Hi, everyone. My name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. I'd like to welcome David Chacko, the CFO and CBO of Erasca. Thanks so much for joining us today in London. Thank you. Thanks, Maury, for having us here. We're going to do a fireside chat format. For those who are new to the story, maybe give a brief intro to Erasca. Sure, absolutely. Erasca is a precision oncology company. We're based in San Diego. We were founded back in 2018 by our CEO, Jonathan Lim, who was previously CEO at Ignyta up until the Roche acquisition, as well as Kevan Shokat from UCSF. They founded the company around the idea of going after the RAS- MAP kinase pathway, which is mutated in anywhere from a third to half of all cancers. Our name, Erasca, is actually a dual meaning. We're not only trying to erase cancer, but also eradicate RAS-driven cancers. I know we'll spend a lot of time today talking about our pan-RAS program, ERAS-0015, as well as our pan-KRAS, ERAS-4001, both of which go after the RAS protein. That idea of eradicating RAS-driven cancers is core to our strategy. We are, oh, that sounds like the microphone is on now a little bit more. We are, as I mentioned, based in San Diego. We've assembled a very strong team, as well as a very strong SAB. We're well capitalized with $362 million as of Q3, with runway out to the second half of 2028. We have the financial capital as well as the human capital to be able to really advance these programs quite well with an aggressive clinical development plan. Got it. You mentioned the two lead assets, 0015 and 4001. Maybe starting with 0015, let's talk about how that's different from some of the other programs out there. There's a lot of interest in Revolution Medicines' Daraxonrasib. What are the key preclinical PK/PD differences versus that drug, and how do you expect these to translate clinically? Yeah, absolutely. Maybe I'll start off with what's similar between the two and then talk about the differentiation. In terms of the similarities, both of them work through the same mechanism of action. They're both CypA, cyclophilin A binders, and they form a tripartite complex. The first step in that is for the molecule 0015 to bind to cyclophilin A, and then that bipartite molecule goes and finds the RAS protein to form the tripartite molecule. It's the same MOA between us and the Revolution Medicines 6236 compound, Daraxonrasib. In terms of differentiation, we believe that there's a number of areas of preclinical differentiation that we've been able to show preclinically. It starts with the fact that we are able to bind to cyclophilin A, that first step in forming that bipartite complex with very high affinity, on the order of about 8-20-fold better binding affinity to CypA compared to 6236. That leads to a number of advantages, including the fact that across maybe 15 or so different cell lines that we've tested that represent a variety of mutations, a variety of tumor types, we're seeing about 4-5x greater in vitro potency. It also translates into better in vivo activity in the form of comparable activity at a fraction of the dose, about one-tenth the dose needed for our drug compared to 6236 to achieve comparable, if not better, anti-tumor activity. We also see, in terms of tumor PK kinetics, that our drug has better residence time as well as better distribution into the tumor compared to 6236. Finally, in terms of the adamine PK properties, our molecule, again, head-to-head across multiple animal species, shows very good PK properties in terms of better clearance, better half-life, and better oral bioavailability. All of those factors lead to a number of forms of differentiation. We will see how all of this translates clinically. What we have guided to is that we will have data from our phase one monotherapy dose escalation in calendar year 2026, and that will be the time when we can see exactly what our profile looks like relative to 6236 in the space. Got it. Yeah, we'll definitely talk more about the clinical studies. For 4001, what differentiates that mechanism of action versus other pan-KRAS molecules? Yeah, so most of the pan-KRAS molecules in the space are actually switch-II pocket binders. This was one of the pockets that was identified by Kevan Shokat, our co-founder. Most of them are switch-II pocket binders. Ours is as well. What we like about our program, in this particular case, unlike the pan-RAS space where there is the clinical structure for 6236 that's available, and so we were able to do head-to-head comparisons there, in the pan-KRAS space, there's very limited information in terms of what competitor structures look like. We haven't been able to do any head-to-heads there. What we do like about our compound is that it shows a number of very good preclinical properties. It is also very potent in vitro against particularly G12X mutations, certain ones of those, as well as G13, as well as KRAS wild type, which is really important when you think about resistance mechanisms. The molecule also has single-digit nanomolar potency against both the GDP state as well as the GTP state of the molecule. That gives activity against both the off and the on state, albeit more so against the GDP state, but still single-digit nanomolar against both. It's got good in vivo activity as well across multiple preclinical models. The adamine PK properties look very nice there as well. One additional area of differentiation there is that our molecule is actually on a different scaffold, a different chemical scaffold than many of the other pan-KRAS molecules. That allows us potentially another form of differentiation there. Got it. What could that do since it's on a different scaffold? In terms of just allowing for—we've heard anecdotally that certain of the molecules that have gone into the clinic initially have had certain issues. To the extent that those issues are related to a certain scaffold, then having a different scaffold could allow us to bypass that. Got it. Okay. Both programs are in the clinic now. Maybe give us a status update on how those phase one studies are going for 0015 and for 4001, and what's the latest progress there? Yeah, absolutely. What we publicly disclosed on these programs is that the INDs were cleared for both of them back in May of this year. We're now currently in the phase one dose escalations for both programs. Enrollment is moving along really well for both. I think that just speaks to two things. Number one, the high unmet need here. There are 2.7 million patients that are diagnosed each year around the world with RAS mutant tumors, of which 2.2 million is KRAS mutant. There is a high unmet need here. I think it also speaks to the differentiated profile that we've been able to, as I've described here, and also been able to show to investigators who we wanted to be part of our trial as well. They have been very excited about that preclinical profile and what it might be able to do clinically. What we've guided to, as I've mentioned, is that we'll have data on both programs, again, the phase I monotherapy dose escalation data in calendar year 2026. That is a broadbanded guidance. We put that guidance out at JPMorgan earlier this year, even before the INDs went in. As enrollment continues, we'll have a better sense of what that's looking like and may be able to tighten up that guidance in the future. Got it. Can you say more just about the studies and how many sites you have open and what the target number of enrollment is? Are there overlapping sites between 0015 and 4001? Yeah, so we've got just about four to five sites for each of the programs for the dose escalation. It's the preeminent sites that you would think about in terms of phase one dose escalations in the oncology space with preeminent KOLs and PIs at those sites. In terms of the two programs, again, it is progressing well through the dose escalation. There is a projected enrollment that's listed on ct.gov. As you know, in terms of phase one dose escalations, what you're trying to do, obviously, is establish a dose and allow for—we are allowing for backfill in certain of our cohorts. That will dictate more what the actual enrollment ends up looking like. In terms of your question around overlap of sites, for the most part, between those four sites for one study, five for the other one, there's actually not overlap. We do have one overlapping site, but this basically allows for the PIs at those sites to enroll patients pretty actively onto those studies. In a phase one, that's all we really need for us to be able to enroll the study quickly. You don't want to have too many sites where investigators and sites actually get frustrated because they can't actually put their patients on the study. This gives us the optimal balance of having enough sites but not too many. Got it. You mentioned there's enthusiasm for the drugs. Is there a preference for one over the other or? You know, I would say that the space, that's still an open question in the space. I was at a different banking conference earlier this year where David Hong from MD Anderson and Ryan Corcoran from MGH were debating the pros and the cons of the pan-RAS and the pan-KRAS approach. I think there are different advantages and disadvantages as well. I think depending on the PI, they might have their own kind of personal preference for one versus the other, but I think they both have really good profiles that are attracting a number of investigators on each. Got it. Okay. For each program, you're enrolling all comers. Presumably, you're getting patients that reflect the epidemiology of the cancers. Is there some enrollment biases early on? You have levers that you can pull at some point to help enrich enrollment. What could that look like? Yeah, that is right, that we are taking all comers as long as they have a RAS mutation. In a phase one dose escalation, your goal is to obviously get to your dose as quickly as possible, as well as identify safety and PK and early signs of activity. Early on in the dose escalation, we're not really putting any guardrails as long as they have a RAS mutation, but otherwise, we're not really putting guardrails in terms of enrollment. If you think about the epidemiology, as you were alluding to in the RAS space, there's the big three tumor types of CRC, pancreatic, and lung. There is the long tail of opportunities that includes a number of different things. In the RAS mutant space, because there are so many patients that unfortunately have this mutation, even those long tail opportunities are still tens of thousands of patients in the U.S. and comparable here in Europe as well. Those are still sizable opportunities. Early on, we'll take all comers. Later on, to your point, we do have the ability to enrich for certain populations if we want to see more of X type of patient. Got it. That decision to enrich, would you disclose that to the public or make some sort of an update on ct.gov? I guess how could that look? We'll probably just announce that once we actually disclose the data, you'll see that there's more patients of a certain tumor type, for instance. Got it. Okay. It will not be until you have the data updates next year. Got it. Yeah. Okay. You have not said a lot on just the dosing strategy. I guess any qualitative perspective on where you are at with dosing and whether you are seeing biological activity at this point? Yeah, so in terms of qualitative, again, we disclosed that we cleared the INDs back in May and that we are on track for the 2026 data readout. Where specifically we are in the dose escalation, we're actually not guiding on that right now, just given how competitive the RAS space is. I mean the broader RAS space of pan-RAS, pan-KRAS, mutant selective. We're not talking specifically about where we are. It would be premature for me to talk about efficacy, but again, stay tuned for the data readouts that are guided for next year. Got it. Okay. For those initial data updates, just talk about what we should expect to see in terms of number of patients and number of doses that you're going to report. Yeah, I'll take each one separately. In terms of, there's some similarities of what I'll describe. In terms of 0015, the pan-RAS molecule, we want to be able to tell an interpretable story here. We want to have enough patients for us internally to be able to understand what the data are showing and also for the external world to be able to do the same. Think about dozens of patients in that update. We'll obviously be looking at safety and PK and then early initial signs of activity as well. With the pan-KRAS program 4001, it'll be very similar in terms of, again, an interpretable story, dozens of patients, initial signs of PK and safety and anti-tumor activity. I think the difference is that because in the case of the pan-RAS class, there is already clinical data that's been disclosed by Revolution Medicines, again, we know a lot more about that space. We know, for instance, that Revolution started at 10 mg and then they went to 20, 40, 80, and that's when they saw their initial signs of activity. It gives us a little bit of a, if anything, like maybe a guide in terms of what could come next for us. I think that's an advantage that we have in this particular case about being second in class, that we know a lot about what they've done. They've been trailblazers in the space, and we think fondly of them. I think it's one of those ones where we can learn a lot in that space. We have learned a lot from them. With 4001, because again, nobody has disclosed any clinical data there yet, that development path is a little bit more unknown at this point. I am not talking about us specifically. I just mean as a class, we just know less about the pan-KRAS space. As people disclose data, we will know a lot more. Got it. Okay. For these updates, are you planning to share data from both at the same time, or is it going to be two separate events? It could be either. We could do them jointly, or we could do them as disaggregated. I think, again, we want to be able to tell an interpretable story on both. If that happens to be at the same time, great. If it turns out that one of the molecules we get there sooner, then we can disclose that one first and then do the other one later. Got it. Okay. For the RevMed data, definitely informs with dosing, probably on the safety side too, because you kind of have some clear goalposts there. For efficacy, I guess, what do you want to show there on efficacy relative to RevMed? Yeah. Actually, I'll talk about safety and efficacy both. On the safety side, I think the bar for us here is non-inferiority because for two reasons. Number one, the high unmet need. There are so many patients with these RAS mutant tumors, as we're talking about. Number two, the fact that there are really only a couple of competitors in this space. There is Rev Med which has the most advanced molecule in the space, and then there is us. There are a few others in other parts of the world, but they are not necessarily advancing global trials. I think given the unmet need and given the relative lack of competition in that space, the bar for us there is non-inferiority. I think on the safety side, I think if we can show a comparable profile to where RevMed is at, I think that would be a home run for us. If we're actually able to show a better profile from a safety standpoint, I think that would be a grand slam for us. Why I think that it matters is that one of the reasons that we were able to bring in this molecule or that excited us about this molecule is the fact that we think that we could have a lower clinically active dose than RevMed with our molecule. Even if we have a comparable safety profile, when you think about certain AEs, especially like GI, which can be driven by drug load in the GI tract, a lower drug load could lead to a better AE profile. If you think about combinations, a lower drug load could also be beneficial when you think about combinations. That is why I think even comparable safety would be a win there for us. On the efficacy side, again, if we are able to show comparable activity at a fraction of the dose, that would be thesis reinforcing for us and very much so a win. I think if we are able to show activity at, call it half the dose of where RevMed is at, I think that would be a home run for us. If we are able to show activity at a quarter of the dose, I think that would be a grand slam for us. As you think about broader, once we identify a recommended dose, RD and an RD minus one, and once we have enough patients there, I think, again, if we are able to show overall comparable activity versus Rev Med, that would be a win. Anything that we are able to show above and beyond would just be additional upside. Got it. Okay. Makes sense. How should we think about 4001's benchmark given there are no pan-KRAS competitor data? Should investors view Daraxonra sib or RAS targeted agents as the best benchmark? Yeah, that one's a little bit harder just given to your point that nobody's released any clinical data there yet. I'm happy to give my thoughts on this. This will likely evolve as competitors do disclose data in the space. The way that I would think about it is in terms of PK, safety, and efficacy. I'll take those three in turn. In terms of PK, if we're able to show dose proportional PK throughout the biologically relevant doses, that would be a win. That would be first in class in this space. On the safety side and tolerability, if we're able to show AEs that are comparable with the class, either pan-KRAS that are disclosed or if you think about the pan-KRAS, I'm sorry, pan-RAS or mutant selective approaches, that would be a win. On the efficacy side, really showing any anti-tumor activity, again, since nobody has shown any clinical data yet, that would be first in class in this space as well. Got it. Okay. For these data updates, is it going to be at a company event or should we expect these at medical conferences? It could be either. We, as a company, have done both. I would say all things being equal, medical meetings are always preferred, but sometimes the timing of when abstracts are due and when you have to do your data cutoff, that may or may not always line up. We have done both. We have done medical meetings. We have done company R&D days. Got it. For 4001, are you excluding prior KRAS inhibitors in the study? Yes. Yes. Okay. Anything else about the patient baseline characteristics that could be different versus RevMed study? I think in the initial phase one, it's as relatively straightforward as you would expect for most phase one studies. Because again, you're just trying to, the goal of any phase one study, as this audience knows, is really to identify your dose and safety and PK. Of course, all of us, ourselves included, are also interested in what that initial anti-tumor activity looks like as well. Really, the main purpose of any phase one study is what I mentioned before: safety, tolerability, dose, those sorts of things. Got it. Okay. Yeah. For 0015, for both of these, it should be an informative update as well. Yeah. Yeah. Yeah. Yeah. Okay. Maybe talk about combo strategy for both the drugs. Just what's your plan there? Yeah. Our plan is really to take a very aggressive clinical development plan, what we refer to as our CDP, because the potential for a pan-RAS and a pan-KRAS is just so broad and just there's so many different avenues that we can explore. We want to have as much ability to be able to do that. I mentioned earlier that we ended Q3 with $362 million in cash. We are well capitalized. We've got runway out to the second half of 2028 that allows us to do just a lot of work with both of these assets and really, as I mentioned, have an aggressive CDP with no stone unturned. I think that differentiates us from some of the others in the space who maybe aren't as well capitalized and therefore can't explore their molecules in the same way. We're going to be looking at potential monotherapy approaches where they could compete well against even combinations. Of course, we'll be looking at combination approaches as well. The classic example there would be, for instance, in CRC, colorectal cancer, where you often want to be able to combine with an anti-EGFR antibody. Also, if you think about lung cancer, where you want to be able to combine with a PD-1. Got it. We will be looking at both standard of care as well as investigational agents that we can combine our molecules with. Got it. Maybe kind of jumping ahead a little bit, but you have got discovery stage EGFR drug. Maybe talk a little bit about that and how that fits into. Yeah. We have ERAS-12. That's our bispecific bi-paratopic antibody going after the EGFR domain 2 and domain 3. This is a molecule that we licensed in from Emerge Life Sciences. They're a Singapore-based company, former Genentech protein scientists, very strong team. We brought this program in because of that ability to target both domain two and domain three. All of the approved anti-EGFR antibodies, so like cetuximab, panitumumab, they go after domain three only versus this molecule has the ability to go after, again, both D2 and D3. We think that that can lead to better anti-tumor activity, particularly when EGF is overexpressed. This is a discovery stage program. It's still early in our pipeline, but we're making advances on it. Could that fit into your strategy with the RAS or KRAS? Yeah. I mean, we're, again, as I mentioned, we are looking at both standard of care as well as investigational agents that we could combine with. Absolutely. I think we, as a company, have shown a history of really identifying what are the best combinations, whether that's in-house proprietary molecules or external ones, and combining there. I think that gives us an advantage in terms of going to where the best science is and for patient benefit. Got it. For the ongoing studies, anything more you could say qualitatively on how safety is looking so far for those programs? Yeah. Qualitatively, I would say that everything is in line with our expectations on both of these studies. I think in terms of more detailed, probably we need to wait for next year's update. Got it. For expectations on on-and-off target toxicity in these programs, such as GI toxicity and RASH, is the GI toxicity mostly driven by the amount of drug that you're putting on board? I guess what are your expectations there? Yeah. Let me start in the pan-RAS side because, again, that's where RevMed has disclosed data and there hasn't been data in the pan-KRAS space. Their number one AE is RASH. Their number two AE is GI. RASH, we believe, is on target, and we will likely also have some amount of RASH. GI can either be driven by on-target or drug load in the GI tract or some combination of the two. If we have a lower clinically active dose of our molecule, that would just lower the amount of drug load in the GI tract. To the extent that your GI tox is driven by that, we should hopefully have a better profile. If it turns out to be entirely on target, then that's a different story. We will know more as we proceed through the dose escalation. Got it. Okay. The other thing I would mention in terms of RASH is that our company has had a lot of experience dealing with RASH with one of our other programs. Naporafenib is our pan-RAS inhibitor that we licensed from Novartis back in December of 2022. That molecule in Novartis's hands had a fair amount of RASH in the phase one and two study. We implemented mandatory primary RASH prophylaxis as part of our phase three study. It has done tremendously well in terms of bringing the rate of RASH down, increasing the relative dose intensity. Our company, both at Erasca and in prior lives, has a lot of experience handling RASH. Got it. Maybe one other quick question, just based on the pan-KRAS space, who are the key competitors there that you see? In the pan-KRAS space? Yeah. Yeah. There is a number of players in this space, both on the big pharma side as well as smaller companies, mostly private companies. Pfizer, Lilly, they have programs that have entered into the clinic. I would imagine that many, if not all, of the big pharmas probably have programs, whether those have been disclosed or not. There are some smaller similar-sized companies as Erasca that are also working on the space. Companies like BridgeBio, Alterome, who is another San Diego company that we are close with. There is a number of companies in the space. I think this is where, again, it is important as that class gets more competitively intense to be on that leading edge, which we think we are in terms of having gone into the clinic, being in the phase one right now, and being able to share data next year. Got it. Maybe just in closing, I think we're out of time. If you just want to highlight key events for investors to focus on for next year. Anything else that we forgot to mention? Yeah. We covered a lot of ground here. Thanks, Maury. I would say just as far as 2026, we have guided to phase I monotherapy data, as I mentioned, for the two RAS programs next year. I think those will be really exciting data updates just given that it will be the first data for both of our programs. It could be the first data in the pan-KRAS space depending on when others disclose. We will also see how our pan-RAS 0015 looks relative to expectations there. Got it. Okay. Thanks so much for joining us, David. Thanks, Maury.