Greetings, and welcome to the Erasca investor update call. At this time, all participants are in a listen-only mode. A question- and- answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Jonathan Lim, CEO and Chairman of Erasca. Thank you. You may begin. Thank you, operator. Welcome to our Erasca Investor Update. We have some exciting news to share and appreciate you joining us today. Here with me are David Chacko, our CFO and Chief Business Officer, Shannon Morris, our Chief Medical Officer, Robert Shoemaker, our SVP of Research, and Dawei Xuan, our SVP of Clinical Pharmacology. We will be making forward-looking statements. Please visit our website at erasca.com to review our latest SEC filings and associated risk factors. At Erasca, our name is our mission, to erase cancer. Our industry-leading pipeline is focused entirely on shutting down the RAS/MAPK pathway. We continue to have confidence in our lead program, naporafenib, which is a pan-RAS inhibitor that is moving into our SEACRAFT-2 phase III trial this quarter for the treatment of patients with NRAS mutant melanoma. Across phase I and II, the combination of naporafenib plus trametinib showed clinically meaningful median PFS and median OS. In addition, we have the opportunity to expand into RAS Q61X solid tumors, which we are evaluating in our SEACRAFT-1 trial. Beyond NAPO, we are pleased to have announced yesterday a series of transactions, including the in-license of a RAS targeting franchise and the pricing of a $160 million equity financing. Our two new exciting RAS targeting molecules include ERAS-0015, a pan-RAS molecular glue with best-in-class potential, and ERAS-4001, a pan-KRAS inhibitor that could be first in class for treating patients with KRAS mutant solid tumors. We have a strong cash position, having ended Q1 with $334 million on a pro forma basis, which does not include the equity financing that we announced yesterday. During today's update call, we will be discussing two main topics. First, the RAS targeting franchise, and second, a corporate update. Our strategy is to comprehensively shut down the RAS/MAPK pathway through three complementary approaches. The two new programs that we in-licensed fit squarely within our second approach of targeting RAS directly, both in its active GTP and inactive GDP states. Ever since our co-founder, Kevan Shokat, pioneered the field of KRAS G12C inhibitors, great strides have been made in drugging the historically undruggable KRAS protein. But opportunities remain to both expand the treatment opportunities for broader populations of patients, as well as addressing resistance mechanisms. Pan-RAS and pan-KRAS targeting molecules can address a broad population of patients with G12X, G13X, and possibly Q61X mutations, and also have the potential to address or prevent resistance by blocking wild-type RAS activation, for example. The RAS targeting landscape can be divided into pan-RAS, pan-KRAS, and mutant-selective approaches. While Erasca has been predominantly focused on internal discovery efforts in the pan-KRAS space with the successful in-licensing of ERAS-0015 and ERAS-4001, we believe we have advanced significantly in both the pan-RAS and pan-KRAS categories, as you can see in the next slide. In the pan-RAS space, Revolution Medicines has been a pioneer, showing encouraging preliminary clinical data for RMC-6236. We believe this space represents such a significant opportunity to help patients. There should be more than ample room for multiple companies to succeed here. As Revolution Medicines succeeds here, that should help us and vice versa. In the pan-KRAS space, there is an opportunity for a greater therapeutic window by specifically targeting KRAS while sparing H and NRAS wild type, as well as the potential for an increased probability of success by targeting KRAS with a more straightforward mechanism via the Switch II pocket binding mode. However, since none of these molecules in this class have shown clinical data yet, the translation into clinical efficacy is still to be determined. In the mutant-selective space, there is the potential for greater potency against specific mutations of interest, but this may be at the expense of resistance mediated by wild-type RAS of the same isoform. We are focused on the top two approaches because if we can get a molecule to work in either or both of these categories, then we will be able to maximize benefit for patients globally. The ideal RAS targeting molecule sits at the nexus of three key attributes: preclinical potency, favorable ADME PK properties, among which oral bioavailability is a must-have, and having a strong proprietary position. Improved potency and oral bioavailability may enable dosing of these molecules at a lower dose, which could translate into avoiding the PK plateau that is observed with another pan-RAS molecular glue in development. A better GI tolerability profile, given the lower drug load in the GI tract and an improved therapeutic window for any potential off-target toxicities. It also has the potential to improve clinical activity if what we see in the KRAS G12C inhibitor class holds true here as well. For example, divarasib, a much more potent molecule than the first-generation G12C inhibitors, has demonstrated significantly higher ORR and progression-free survival than adagrasib and sotorasib in G12C non-small cell lung cancer. In terms of ORR, the first-generation G12C inhibitors had an ORR between 33%-43%, while Diva had an ORR of 56%. And in terms of median PFS, Ada and Soto had an mPFS between 5.4-6.5 months, while Diva had an mPFS of 13.7 months. I acknowledge that this is a cross-study comparison, but the values still are impressive for the more potent molecule in this class. Finally, having proprietary molecules bolsters our ability to maximize the clinical and commercial value of these potentially best-in-class molecules in a highly competitive market. In the next several slides, we'll explain how ERAS-0015 and ERAS-4001 perform favorably across these three attributes. ERAS-0015 and ERAS-4001 exhibit competitive profiles that exceed our target product profile. Starting first with ERAS-0015, this pan-RAS molecular glue for treating patients with RAS mutant solid tumors has demonstrated approximately 5x-10x greater potency, as well as favorable ADME and PK properties in multiple animal species versus the leading pan-RAS molecular glue in development. In terms of preclinical in vitro potency, this molecule showed nanomolar, and in some cases, subnanomolar potency against KRAS G12X, G13D, and KRAS wild type, and was also active against HRAS and NRAS. In vivo, this molecule was able to achieve tumor regression at low doses of only 0.3-5 mg/kg or MPK. Oral bioavailability, which we target to be above 10%, has been shown to be high for this molecule, and we believe that the IP protection goes until at least 2043. In terms of ERAS-4001, this is a potential first-in-class pan-KRAS small molecule inhibitor that spares H and NRAS wild type, which is predicted to potentially provide a greater therapeutic window and also address KRAS wild type activation to prevent resistance. Its preclinical in vitro potency also showed good activity against KRAS G12X and G13D mutations, as well as KRAS wild type, and it had no activity against H or NRAS wild type. In vivo, it showed good tumor regression in multiple models. In combination with anti-PD-1, it was able to achieve complete disappearance of tumors in 7/ 7 mice. It has good oral bioavailability, with 21% in mouse, 5%-27% in rat, and 16% in dog. At this point, we don't know if mouse, rat, or dog PK will be most predictive of human PK for this molecule. We believe that the IP protection for this molecule also lasts until at least 2043. By bringing in these two compounds, we could be one of the only companies in the world with the ability, down the road, to potentially combine both molecules to create what we call a RAS clamp combination, that could uniquely shut down RAS MAPK pathway signaling in KRAS mutant solid tumors with complementary mechanisms of action. Now, we will discuss the pan-RAS molecular glue. ERAS-0015 works by a similar mechanism as RMC-6236, in that it forms a tripartite complex with Cyclophilin A. As shown in this table, ERAS-0015 has roughly a four-fold greater binding affinity to Cyclophilin A relative to RMC-6236, which we believe may enable more potent RAS inhibition. In fact, looking at multiple in vitro cell lines that represent mutations in KRAS G12X, Q61R and G13D, as well as KRAS wild type. ERAS-0015, shown in purple, showed superior potency than RMC-6236, shown in red, in nearly all cell lines tested. In one model, PK-59, which is a KRAS G12D model, ERAS-0015 and RMC-6236 showed equipotency. Despite the in vitro equipotency in PK-59, when these molecules were run head-to-head in vivo, ERAS-0015 demonstrated tenfold higher potency than RMC-6236. For example, if you look at the dark green line, which represents RMC-6236 at 3 MPK, and compare that to the purple line of ERAS-0015 at 0.3 MPK, you see similar tumor regression, even though ERAS-0015 was dosed at just one-tenth the dose of RMC-6236. As I walk through several more in vivo studies, you'll see a consistent theme that across several studies, ERAS-0015 demonstrated about a tenfold higher potency than RMC-6236, achieving comparable tumor growth inhibition to RMC-6236 at one-tenth the dose. The PK curves and tumor tissue dynamics are shown here. At the top, we see linear PK for ERAS-0015 in whole blood. The bottom two panels show whole blood and tumor tissue concentrations for RMC-6236 on the left, dosed at 1 MPK, and ERAS-0015 on the right, dosed at one-tenth the dose. With RMC-6236, there's a marked decrease in the tumor tissue concentration, shown in the white bars, from 4 hours to 24 hours. Whereas ERAS-0015 showed good persistence of the drug in the tumor out to 24 hours. In other words, ERAS-0015 distributed preferentially into tumor tissue with long residence time, such that even at the blood concentration shown in black, as that drops over time, the tumor continues to be exposed to the drug. This might help drive improved efficacy while maintaining reasonable tolerability. Now, looking at the NCI-H727 model, which is an insensitive KRAS G12V model, ERAS-0015 was able to achieve tumor regression at 1 MPK relative to RMC-6236 at 10 MPK. We were pleased to see this level of activity at such a low dose in what is typically a fairly insensitive model to KRAS inhibitors and a bellwether of sorts in terms of identifying truly potent pan-RAS or pan-KRAS-targeting molecules. In this same H727 insensitive model, the dose of ERAS-0015 was lowered to 0.3 MPK in order to be able to observe a potential benefit in combination with docetaxel. On this slide, you can see that ERAS-0015 + docetaxel showed both combination benefit and tolerability. Looking at the SW620 model, another KRAS G12V model, RMC-6236 required 25 MPK to show tumor regression, while ERAS-0015 achieved comparable tumor regression at 3 MPK. In a KRAS G12R PSN-1 CDX model, G12R is a mutation found in pancreatic cancer. ERAS-0015 was able to achieve significant tumor regression at a low dose of 5 MPK. In this same PSN-1 model, the dose of ERAS-0015 was lowered to evaluate a head-to-head comparison versus RMC-6236, and you can see that ERAS-0015, again, was able to achieve comparable TGI to RMC-6236 at one-tenth of the dose. Looking again at the tissue dynamics, and specifically at the white bars, we see a similar picture as before, in which the drug persisted in the tumor for ERAS-0015 at 24 hours, whereas RMC-6236 showed a notable decrease by 24 hours. Note that RMC-6236 was dosed at 1 MPK, whereas ERAS-0015 was dosed at one-tenth that dose at 0.1 MPK. This preferential distribution and long tumor tissue residence time of ERAS-0015, therefore, is not a model-specific phenomenon, but was demonstrated in multiple models. One final in vivo model is shown here. It is a combination of ERAS-0015 with anti-PD-1 therapy, which showed very strong tumor regression with the combination, even after treatment was stopped on day 31. Furthermore, looking at the rightmost panel, after re-challenge with KPC tumor cells, which involves injecting the tumor cells in the contralateral side of the animal without administering any drug therapy, ERAS-0015 + anti-PD-1 therapy was able to flatline the tumor in 7 out of 7 mice because the immune system had already been primed to fight the rechallenge. ERAS-0015 showed promising PK in multiple species. Here, we show a head-to-head comparison of ERAS-0015 in purple versus RMC-6236 in red. I'll highlight for you 3 rows in particular: clearance, half-life, and bioavailability as measured by%F, in which you can see that 0015 outperforms 6236 on all three metrics pre-clinically. We believe that these favorable PK properties, lower clearance, longer half-life, and higher bioavailability demonstrated across all species tested, will provide ERAS-0015 with an advantage in the clinic versus RMC-6236. ERAS-0015 has good ADME properties. The kinetic solubility of ERAS-0015 in fasted state simulated intestinal fluid, which is called FaSSIF, is a metric of how a drug can be dissolved and potentially absorbed in fluid from the upper intestine, and this value of 127 was approximately 10x higher than RMC-6236, which has a published FaSSIF value of about 13. Thus, we believe that ERAS-0015 at this low dose is unlikely to have solubility-limited absorption issues, which could be a cause of the exposure plateau for RMC-6236 observed in the clinic. The CYP450 inhibition data suggests no major drug-drug interaction liabilities as a result of potential CYP inhibition. The hERG IC50 was greater than 10 micromolar by manual patch clamp, which suggests no cardiovascular concern. Now we'll talk about the pan-KRAS molecule, ERAS-4001. The SPR data shown here demonstrated high affinity and long target residence time against multiple KRAS G12X mutations, as well as KRAS wild type, and very low affinity for HRAS wild type and NRAS wild type, which is what you would expect and hope to see for a pan-KRAS inhibitor. ERAS-4001 potently and selectively inhibited multiple cell lines that represent KRAS G12X, G13D, and wild type. You see single-digit nanomolar potencies across multiple cell lines. In two KRAS-independent cell lines shown at the bottom, ERAS-4001 showed no activity. In vivo, in the PDX-0403 model, ERAS-4001 was able to achieve better TGI at 100 MPK compared to MRTX example 5, also dosed at 100 MPK. ERAS-4001 was well-tolerated at doses up to 300 MPK BID for 28 days. ERAS-4001 achieved tumor regression in 2 additional KRAS G12X CDX models. On the left is the PK-59 G12D model. On the right is the RKN G12V model. 4001 was well-tolerated in both studies at doses up to 300 MPK BID. The NCI-H727 model is shown here. Because this is an insensitive model, as I mentioned earlier, a higher dose of 300 MPK BID was needed to achieve tumor regression. 4001 was well-tolerated in this model at doses up to 100 MPK BID, but had borderline tolerability at 300 MPK BID. This observed borderline tolerability may be specific to the model or the study. Under a material transfer agreement, Erasca was able to reproduce the in vivo activity of ERAS-4001 in the KRAS G12D CDX model called HPAC. Here, we saw good tumor regression at doses of 50 and 100 MPK, and ERAS-4001 was well-tolerated at doses of 100 MPK. Finally, this in vivo model showed the combination benefit of ERAS-4001 plus an anti-PD-1 therapy, shown in purple. Even after treatment stopped on day 38, we continued to see flatlining of the tumor. Around day 80, a KPC rechallenge in which tumor cells are injected in the contralateral side of the animal, as I'd mentioned earlier, but because the immune system had already been primed, the animal was able to fight off the rechallenge without administration of more study drug. As seen in the table, the combination of anti-PD-1 and ERAS-4001 was able to achieve a complete response at day 50 in 7/7 mice. ERAS-4001 showed promising PK in mouse, rat, and dog. This slide shows data generated by the licensor. In particular, I'll call your attention to the final row, which shows good bioavailability that has been demonstrated across the three species tested. ERAS-4001 demonstrated good ADME properties in vitro. The CYP450 IC50s showed no DDI liabilities for CYP. In addition, the hERG IC50 is at around one micromolar, but the predicted hERG safety margin is high at 230-740-fold. We will evaluate this further in our GLP studies to see what, if any, monitoring is needed in the clinic. With that, I'll hand the call over to Shannon to talk about our clinical development plan for these two programs. Shannon? Thank you, Jonathan. The goal of this slide is to illustrate that KRAS alterations are found most commonly in patients with colorectal cancer, pancreatic cancer, and non-small cell lung cancer, which will be a key focus of the clinical development program. In addition, it's important to note that there is a large group of patients with KRAS alterations and other tumor types that could also benefit from our RAS targeting franchise. The purpose of our innovative clinical development plan is to maximize the efficiency of our trials while minimizing clinical and regulatory risk, to be able to advance these molecules as quickly as possible for the benefit of patients. I'd like to highlight four key points here. First, as I previously mentioned, we will focus on tumor types with the largest unmet need, as represented by the number of potential patients, specifically non-small cell lung cancer, pancreatic cancer, and colorectal cancer. Second, we plan to move swiftly into strategic combinations, while in parallel, characterizing the monotherapy activity and combination potential of each program. Third, a focus on continual evaluation of the probability of success for each molecule and each potential indication, taking into account the context of clinical unmet need and the competitive environment, should allow us to prioritize the most promising pathway forward. And finally, we plan to capitalize on our unique portfolio, which has complementary mechanisms of action and target profiles to more efficiently bring novel combinations to patients in need. And with that, I'll hand the call over to David to talk about the key license terms. David? Thanks, Shannon. I'll start first with the pan-RAS molecular glue. This is an exclusive license with Joyo Pharmatech, covering ERAS-0015 in all fields of use. The territory is worldwide, excluding China, Hong Kong, and Macau, subject to the China buyout. Under this China buyout option, at any time prior to the first patient dosing in phase II or NDA submission by either us or Joyo, we can convert the territory to worldwide at our sole discretion with a one-time payment, and the amount of that payment depends on when we exercise the option. The financial terms are shown on the right. The total upfront is $12.5 million, with development milestones of up to $17.5 million. Total regulatory milestones of up to $34 million, which covers multiple indications in the U.S., Europe, and Japan. Total commercial milestones are $125 million, of which there are no first commercial sales milestones, and these are all back-ended, tiered sales-based milestones. The total deal value before royalties and the China buyout is up to $189 million. The China buyout and associated milestones could add an additional $56 million-$156 million, and the royalties are tiered in the low- to mid-single-digit percent range. The key license terms for the Pan-KRAS inhibitor, ERAS-4001, are shown here. This is an exclusive license with MedShine Discovery, covering 4001 in all fields of use, and the territory is worldwide. The total upfront is $10 million. Total development milestones are up to $10 million. Total regulatory milestones are up to $20 million, which covers the U.S., Europe, and either Japan or China. The total commercial milestones are up to $130 million, of which there are no first commercial sales milestones, and they are all back-ended, tiered sales-based milestones. Total deal value before royalties is up to $170 million, and the royalties are in the low double-single-digit percent range. With that, I'll hand the call back to Jonathan to provide a corporate update. Jonathan? Thank you, David. In association with these in-licensing transactions, we have reviewed our overall cost structure to optimally focus on and accelerate development of lead program naporafenib and these two new RAS targeting programs. As a reminder, this is what our pipeline looked like prior to the licensing transactions. The data-driven prioritization and reorganization actions that we have undertaken are summarized here. HERCULES-3, the phase I-B/II trial of our ERK inhibitor, ERAS-007, for patients with BRAF mutant colorectal cancer, has been deprioritized as the clinical efficacy data do not support continued evaluation. We are pausing THUNDERBOLT-1, the phase I trial of ERAS-801 for patients with GBM, so that we can focus internal resources on advancing naporafenib and our RAS targeting franchise. We are also exploring further advancement of 801 via select investigator-sponsored trials, or ISTs. With the in-licensing of ERAS-0015 and ERAS-4001, we have discontinued our internal pan-KRAS program, ERAS-4. Although certain molecules from that program are covered by the new license agreement and are potential backups for ERAS-4001. The above changes have unfortunately impacted certain team members, and we will be reducing our workforce by approximately 18%, primarily affecting those employees working in drug discovery functions and on deprioritized programs. We recognize this is a challenging time for our highly talented employees, particularly those affected by these changes. On behalf of Erasca, I sincerely want to thank all of our employees for their work toward our mission of erasing cancer. On that note, helping patients is our guiding light. We will be launching the AURORAS-1 trial to assess the ERAS-0015 pan-RAS molecular glue, for which an IND is targeted for H1 2025, and BOREALIS-1 to assess the ERAS-4001 pan-KRAS inhibitor, for which an IND is targeted for Q1 2025. And fittingly, for those of you in the Northern Hemisphere who recently saw the rare sighting of the Northern Lights, we plan to explore novel combinations of the two molecules in the future AURORA Borealis trial. To support our renewed focus on those opportunities that target the highest unmet needs for patients, our revised streamlined pipeline is shown on this slide with naporafenib, ERAS-0015, ERAS-4001, and ERAS-12, our bispecific EGFR antibody. Our anticipated milestones are shown here. Naporafenib is our pan-RAF inhibitor in the SEACRAFT-1 and SEACRAFT-2 studies. SEACRAFT-1 is our phase I trial for patients with RAS Q61X solid tumors. We have sharpened our guidance on the anticipated timing for this readout to Q4 of this year for the phase I-B combination data. SEACRAFT-2, our phase III trial for patients with NRAS mutant melanoma, is on track to be initiated this quarter, with phase III, stage 1 randomized dose optimization data expected in calendar year 2025. ERAS-0015 will be in the AURORAS-1 trial with an anticipated IND filing, as I mentioned, in H1 of 2025, and phase I monotherapy data are anticipated in calendar year 2026. ERAS-4001 will be in the BOREALIS-1 trial, with an anticipated IND filing in Q1 of 2025, and Phase I monotherapy data also anticipated in 2026. In summary, we're beyond excited to be bringing in these two RAS-targeting molecules to complement our stable of RAS/MAPK pathway targeting agents for the potential benefit of patients worldwide. We've strengthened our pipeline and balance sheet, and we have the team to be able to execute on these programs, which we believe significantly advance our mission of erasing cancer and specifically eradicating RAS-driven cancers. I'd like to thank you again for taking the time to join us today. With that, we'll conclude our formal remarks, and I'll turn the call back to the operator for Q&A. Operator? Thank you. If you'd like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from the line of Anupam Rama with JP Morgan. Please proceed with your question. Hey, guys. Thanks so much for taking the question. I had a quick question. Just, you know, if I think about your prior commentary, it did look like you were seeing some sort of minimal stable disease signal with 801 in a pretty refractory population. So kind of what drove the decision away, to move away from that program, given you had some patient-level data and prioritizing it for IST programs? I get the broad commentary of focusing on the new RAS targets and NAPO, but at the bottom of your revised slide, pipeline slide, I think you still have an interesting sort of EGFR-type target. So maybe you can help us there. Thanks so much. Yeah. Hey, Anupam. Thanks for the question. Yeah, no, we're still, I would say, excited about ERAS-801 and the possibility for patients there. I'd say that we're not seeing a stunningly positive signal, and we're also not seeing a negative signal based on the phase I data. We are continuing to track patients that are on study, but— I would qualify the data as being sort of in the gray zone, where, as the data mature, we do think that exploring proof of concept in various ISTs, where we have investigators that are enthusiastic about exploring different indications, whether in combo or in the frontline setting, or even in window of opportunity types of settings, where there can be potentially unambiguously positive signals, that that's really because GBM is such a difficult disease, we just think there's going to be a little more work to identify the optimal indication for that program. So we really think it's an important therapy, but we would like to leverage ISTs to be able to explore those other signals rather than devote company-sponsored trials to go signal-seeking. Got it. Thanks so much for taking our question. Thank you. Thank you. Our next question comes from the line of Jeff Hung with Morgan Stanley. Please proceed with your question. Thanks for taking my questions. For both ERAS-0015 and ERAS-4001, you showed a combination benefit with anti-PD-1 therapy. So relative to the monotherapy data that's in 2026, when might we see initial combination data in AURORAS-1 and BOREALIS-1, and is it possible to see it around the same time as the monotherapy data, or is it likely to be later? And then my follow-up. Thanks. Yeah. Hey, Jeff, thanks for the question. As Shannon mentioned, we will be exploring combination dose escalations. Those tend to be staggered from monotherapy dose escalation. So, you're, you're right on it. It's not going to be stacked on top of the monotherapy data readouts in 2026, but there will be some, some stagger, so there'll be a little later. Great, thanks. And then with the additional capital restructuring and the pipeline updates, what is your update for cash runway and how far that will fund operations? Thanks. Thanks. David, you want to take that? Hi. Yeah, this is David. As we announced this morning, the revised cash runway is now into the first half of 2027. So we're really thankful to the investors that helped us advance, you know, not only the cash runway, but also to be able to fund these two new programs. Thank you. Thank you. Our next question comes from the line of Jonathan Miller with Evercore ISI. Please proceed with your question. Hi, guys. Thanks so much for taking my question, and congrats on bringing in what looks like some very interesting assets. I would love to ask about combinations beyond PD-1. Obviously, with some of the other mutant selective KRAS inhibitors that we've seen, there have been tolerability issues with PD-1. That's not necessarily to say that yours will show similar things, but obviously, with multiple assets across the MAP kinase pathway, do you view there to be a good possibility for combination regimens beyond PD-1, multiple targeted agent combinations, and which of those might be priorities as you move into phase I? Yeah. Jonathan, thanks for the question. It's a great one. I'll have, Shannon comment shortly, but maybe I'll tackle your PD-1 combo, question first. So I think you're absolutely right. PD-1 combinations in targeted therapy have been tough. I'd say within the, KRAS space, the combinations of PD-1 with G12C inhibitors, for instance, has led to, certain liver signals. One of the mechanisms to think about there. There are scientific, papers to suggest that because of the covalent mechanism of action of G12C inhibitors, when you combine those with PD-1, there has been, a process called haptenization that has led to some of the liver tox. Because the pan-KRAS agent that we're bringing in, ERAS-4001, is a reversible agent, we don't believe that the combo of that with PD-1 will result in haptenization. Now, of course, you know, we'll have to show that in the clinic. And then likewise, I think, Revolution Medicines is combining their pan-RAS molecular glue with PD-1, and so I think we'll understand better whether that modality can be combined successfully with PD-1. We don't anticipate haptenization for that class of molecules to result in the same type of haptenization either, but we'll see if there's other, you know, potential risks that we're unaware of at this time. Shannon, do you want to comment on other combinations that could be looked at in the future? Sure. Well, first, I'd just like to sort of echo what you've said. There's, you know, nothing in the preclinical data to suggest that there will be any predicted difficulties in combinations. We're just going to have to see how it works in the clinic. I think in terms of, you know, combinations, obviously there's lots of different opportunities. Our focus will be on those tumor types I think I mentioned, which is, you know, non-small cell lung cancer, pancreatic, and colorectal cancer. You know, certainly looking to what the standard of care is in those particular tumor types and focusing on an ability to fit within that treatment paradigm, again, to move as quickly and efficiently as possible or quickly as efficiently, forward as we can, I think is probably going to be our major focus. Obviously, PD-1, PD-1, PD-L1 inhibitors will be part of that, but certainly looking at other targeted therapies, standard of care therapies will be a major focus as well. Thanks. Thanks. Thank you. Our next question comes from the line of Michael Schmidt with Guggenheim Partners. Please proceed with your question. Hey, guys. Good morning. Thanks for taking my questions. On ERAS-0015, so just curious to this thesis on the potentially greater therapeutic window. When you think about—f irst of all, given the higher potency, are there any particular on-target adverse events that you're watching as you kind of move into the clinic next year? I think, you know, with these pan-RAS inhibitors, that there is a theoretical concern of on-target side effects, so from the MAP kinase pathway inhibition. And then, yeah, so I think the Revolution Medicines drug has been fairly clean, though. And so, yeah, what sort of- what are some of the off-target AEs that should, what a molecule could differentiate given the therapeutic window? Yeah. Thanks, Michael. So I will say that, you're absolutely right, RMC-6236 seems to have, you know, be well tolerated in the clinic, and I'd say the highest frequency TRAE seems to be the rash. I'd say in terms of the therapeutic window, given that the IND-enabling tox studies have not yet been completed, those will be in the second half of this year. It's difficult to speak to the therapeutic window of ERAS-0015, but hypothetically, a more potent molecule could have a wider therapeutic window for off-target toxicities. However, in the absence of the tox studies, it's not clear if ERAS-0015 will have any off-target toxicities. I'd say based on it, it has the same mechanism of action in terms of forming a tripartite molecular moiety with both Cyclophilin A as well as RAS, as I mentioned, whether it's in the GTP or GDP state. There was a 300 kinome scan that was run on this molecule, and that came up clean. So we don't anticipate many off-target toxicities due to the mechanism as well as the preliminary work that's been done, but of course, we'll be figuring that out in the coming months. Right. And then again, just given the high potency of the molecule, you know, I guess, what is your confidence level that that could result in higher clinical efficacy? In particular, you know, and how can we differentiate, you know, of bypass mechanisms being responsible for the ceiling effect in terms of efficacy versus insufficient on-target inhibition? Yeah. I think first of all, you know, I think the fact that potency does seem to matter and can translate into higher efficacy, at least in the G12C space. We do think with a five to 10-fold higher potency molecule against RAS, that this molecule has a chance of demonstrating that. And also, I think based on the human predictive active dose in human for this molecule is somewhere in the range of 10-40 mg QD. We don't anticipate that there will be the same solubility limited absorption that's observed in this class so far. So we do think that if there's more linear exposure and higher potency with an appropriate therapeutic window, this molecule could perform very well. Okay. Then last one, just comparing 0015 versus 4001 for the pan-RAS versus the pan-KRAS. Again, sort of how would you expect the different binding affinities and selectivity profiles of those drugs to play out in the clinic? So what would be—i s there a differential utility for either one of the two new assets? Yeah, great question. I think what we do not know, because the world does not have any clinical data yet with pan-KRAS small molecule inhibitors. So what we don't know is, to what extent is there a therapeutic window advantage for H- and N-RAS sparing? So we've seen very good safety and tolerability with pan-RAS. In fact, I think it's been surprising that H-, N- and KRAS wild-type expression has been as well tolerated as has been reported. So, you know, we're really excited about that space, but if there is a therapeutic window advantage of just being KRAS selective, then you could have envisioned, maybe in certain tumor types, whether it's CRC or other tumor types, whether the pan-KRAS could have a potential advantage. So that's going to be something that we're gonna sort out in the clinic. You know, we have some hypotheses there, but I think we'll need to prove that out in the clinic. And the nice thing about having the two different molecules is we're going to be playing in both the pan-RAS and KRAS space. And then there could be the opportunity, as I mentioned, for the novel combination of the two, where you could be maybe hitting KRAS mutations really hard with a pan-KRAS inhibitor, and then having a little bit of pan-RAS molecular glue on board to address any of the GTP state, you know, resistance mechanisms, for instance. So that sort of RAS clamp approach could be very interesting as well. Okay. Maybe just one more. On SEACRAFT-1, which is now focused on the Q61X mutation, does ERAS-0015 hit Q61 as well? I didn't see it listed on your slide, I think. Yeah, how would that be positioned then, relative to the pan-RAF relative to the pan-RAS, specifically in the Q61X subset? Yeah, we believe based on the mechanism of action, and Robert can chime in here, the ERAS-0015 should hit Q61X, 'cause it is a GTP and GDP state inhibitor based on the mechanism of action through that tripartite molecular glue. But Robert, you want to comment further? Yeah, Jonathan, I totally agree. So I think there's potential for activity against Q61 mutants with our molecular glue. Great, thank you. Thank you for the questions. Thank you. Our next question comes from the line of Graig Suvannavejh with Mizuho. Please proceed with your question. Hi, good morning. This is Sam on behalf of Graig. Thanks for taking my questions. Maybe just a quick one for me. For the 4001 license agreement, can you just, I think I heard correctly, but can you just clarify in terms of the territories? Is it U.S., Europe, and either Japan or China, or including Japan and China? Thank you. Yeah. Thanks, Sam. For 4001, that, that's a global deal, so it is basically a, a worldwide license. Got it. Okay. And then I guess in terms of the difference for ERAS-0015, that is worldwide ex the Asian territories mentioned, correct? That's right. Yeah. It's worldwide with the exception of China, Hong Kong, and Macau. All right, great. Okay, thank you so much for taking my question. And Sam. Thanks a lot. Sam, I think what you may be referring to is the regulatory milestones are split by certain regions. So that may be what you're referring to in terms of Europe, Japan, etc. Ah, okay. Thanks for the clarification. Yep. Thank you. Ladies and gentlemen, this concludes our question- and- answer session, and thus concludes our call today. We thank you for your interest and participation. You may now disconnect your lines.