutations in RAS. Others have dependency even on the wild type, so obviously a critical target. I think, you know, how one targets it, and it was undruggable, or I don't know if I love that phrase because we only use it after we've overcome that liability. It's a challenging target because there's not a clear small molecule binding site, and GTP has picomolar affinity, so you can't compete with it like you can ATP on kinase. But Kevan Shokat made this key discovery that you can inhibit the off state by binding directly to KRAS. We came together with Frank and said, that's great, but why can't we actually inhibit the on state, the one that actually signals? And so we took that approach. At At the time, the dogma was you couldn't do it. We obviously have done it with 8520. We've repeated it with 818. And then the other thing we brought to the table is this RAS PI3K alpha breaker, which is a first-in-class novel approach to inhibit the second most mutated oncogene, but to do it in a RAS-dependent manner. So, it's not only that RAS is critical in driving many, many, many human tumors, it's also that we take this approach that we feel is innovative and novel that will enable us the therapeutic index to drive to high levels of inhibition. Okay, that's helpful. So with regard to 8520, can you kind of walk or talk through the efficacy and the safety demonstrated by the molecule to date? Yeah, we've shared some data, early clinical data from the dose escalation. We shared monotherapy dose escalation through the first three cohorts. That was 100, 200, and 300 mg qd. Across those cohorts, we saw a 60% confirmed overall response rate. And also, so very encouraging early efficacy, but also very importantly, we saw a very differentiated safety profile, which, through those three cohorts, we saw no grade three toxicities at all and absolutely no changes to liver enzymes, so no liver toxicity. And I think that's really the power of the on state, as a covalent inhibitor, you can act as a hit-and-run mechanism. You get residence time on the protein, but the compound can clear, and you can only do that if you're actually inhibiting the on state. Off state inhibitors can't do that. They are plagued by liver toxicity that gets worse when you add a checkpoint inhibitor. Our approach here enables us to get the efficacy but have a very different therapeutic index, which we think sets us up to be the combination agent of choice with pembrolizumab. Interesting. All right, so then when we get this update in the first quarter of 2026, what kind of details can we anticipate and what are you hoping to see when you take this next look at the data? Yeah, we hope to be able to share the monotherapy dose escalation where we have, you know, good efficacy, differentiated safety, and then we can combine with pembrolizumab at an active dose. So all the other inhibitors that have shared data in combination with checkpoint inhibitors have had to reduce their dose primarily for liver toxicities to the point where they're going forward with doses of monotherapy that aren't particularly active. Our hope would be that we're able to combine with pembrolizumab at actually an active dose. As I like to say, our trial is an escalation with pembrolizumab, not a de-escalation. So our hope is we're going to be able to show the full monotherapy dose escalation and safety data with pembro, and then hopefully early efficacy in pembro combination. If you see what you hope to see, what would be the logical next steps here? Yeah, I think, you know, we're going to have to look at the 8520 data as holistically against everything else in the portfolio because we are fortunate to have the runway to test all three programs, and they're all in close proximity. We're not a biotech that has one agent that's three years ahead of the rest. We have these three readouts that are on the slide coming up. So towards the, you know, second half of 2026, we'll have clear data and be able to prioritize over the portfolio. Specifically for 8520, you know, we think that on-off mechanism will be differentiated, particularly in combination with pembrolizumab. And so we think there's still an opportunity there in the front line with TPS less than 50%, where off inhibitors activity is, you know, modest, I would say, and grade three toxicities are in the 30%-40%. So I think there's still white space and opportunities in G12C. As far as next steps, we're going to do that as a portfolio-wide evaluation and prioritization. Okay, makes sense. So then for 10203, the RAS PI3K breaker, can you kind of talk about how this molecule is discovered and its unique potential for differentiation? Yeah, so I think through the years, the RAS's activation of PI3K alpha has been underappreciated. And part of that is it's much easier to study RAS's activation of RAF. So the way this was discovered, actually, there was a glue compound that was found that enabled the crystal structure of PI3K alpha and RAS. And that's then highlighted to us the ability then to transform that compound through structure-based design into a breaker. So it's a covalent inhibitor binds specifically and selectively to the RAS binding domain of PI3K alpha, and it blocks the ability of RAS to activate it. Doesn't touch the kinase activity of PI3K alpha, which is really critical for the therapeutic index. What we've found through this compound is that RAS activation of PI3K alpha is very important in many tumor genetic settings, but it does not play a role in hyperglycemia. It doesn't have any role in glucose homeostasis. Our pre-clinical data is so strong on that point. Our clinical trial, which is ongoing, has no restriction on HbA1c status for patients entering. No one else in the PI3K space is doing that. And so, you know, we get the efficacy by inhibiting the pathway, but we avoid the common kinase inhibitor toxicities of blocking this pathway. So, you know, we'll see as the data matures, but it could really be, you know, a completely different way, a novel way to inhibit this pathway that, again, allows the high levels of inhibition in a safe manner. Which I think brings up maybe another point that I want to highlight is that for years, for probably about 25 years, myself included in those efforts, we were trying to inhibit the MAPK pathway and the AKT pathway simultaneously in human tumors. These are arguably the two most important oncogenic signaling pathways, but when we first tried to do it, we had MEK inhibitors, we had PI3K inhibitors. They were not selective, right? They were wild-type targeting. Toxicity was very poor, even in mice. A few companies tried to take those into the clinic with, as one would expect, poor results. We feel that we are uniquely positioned to do that combination now internally because of the nature of the inhibitors we have. We have our KRAS mutant selective inhibitors, and then we have the breaker, which you can think of as a pan-RAS inhibitor of PI3K alpha. And so I think that's another opportunity that we have within our portfolio to really make a difference for patients with RAS-driven tumors. So when we see the data, this first look at data and sometime in the first half of next year, can you give us a sense of the information you'll be able to provide, maybe what you're looking for, how many cohorts, number of patients, things like that? Yeah, so what we hope to be able to show in the first half is monotherapy dose escalation, where we show a differentiated safety profile where we show that we're clearly at the right dose level. That includes, you know, a modest target efficacy threshold, as well as we have a target engagement assay in blood that we hope to be able to show high target, high levels of target engagement. And then, you know, depending on how the trial progresses, we should be able to also share early combination data. We're looking at three different types of tumors in this early trial, and these three genotypes arose from preclinical studies as sensitive genotypes for this mechanism. That's HER2-amplified, so HER2-amplified breast, hormone receptor positive breast with PIK3CA mutants, and then the KRAS mutants. Now let me just highlight for a second, you know, I mentioned the combination potential that we have here. It also is unique for us as an inhibitor of the PI3K alpha pathway to be able to combine with RAS inhibitors. Wild type targeted PI3K alpha inhibitors, whether that's an alpelisib or inavolisib, will not have the therapeutic index to combine with a RAS inhibitor. If you are a H1047X selective inhibitor, you will also not be able to combine with RAS because 90%-95% of RAS mutants are wild type for PIK3CA. So not only can we do that combination within our portfolio, that is a unique, large, addressable patient population for us. So to get back to what you should expect, you should expect monotherapy, differentiated safety. You should expect high confidence in the dose that we then roll into combinations in those tumor types, HER2-amplified hormone receptor positive KRAS mutants. Okay, so then last but not least here with the third program, 11818, your pan-KRAS, be interested in your views and kind of the landscape in this area and where you kind of believe or hope your program has the potential to differentiate. Yeah, so I think I would start with, as I mentioned, all of these programs were discovered in-house through structure-based drug design, medicinal chemistry. 818, you can think of as a first cousin of 8520. It's able to bind with high affinity to the switch II pocket by really optimizing the binding interactions deep in that pocket. So it differs from 8520 that it's non-covalent because it's hitting multiple, it's hitting KRAS, pan-KRAS and G12X mutations of KRAS. You know, we believe the best way to drive the high levels of inhibition for these patients is to be selective over H and N. There's preclinical data that strongly suggests that when you inhibit KRAS in normal tissue, H and N will compensate as opposed to one that inhibits all the RASes. And so we think that that's the best way to provide benefit for patients with KRAS, G12D, and V-driven tumors is to have a pan-KRAS inhibitor that spares H and N, and that will enable us to drive to high levels of inhibition. So when we get to a point where we'll see data as early as the second half of next year, kind of what are the key benchmarks then that you'll be looking for? Yeah, you know, I think we'll be looking across tumor types that, you know, KRAS plays a role, so, you know, colon, pancreas, lung. You know, I guess there's benchmarks from RAS multi and then maybe some G12D inhibitors. So, you know, there's a lot of activity in the field. We really haven't seen a pan-KRAS on-off inhibitor. You know, I would hope we would have the therapeutic index that the preclinical data suggests and then good activity across those types, those KRAS mutant tumors in colon, lung, and pancreas. Okay, so tough, not really fair question for you, but the favorite child question. When you look at this, like this initial portfolio that you've built, you know, across these three programs we've discussed, is there one that you're most excited about, just either given the target, the preclinical rationale that you have, the unmet need, the potential difference, is there anything there? I know it's going to be driven by data at the end of the day, but. Yeah, I mean, I actually am fortunate to have three adult children, and I don't have a favorite. I don't have a favorite here either. I mean, I think the beauty of the combination that we did with Cormorant's SPAC was it gave us the runway to turn over the cards on all three of these programs and be data-driven. I think, you know, we would not be doing what's right for patients or the company if we picked a favorite in the absence of data. And so we have that runway to turn over those cards, and so that's exactly what we're going to do, and we're going to be data-driven. Now, you know, can we do this all ourselves? You know, probably not. We're going to need help along the way if, you know, all three of these hit as we expect, but we'll have a lot of optionality and be able to do that. You're doing a very good job of anticipating my questions because the next question was, just given how competitive the RAS space is, how do you think about like the strategic evolution of the company, partnering, things like that? Yeah, I think that's a great question, Cory. Given the proximity of these data releases that we're guiding towards, I think we are in that position to, based on the data, to first of all prioritize, and second, then think of, as you can imagine, strategic partnering is always ongoing, but to be able to figure out which program we will likely take forward, and then the others could be valuably co-partnered. So, like, when you think about partnering though, is it, would a partner be brought in because of the capital resources that they provide, or is it more, do you need the added bandwidth from a clinical development point of view and strategically taking on the right tumor types? Yeah, I think both, because these are big indications, these are big trials once you start getting onto the registrational pathways, and hence, once we make our choice for the sort of the other programs, you will need not just capital, but also executional capabilities. Okay, and so it sounds like the plan is, if I'm like hearing everything correctly, you get all this data next year, kind of, and then have that sort of portfolio review and determine the appropriate next step. Yeah, we continue to do portfolio review with all the data sets that are emerging all the time, but to your point, yeah, to make decisions and actually execute on those will probably be done once all of these data cards are flipped. How much work is going on behind the scenes from a preclinical point of view for additional follow-on assets down the road? Yeah, we have a great research team. I know my background is research. We still do active research on new targets. You know, we're not really ready to discuss that yet, but that's really, that's my DNA really. That's where I cut my teeth in the industry. And so, you know, we continue to do, I think, exciting research that should make a difference for us. You can just be assured, three is not enough. There's more. I love it. All right, well, since you took my sneak peek question, already at the beginning of this discussion, I don't have to go there and we can end it right now. Thank you guys very much. I appreciate it. Thank you, Cory.