Hi, everyone. My name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. And I'd like to welcome the CEO of Erasca, Jonathan Lim, and the CFO, David Chacko. Thanks so much for joining us today, and thanks to the audience as well. Jonathan's going to start off with a presentation, and then we'll switch over to Q&A for about 15 minutes. So it's going to be a hybrid-type format. But without further ado, I'll turn it over to Jonathan and let him tell you more about Erasca. Thanks, Maury. It's great to be here at the Jefferies London Conference. I will be making forward-looking statements, so please visit erasca.com for our latest SEC filings. So Erasca, our vision is to erase cancer. We have really an amazing pipeline anchored by a phase 3 asset called naporafenib. I won't have time to talk about that, but maybe in the Q&A we can cover that. That is targeting NRAS mutant melanoma. I think there's a lot of excitement around the RAS targeting franchise anchored by ERAS-15, which is a pan-RAS molecular glue, and ERAS-4001, which is a pan-KRAS small molecule inhibitor. We're very well capitalized with cash guidance out into the first half of 2027. We have a world-leading SAB that's entirely focused on our mission of erasing cancer by targeting the RAS-MAPK pathway. And so it's really a who's who of people from industry and academia. Our singular focus is on the RAS-MAPK pathway. We have a threefold approach. The first is to target upstream and downstream nodes, as we are doing with naporafenib and trametinib, for instance. The second is through direct RAS targeting, as we are with ERAS-15 and 4001. And then we also are on the lookout for ways to shut down the pathway more broadly. Our pipeline is anchored by naporafenib. We just reported data on SEACRAF1 showing 40% response rates in NRAS mutant melanoma, very good durability. So that's an exciting path forward with a dual primary endpoint of PFS and OS. We are in SEACRAF2, which is a registration-enabling phase III trial for NRAS melanoma. And then for our ERAS-15 and 4001 assets, we plan to initiate AURORAS and BOREALIS. And when you put them together, you get the Northern Lights. So I'm going to start with ERAS-15. This has best-in-class potential. I think the comparator out there is very exciting in terms of RMC-6236, but we do have a lot of attributes that we are excited about. And so let's talk about that. First of all, this has significantly higher CYPA binding affinity, about 8- 20-fold higher binding affinity than RMC-6236. RMC-6236 is a fantastic drug, and it really has validated this class of CYPA binding. But by binding with 8- to 20-fold higher affinity, it translates into a number of key benefits. Some of those include potency. So this is quite an eye chart, but what you're looking at is comparative IC50s in cell lines across different G12X, G13X, and Q61X cell lines. And in red is RMC-6236. And if you look in purple at ERAS-15, you could see significantly higher potency, as exemplified by lower nanomolar IC50 across all of the different cell lines. I'm going to show you a number of in vivo xenograft models that basically are variations on the theme of, this is eight- to 10-fold higher potency in vivo, and it's really driven by that higher CYPA binding, so this is a PK59 model, G12D. You could see that with RMC6236, it took three MPK to achieve tumor regression. With ERAS-15, it took 0.3 or just 1/10 of the MPK of the dose to be able to achieve a similar degree of tumor regression. Same thing in a very insensitive model. This is called H727. A lot of KOLs will tell you this is sort of the bellwether model of G12V lung, where if you see activity here, that's something to get very excited about, so in this model, it took about 10 MPK of RMC-6236 to achieve tumor regression. You can see with just one MPK of ERAS-15, you're able to achieve the same level of regression. And then this is combination with docetaxel. As you can imagine, different combos, for instance, in pancreatic and other tumor types may be important to look at in the future. You could see very good combination benefit and tolerability. You can also see in this G12V CRC model and SW620 model about an eight-fold higher potency of ERAS-15 versus RMC-6236. And then this is a very difficult-to-treat G12R mutation in PDAC. And you're seeing very good tumor regression with a low dose of just five MPK of ERAS-15. Now, this is also a repeat of G12R PDAC, where you're showing comparison to RMC6236 and ERAS-15. Again, just 1/10 of the dose is required. Now, combination with PD-1 is par for the course in lung. What's really cool about this asset is when you combine it, you see just complete eradication of tumors in about seven out of seven treated mice. Even on tumor re-challenge, the immune system has been activated to be able to fight off the re-challenge. Now, that's all the in vivo and in vitro potency benefit. The other key feature is better tumor tissue concentration or residence time. There's more CYPA in the local tumor tissue. With that higher 8- 20-fold higher binding affinity, you get a lot longer tumor tissue residence time. For instance, in light blue, you can see the blood levels of ERAS-15 and CYPA6236 at 4 and 24 hours. They diminish quite a bit. These are two different models. The message is the same irrespective of model. In dark blue, you could see the tumor tissue concentration. These are all dose-adjusted. You can see at 4 and 24 hours a drop-off of the amount of CYPA6236. When you look at ERAS-15, it remains persistently high even at the 24-hour mark. That really is a function of the CYPA binding. I'm going to talk about PK and end with ADME. From a PK perspective, the readout to really focus on is the bioavailability, the F%. Across multiple species, small and large, including monkey, you could see very high oral bioavailability, long half-life, low clearance. From a PK standpoint, this also looks to be very promising. Finally, from an ADME perspective, the kinetic solubility is really nice for this compound. It remains high and soluble irrespective of the fed or the fasted state. The same cannot be said for the comparator compound. And then in terms of CYPA binding, this should have minimal DDI in terms of the CYPA profile. So that's ERAS-15. I'm going to talk briefly about 4001. This is a first-in-class, best-in-class approach. The key feature of this molecule is it's a small molecule binder to Switch II pocket, just like other small molecule inhibitors. But it is K-selective, and it spares H and N. And so as a result of that, it could have a wider therapeutic index than the pan-RAS class of molecules, especially as you think about some of the rash and other tolerability issues seen there. It also hits KRAS wild type, which you want to see that profile because of the propensity for KRAS wild type amplification. But it is H and N sparing. Now, I won't go through the cell line data, but it's very potent across different KRAS cell lines, D and V especially, including C, for example. And then, in terms of, it's really important to have both GTP as well as GDP activity, especially as D and V and other G12X variants tend to cycle more in the active state. And so having both GTP and GDP activity is a key feature of this class of molecules. And then I'll show you a number of different preclinical models. All of them are, again, variations on the theme. You will notice that whether it's the PDAC CDX model here of Panc 04.03 or PK59, there are higher doses required for this molecule than for ERAS-15. ERAS-15 is just incredibly low in terms of just how highly potent it is. But with this one, this is more traditional for this class of small molecule inhibitors. And then this is that bellwether H727 model. And so just as a point of reference, it took one milligram per kilogram of ERAS-15 to show tumor regression. With this one, we are seeing tumor stasis, but it takes 300 MPK. I think it's BID, yeah, BID. So it's pretty high dose, but you are getting there, which is nice to see for this class. And we reproduce these data. Now, the combination benefit is also very promising here, where you're seeing complete eradication when you combine this with an Anti-PD-1 agent. And then oral bioavailability also is very nice across mouse, rat, and dog, so across small and large animal species. ADME property also is very promising. The one yellow flag that we noted in our diligence for this molecule was the hERG, which is at about one micromolar. But we are doing a dog CV study to de-risk this. And at worst, there might be additional cardiac monitoring in the clinic. Now, KRAS is very common. The big three tumor types are PDAC, colon, and lung. There is a very long tail. But long tail in this case is very high frequency. And you're talking tens of thousands of patients. So our CDP is really focused on those big three as well as the long tail. So we're going to look very comprehensively with both assets. And so we're parallel processing both of those. Our milestones coming up, I think people are very excited about the possibility that we'll be filing INDs for both of these molecules in H1 and Q1 respectively for ERAS-15 and 4001. So that's just around the corner. Then for naporafenib, we also are having a SEACRAFT-2 readout from the dose optimization stage. That's next year, next calendar year. We will be guiding towards phase one monotherapy in calendar year 2026 for both of the RAS assets. I think people are very excited about that as well. So with that, we'll take questions with Maury. Yeah, thank you. I think that was a great intro and overview. Just as background, I just initiated on Erasca at the beginning of this week. One of the things that I thought was interesting is that with these two assets, even though they're early stage, they could address pretty big market opportunities. You mentioned the number of patients up there. Maybe starting off, if you can contextualize that, and also one of the key competitors in the space is Revolution Med, which has a pretty high valuation too. What do you think about where you're at in development stage and the competitive landscape and getting into these pretty big market opportunities? Yeah, no, great question. Thanks a lot for initiating. We were excited to get you on board the team, and I think it's great timing to have you start to cover us, and so to contextualize it, the opportunity, there's about 2.5 million patients worldwide that have these KRAS mutations across different solid tumor types. So it's a huge unmet need. I think what's really exciting about this class of molecules in terms of the pan-RAS molecular glue is, first of all, the validation that Revolution Medicines has done a nice job of providing, but then also, it's the scarcity value. So I think it's a pretty high barrier to entry. You don't have dozens of CYPA binders out there because it's actually the complexity of making these molecules and finding free IP space is actually non-trivial, to put it mildly, and so there's really just a handful of us. There's Revolution Medicines. There's us. I think people view us as being sort of the second in second place, and then there's a Chinese company called GenFleet that also has a similar MOA that they're doing, but they're a little bit behind us, so it's really just the three of us that we're aware of. I think other people are trying, but it's really a short list at this point. I think in the pan-KRAS class, there's big pharma like Lilly and Pfizer and then smaller biotechs that are taking these switch II pocket approaches to being able to inhibit KRAS, and so I think 4001 has a little more competition, but it also is in that vanguard of the first wave of molecules, so we're in the mix, and then I think we have this unique ability to combine the two assets. And so as you think about hitting G12D or G12V or G12X really hard with 4001, that's H and N sparing, and then having a pan-RAS molecule on board for potential isotype switching or mutations that arise elsewhere in RAS, I think that could be a very interesting combination to pursue as well. Got it. Yeah, makes sense. And for these two assets, you guys did a lot of diligence on them. Maybe talk a little bit about that process. And as you were reproducing some of the data from the originators of the assets, I guess, were there any positive or negative surprises with some of the preclinical work you did? Yeah, so we had an ERAS-4001 discovery program where we were working on pan-KRAS molecules. And then we came across some IP from WuXi that read on what we were doing. And so we engaged with them. We know them well and had friendly discussions about that. And then we became aware that 4001 was available for global licensing. And so we were able to work on that together. And then WuXi kindly introduced us to the originator or to the licensee of the pan-RAS molecular glue. And so it was about a 17-week process from when we first started our first trip to China earlier this year in February to the culmination of both deals simultaneous with the financing that we did. All that happened in mid-May. And so it was very brisk. And then I would say that we're very excited to work with our partners on pushing this forward. Got it. OK. And for starting the initial first-in-human studies, maybe talk a little bit about the plans there, what those studies could look like, and the types of patients you could enroll into the studies. And when could we potentially see data from those? Yeah, so in terms of a few weeks ago, we disclosed that we had finished the in-life portion of the GLP tox in both large animal and small animal species for ERAS-15. And then we were near completion for 4001. So that gives you a sense that that's sort of typically the long pole is the GLP tox. We also reiterated our guidance or reaffirmed that we're on track with the CMC. That's the other long pole. So both of those are working well. There's a lot of excitement for both of these programs in the investigator community. So there will be some sites that will open up with both molecules, others that open up with one or the other. It'll be a traditional dose escalation. You can imagine it'll enroll very quickly, just unfortunately because there's so many patients with RAS mutations, especially KRAS. So I think most, if not all, of the patients will probably have a KRAS mutation. I would say with ERAS-15, we don't have to get to very high doses to see some PD, if not efficacy activity there. And so I think our guidance is 2026. As As to when in 2026, I think we'll know more once we're in the clinic. Got it and for RevMed, they tested a wide range of doses from 10 to 400 mgs. Could you potentially leverage that and accelerate your dose escalation strategy? Yeah, I mean, I think the GLP talks will dictate what our starting dose is. And then I think with 6236, they saw efficacy starting at dose level four. So I think it won't take a lot of dose escalations for us to hopefully see some signs of activity. But we'll really do the right thing in terms of exploring the right dose and do a fulsome dose escalation before expanding. But along the way, I think we'll enroll all comers with different tumor types and see what the signal looks like. Got it. Makes sense. And then for RevMed, do you think their dose escalation study timeline is a good benchmark for you guys as well? Yeah, I think that's reasonable. Got it. And showing strong RAS-on activity is an important characteristic of 6236. Based on your preclinical studies, how active is ERAS-15 on RAS-on versus RAS-off compared to 6236? It's no less active than 6236 because it's an identical mechanism, and I think what's been really cool about what RevMed has shown is just the translatability of the preclinical to the clinical setting, whether it's with 6236 or 6291 or 9805. I think the preclinical efficacy models are quite predictive of what you could see in the clinic, so we have a lot of confidence based on the preclinical data that we've generated that hopefully for this class of molecules, the same is true. Got it. And you've talked about the greater potency potential versus 6236. How do you think about selectivity for the target, given it's more complicated with the different mutations that you're going to be targeting all at once? Yeah, they're both very selective. So it is this tripartite moiety. So you've got sort of the agent itself that goes hunting for Cyclophilin A. And then because we have a much higher binding affinity, 8- to 20-fold higher, you form these dipartite moieties. But we just have a lot more Pacman molecules made because of the 8- to 20-fold higher binding affinity. And then those Pacman molecules go hunting for RAS. And because of the RAS-binding mode, it's very selective for RAS, irrespective of on or off state. Got it. OK. And so let's talk about 4001. There are multiple current players currently developing pan-KRAS inhibitors. You mentioned Pfizer and Lilly. Noting that these are all in early stages with very limited preclinical or clinical data, based on your understanding so far, how does your drug compare to and differentiate from the other ones in development? Yeah, I will take that. Yeah, absolutely. So yes, there's limited data to date on the pan-KRAS class. And so as Jonathan mentioned, we are in that vanguard of the leading set of molecules. I think our molecule, based on the data that we reviewed here today, looks quite favorable in terms of its in vitro potency, in terms of its in vivo activity, in terms of its ADME PK properties as well. And so as the class continues to evolve, as there continues to be new clinical data that are generated, both by us but also by others, we'll continue to see how that plays out. But we feel good about this molecule's profile. Got it. OK. And with 4001, you mentioned it's a switch II pocket binder. And so it has higher activity for RAS-GDP versus RAS-GTP. Given that ERAS-15 is a molecular glue with a different mechanism, could you potentially combine these two molecules? And would there be any benefit to that? Yeah, absolutely. We're really excited about the combination potential. And even though there's sort of a four-fold higher potency for 4001 against the GDP state, it still is about 6 plus nanomolar IC50 against the GTP state. So there's still sufficient activity to see activity against the on state. But because of that orthogonal mechanism of action, we really like the combination potential with the pan-RAS molecule, to your point. Got it. And which indications do you expect a pan-KRAS inhibitor would be more effective or safe versus a pan-RAS inhibitor? I think it has to do with potential combinability. So if RAS becomes an issue for ERAS-15, as there's been high frequency, maybe lower severity of RAS observed with the other pan-RAS molecule, if that becomes an issue, then combining with anti-EGFR, for instance, which also causes quite a bit of RAS, that stacking talks might not be what you want to do. And so that might be where a kinder, gentler approach of H and N sparing with 4001 could be a better use case for that in terms of combining with anti-EGFR, for instance. Got it. OK, and let's shift gears to naporafenib. I wanted to ask a couple of questions there. Maybe if you could just comment on enrollment pace for stage one so far, and how many patients are you planning to enroll? And how long do you think enrollment could take overall? Sure. Yeah, so naporafenib is the pan-RAF inhibitor. And enrollment, we kicked off the study in Q2 of this year. And I would say that enrollment has been good. Site enthusiasm, investigator enthusiasm has been very high. And with the data that we shared at the Triple eeting last month from our SEACRAFT-1 study showing a 40% response rate in melanoma and a good tolerability profile, I think that has only added to the enthusiasm. We have guided to having stage one data from that study of the phase 3 portion of the study in calendar year 2025. That'll be between 60 and 120 patients. It's an open label study. So we'll be able to see the data as it comes in and be able to make a call somewhere between 60 and 120 patients before we move into stage two, which is guided to 350 total patients. Got it. And what do you want to see in that stage one in order to make a call? I guess, what are you going to be looking for there? So we're looking at a combination across the board of the efficacy, the safety, tolerability, other factors as well. What I will say is that the profile that we showed with the 201 dose at the triple meeting in the SEACRAFT-1 study looked really good. So I would say that that is our presumptive go-forward dose. But we're also evaluating two other doses in SEACRAFT-2 stage one. So between the three, we can then choose one to move forward with. But that 201 dose looked really nice at the triple meeting. Got it. OK. So I think we're pretty much out of time. Maybe to close out, David, if you want to comment on cash position and if you guys want to talk about key catalysts that investors should be focused on. Sure. So in terms of cash, we ended Q3 with $463 million in cash. That gives us runway out to the first half of 2027. In terms of catalysts for naporafenib, we have our phase 3 stage 1 data in calendar year 2025. For the two new RAS assets, the IND filing for 4001 is in Q1 of next year. For 0015, the pan-RAS molecular glue, that IND filing is in the first half of next year. Then both of them are guided to phase one monotherapy data in calendar year 2026. Got it. Thanks so much for joining us today.