Good afternoon, everyone. Thanks for joining Jefferies Healthcare Conference in London. My name is Clara Don. I'm one of the biotech analysts here at Jefferies. I'm joined by Dan, President and Chief Executive Officer of Verastem, and Jonathan is Chief Scientific Officer of Verastem. Welcome. Thank you. Great to be here. Dan and John, why don't you kick off by giving the audience an overview of Verastem first? Sure. Verastem is developing small molecules to target the RAS pathway. We've got a commercial product that launched earlier this year. It's actually two drugs, avutometinib and defactinib, that were approved for a rare form of ovarian cancer called low-grade serous ovarian cancer. It's a cancer that strikes younger women. There's about somewhere between 4,000 and 8,000 women in the United States that are afflicted with the disease, very resistant to chemotherapy. We had a priority review. Even with the priority review, we got approved two months before our PDUFA date. We've had a partial quarter and a full quarter each time, beating consensus by about 100%. That launch is going quite well. We're seeing good uptake, pretty broad, both in the community and in academic centers. That is going quite well. We think kind of the core business, if you will, around avutometinib and defactinib should be self-sustaining in the next two, three quarters or so. We also have a G12D inhibitor. We licensed it from a company in China called GenFleet. GenFleet treated a couple hundred patients in China. We started a phase 1 here in the United States. Because of the Chinese data, which we were able to include in the IND, we were able to skip through a lot of the phase 1. We started our phase 1 at an effective dose. We've gone through the first two dose levels, including what was declared the phase 2 dose in China, no dose-limiting toxicities, starting to see some early signs of efficacy. I think importantly, even though there was really nice efficacy in the Chinese study, there was some nausea and vomiting that concerned some. We instituted, when we started in the United States, some pretty aggressive measures around making sure the patients were fed and were given prophylactic antiemetics. What we reported recently is in those first few dose levels, we saw no GI tox above grade one. We are very pleased to see that. We are moving that forward aggressively. We have also started combination studies in the United States. We are looking to do combinations with cetuximab in colorectal cancer, Abraxane in pancreatic cancer, and then PD-1 chemo in lung cancer. We are looking forward to moving those forward rapidly based on the initial efficacy signals we have seen out of China, where they seem really exciting data in both PDAC and lung cancer. Great. Thanks. We'll definitely get to G12D a little bit later. Maybe let's start with CO-PACK, the approval in low-grade ovarian cancer first. Maybe just talk about the significance of this approval for the company and for the patient as well. As I am aware of, this is the first FDA approval for those patients. Yeah, I'll start with the patients first because, of course, they're most important. There's never been anything specifically approved for low-grade serous ovarian cancer before. As I mentioned earlier, it does strike younger women. They tend to live roughly 10 years with the disease, undergoing constant therapy. The current therapies tend to be not particularly tolerable, and response rates anywhere from 5% to 13%. Again, not well served by the current therapies. We're very excited to get that launched. Uptake has been very promising. We continue to move forward with that and looking forward to both Q4 and 2026. As you said, the early launch, the revenue numbers have really beaten sales expectations. Maybe just looking at the trends you've seen in terms of the demand, the treatment duration, and patient retention, anything you can share with us in terms of those metrics? Sure. I mean, the demand continues to increase. In low-grade serous ovarian cancer, there's really two main categories: KRAS- mutated, which unlike other cancers actually has a good prognosis, and KRAS- wild- type, which has a poor prognosis. Our current label is KRAS- mutated. Obviously, we're seeing the bulk of usage in that setting. We are seeing KRAS- wild- type patients as well. Reimbursement seems to be going well with both groups. It's a little early to speak about duration. The reason that's so important, if you think of the dynamics of this launch, in our trial, patients were on therapy for, on average, 18 months. We would expect to see kind of a stacking and growing of an annuity over time. It's really too early into the launch to see what that's looking like. Over time, we expect to see the effect of that. What that would mean is every subsequent quarter, we should be able to have a larger number of continuing patients and become less dependent on new patients coming on. Early signs are good, but it's too early to really look at duration. Kind of just to follow up on the point you mentioned, you are seeing use in both KRAS- mutant and wild- type, and you are seeing reimbursement in both populations. How should we think about, you know, you've already submitted for NCCN guideline inclusion. Could the potential outcome have any impact on the reimbursement as well? What's a timeline? Should we think about the NCCN Guideline? Yeah. We submitted. They had their annual meeting in October. We've been told it was reviewed. Sometime after the first of the year, they should post updated guidelines. It would, of course, be a good thing if we get on guidelines, both from really a visibility perspective, and then it tends to make reimbursement in the United States easier. What I say normally is right now with reimbursement, and this is common in an early launch, where you get new-to-market blocks, you have to do prior authorization. You'll often get kind of a reflexive denial of the first claim. Then we've got data packets that go in, and we're seeing pretty good success in it getting accepted based on the data. That becomes easier with NCCN guidelines. We're going to continue on the path we're on now and, again, hopefully get on the guidelines and make it a little easier. Now, having said that, while we can't promote off-label, our publications actually on our studies, we studied both wild- type and mutant. Because of the poorer prognosis in wild- type, we believe it's adding value to those patients as well. We are able to distribute the publications. We can't promote on it. There is some awareness around it. We've also been working in this space with the KOLs for the last couple of years. Our medical science liaisons have been out there doing scientific exchange, educating on this. All of that, I think, has helped with uptake. A really important thing for us is to make sure that we can replicate what we saw in the clinical trials, which is that long duration of therapy. We have oncology nurse educators who, when we get a first patient at a given site, go in and educate the entire staff on how to optimally use the drug, how to educate patients on what to expect. A lot of the more common side effects they might see are things that are very transient. As long as they know they're coming, they get through it, and then hopefully then stay on the drug long- term. Regarding NCCN guidelines, just to be clear, for the labeled population, the KRAS- mutant recurrent low-grade serous ovarian cancer, we're on level 2A. We got it on the day after approval for the KRAS- mutant low-grade serous ovarian cancer. It is just the wild- type that we're saying that there might be an update beyond that. Great. Can we also talk about the distribution channel for the CO-PACK right now? What role do specialty pharmacies play in the distribution here? Yeah. We have a closed distribution model. It is two specialty pharmacies. Because we launched early, we actually launched only with the specialty pharmacies. They tend to serve the smaller practices or the one-offs. It is a very white- glove individual patient. We work through and get the drug out to the patient and interact with the patient to make sure they are getting their refills, if they have any questions on the drug. If the practice has any issues, we deal with that. Really last quarter, we started to bring up we have four specialty distributors. The importance of the specialty distributors is they serve the larger customers. They also tend to be associated with group purchasing organizations. A key part of our launch strategy was we have a relatively small sales force. About half of all patients are concentrated in 100 sites in the country. The sales force concentrates on one-on-one calls to physicians in those sites. The rest of the market tends to be distributed out in the community, doctors who may see one or two of these patients a year, where it would not be either cost-effective or, frankly, a great use of time to try and call on those doctors. Luckily, most of those practices belong to large organizations that are affiliated with the group purchasing organizations. By contracting with the group purchasing organizations, they allow us to attend their meetings, and we get to educate the physicians in large groups. All the ovarian doctors may get together, and we will have either a medical science liaison or John, our CSO or our CMO, go talk to them as a group. We work with the organizations to make sure we're embedded in their electronic medical record. We have standard order sets. It's much more of a one-to-many sales process instead of one-to-one. It's much more efficient. Instead of trying to grab a doctor in the hall for a two-minute detail, we're getting a 30- to 40-minute audience where we present our slide deck. It's a very different dynamic. It's really where the market's moving for these doctors that are more distributed out in the community. Coming out of Q3, you also shared some updates regarding the confirmatory phase 3 trial, RAMP301 study. You mentioned the Independent Data Monitoring Committee recommended enrolling 29 additional patients across both cohorts. Maybe just explain to us what analysis kind of drove this recommendation and how should we interpret this recommendation? Does that change any of the regulatory timeline? Sure. Just as background, when we designed the study, our pivotal study that we used for approval, the endpoints were not locked down yet. It was not completed. The comparators we used were some phase 3 studies that had been done a number of years ago where KRAS- mutant and KRAS- wild- type patients were not prospectively broken out, and they did not measure it in all the patients. The prior therapies were slightly different back then. Bevacizumab was not used then. We allowed prior MEK inhibitors. There were not prior MEK inhibitors. We were basically sizing the study in an environment where we did not have perfect comparators. What we built into the study was, and at the time, I did not know you could actually do this. What we built into the study was an interim analysis that was to be planned at approximately 50% of the events. What the interim analysis was designed to do was look at the data from the actual study, use that to resize the study back to an 85% conditional power so that we could then go forward. The study actually accrued quite a bit quicker than we expected. When a study accrues more quickly, you do not have all your events yet. We made the decision when we finished accrual, we could either let the study lay fallow for three months, lose our sites, and potentially have to restart all over again, or do the interim analysis early, which we chose to do. The Data Monitoring Committee told us, based on the number of events they had and the current conditional power, they recommended we add 29 patients, about a third of them to the mutant and two-thirds to the wild- type, which told us that we're in a pretty favorable zone adding a small number of patients. We were quite excited we were able to do that. What typically happens when there's an interim analysis and you upset the size of a trial, it's typically viewed as negative. I think there was a knee-jerk reaction and a little bit of reaction in the stock in the short term, as I think the more sophisticated investors who understood this and we have gotten the word out, I think it's understood that it was probably a pretty favorable thing to only add 29 patients. Since we had finished the accrual early, even with the additional 29 patients, we'll finish the accrual in the first quarter of this year. It doesn't change any regulatory timelines. We're feeling pretty good about both the mutant and the wild- type in the study. The Data Monitoring Committee could have had us just add patients to the mutant. That might have signaled that the wild- type wasn't doing particularly well because you couldn't add just to the wild- type the way the statistical plan was written. We're feeling good about it. Timeline shouldn't change. The final analysis will be with a PFS as a primary outcome and will be second half of 2027. That's unchanged. It doesn't change our regulatory timelines. Great. That was really helpful. Before we move to G12D, I also want to quickly touch on the opportunities beyond ovarian cancer and what kind of development you are working on. Yeah. Low-grade serous ovarian cancer has a very high un met need. We're excited to be there. It's not the biggest market in the world. For the last two years, we've been using the same regimen combined with standard chemotherapy, gem/Abraxine, in frontline metastatic pancreatic cancer. We've reported interim analysis from that study where we had a confirmed response rate of 83%. Standard of care is about 30%. This is an unprecedented result. We have an expansion phase of that study. It's completed accrual. In the first half, probably mid next year at a medical meeting, we'll be reporting the larger data set. Very excited about that because that obviously expands the opportunity for this regimen many-fold. We also have the G12D program. We're excited about this. Since we have a number of different shots on goal for pancreatic cancer, we will only go forward if this extraordinary result continues. If it does hold up, we believe it's enough to get Breakthrough Therapy Designation from the FDA. We're quite excited about that. As we'll talk about when we talk about the G12D program, obviously, pancreatic is very important there as well. Yeah. Let's talk about G12D. Maybe for the folks who might be less familiar with the collaboration, just give us a high-level overview of your collaboration with GenFleet and maybe some data updates you shared and your partners shared as well. Sure. So just a bit of history. About four years ago, we did analysis of why our market cap was different from similar companies that had lead programs that looked similar to ours. The big difference was we did not have a discovery capability. Our model had been to in-license drugs. John led a team where we went and we looked for a partner that had a discovery and a chemistry capability where we could work on targets that were relevant for the RAS pathway. They were on strategy for us and really worked together collaboratively to find molecules. We found GenFleet. We knew that they had a capability to develop KRAS inhibitors because they had the first G12C inhibitor approved in China. We worked collaboratively with them to develop a G12D inhibitor. That That was a target we were quite interested in. They made over 200 molecules. We worked together with them to do the preclinical work to choose the lead. They brought it into the clinic. They started the phase 1. We have now taken over outside China. They are continuing to develop it in China. Extraordinary results so far that I will have John go through. The collaboration includes two additional targets. It truly is a discovery capability for us that is going to allow us to have three additional targets in the market. We are very excited about where it is going. John and I were actually over in Shanghai a couple of weeks ago. We did a joint investor event with GenFleet and then had a number of planning events with them planning our joint development together. John, maybe if you can talk about the results they've seen to date and where we think this is going. Yeah, exactly. I will start with the differentiation. I think KRAS can exist in an on-state, which is bound to GTP, and an off-state bound to GDP. There are G12D inhibitors now and pan-RAS inhibitors that only hit the off-state, and they appear to be less effective. I think Quanta recently had a result and did not have single-agent activity with the G12D off only, as far as I could tell. Revolution Medicines targets the on-state only. I think there are some limitations there. Ours is a dual G12D on-off targeting agent. When we compare it in preclinical models, for example, to the Revolution Medicines on-only agents, we see better durability, and we see deeper regressions. As we turn to the clinical data, as Dan said, GenFleet is really running very quickly and enrolling on the order of 200 patients. At World Lung, they reported a 69% response rate as a single- agent for the G12D inhibitor in G12D non-small- cell lung cancer, which is unprecedented and high and reflects the preclinical profile. Recently at ESMO, they reported on the pancreatic cohort. When they reported at ESMO, about 70% of the patients were third-line and later, whereas many people are looking just at second-line who tend to do better. Recently, when we were out there at the event in Shanghai, they broke down second-line versus third-line and showed that for second-line, which is now 12 patients, but they are growing that number, they had a 58% response rate. When you compare that to a G12D on-only from Revolution Medicines, they are at about a 30% response rate in that setting. The pan-RAS from Revolution Medicines is at about a 29%-35% response rate. These really high response rates of 69% in lung cancer and 58% in second-line pancreatic really opened doors for us. I think potentially accelerated approval could be a possibility in the second-line setting. We're also thinking that given these really strong response rates, it's possible that we could pursue single- agent in the front line setting in lung and pancreatic. We need to see the durability and then ultimately need to move to the front line. We have a lot of options based on this really best-in-class G12D on-off profile that's translating to the front line. A little context around the pan-RAS and the G12D RAS space. If you go back a year and a half, two years ago, it was incredibly crowded. You look at the number of studies that were preclinical, everything listed on clintrials.gov. There has been a lot of attrition. These are quite large molecules. Getting oral bioavailability has been a challenge. I think if you look at the space right now, I mean, clearly RevMed's in the lead. They've shown some really nice clinical data. We've obviously shown some nice data in the clinic. There are very few that have actually made it through and are showing clinical data. It has evolved quite quickly. We are very excited to be moving forward. You're obviously running a phase 1 study in the U.S. as well. Maybe talk about the dose level you are using in the U.S. versus a study in China and what kind of other different protocols you are implementing. Sure. In China, they selected 600 milligrams once daily as the recommended phase 2 dose. As Dan mentioned, when we talked to the FDA to get the IND approved, we shared Chinese data. We started at 400, and we completed 400 and 600 milligram cohorts. Again, showed no DLTs and showed that really low-level GI toxic work. I mean, no greater than grade one of GI safety. We have started the 900 milligram cohort as well, which will be the final escalation cohort before we choose the recommended phase 2 dose as a single- agent. Once we completed the 600 milligram cohort, we also started into the combination. The cetuximab combination cohort is ongoing now. That will be our main approach for second-line colorectal cancer. Very shortly, we will be starting chemo- pembro, as Dan mentioned, to get into front line lung cancer. We're also evaluating combination with gem/nab- paclitaxel. It is a robust study. We started with five excellent sites in the U.S: David Hong, Melissa Johnson, very experienced principal investigators, for example. Now that we have these expansion cohorts coming, we're adding sites in the U.S. We're adding sites in Europe as well. You recently actually shared some high-level updates for your U.S. phase 1 study. How confident are you that the efficacy we're seeing in the phase 1 study from GenFleet will be translated into the U.S. phase 1 study? When should we expect the next update? What should we expect to see on the next update? We know in prior therapies in lung cancer are quite similar in terms of chemo- IO being the standard as it is in the U.S. Pancreatic, similarly. I I think that ultimately the proof is in the pudding. We'll have to show it in the U.S. Again, we want to show similar efficacy and that we can improve the safety signal as we've already started to see. Great. Where are you in terms of maybe exercising additional options to license molecules from GenFleet? We have been working on target two and three. We'll probably release the second target probably sometime next year. It's one of these interesting things where it's nice to have additional targets, but investors don't want us to invest in other things because we have so many things going on. Our focus now is really on maximizing our approved drug and getting it used in other broader settings and then rapidly getting to market with the G12D. That's really the focus for us. I also want to emphasize the synergies in our portfolio. I think we're, as Dan mentioned, we're targeting RAS-directed cancers, RAS-driven cancers. Our drugs can work together, but we're also talking to the same investigators in pancreatic cancer for the different programs. I think there's a lot of synergy in the efforts that are also helpful for our progress. Maybe lastly, can you just lay out what are the key milestones coming up that investors should look forward to? What's your catchphrase right now? Key milestones is we have to continue to deliver on the commercial product. We have quarterly earnings coming up every quarter. We have to continue to execute there. We will have additional data on the front line pancreatic study, which is the avutometinib-defactinib plus Abraxane, first half of next year. We will have additional data on the phase 1 study, including some data on the combinations first half next year. By the end of this year, we will give an update on we do have an ongoing study with avutometinib-defactinib and Sotorasib in G12C lung cancer. That is still going. With all those catalysts coming up, we expect to keep moving the stock price forward. Great. Thank you. Thank you for the very insightful discussion. Thank you, Dan and John. Thank you to our audience for joining us for this session. Enjoy the rest of the conference. Thank you. Thank you.