One of the Biotech Analyst here. Please join me and welcome Mr. Dan Paterson, CEO from Verastem, for this first chat session. Welcome, Dan. Thanks. Great to be here. Congratulations on the recent approval for low-grade ovarian cancer. Before we get into details, maybe you could give us a brief intro for the company, Verastem, and this novel combo, the recent approval, and your interesting pipeline. Sure. No, I was just talking with my colleagues earlier, and we're halfway through the year. We've been saying all along that 2025 will be a transformative year for Verastem. Just reflecting where we've come in the last six months, we are developing small molecules to target the RAS pathway. As you pointed out, we did just get a first-ever approval in low-grade serous ovarian cancer, which is a rare subset of cancer for which there really was no approved treatment. If I look at what we've accomplished over the last six months, we got the approval. We got the approval almost two months early based on a priority review, so even earlier, which we were getting a lot of inbound calls from investors wondering if the FDA was working. I can tell you they are, and they were. It was an amazing interaction. I would say our team was very impressed with the people we were interacting with. First and foremost, we got that approval. We got our debt refinanced. That put us in a position where we had optionality. We got a fundraising done to take over the financing overhang of the launch in a very tough environment. During the middle of the process, our stock went as low as $4 based on external influences, nothing we were doing, and we were able to pull off financing at a pretty attractive rate. We have advanced our pipeline. We exercised the option on our G12D from GenFleet so that we are now actively working with that. We reported some amazing frontline PDAC data, 83% response rate, which confirms the initial data we had at ASCO a year ago. A lot of great things going on. Obviously, the stock reaction at ASCO is not what we would have wanted. As we think about that, year to date, we were up 45%, with the XBI being down 12%. I think that was a natural sell into the news when that is happening. Right now, we are very focused on the launch, extremely excited about that PDAC data I mentioned. The GenFleet data that came out at ASCO clearly shows it is an active agent, 54% response rate in PDAC, 43%, I think, in non-small cell lung. Obviously, it is early, and it is confirmed and unconfirmed responses. Clearly, it is an active agent, and we are in the ballgame. Very excited. Fantastic. We'll come back to the launch later. Given ASCO at last week and your G12D data is really one of the key topics at the conference, and you have several presentations and hosted an R&D event, maybe we can go through the data details on both efficacy and the safety, what has been the learnings and physician feedback on this novel G12D inhibitor. Yeah. I would say the initial data that was off a pretty good cohort of patients out of China showed clearly there is efficacy, a great response rate. If you looked at the swimmer's plots, patients were either still on or had been on for a while. It is everything we could have hoped for. We were talking to a number of researchers about why was not there more clinical G12D data at ASCO, because it is a pretty crowded field preclinically. I think not a lot of things are moving forward. These are big molecules. They are hard to get, bioavailability, which clearly we showed. We were very pleased to see that. I think there was a little bit of a negative reaction to the AE profile. I think a lot of the focus was on GI tox. One of the things that we learned is the study in China was done without any prophylaxis around those things. That is standardly what we do. One of the things we made sure we did as we get into the clinic here in the United States is we have chosen very experienced investigators who have worked on these molecules. Two of them were at our event. Their attitude was, these are things we deal with all the time in drug development. We figure out how to do it. There is a reason we prophylax for nausea and vomiting in the United States. There is this thing called anticipatory nausea. Once you get it once, you are going to get it again. That is why we treat these things and have for the last 30 years. I think we will work to optimize things. We are very confident, based on the molecules we have, that we have got something pretty exciting here. Okay. To build on this China trial data, where are you to prep the U.S. phase I study to start? Also, regarding the AE, what is your plan on the dosing regimen for the U.S. trial? Yeah. So a couple of things. One, we've got three sites open, and so we're ready to go. That's really the right amount of sites when we're doing the dose escalation. The nice thing about being able to leverage the Chinese data, and there's been a lot in the news back and forth about how much you can use Chinese data, and it's really tough for confirmatory studies and really your pivotal study. We did submit the Chinese data to the FDA as part of our IND. We've been cleared to start at the 400 mg dose, which is clearly an active dose. We're not going to have to do dose escalations through a range that's not clinically active. We think that really advances the program. We are going to escalate from there. We may end up de-escalating, because with Project Optimus, obviously, we have to correlate blood levels with both efficacy and safety. There will be some work to be done there. The good news is we can start in active levels and start that exploration right away. Fantastic. Could you help us to understand how big is the potential for G12D relative to G12C, given that prior acquisition on G12C inhibitor actually reached multiple billion dollars? Yeah. I mean, G12D is the largest variant of KRAS in cancer. Full stop. It's a much bigger opportunity than G12C. I think there's been a lot written about the first generation G12C inhibitors that were largely KRAS off. The RevMed molecule in G12D is KRAS on. We're KRAS on and off, which, if you've ever heard any of the talks John Pachter has given, clearly, we think that's a benefit. It's a huge commercial opportunity. We believe, relative to other therapies out there, I mean, a year ago, who would have thought about talking about second and third in line PDAC with 30% response rate? I think we're really transforming the area. I think what's lost in a lot of this, and we've had a lot of discussions with investors and analysts, and everyone's all excited about G12D, and we are as well. It's a huge opportunity. Everyone keeps forgetting our frontline PDAC study, 83% response rate, which is unprecedented. This is a disease where we've made very little progress over the last 20 years. Standard of care regimens are anywhere from low 20s to mid 30s response rate. PFS, five and a half months. If you look at even our early data, almost all the patients are either past that benchmark or still on therapy. We are very optimistic. In a way, we've got an abundance of riches here, because as people look at catalysts, we have a launch that's ongoing. We were able to get drug in the channel four or five days after the launch, even though it was two months early. We're still catching up on certain things. The inbounds have been incredible. That's going well. Obviously, the PDAC program is very exciting. The G12D program, there's a lot of attention on that as well. A lot going on. Still early days, but curious for this G12D inhibitor. What indications do you consider to carry forward for future studies? The obvious ones would be PDAC in non-small cell lung cancer. That is where the early data was, both from RevMed and from us. We believe both have molecules that, obviously early, but appear to be better than standard of care. One area we are going to focus on is CRC. If you look at the RevMed data as a single agent, and I think it was about 9% response rate, their pan RAS has a fair amount of rash, which, combining with cetuximab, which is the likely way to go, we think is a natural path for us to go. We will go there aggressively. We are looking at a number of other indications that we have not disclosed. I see. Do you see biological rationales to combine this G12D with either RAS or FAK inhibitor from your own pipeline? Yes. Okay. Yeah. Sorry, I'll give a longer answer. Preclinically, we've done a lot of work there. Clinically, I would say our combination with sotorasib, which is defactinib, avutometinib, and sotorasib, is in many ways proof of principle for adding a FAK inhibitor more broadly to a G12D or C inhibitor, so any of the KRAS inhibitors. When you speak of preclinical data, our preclinical data combining avutometinib with cetuximab is just amazing. If you haven't had a chance to listen to any of the presentations that John has done, all the animals had CRs, and they continued after the drug stopped. I mean, of course, we've cured mice for years, and you can't put too much stock in preclinical data. It's pretty amazing data and has really gotten us excited to move forward very quickly with that combination. Fantastic. Where are you in terms of exercising additional option to license molecules from GenFleet? You still have two programs left under the agreement. Yeah. There were two other discovery programs. Again, for those who are not familiar with our GenFleet deal, we did an assessment probably four years ago. We were looking at the difference in market cap between where we were with similar molecules in the clinic and other companies. The big difference was we did not have a discovery capability. Obviously, that is a big expense to take on. Really, what we did with the GenFleet collaboration, our team found them after spending a lot of time looking at different companies in China. We were arguably ahead of the wave of bringing molecules out of China. We found this company that was really good at making molecules and was looking for a partner that was good at translational research and clinical development and had a lot of good relationships with KOLs in the United States. It was a natural fit. This was not a situation where we basically licensed a molecule. They made hundreds of analogs. We worked together preclinically and chose what to go forward. We are in that process with the other two. We have not disclosed what they are. We have identified some molecules we are working on and doing some work on. Hopefully, we will have some additional news there. I am not sure we can afford any more news with everything going on. We have a lot of exciting things coming up. That does continue to move forward. Looking forward to it. Maybe let's switch the topic to the recent approval for low-grade ovarian cancer. Given this is the first FDA approval, could you help us to understand the size of the disease market? Can you also comment on my needs? Sure. There are roughly 6,000-8,000 women living with LGSOC in the United States. The reason I bring up the prevalence as opposed to just the annual incidence, this is a disease where there are a lot of things thrown at it. It typically has been historically things that are used for high-grade ovarian cancer. Efficacy has not been great. High end might need. They tend to be symptomatic. They need to be treated. They cycle through therapies for a period of 10 years or so. That is why that prevalent population or the number living with the disease is an important number, because unlike a lot of cancers where you get an opportunity to try and treat, they do not do well. Then they are not really an available population anymore. These women do go through multiple cycles of different chemotherapies and hormonal therapies over a period of 10 years. That is the population sitting out there where, based on our market research, there's a really good chance when they come off the current therapy. In the relapse refractory setting, it's probably a PFS of six months or so. Every six months, about half of them are available to us. That is where we've spent a lot of time educating both the HCPs and the patient community. There's a really strong patient community that's been great to work with. We've been spending a lot of time educating them. Now that we're out there, we're starting to get inbound calls from people looking for the drug. We've got our field force out there, our MSLs, our market access team. We're kind of blanketing that market, but also getting a lot of inbound interest. Fantastic. When we think about the launch trajectory, would you expect early bolus of patients in the early months? No. It's interesting. We previously played in the CLL, FL space, where there's this kind of watchful waiting, and people will be sitting around waiting for something. I think these patients tend to be on active therapy. I think we will get them over time as they come off what they're on now. What we've guided is we don't think there's a bolus of patients sitting out there. There'll be a slow, steady growth over time. I think the different launch dynamic here will be, once they get on, they stay on for a long time. It's almost like a rare disease where you build an annuity where patients will stay on for 18 plus months, and it'll just build over time. Okay. Great. Any update on the reimbursement front? We're out there actively doing that now. I will say, from what we can tell with early experience, and this may be the honeymoon period, we've not had a lot of pushback. We had mentioned we've applied for NCCN guidelines, which we did the day that we were approved. We got it for the FDA label almost immediately. I think it was almost an administrative action. One of the implications of launching two months early is a key part of going for NCCN guidelines is having peer-reviewed publications. We got approval before our publications came out. They've now both been approved and accepted. Both the RAMP study and the FRAME study have been accepted for publication. We've been advised to submit those publications, which we will in the coming weeks. We're still in the process there. I would say early experience so far with payers has been, knock on wood, pretty well. I think our team is pretty equipped with all the information you need to justify usage and all of that. Again, with such a high unmet need, it's a case you can make. Fantastic. Maybe you can elaborate a bit on the NCCN guideline, because that included the entire population regardless of KRAS mutations, different from label. How should we think about the uptake of this combo to separate populations? Yeah. I would say the way we've modeled it, we do think there'll be quicker uptake in the KRAS mutant. We do think there'll be significant uptake in the KRAS wild type, just because the patients did quite well on the study. Again, that'll come out in the peer-reviewed publication. We do believe mutant will probably have uptake quicker than wild type. We'll get both. As I mentioned, now that we have our peer-reviewed publications, we're submitting them to NCCN. We'll go through that process. I see. Maybe we can talk about pricing on the approval call you mentioned, that the wholesale acquisition cost for a 28-day prescription of the two medicines will be $48,500. Could you talk about the rationales for you to get to this price point? Also, what are the available, the current therapies for this population? Yeah. We did extensive payer research. This is two drugs. They are packaged together, two drugs. If you look at recent launches in smaller indications, I think one impact over the last year or so of the IRA is people are expecting a fair amount of pressure on net price. We have seen gross prices going up. We felt it was really important to make sure we had an incredibly robust patient assistance program so we could shield patients from the price, but make sure that we had priced it in a way where we could afford to do those programs. It was consistent with other analogs that have come out in the last year. Okay. As we look forward to the initial launch performance, what do you think could be the parameter for assessing the launch performance? What kind of launch metrics do you plan to share? Obviously, sales and number of prescriptions. We're still finalizing some of that, because we want to make sure that as we start putting metrics out into the market, they're both reliable and repeatable. In the early days, everyone's asking us, is the data going to IQVIA and all that? We're not blocking any data. I think it's important for people to understand it takes a while to calibrate those numbers over time, because nobody captures 100% of prescriptions. You have to understand where your business is coming from and where it lines up to where the data is really accurate. We will report, obviously, the things you need to report for your SCC, the things that will give a flavor of how things are going. Number of physicians prescribing, repeat prescriptions, to the extent we can measure it. There are parts of the channel you can measure these things, parts you can't. Try and look at duration of therapy, amount that's paid for versus amount we have to give away, things like that. We'll start establishing a pattern as we get out with our first quarterly earnings. Great. Also, any analogs we can use to predict the launch trajectory? Every launch is unique. On this one, where there is no competition or counter-detailing, I think that's a factor that's hard to take into consideration. You look at the ELAHERE launch in ovarian. That may be one. There are some differences there. It went up very quickly. Patients do not stay on as long. There might be some dynamics there. The SpringWorks desmoid tumor might be one to look at. I think every launch is unique. We will establish a pattern here. We will go on from there. Fantastic. Also, the confirmatory phase three study, the RAMP 201 study, is now ongoing. Obviously, that's in the all-comers setting. Perhaps talk just about how enrollment has been going so far, especially any difference you noticed after approval and also physician feedback overall. Yeah. I would say it's going quite well. Accrual is at least on track. We haven't noticed any differences yet. One of the things we had worked closely to do is to make sure we front-loaded our U.S. sites and then added a lot of ex-U.S. sites to make sure we'd be able to complete on time. I'd say the accrual we're getting from outside the U.S. would be enough to support getting done on time. Every indication is we should be able to do that with both the wild type and the mutant. Great. We also want to get a sense of where you are for the ex-U.S. regulatory development. Maybe in Europe, what has been the discussion and the feedback regarding using phase two data for regulatory approval? Also, in Japan, you're running a bridging study to support potential approval. What has been the feedback? Yeah. Europe first. We have been in contact with the regulators there for a while. We're really following the same path we did in the United States, which first established that it's a rare disease, that it's different from ovarian cancer. Make sure we make that clear. We've gotten our pediatric waiver, which is an important step forward. We're preparing to get regulatory guidance on the key question you brought up appropriately, which is, do you get approval on a phase two, or do you have to do the randomized phase three? We don't know the answer to that yet. I will say it's likely to get robust reimbursement. We'll probably need the phase III study. I think us, like everybody else, is looking at what the implications of most favored nation pricing is and what might happen there. There is some question around at what point we would start having revenue in Europe. I would say we have a clearer line of sight in Japan. First of all, the regulatory path there was a little more straightforward. We can do a bridging study, which is well underway, small number of patients where we can get what is called conditional approval, which you get full reimbursement, everything when you have that. We will immediately roll those sites to participate into 301, the confirmatory study. Reimbursement in Japan is obviously somewhere between Europe and the U.S., but better than in Europe. Great. You have mentioned the combo showed a pretty compelling response rate in frontline pancreatic cancer. You presented at ASCO. Also, this combo is going to expand it to lung cancer. Can you maybe elaborate what is the plan here regarding moving forward to the next phase and what kind of signals you need to determine RP2D? I'll start with the lung one first. I mean, that I had mentioned earlier. We have the triple combination with avutometinib, defactinib, and sotorasib. That's ongoing. We've completed the safety cohort, if you will. That was important to being able to open sites in Europe. That should go more quickly now. We're hoping to have some additional data there by the end of the year. On the frontline PanC, the way the study was written, it was a Simon II stage, which we'd actually hit the parameter to expand with the first six patients. Now, technically, we've done the 12, and we've got the 83% response rate going forward. We're opening the expansion cohort, which will be a total of 29 patients. Because the results we've seen to date have been so amazing, we talked about the response rate in cohort one. If you look at across all the cohorts, we've had, I think, 92% of the patients had some level of tumor reduction. Even though it's clear to us that cohort one is the one to take forward, and that's the one that'll be in the larger study, it does look consistently pretty good across all of them, which gives us, I think, even more confidence that there's a there there. When we had the first six patients a year ago, I think people are interested, but it's a small number. You go and you replicate the exact same thing. I'd say the investigators, who because of our relationship with PanCAN are extremely experienced, are very excited about it. They see a lot of these patients. Fantastic. Lastly, besides the initial launch performance of the combo, what are the other key catalysts investors should look out for in the next 12 months for Verastem? Yeah. I'd say it's launch performance, updated data on the lung study, continuing progress on the frontline PDAC. I'm really excited to get the G12D inhibitor in the hands of our investigators here, who I'd mentioned are extremely experienced and very excited, and to be able to start getting out early data on that. There'll be more to come on earlier stage things as well. Fantastic. Thanks again, Dan, for a great discussion. Thanks, everyone, for attending. Thank you for having us.