Hey everyone, thanks for joining us today. I'm Laura Prendergast and I'm hosting David Chacko, the CFO/CBO of Erasca. Erasca, to my knowledge, is the only company that's developing both a pan-RAS and a pan-KRAS. They have one of what I believe is one of only two pan-RAS being developed in the U.S. so we're going to spend a lot of time talking about that today and if you want to maybe give a little bit of introduction to yourself and the company, we'll start from there.
Thanks Laura, and thanks for having us here. Yeah, I'll do a quick intro on me and spend maybe a little bit more time on the company. So I'm David Chacko, CFO and CBO with Erasca. I've been with the company for I guess about six years now. Before this worked on the investing side at Versant Ventures, spent some time in large cap companies. I worked at Alcon as Chief of Staff to the CEO, was also a Consultant and by background did medical school and business school, but have been on the business side since. Now in terms of the company, Erasca, we were founded in 2018 by our CEO Jonathan Lim. He was CEO previously at Ignita until the ultimate acquisition by Roche.
Our other co-founder was Kevan Shokat at UCSF, who this audience knows well because of his discoveries in the RAS space as well as others. The two of them teamed up to co-found Erasca really around the idea of going after the RAS- MAP Kinase pathway. Our name is a portmanteau with a dual meaning, not only to erase cancer, but also to eradicate RAS-driven cancers. I know we will spend a lot of time talking about the RAS programs today and those fit very squarely within that strategy. We have built an excellent team, an excellent SAB that includes leaders from industry and academia, and we are really excited about these programs that we are now moving through the clinic. I know we will spend a lot of time talking about those.
Absolutely. Focusing on ERAS-0015, which is your pan-RAS, this was in-licensed from Joyo in May 2024. This is obviously a very highly desirable asset. Right now, RevMed is the only other U.S. company running clinical trials with a pan-RAS. How did you guys find this asset? It seems like there would have been a lot of high demand for such an asset.
Yeah, absolutely. I would say that it comes down to a combination of things including the fact that we try to be very well networked. We have done eight in-licensing or acquisition deals in the time that I have been at the company. A lot of that comes through relationships either with the investor community or with BD partners or whomever. This one was no exception where we had learned about other assets in the space via some of our connections into both the BD side as well as the investor side. Through that we were able to kind of navigate and evaluate, get over to what eventually became this 0015 compound to be able to get that. Of course, as with anything in the work that we do, there is also a fair amount of luck that goes into it as well.
Yeah.
But to your point.
Sorry, but to your point. Yeah, highly desirable assets. I would say that within a short amount of time. We announced these in-licensings in mid May of 2024. Just a couple weeks later at ASCO, all of the big pharma companies knew about the assets, several of them even commenting on the fact that what a great find that their teams were not necessarily aware of the assets.
Yeah, I'm surprised that we haven't seen a pan-RAS asset bought forward by large pharma yet to date. So my assumption there is that the IP isn't something easy to do, especially with the tri-complex technology.
That's right.
On that note, you guys just last week announced that you have gotten Composition of Matter Patent for this asset. Maybe can you elaborate a little bit more on that milestone that you guys announced?
Yeah, yeah, so that's right. Last week we announced that we received a U.S. patent that was issued for ERAS-0015 covering the composition of matter for the molecule out to 2043, absent any PTAs or PTEs. That was great to see. I would say that for us it was perhaps more confirmatory in nature in the sense that we already felt reasonably strong about the IP position. We had done a lot of diligence around the asset before we brought it in. Ever since it's been in our hands, we have a very good internal IP team as well as external IP counsel that does a great job of monitoring the entire landscape. We have always felt good about our IP position. Last week's announcement just further solidifies that.
Absolutely. Can you provide any commentary to how 0015 is structurally different from daraxonrasib or any functional differences?
Sure, maybe I'll start off with how it's similar and then I'll talk about how it's different. In terms of similarities, both our molecule 0015 as well as daraxonrasib, otherwise I may also call it 6236, they work through the same mechanism of action. They are these tri-complex molecules. Basically, our molecule 0015 binds to cyclophilin A to form a bipartite compound. That bipartite compound then goes and finds the RAS protein to form a tripartite compound. That's the same MOA for us as well as for the RevMed molecule. That's what I meant in terms of the similarity.
Now, in terms of the differences, the molecule that we have has a couple of key modifications from a chemical standpoint that not only provide a structurally different molecule or a different molecule based on those modifications, but also it leads to a number of key advantages. For instance, our molecule has better binding to cyclophilin A. I mentioned that. That's the first step in eventually forming this tripartite complex. We have about 8 to 20-fold better binding affinity to cyclophilin A. That leads to a number of advantages, including better in vitro potency on the order of about 4x-5x, better in vivo activity in terms of we're able to achieve comparable anti-tumor activity with about one-tenth the dose, better tumor PK kinetics, and better PK and ADME properties overall. A lot of that is enabled by these structural differences.
You guys have in your corporate doc, you have some slides showing preclinical data that shows exactly what you've said. How are you thinking about therapeutic window now that you guys have this drug in the clinic? What optimization do you think you could actually provide on that front versus daraxonrasib ?
Yeah, great question. I mean, I think there's a couple of ways to look at that. First of all, I think if we ultimately are comparable to RevMed, I think that is a huge win in and of itself for a number of reasons. First of all, the fact that there's a huge unmet need in this space. There are 2.7 million patients that are diagnosed annually around the world with RAS mutant tumors. Unfortunately, there are just way too many patients out there and the space can easily support multiple players, let alone two. To your earlier point, that really it's us and RevMed that are advancing these trials in the U.S. There are other companies as well, OUS, but it's primarily RevMed and us, and it can easily support two players.
I think the level of enthusiasm that we've seen in terms of what our preclinical profile looks like and what that could mean for patients, especially in this area of high unmet need, just speaks to why we think that even a comparable profile could be sufficient here. If it turns out that we have a superior profile, of course that would just provide even additional upside beyond that. In terms of the therapeutic window, I'll give you a couple of hypotheses that we can discuss further as needed. For instance, we anticipate that for the various reasons that I mentioned around better binding, CIP, more in vitro potency, better in vivo activity, that we anticipate having potentially a better profile or a lower dose compared to where RevMed is at with their dose.
That can lead to a couple of advantages, one of which for instance is GI tox. RevMed's number one AE is rash, their number two AE is GI. GI can be driven by on- target. It can also be driven by just drug load in the GI tract. To the extent that the AEs that are seen from a GI standpoint are driven by drug load in the GI tract, if we have a lower dose than RevMed, then we should have hopefully a better GI profile. The other thing I'll mention too is that you do see if you look at the KRAS G12C class as an example, you do see that potency matters.
What I'm talking about is if you look at first-generation molecules like the adagrasibs and sotorasibs of the world, and then compare that to later generations like divarasib from Roche/ Genentech, divarasib has better response rates and durability, and so a more potent molecule seems to translate into enhanced efficacy. Again, I don't think it's necessary for the reasons I said that we have to be better, I think comparable is fine, but if it turns out that we are better, then of course that provides even further upside.
Absolutely. Before we get into the ongoing phase I studies that you have up and running, is Joyo pursuing this drug in China at all? Is there ongoing studies there as well?
Yeah, there is. When we did this deal with Joyo, we took the license from them. Joyo is a Shanghai-based company. They have a couple of other programs. They are a great company with very good development capabilities within China. They were looking for an ex-China partner. What we negotiated with them is that they would maintain rights in China, Hong Kong, and Macau, and we would take on rights everywhere else subject to a buyout provision that allows us, if we so choose at our election, to make a one-time payment and then we can actually buy those rights for China, Hong Kong, and Macau. Yes, because they do have China rights, they are pursuing a phase I dose escalation study in China as well.
Are you guys able to leverage any learnings from the dose escalation or the safety efficacy in China for how you think about your development?
The U.S. yeah, I would say and I'll step back a little bit and provide even broader context on that. I think that for us, we've been able to learn a lot in this space. RevMed has done a tremendous job of being trailblazers in this space in terms of showing us as the world that pan-RAS is a great target to go after. You know, we have a tremendous amount of respect for them. I think because of them having gone first, we've been able to learn a lot about pan-RAS from them. That certainly has been incorporated into how we're thinking about our approach to the clinical development plan.
Also, specific to this molecule 0015, because we do have our partner Joyo that's advancing this molecule in China, we are seeing not only what happens with our drug in our hands, but also what's happening over in China, and the two companies, U.S. and Joyo, are very nicely communicating, having multiple interactions at multiple levels of the company, including a joint development committee that I sit on as well. There are multiple avenues for discussion and cooperation and making sure that we're doing the best thing for this molecule to bring it to patients.
Great. On that note, can you introduce us to the ongoing phase I studies that you have for both this pan-RAS and the pan-KRAS molecule and maybe start with when these studies initiated?
Yeah. So we publicly announced that we cleared INDs for both ERAS-0015 as well as ERAS-4001, our pan-KRAS. We announced that in May of this year. We've publicly guided that we'll have data for both programs, phase I monotherapy dose escalation data in calendar year 2026. I know that that's pretty broad-banded guidance, but we put that guidance out at JPMorgan earlier this year. That's where we are in terms of a rough start and where we'll be in 2026. What we're thinking about for the data update for next year for both the AURORAS- 1 trial, that's the one encompassing ERAS-0015, and then the BOREALIS- 1 trial, which covers ERAS-4001, both of these studies, or both of these readouts.
We want to be able to tell an interpretable story, not only for us, but also for the external world to know what these assets can do. Think about that in terms of dozens of patients in each of these studies. We'll, of course, be looking at PK safety, as you would expect in any phase I study, as well as initial signs of antitumor activity.
How do you. This is a broad solid. Both of them are broadly enrolling patients with RAS mutations or KRAS mutations in solid tumors. Should we expect an enrichment for the big three, PDAC, colon cancer, colorectal cancer.
Yeah. The epidemiology of KRAS mutations is exactly what you just mentioned. In terms of the big three, there's also the long tail of opportunities. Just given the prevalence of RAS mutations, those long tail opportunities, several of them are still tens of thousands of patients in the U.S. So there's still sizable opportunities. During the initial part of the dose escalation, we just want to get through to higher doses as quickly as we are able to. There's no need for us to enrich for certain tumor types. I imagine that the distribution will sort of more or less follow the natural distribution. We do have the ability later on in the dose escalation that if we so choose, we can put our thumb on the scale to enrich for certain tumor types.
Regarding the mechanism of action, there's been quite a lot of excitement around RevMed's pan-RAS, but since it's not yet approved, it's hard for docs to get access to this for their patients. Do you think this has funneled through to enthusiasm for your pan-RAS as well?
Yeah, absolutely. I mean, we. I think, again, there's just such an unmet need here in terms of the number of patients that have these mutations. You know, I think. That speaks to the fact that our enrollment has been going well. You know, I'd also say that shortly after we brought these molecules in, we did share the preclinical profiles with a lot of investigators, and they also love the profile of the two compounds, 0015 and 4001. I think they see the unmet need broadly and then also the differentiation of 0015 and 4001. That has been reflected, as I mentioned, in terms of good enrollment across both trials.
Have you guys disclosed to date where you are with dose escalation?
We haven't. Other than what I kind of vaguely painted in terms of IND filings and clearances back in May and then data update next year.
Got it. So thinking a little bit about strategy, you've outlined a couple different possibilities for us. You know, there are we mentioned the big three from just even just my conversations with KOLs, such as biliary cancer, tract cancer doctors or endometrial doctors. There seems to be massive unmet need across other indications as well. You know, strategically, are you planning on competing in PDAC with RevMed or are you planning on maybe pursuing other indications? Or is this just going to be a pure data- driven decision? Once you see how your profile looks.
Yeah, ultimately it will be data driven. We're definitely looking at the big three, but also the long tail. Our plan is to leave no stone unturned. We want to be able to explore what all our programs can do. And to your point, there's a huge unmet need not only in the big three, but also those long tail opportunities. We certainly want to be comprehensive in how we're thinking about it. I think, you know, those of you who are following the story closely know that we were able to extend our cash runway guidance earlier this year. Our cash runway guidance is out to second half of 2028. As of our last filing, which was Q2, we had $387 million in cash. Both of those speak to the fact that we're well- capitalized.
I think you need to have a well-capitalized balance sheet to be able to fully see what these molecules can do. I think that's one area where we want to have the ability that if we see a signal here and here and here, to be able to run after those and try our best not to be rate limited.
Absolutely. Some investors are already kind of painting this picture where a pan-RAS becomes the backbone of a lot of combinations in the future. How are you guys thinking about moving into combination studies as well? Is there anything that's top of mind perhaps?
Yeah, I think we are looking at different areas for monotherapy, but also combinations. I think combinations, both the pan-RAS as well as the pan-KRAS, are super important. When you think about the RAS-MAPK pathway as a whole, it just has a propensity to find ways to continue the oncogenic signaling. Oftentimes, combinations are the name of the game in terms of how to shut down the pathway. A classic example of that is CRC, for instance, where you almost certainly want to be able to combine with an anti-EGFR inhibitor. Yeah, we're definitely looking at combinations. I think one other thing that's really important, especially with regard to the pan-RAS, is the scarcity value, because there's really only U.S. and RevMed that are playing in this space.
Because there's such a huge unmet need and that scarcity value, sort of like to the extent as you're mentioning that pan-RAS becomes a backbone of different combinations, the fact that there's essentially, again, RevMed and us, that leads to some potential good outcomes as well.
On that note, are you guys open to partnerships or have there been any ongoing discussions with partnerships revolving around any combinations or development pathways?
Yeah, we are open to partnerships. We want to be able to see what is the best way to bring these drugs forward to patients as quickly as possible. Again, just with the high level of unmet need, we want to be able to try to address that as quickly and in the best possible way. If that's via partnership, if that's independent, if that's whatever, we want to certainly do that. Yes, we are open to that. Again, the breadth of all the different things that we can potentially pursue in the RAS space is actually quite large. Finding the best way to go after that is certainly in everybody's best interest.
Absolutely. Since you guys are very uniquely positioned as having both a pan-RAS and a pan-KRAS, you're probably one of the best people to talk to about where you think one asset might play better versus another. As you're developing both together strategically, how are you thinking of positioning clinically, one in one area, one in the other?
Yeah. I was actually at the Guggenheim conference yesterday up in Boston, and I was asked a similar question, coincidentally by the analyst who also earlier this year hosted a panel session with Ryan Corcoran and David Hong, where he asked them a similar sort of question. They gave a very good kind of back and forth. It was a really engaging discussion earlier this year between the two of them. What I would say here is that our sense is that these molecules, Pan-RAS and pan-KRAS, will ultimately probably have their own swim lanes. I'll say that based on two things. Number one, if you look at RevMed as an example, they've disclosed the most amount of data in PDAC, second most amount of data in non-small cell, and comparably very less data in CRC.
That could potentially be because of, I do not know, it could be any number of different reasons, but potentially AE driven or otherwise. Now, pan-KRAS, one of the hypotheses around pan-KRAS is that because you spare H- and NRAS, is it a kinder, gentler version that allows you to have a more tolerable profile? That is one where potentially by sparing again H- and NRAS, maybe you have a better rash profile that allows you to go after CRC, where ultimately, again, you probably do want to combine with an anti-EGFR antibody like cetuximab or panitumumab that ultimately do have their own rash profile. That is one hypothesis of different swim lanes for one versus the other, based in part on, you know, where RevMed has disclosed data. It is also based in part on our own experience with our naporafenib program.
This is one that we do not talk much about, but this is a pan-RAF inhibitor that we were advancing in NRAS mutant melanoma, where there was a fair amount of rash. Given that this is NRAS melanoma, we have learned from that as well that maybe again, by sparing H- and NRAS, you might have a better rash profile.
Since you mentioned naporafenib, you previously guided that you were pursuing partnerships with this asset. Is this still something that's ongoing or something that could maybe help prolong cash runway?
Yeah, yeah, those discussions are ongoing. You know, the nature of sell side BD is that it's so speculative, so we do not give specific guidance around it. Yes, those conversations are ongoing, and we are encouraged by the discussions that we have been having. The cash numbers and the runway that I mentioned earlier in this talk, that does not include any proceeds from us doing a naporafenib deal. If we do do a deal, that would just be further upside to our cash and our runway.
Great. Regarding cash runway, how much is built in as far as development of both of these assets beyond just the phase I initial dose escalation?
Yeah. We want to take a pretty aggressive turbocharged CDP here, clinical development plan across the programs, and see wherever the most promising signal is and go after that. We do have quite a bit baked in, not only from the phase I dose escalations, but also expansions and then initiation of phase IIIs. There may be opportunities as well for us to even accelerate our timeline as well.
Got it. Coming back to the mechanism of action of the pan-RAS using the tri-complex technology. Are you guys seeing the same GTPase activating activity that daraxonrasib is seeing?
Yeah, so again, because the molecules actually have that similar MOA and, you know, in many respects structurally are similar, although they are distinct, you know, they. Yes, we do have that as well.
Okay, I'll pause here to see if there's any questions in the audience. Yep. I'll keep asking you questions.
Sure.
Yeah, yeah.
These are great questions.
RevMed has been a little bit more vocal about pursuing a RAS inhibitor doublets where they combine their pan-RAS with a selective inhibitor. How are you guys thinking about this as a potential strategy as this does emerge as something that maybe pushes efficacy beyond pan-RAS in monotherapy?
Yeah, I mean, as we were talking about in a different question, we'll of course be data driven about this in terms of what we're seeing, not only from our own data, but also anything else that's disclosed externally. Yeah, we have different combinations that we could potentially pursue that could be with standard of care agents. You know, I mentioned anti-EGFR as an example, but you know, Pembro is another one that you would think of, for instance, in lung. It could also be with investigational agents and those could be within our own pipeline. It could also be external agents as well. We've shown a history as a company not only with the RAS programs, but even, you know, prior programs that we've had in our pipeline of really going to wherever the best science is.
If that's our internal pipeline, if that's external, that's fine. We're going to go where we think the best opportunity is to help patients.
Absolutely. Do you have any thoughts on the RAS-ON versus RAS-OFF or ON/ OFF type inhibitor approach? Your pan-KRAS is an ON/ OFF inhibitor, correct?
Yeah, yeah, absolutely. Yeah. I think they're both interesting approaches at this point in terms of until we have more data across both types of approaches, it's still more speculation than anything else. I do think that they are both viable approaches. I do think that, you know, one of the advantages we have with 4001 is because it is that on/off inhibitor, this molecule has single-digit nanomolar potency against both the GDP and the GTP state, albeit more potent against the GDP state. That could also lead to an ability for us to go after RAS both in the on and the off state. You know, whether it's the pan-RAS or the pan-KRAS on top of that.
Got it and regarding EODPR pipeline, I believe you guys also have an EGFR inhibitor too. Where is that? In development stage.
That's an early stage program. It's in discovery right now. ERAS-12 is our bispecific biparatopic antibody going after EGFR domain II and domain III. The approved EGFR antibodies like cetuximab and panitumumab go after domain III. Only this molecule would be able to go after both domain II and domain III. Both the closed domain III, but also the open conformation as well with domain II. That could hopefully lead to better antitumor activity. This is still an earlier program in our pipeline within the discovery stage.
Absolutely. Thinking about the data sets that you're going to have in 2026, should we think about, because they are overlapping in indications where they could be used, should we expect the data to be shown together to kind of tell a full story for the company, or do you think there will be two independent data sets?
It could be either. I think it'll probably be more driven by. We want to be able, as I mentioned earlier, to tell that interpretable data set for us as well as for the external world. If it so happens that we get to the same sort of point at the same time, great, we can do them together. If it's the same point, but at different times, we can do them separately. We can do them either way.
Okay, and are you guys planning to target a medical meeting next year or is it too early to even at least answer to that?
Historically we've done both where we've done medical meetings and we've also done R&D days, you know, all things equal. Medical meetings, you know, is what we prefer. Sometimes just given the timing of when abstracts are due, given what's happening in the market, given what's happening, you know, just generally, the timelines may not always line up, but we have done, again, both the R&D day approach as well as medical meetings.
You know, just regarding expectations for that data, you have made it clear that you want to have a mature enough data set that it is able to tell a story on, you know, what the company has and the value of the assets. Should we assume that this is going to also involve durability data when you do present?
Yeah, that'll depend in terms of when it is that we disclose. Obviously, if you have, you know, an early versus a mid versus a late readout, you're going to have more patients, more dose levels, more follow up on patients. It'll depend in terms of our timing of when the data release is. I think for, you know, I don't know that we necessarily have to have that durability in the initial data set because I think, you know, if I think about the profile of what attracted us as well as others to 0015, you know, again, I think if we have a comparable profile to what 6236 has shown and that in and of itself is a win. Now if we have similar, if we have better for instance safety, I think that would be just even better.
I think on the efficacy side, if we're showing anti-tumor activity at a fraction of the dose of where RevMed is at, that would be thesis reinforcing for us. I think depending on where it is in terms of the fraction, that would lead to different scenarios for us. For instance, if we end up at, call it half the dose of where RevMed is at, I think that that would be a home run for us. If we end up at, you know, a quarter of the dose, I think that that would be a, you know, a grand slam for us. You know, I think that there are multiple ways that we can potentially win.
Even if we have a comparable profile from an efficacy standpoint, but with a fraction of the dose, that could be a win because it could also enable better combinations when we think about what else we might want to combine with.
Yep. I am going to wrap it up here. I do not have any other questions left but this has been incredibly helpful and I thank you for joining us here today and really look forward to seeing the data and how the company evolves next year.