Hi, everyone. My name is Maury Raycroft, and I'm one of the biotech analysts at Jefferies. It's with great pleasure that I'd like to welcome Jonathan Lim, the CEO, and David Chacko, the CFO of Erasca. Thanks so much for joining us today. We're going to do fireside chat format. Maybe for those who are new to the story, if you can give a one-minute overview of the company and your two lead drug candidates currently in development. Yeah. Thanks, Maury. It's great to be here at Jefferies. We really enjoy this conference in New York every year. Erasca, we're named for our mission to erase cancer and to eradicate RAS-driven cancer. In that vein, our pipeline is really focused on two main RAS-targeting agents. The first is ERAS-0015, which is a pan-RAS molecular glue. This is a cyclophilin A or CypA binder that has about eight to 21-fold higher binding affinity than RMC-6236. From that leads a number of different advantages that have manifested in the clinic, which we can talk about. The second program is ERAS-4001, which is a pan-KRAS reversible binder of the switch-II pocket. Both of those agents, ERAS-0015 and 4001, are in phase I trials. ERAS-0015 is in the AURORAS-1 trial, and ERAS-4001 is in the BOREALIS-1 trial. In the future, if we put them together, that'll be the Northern Lights trial. Got it. Yeah. Great overview. It's an exciting time in the space. There's data at ASCO, which we'll talk about in a bit. First, wanted to dive into your ERAS-0015 program where you had some data recently. You reported data from both the U.S. and China. Can you give a brief overview of the key takeaways from each study? Talk about efficacy signals, dose exposure, and safety, and any notable differences between the two data sets. Yeah. We ran two independent phase I studies, one with Joyo in China, the other was Erasca sponsored in the U.S., the AURORAS-1 trial was the name. The studies were largely similar in terms of dose escalation, but with some minor differences. Both studies started at a 2 mg dose. In the U.S., we dose escalated all the way to 40 mg. In China, they went from 2 mg to 32 mg. I'd say the patient populations were largely comparable with the exception that I think the U.S. population was a little more heavily pretreated than the population in China. The ECOG status or the performance status was slightly better in the U.S. than in China. We believe those characteristics net out. Importantly, from an efficacy and safety perspective, I think the U.S. trial was very interesting in terms of seeing 60% response rates in the pharmacologically active dose or PAD in non-small cell lung cancer. In China, the response rates were about 63% at the PAD. I think those were largely comparable in terms of the efficacy in non-small cell lung cancer. In fact, at the PAD, globally, the response rates were 62% in RAS driven G12X non-small cell lung cancer. In a subgroup of patients that were docetaxel eligible, so they were post checkpoint, post platinum, second, third line only, that objective response rate went up to 75%. You're now sort of in rarefied air when it comes to targeted therapies in non-small cell lung cancer, so having a response in the 60%s to mid 70%s is really exciting. In pancreatic cancer, I know we'll talk a little bit about that, in the second line setting at the RDE, we saw 41% response rates in China. In the U.S., the data were less mature in pancreatic cancer, I would say that at the RDE of 24 mg and 32 mg, the response rate was about 27%, but that's maturing with a number of patients that are still, as of the data cutoff, we're in stable disease, but still on therapy. Over time, we're bullish that if three of the four legs of the efficacy stool, so to speak, are looking promising in terms of differentiation, that fourth leg, there's no reason to believe that that won't also come in line with the other three. From a safety and tolerability perspective, we saw lower frequency and severity of rash, nausea, vomiting, diarrhea, as well as stomatitis, and also very good PK in terms of dose proportional PK at all doses tested. Got it. Yeah, great overview of the data. Digging into the data, I had a specific question where you showed encouraging data with comparable PK between the China and U.S. studies, and you dose up to 40 mg in the United States versus 32 mg in China. What drove the 32 mg cap in China? Did you see a DLT above 32 mg, or was it a protocol operational decision? Yeah, I think in China, that was more protocol operational. In the U.S., we really wanted to push the dose as high as we could, because you got one shot at that. While we didn't see DLTs per se at the 40 mg, we did see a meaningful increase in terms of the severity and frequency of rash. We saw more grade three rash. We saw a little more intolerable rash. We deemed that the MAD, which is the maximum administered dose. That dose was not explored in China. Got it. Okay. In a pharmacologically active doses, you're showing strong depletion to G12X allele fractions. How predictive has this biomarker been for clinical efficacy in your view? Well, historically, G12X has been tough. I mean, RAS, not too long ago, was deemed an undruggable target. I think all of the great strides that have been made in the G12C space as well as the molecular glue space has been really exciting. I think G12X versus G13X and Q61X, in terms of that mutation type, I think based on Revolution Medicines' experience as well as ours, it seems to be a more prevalent target and potentially more tractable relative to, let's say, the Q61Xs. I'd say G13X seems to behave similarly to G12X, at least for our molecule. There's just not enough data to know between G12X versus non-G12X whether there's a fundamental difference yet. I think over time, we'll see. Preclinically, we would predict that our molecule has very good potency and activity against all of the different RAS mutations. Got it. Okay. You mentioned the lung cancer data where you're seeing pretty high response rate there in China and in the United States. How should we contextualize those rates versus RevMed's approximate 38% response rate in dose escalation? What does that imply for durability as follow-up matures for you guys? Yeah. I think what was interesting is in an early phase I setting to have an agent that's showing 62%-75% response rates and the lower bound of the 95% confidence interval on the 62% ORR actually excluded the 38% that's been demonstrated by the comparator. I think that was encouraging. We didn't expect to see that, but there was a meaningful bump up in terms of the efficacy at that PAD, the 16 mg-32 mg, which we deemed to be a pharmacologically active dose. Yeah, super exciting, and I think non-small cell lung cancer, if you look at the history of targeted therapy, non-small cell lung cancer and melanoma, those are two types of indications that seem particularly responsive to single agent targeted therapy. We weren't quite expecting to see such high response rates. The fact that we did, I think, is sort of in keeping with historical precedents where some of the oncogene fusion TKI-directed therapies, for instance, you can see response rates as high as that. The fact that we're hitting different RAS mutations and achieving that level of ORR, hopefully with more data that holds because that will be just incredible for patients. Got it. Yeah, how could that translate to durability as your data matures? There tends to be some correlation with response rate in terms of the strength of the response rate and durability. What's interesting about the patients that we had disclosed, if you look at the swimmer plots, most, if not all, of the patients were still on therapy. In China, I believe all the responders were still on therapy as of that data cutoff. In the U.S., six of the seven patients were still on therapy. One of them had dropped off, but that patient was at the 16 mg dose. At the higher doses, the patients that were in response were still in response as of that data cutoff. Got it. Okay. You talked a little bit about baseline differences between China and the U.S. You mentioned the U.S. has had a lower ECOG status. What else should we know about the baseline differences, and how does your U.S. cohort baseline compare to RevMed's for their dose escalation? Yeah. I don't think I have enough info to know how comparable our population is to theirs. I think in terms of China, I talked about the ECOG differences as well as the sort of the pre-treatment status. I'd say the types of treatments in terms of lung as well as pancreatic are largely similar between the two regions, so no major differences. I'd say one interesting phenomenon that we saw was that in pancreatic cancer in China, we saw a lot of responses at the 16 mg dose, which is the lowest end of the PAD of 16 mg- 32 mg. In the U.S., we had eight patients that were dosed at 16 mg, and none of them had a response. I'm not sure if it's a body weight issue or some other variable that's at work there. It does seem, at least in the U.S., that dosing higher at 24 mg or even 32 mg seems like a more promising approach. In fact, small data set, but at 32 mg, we had four patients treated in the U.S., and two of them had responses. It's only four patients, but a 50% response rate is more promising versus 0% at the 16 mg dose. Got it. That makes sense. That kind of supports why you potentially saw a difference in the PDAC response rate for China versus the U.S., where you saw a lower response rate in the U.S. Could be just because of the dosing. Yeah, that's my belief. Then also, the China trial started about four to six months before the U.S. trial, and it enrolled very quickly, and they were able to get up to. They used an accelerated titration scheme, which allowed them to skip certain doses and then enroll and backfill patients at higher doses in the PAD between 16 mg and higher. As I mentioned, because of the sensitivity in China to the 16 mg dose monotherapy, I think the fact that they saw a 40%+ response, I think it was a 45% response rate at 16 mg. That's much higher than what we've, you know seen in the U.S. clearly Got it. You commented a little bit about durability, but I guess, what are your expectations for what you want to see on durability here versus daraxonrasib? Yeah. I think in terms of the durability that daraxonrasib has shown, especially from the median OS perspective, is super impressive. I would say that I think there's something about this mechanism of action of CypA molecular glue that seems very promising from a durability standpoint. All I have is the phase I data to point to in China and the U.S. in terms of the swimmer plots, and it's very promising. Out of 19 patients treated in China that were in response, 16 of them stayed in response and three fell out of response, and those three were really at the lower doses. Anyone that was treated at higher than 16 mg was still on therapy. All of the patients in the U.S. that were in response were still in response as of the data cutoff. Early days, but I think just based on the swimmer plot, which is really the only tool we have at this point to look at durability of these patients, it's promising for sure. Got it. One of the key differences that stands out in your data set is the safety profile, where you're showing better safety than RevMed's drug. How should we think about that? Could that contribute to durability? What are your thoughts there? Yeah. I think that's really interesting. No matter what you believe about the efficacy, let's say in pancreatic cancer, if our U.S. data end up demonstrating a degree of differentiation that our data in China for pancreatic have shown, then you have a both/and type situation. You have both promising efficacy as well as promising safety tolerability. Now, let's say that doesn't come in. You still have the safety tolerability, which will translate into potential efficacy benefit. What I mean by that is that if you can just hold the dose with much less dose modification in the form of interruptions, reductions, discontinuations. We're already seeing that in the phase I setting, we're seeing fewer dose modifications than an analogous stage of development for the comparator compound. On top of that, as time goes on, we've seen from the phase III data set, even with primary prophylaxis, there's still a meaningful uptick in terms of the grade three and above TRAEs, the rash, the stomatitis, especially, in terms of rash and stomatitis, despite primary prophylaxis. There is an opportunity for an agent like ERAS-0015 to show potentially a more promising safety and tolerability data. On top of that, especially in combination with chemotherapy, you can have less dose modification that hopefully can translate into more promising efficacy as well. Got it. All makes sense. For the safety data from the data update that you guys did, we didn't see the detailed safety data from China. What can you share about the main safety differences between China and the U.S.? Yeah. I would just say stay tuned on that because I think the focus was on the U.S. to just be able to draw an apples to apples type of context there. China will be forthcoming in the future. Got it. Okay. Your safety summary excludes the 8 mg cohort. Does the 8 mg data change the profile for some reason? Wanted to check too if you guys have seen any grade four toxicities. From the R&D day deck, we actually had two columns there. One was the safety at the PAD, which was 16 mg-32 mg. We also showed on the other side of the page the safety at 8 mg and above, which did include that. The rates in terms of severity and frequency of the different TRAEs was not materially different. Got it. Okay. For the grade five pneumonitis case, there has been less focus on this from investors since the top-line update. Can you recap what the patient's background and preexisting risk factors were and comment on total pneumonitis events from both the U.S. and China experience? This was unfortunate because this patient was pretty sick, was heavily pretreated, had lung metastases, had cryoablation of his lung. When he had a grade five pneumonitis, he was treated with supportive care, responded to that, after a week, decided that because he was pretty advanced in his disease, he, with his family, decided to stop further treatment. Unfortunately, he ended up passing away. I think the circumstances of that situation are understandable what happened, and this is not an isolated event in terms of this being the only pan-RAS molecule that has had pneumonitis. We had one other case of pneumonitis, grade one pneumonitis, and out of 80 patients, that's a frequency of about 2.5%, which is pretty much in line with most targeted therapies. If you look at adagrasib at 4% or Enhertu, which is a great targeted therapy, at about 10%+ pneumonitis rates, even recently with RMC-6236 reporting a grade five pneumonitis, it unfortunately is a consequence of some of these targeted therapies. Yeah. Makes sense. How are you thinking about the frontline PDAC study design for a pivotal study following RevMed's presentation at ASCO? What would that trial look like, and what is the time horizon you have to move to get to registrational study there? Yeah. I think this year we're really focused on figuring out the combination dose of ERAS-0015 with chemotherapy. We want to figure that out and move into a combination study as soon as we possibly can. I think there's sort of a finite window here. I think appropriately there's a lot of excitement around what they've demonstrated in the second-line setting. I think we're positioned to be able to be the next one on deck to see if we can offer patients an attractive option for therapy in pancreatic cancer. Got it. Can you say where you're at with the dose finding with chemo and when there could be some sort of an update there? Yeah. We're doing the dose finding predominantly in the second half of this year, and then we hope to be able to give an update next year. Got it. Yeah. Okay. Given the recent RevMed update at ASCO, where do you think the biggest points of differentiation will come from? Maybe talk about depth, durability of response, tolerability, and combo flexibility. I think clearly from an efficacy standpoint, we're seeing something pretty special in non-small cell lung cancer that's meaningfully different from what's been reported before in this class. I'd say that in pancreatic cancer the data are maturing, and so stay tuned on that. I think in colorectal cancer, that's another area of high unmet need, and the fact that we've shown in our three patients in the U.S. have been dosed with 16 mg of ERAS-0015, which is the low end of the PAD. In those three patients, there were no DLTs. Two of those patients had cleared the DLT window. If we do clear that level, and the first patient that had first efficacy evaluable scan had a partial response, which was really exciting to see because as you all know, panitumumab has a 0% response rate in patients with RAS-driven CRC. Seeing a response, one out of one response, that's a statistical anomaly. It has to be the synergy between ERAS-0015 with panitumumab. We're really happy that 16 mg is an active dose. If we clear that level, then we'll expand out that dose level, and then we'll also potentially explore a combination with 24 mg. I'd say that's a little different than what's been described with other pan-RAS molecules in terms of promising combinability with an EGFR antibody, which is a very important approach to shut the door in terms of address primary and acquired resistance in CRC. Yeah Through EGFR. Yeah. The panitumumab combo data is a small data set, but you're basically showing some proof of concept there on efficacy and safety, which I think safety is kind of the key thing that we've been hearing a lot about lately. Maybe talk about some of the feedback on that from investigators from ASCO. There's a lot of excitement around that because it's the most objective evidence that maybe the rash that we're seeing with our molecule is a little different from what's been seen with others. I just think the most objective thing is if you can take our molecule and combine it with another molecule that is known to have skin tox and you don't get synergistic toxicity from a skin perspective, well, that seems to be behaving differently. If we clear that 16 mg dose, that would be sort of a first in class type of achievement. Got it. For ERAS-0015, when could we see the next data update from the program? I'll start with that. Our guidance is first half of next year. I'd say that we're continuing to follow all the patients, and we're enrolling a lot of patients from both a monotherapy perspective at the RDEs, which are 24 mg and 32 mg in both lung and pancreatic. We also are enrolling different combinations. We've started in addition to the pani combination, we've started pembrolizumab combinations, and we have a CTCSA with Merck for access to a free drug from a PD-1 perspective. We'll have a lot to talk about in the first half. I'd say we also have options to electively provide updates later this year if we so desire, but no formal guidance on that in terms of expectation setting. Got it. Okay. For colorectal cancer, maybe just talk about next steps there and the development plan. At the time of the update, we said that we had those three patients. If we clear the 16 mg dose cohort, then the plan would be to expand that out to about 15 to 20 patients, while also dose escalating up to the next level, which would be 24 mg. Got it. Okay. Want to switch gears, talk about ERAS-4001, which is your pan-KRAS inhibitor. Where are you at in enrollment there, and which indications are you enrolling right now? Yeah. ERAS-4001 is our pan-KRAS inhibitor. That is moving along through its dose escalation. We initiated that study in Q2 of last year. We're on track for a second half data readout this year. In terms of tumor types, as long as you have a KRAS mutation, it is an all-comer study. It's a dose escalation, we're trying to move as quickly as we can in terms of identifying a dose. We'll be able to share information in our second half update around the safety, tolerability, PK, as well as initial signs of activity. Got it. What's the right benchmark for early activity? There's not a whole lot out there with pan-KRAS clinical data, is daraxonrasib still the key reference point? Yeah, you're right. There's not a lot out there. Two companies have released data, and even that's been somewhat limited data to date. I think we, as a field, will learn a lot more as more and more players put out data into the space and the benchmark will evolve as we know more. I think initially you mentioned RMC-6236 in terms of a benchmark. That could be an appropriate benchmark in terms of where they've disclosed data to date. I think a lot of it will come just as we see more data from the pan-KRAS space. Got it. Makes sense. Conceptually, where do you think pan-KRAS drugs can differentiate versus pan-RAS? Maybe talk about some of the factors like the therapeutic window, resistance, combinability, and tumor coverage. Yeah. The theoretical benefit of a pan-KRAS is that by sparing HRAS and N RAS, and going after just KRAS, that you could get a wider therapeutic window, particularly on rash. I would say up until about a month and a half ago, meaning prior to our R&D day on ERAS-0015, that was the hypothesis that you probably need to spare HRAS and N RAS in order to have less rash toxicity. Certainly, some of those companies that I mentioned earlier, some of their data does indicate that you could get less rash. I think what came out of the dataset that we shared about a month and a half ago for ERAS-0015 is that you actually can have a pan-RAS that has a good rash profile. For instance, our rate of grade three- plus rash, TRAE, was only 2%. That is the hypothesis around the pan-KRAS, but our data also provides a different perspective on the combinability of pan-RAS. In addition, I think that one of the advantages of a pan-KRAS, or for that matter a pan-RAS over the mutant selectives is that pan-RAS, pan-KRAS approaches generally hit wild type. You brought up resistance. If you don't hit wild type, you can get wild type amplification that could be a mechanism of resistance. A pan-RAS or a pan-KRAS by hitting wild type should have a durability advantage there as well. That's something that you'd have to look at as well. The final point I'll mention with pan-KRAS is that you generally do need to dose a little bit higher. We've seen that with some that have disclosed data to date. When you dose higher, that can lead to some GI AEs that you'll also have to manage. Got it. Okay. For your update second half of this year, how are you setting expectations there for number of patients and how much data you could show? Yeah. Number of patients will be dozens of patients, and as I mentioned, it being the phase I dose escalation, we'll be looking at safety tolerability, PK, and initial signs of activity. Okay. Would it be at a medical conference or a company update? We as a company have done both options in the past, and so, either one is on the table. Got it. Wanted to talk about the letter from RevMed, which has come up as far as the IP situation goes. Can you summarize your view on RevMed's claims and what you expect the next steps to be? We received a letter from RevMed at the end of April alleging three points, all of which we feel are without merit. The three points that they allege are, number one, IP infringement, number two, trade secret misappropriation by a third party, not by Erasca, and then thirdly, the preclinical comparisons not being appropriate. Let me take through each of those. In terms of the IP infringement, they're not alleging literal infringement. They're actually alleging something referred to as the doctrine of equivalents, which courts are hesitant to apply just given that, as this audience knows, small differences from a chemistry standpoint can actually lead to outsized impacts in terms of different binding, different PK/PD, different safety efficacy, which our compound shows those characteristics. The second claim with regard to trade secret misappropriation, as I mentioned, this is not something that they're alleging that Erasca did, but rather a third party. They provided no such evidence of any sort of trade secret misappropriation, nor are we aware of anything that happened. As we've laid out a timeline in our corporate deck, I encourage you to take a look at it, which shows an 11-month window between when RMC-6236 patent was published and when ERAS-0015 patent was filed. 11 months in the chemistry world, as this audience knows, is a very long time for just good old-fashioned chemistry work to develop new compounds and new improvements. You see that with the fact that there were at least seven other companies in that same timeframe of 2022, 2023, that have a priority date in that window. On the third claim with regard to the preclinical comparisons, all of these studies that we showed were run in head-to-head assays under the same conditions. We feel that they were appropriate. Got it. Yeah, I think that you covered a lot there. I think maybe in closing, if you can comment on cash position and key catalysts ahead that investors should be focused on. Cash position, as of our last filing, we had $409 million of cash. We had runway out to second half of 2028, so we are well capitalized, and we as a company have always been very efficient in terms of our use of capital. In terms of what that covers, it covers all of our publicly disclosed milestones that we lay out in our deck, including the readouts for ERAS-0015 and ERAS-4001, as well as initiation of phase III registrational studies. Got it. Jonathan, David, thanks so much for joining us today. Thank you. Thank you.