Good morning, everyone. Welcome to the Jefferies Global Healthcare Conference. My name is Henry Hill with Jefferies Investment Banking, and it is my pleasure to introduce Jonathan Lim, Chairman and CEO of Erasca. Thank you. Thank you, Henry. Good morning, everyone. It's really exciting times at Erasca, and I'm looking forward to giving you an update today. I will be making forward-looking statements, and I encourage you to visit our website at erasca.com, where you'll find our latest filings. At Erasca, our name is our mission to erase cancer. It also stands for eradicating RAS-driven cancer. In that regard, really excited to say that we're really pleased to have brought in a transformative set of deals in terms of announcing the successful in-licensing of a RAS-targeting franchise, namely ERAS-0015, which is a pan-RAS molecular glue with best-in-class potential in RAS-mutant solid tumors. ERAS-4001, which is a pan-KRAS inhibitor with first-in-class potential in KRAS solid tumors. I'll spend the bulk of today's presentation talking about those assets, but we're also excited to be bringing naporafenib into phase III. That's our lead clinical program. We also finished an oversubscribed financing of $184 million, so we're well-capitalized, and we pushed runway into the first half of 2027. We were founded in 2018. Dr. Kevan Shokat was a Co-Founder of the company from UCSF, and he's really a pioneer in the field of targeting KRAS in general. And he's surrounded by just amazing talent on the SAB. Our strategy is to focus exclusively on the RAS-MAP kinase pathway, taking a threefold approach. So the first is to target upstream and downstream nodes, which we're doing with our pan-RAS inhibitor, naporafenib, along with MEK. And we also have in-house SHP2 inhibitor and an ERK inhibitor called 601 and 007, which are basically in the research phase right now. We also target RAS directly, and so the recent BD deals exemplify this approach. And then the third is to target key escape routes. Using that approach, we've assembled a deep modality-agnostic, pathway-focused pipeline. I mentioned that naporafenib is in the clinic right now. It's in a phase I-B trial called SEACRAFT-1, targeting pan-RAS Q61X solid tumors. We have a planned SEACRAFT-2 trial, which is a phase III pivotal study that is planned for initiation basically this quarter, so i.e., this month. Our pan-RAS inhibitor, ERAS-0015, we're planning a trial called AURORAS-1. For our pan-KRAS molecule, ERAS-4001, we're planning BOREALIS-1. For those of you who recently saw the Northern Lights, when we put those together, that'll give rise to the Aurora Borealis trial in the future. ERAS-12 is our bispecific EGFR antibody that we're also very excited about. So I'm going to start with naporafenib. This is a pan-RAF inhibitor, so it targets BRAF and CRAF in particular. It also synergizes with downstream targeting agents such as trametinib or even ERK inhibitors. You can see, based on the profile on the left, the biochemical activity has sub-nanomolar potency against both BRAF and CRAF, single-digit nanomolar against ARAF. Based on the KINOME scan on the right, you can see it's highly selective for these targets. We really like this program because when we in-licensed it from Novartis, it had already been dosed in more than 500 patients, establishing safety, tolerability, and preliminary POC, as I'll show you. We are taking a two-pronged approach, developing this for RAS Q61X solid tumors with SEACRAFT-1. This is a high unmet need, and we will report, actually, data from the phase 1b in the fourth quarter of this year. On the right, you can see NRAS mutant melanoma. We're targeting that with SEACRAFT-2. This is a phase III of naporafenib and trametinib that, as I mentioned, we're initiating this quarter. So I'm going to talk about SEACRAFT-1 first. So this is basically targeting RAS Q61X solid tumors. You can see the frequency is really concentrated in about half a dozen tumor types, mainly melanoma, thyroid, and GI cancers. The data that got us interested in taking this tissue-agnostic approach is seen on this slide. So on the left, you can see the NRAS mutant melanoma data. There's a high degree of overlap between NRAS and Q61X, so about 90% overlap, or in other words, 90% of NRAS mutations in melanoma are RAS Q61X. And so you can see, based on the waterfall plot, 44% response rate in 16 patients. 15 of those had confirmed RAS Q61X mutations. On the right, you can see KRAS mutant non-small cell lung cancer. This is a smaller data set, but interesting signal of activity. Out of the four patients with Q61 or G13R, three of those patients had Q61X mutations, and two of those three patients had confirmed responses for a response rate of about 67%. So in two histologies, you have ORRs ranging from 40%-67%. And if that signal holds both in these histologies as well as some of the other tumor types that I mentioned, then that could potentially form the basis of a tissue-agnostic label. And if not, then we'll take tissue-specific approaches for this mutation. So now, turning to SEACRAFT-2, I'll draw your attention to the graph on the right. So the current standard of care for this highly aggressive disease, which is probably more aggressive than BRAF mutant melanoma, NRAS happens in about 20% of all patients with advanced-stage melanoma. You can see the approved standard of care in the US is dacarbazine or chemotherapy with only a 1.5-month median progression-free survival and very low response rates of 7%. Single-agent MEK inhibitor, binimetinib, was never approved in this indication, but it is on the NCCN guidelines. It has about a 2.8-month PFS and a rough doubling of the ORR, but still a very high unmet need and opportunity for improvement. So we have FDA FastTrack designation for this indication. And you can see, based on the data that we submitted to FDA, the basis for that FastTrack. So you could see basically superiority across ORR, DCR, mDOR, as well as mPFS. And in fact, the PFS of around five months for naporafenib and trametinib, irrespective of the dose, is meaningfully better than what has been shown by historical controls of chemo and single-agent MEK. We think that the PFS for naporafenib and trametinib is very promising if the phase III is able to reproduce some of the data seen in the early phase I and II studies. But importantly, OS is the ultimate endpoint for any of these precision oncology trials. What's really encouraging for us, and we reported this earlier this year, is that the benchmarks most like the SEACRAFT-2 patient population in terms of single-agent MEK and chemo is about seven months. You can see, based on the maturity of the OS data from the phase I and II settings, a meaningful advantage in OS of about 13-14 months, almost doubling of what has been seen historically. These PFS and OS endpoints are basically dual primary endpoints. You can see, based on the data generated to date, the potential to win on either or both of those primary endpoints. In terms of safety and tolerability, you could see on this tornado plot at the two different doses that have been tested. In terms of the RDEs, you could see rash really is the most frequent and severe TRAE. We are implementing primary prophylaxis of the rash in both SEACRAFT-1 and SEACRAFT-2. We envision that that primary prophylaxis, which means treating the rash before it even appears, should have a meaningful impact on safety and tolerability. So this leads me to the last slide in this section, which is the design of SEACRAFT-1 and SEACRAFT-2. SEACRAFT-1 is a single-arm, phase 1b, RAS Q61X all-comers, naporafenib and trametinib at 200 + 1, looking at ORR and DOR in between 30-100 patients. And that then could support either tissue-specific or tissue-agnostic approaches, depending on the data. SEACRAFT-2 is a two-stage design of dose optimization, where we are randomizing two different doses of naporafenib and trametinib versus trametinib single-agent alone. And that is a data set we're reporting next year. And then, based on that data that we report to FDA as well as externally, we'll then go into possible stage two, where we'll randomize the dose selected from stage one and randomize that versus physician's choice of chemo or single-agent MEK. And as I mentioned, the study endpoints are a dual primary of PFS and OS, but we'll also be looking at ORR and DOR as secondaries. All right. Now, turning our attention to the pan-RAS and pan-KRAS therapies. On the left, I would say that KRAS G12C, that approach to drugging what was historically undruggable, was a historical achievement by Dr. Shokat et al. Really, you know, that's launched a renaissance of targeting this undruggable target with mutant selective approaches. Now, there are still a lot of challenges with the mutant selective approaches. There's a number of different mutant selective approaches that are in the clinic or soon to be in the clinic. But on the right-hand side, we're also very excited about sort of broader approaches. The pan-RAS approach, as pioneered by Revolution Medicines, is super exciting. And then also pan-KRAS, which is an area that we have historically been focused on with our internal discovery efforts. But with the in-licensing of both a pan-RAS and pan-KRAS inhibitor, we're now playing in both lanes. So the ideal RAS targeting molecules integrate three key attributes, namely potency, oral bioavailability, which is a non-trivial attribute to dial into the chemistry, and then a proprietary position, which can help bolster and maximize clinical and commercial value in what is becoming a very crowded market. In terms of potency and OBA, this could enable lower clinically active doses, which could translate into a number of key benefits, including sort of better exposure than what's been seen with some of the other approaches, as well as potentially better tolerability or even wider therapeutic windows. And so we have seen, based on what's happened in the KRAS G12C inhibitor class, the benefit of having higher potent drugs that can actually translate into even better efficacy, such as sort of the next-generation G12C inhibitors versus the first-gen inhibitors. So with ERAS-0015 and ERAS-4001, these both exhibit competitive profiles that exceed our target product profile across each of these three dimensions. And so starting with ERAS-0015, we call this a molecular glue, but it's basically a similar mechanism of action in terms of binding cyclophilin A as well as RAS in a tripartite sort of moiety. And so you could see, based on the preclinical activity, I won't go through all of this in detail here. There's really an executive summary, but it's highly potent, highly orally bioavailable, and very strong IP position out to 2043. The same can be said for 4001, the pan-KRAS inhibitor, very potent both in vitro and in vivo. It does take higher doses to achieve tumor regression in the in vivo models, but the oral bioavailability is strong, especially in mouse and dog. And then the IP also covers this to 2043. Now, what we're really interested in strategically, and this is down the road, and I mentioned the Northern Lights trial, but this notion of putting these molecules together. So for instance, taking a KRAS selective molecule like ERAS-4001, hitting the target really hard, and then having the molecular glue to mop up afterwards is a really interesting idea of just really clamping down on RAS and not allowing RAS to escape. And as a company, we are uniquely able to evaluate this scientific hypothesis with two molecules that have orthogonal, if not complementary, mechanisms of action. So I'm now going to do a deep dive on ERAS-0015, which has about five to 10-fold greater potency than 6236 and also has favorable ADME properties and PK performance in animal models. So you could see, I mentioned, this is a CypA binder. The binding affinity on the rightmost column, you could see that it's about four-fold higher affinity than the comparator molecule. This stronger CypA binding enables more potent RAS inhibition, as you can see on this side-by-side comparison. ERAS-0015 in purple versus the comparator molecule in red, you can see that systematically across nearly all of these mutations, there's significantly higher potency in terms of lower is better. There's single-digit nanomolar to subnanomolar potency in these CTG3D growth assays. One exception you'll note is PK-59, where they look equipotent. But if you take a closer look in vivo in that same PK-59 model, this is an in vivo data set that shows you that the comparator molecule in green requires 3 MPK to achieve tumor regression, whereas in purple, you can see ERAS-0015 only requires 0.3 MPK QD, or about 1/10 of the dose. So that translates into 10-fold higher potency than the reference compound and really is very impressive. If you take a closer look at the tumor dynamics within this same model, what's interesting is that the comparator molecule on the lower left, you can see that. Pay attention to the clear bars where the tumor tissue levels of the drug are fairly high, and they taper off at 24 hours. But on the lower right-hand corner, you can see ERAS-0015 maintains persistently high tissue concentrations in the tumor tissue for a longer tumor tissue residence time. So these favorable attributes could also support enhanced anti-tumor activity. And that may be a function of its tighter binding to CypA. So I'm now going to walk you through a number of in vivo models that basically reinforce the same point. So whether it's sort of what we call the bellwether TGI model, NCI- H727, which is really largely an insensitive model to most pan-KRAS inhibitors. The TGI here, you can see it only requires about 0.3, or actually 1 MPK to see tumor regression, versus the reference compound requires 10 times that amount. So again, 10-fold higher potency in this model. There's a good combo in this same model of 15 with docetaxel. In fact, you have to sort of dial down the dose of 15 to then get a good dynamic range to assess its combination activity with docetaxel. And then in an SW620 model, you can see a similar story where it requires a much lower dose to achieve comparable tumor regression. This is a KRAS G12R model called PSN-1, which, again, 1/10 of the dose relative to the reference compound is needed to achieve tumor regression. Similar tumor dynamics. So in this second model, you can see it's not a model-specific phenomenon, but this longer tumor tissue residence time and preferential distribution in the lower right-hand corner really makes this a very interesting compound. Even though the blood level is tapering off, the tumor tissue concentration is maintained at a persistently high level. This is a combo study with anti-PD-1 in a KPC model, which is a G12D model. You can see the red line on the left-hand corner, which is superimposed on the x-axis, basically just complete regression or complete response in seven out of seven mice was achieved. What's interesting is that on the rightmost graph, on re-challenge of the KPC tumor cells, which means just taking tumor cells and injecting it in a different area of the mouse without any more study drug, you can see that the immune memory basically fights off the KPC re-challenge. So the immune system has already been stimulated to have anti-tumor activity. From a PK perspective, you could see that ERAS-15 performs very well with lower clearance, longer half-life, higher bioavailability as measured by F% across all species tested versus the reference compound. And even in monkey, very high oral bioavailability, which is not easy to achieve with a small molecule. In terms of the ADME properties, the ADME properties also are very good. CYP profile and hERG, as assessed by manual patch clamp, show a very good margin. So I'll now say a few words about 4001, the pan-KRAS inhibitor. So this is basically very potent against pan-KRAS, so D, V, even C. It does hit KRAS wild type as well with a little bit of selectivity of the mutants versus KRAS wild type, which is also nice to see. And then, as I mentioned, the key feature here is the HRAS and NRAS sparing. And so it does not inhibit HRAS or NRAS wild type, which could lead to a potentially wider therapeutic index. And so you can see, based on these cell growth inhibition assays, very good single-digit nanomolar to even subnanomolar potency against the key mutations of interest, such as G12D and G12V. Even G12C, you can see very strong potency and then reasonable potency against G12A and even KRAS G13D. In terms of animal models, I'll show you a few. So this is a Panc 04.03 model, where you can see tumor regression achieved at around 100 MPK. In terms of phospho-ERK inhibition and mouse plasma PK, those look very promising after a single dose. And then these are both D and V models on the left and right, respectively. You can see good tumor regression with doses as low as 30 MPK BID. All of these, the animals basically tolerated these doses very well as well. And then this is another combo with anti-PD-1. I think one of the issues in the G12C class is that you've probably heard about the liver tox. That is potentially due to the covalent or irreversible binding mode, where those inhibitors could, because of the binding mode, cause haptenization in the liver, which leads to the liver tox. This is a reversible inhibitor. We're hopeful that by combining with PD1, there may be less liver signal. Again, seven out of seven mice with this, including KPC re-challenge, showed complete response, which was really amazing. PK and oral bioavailability in mouse, rat, and dog is very high. I did note for you in the executive summary that in rat, the BA is somewhat variable. It really, that then is a matter of if the rat is the most predictive species versus mouse or dog, then we might have to have a higher dose. We're hopeful that mouse or dog are more representative. Then very good ADME properties in vitro. In terms of the epidemiology of KRAS, unfortunately, the frequency is very high. You can see just in the United States, the big three of colorectal, non-small cell lung, and pancreatic, very high frequency in those disease states. And then a long tail. But unlike TRK, the long tail is actually tens of thousands of patients, especially in GU and GYN. In terms of our clinical development plan, I won't go in detail there, but suffice to say that we'll be focused on tumor types with the largest number of potential patients. We'll be assessing combinations, including with each other in terms of 15 with 4001. We'll continue to be data-driven, as we have throughout our history. And we'll capitalize on our unique portfolio of molecules with complementary inhibitory mechanisms, as I mentioned. So the key milestones and clinical trial readouts I mentioned for naporafenib, SEACRAFT-1 in RAS Q61X solid tumors is on track for a Q4 readout later this year. SEACRAFT-2 for NRAS mutant melanoma is on track for phase III pivotal trial initiation this quarter. And then we will share data from the phase III stage 1 randomized dose optimization portion in calendar year 2025. For ERAS-15, we're targeting an IND filing for AURORAS-1 in the first half of next year. And then for BOREALIS-1, we're targeting a Q1 2025 IND filing. And then we're guiding to phase I monotherapy data for both programs in calendar year 2026. So to summarize, we have an experienced team with a track record of success, a world-class SAB, really a broad pipeline to erase cancer. We're excited to be transitioning into a phase III company. With naporafenib, it allows us to really build the capabilities and infrastructure for late-stage development, which then the RAS-targeting franchise can just sort of draft behind that very quickly. And we have multiple shots on goal for near-term and long-term value driving. So with that, we might have time for a question or two. But otherwise, thank you very much for joining us today. Oh, sorry. Regarding the pan-RAS, could you talk a little bit about what your expectations might be for, I guess you could call it, off-target activity on wild-type RAS in different tissues? Because presumably it has its normal function. So what are you thinking about there? What might have you seen in animal models that might reflect toward humans? Yeah, good question. So with pan-RAS, first of all, it does have wild-type activity, so against K, H, and N. And actually, I think we, and I use the collective we, like we in the world had no idea what would happen if you actually hit all three wild types. So I think what was amazing is Revolution Medicines with RMC-6236 showed that there is a therapeutic window by targeting pan-RAS. And so I think the best data is really their phase I data, where they show that sort of the highest TRAE is rash, and then next is GI, and then a distant third is the stomatitis. But I would look at that data. And that basically is the totality of what the world knows on the consequences of pan-RAS inhibition in terms of wild-type inhibition.