To Dan and Verastem for being here with us this morning. I appreciate the opportunity to get to grill you a little bit. Great. All right. So let's dive right into it. Your lead programs are in the RAS, MAPK pathway, generally pretty familiar to folks, but you're operating in a different part of the cascade to maybe a lot of the more familiar programs here. Yeah, I would say at least our lead program, which is a RAF-MEK clamp, actually binds MEK, but then it hinders RAS, so it can't have really a feedback loop to reactivate it. And then we also add on a FAK inhibitor, which, based on preclinical data, and it's borne out in the clinic, actually helps fight resistance. And so we've had better results with the combination than the single agent. And that's really carrying through our programs now. The go-forward regimen that we used in our pivotal study was the combination of the two drugs. We've just added defactinib to our lung cancer program, so very excited about that. And our pancreatic program has both of those drugs as well. Pretty unique mechanisms of action here. I'd love to dive a little bit more into that differentiation. Particular for maybe defactinib, for the FAK, same pathway as PI3K, as AKT, as mTOR, which are very familiar places for folks to focus. What's FAK getting you that those other places in the same sort of vertical aren't? I would say, you know, first and foremost, the side effect profile. It's a very benign drug. I mean, we've treated hundreds of patients with it, and it contributes very little toxicity. And then it is kind of upstream. And then really building on work that we had done preclinically and then early in the clinic when we started the so-called FRAME study in the U.K., we actually took serial biopsies from patients. And we found if you take a baseline biopsy and then treat with the RAF-MEK clamp, pFAK goes up considerably. And then when we treat with the FAK inhibitor, it goes back down. And that really recapitulated what we'd seen in animal studies. And we think more data is coming out every day on really the role of FAK as somewhat of a universal resistance mechanism. You know, there was some interesting data at ASCO. A Chinese company, InxMed, had their G12C inhibitor, and they added a FAK inhibitor in frontline non-small cell lung cancer and had a 90% response rate. We're starting to get a lot more interest in adding FAK onto other regimens. You know, it's a bit of a unique situation. Typically, when you don't see a lot of single agent activity with a drug, it just gets killed. Yeah. You know, we had plenty of studies as a single agent where we didn't see a lot, but we were really encouraged by the preclinical data to really try adding it on to avutometinib in particular and saw a pretty stark difference. So the right place to add a combo agent to that RAS, MEK sort of cascade. Yes. Makes sense. So let's dive into some data. Sure. Obviously, the lead here, low-grade serous ovarian. You've recently showed already a potentially registrational phase 2 data set, very strong signal, especially in that KRAS mutant population. I think 22-month median PFS. PFS. Very impressive number for the indication, considering standard care chemo is coming in less than a year. Yep. So I know that there's other data coming out of MEK inhibitors in the setting too. Can you give us some context for other next-gen or improved data sets? You know, really in low-grade serous ovarian cancer, which is, you know, it's a relatively rare cancer. It's a slower-growing tumor, and so when you've seen over the last couple of years, you know, the classic high-grade ovarian, you know, very responsive to platinum, PARPs have made a great inroad there. You've not seen that in low-grade, and, you know, it used to be low-grade patients were just lumped in the trials, and a number of years ago, the World Health Organization recognized it as a distinct disease. We, after a number of efforts, got the FDA to recognize that when we got orphan drug status, it was a distinct disease, and it acts very differently. It's very chemo-resistant. It's morphologically very different. It has different mutations, so when you think of BRCA and those classic things in ovarian cancer, you don't see that. This is very much driven by the MAPK program. If they had them, they'd be high-grade. Yeah. And so, you know, it's been really encouraging to be able to see the kind of results we've had. You know, there are other MEK inhibitors that have been used in this disease with pretty interesting results. I mean, trametinib had a 26% response rate in the phase three study. The challenge is its usage in general practice has been limited by the toxicity. And, you know, the thing about a slower-growing tumor like LGSOC is you have to be on therapy for a long time. And it's not like taking chemo when you're four to six cycles. You can muscle through no matter what. You know, if you're a patient that's taking a drug that's very toxic with kind of no end in sight, it's like you're going to take it until your tumor progresses. It's really hard. When you talk to these women, it's just heartbreaking to hear the experience they have on existing therapy. Trametinib is not an easy drug to. No, no. And again, I don't think anyone would argue it doesn't have efficacy. It's really been the tolerability as a single agent in diseases where you have to stay on it for a long time. What about KRAS or other pan-RAS or pan-RAF programs that haven't looked at low-grade serous? But, you know, would those also, would you expect to see good efficacy from those interventions as well? I mean, there's a potential. And again, you know, there's the pan-RAS, and then there's the variant-specific ones. And you have to look at the breakdown. You know, there are some G12C, there's some G12D. We've not seen a lot of activity there. I think you're seeing people really going after the larger diseases to start with. And, you know, frankly, we're doing the same thing with our program. And the pancreatic data that we reported at ASCO this year, you know, was quite compelling. And it was a small cohort of patients, but in frontline metastatic pancreatic cancer combined with gem-Abraxane, we had an 83% response rate. Now, we'll have a larger data set early next year. But I think part of the issue is if you're starting a de novo drug development program, I'm not sure you'd go after low-grade serous ovarian cancer. Yeah, that's unfair. And even drugs like trametinib, you know, they have not tried to get registration. And there'd be a fair amount of work to be done in that one. It was a cooperative group study. It wasn't a company-sponsored study. So we're not seeing a lot of competition there. It is really nice to actually be developing a drug that will be the first one ever for a given disease. And we've really been embraced by both the HCPs as well as the patient community because there aren't a lot of options. There's not been a lot of attention played to the disease. And we've spent a lot of effort over the last 18 months or so trying to educate, raise awareness, help understand that it's a distinct and different disease and deserves its own therapy. Makes sense. Now, the very impressive data that I cited earlier, that's in KRAS mutant patients. Yes. In the KRAS wild-type patients, it does look like you're a little bit better than chemo, but maybe not as dramatic. The 6%-13% response rate that's typically quoted for standard of care is across KRAS mutant and KRAS wild-type. But I wouldn't expect. Do you see that standard of care has a differential? It does. It does, and it typically shows up in PFS and survival, probably more so even than response rate, but in the last couple of years, it's really been recognized that KRAS, and this is different from other cancers. In other cancers, a KRAS mutant will do worse. In LGSOC, KRAS mutation is a positive prognostic factor, and so when we quote a 10-year median survival in LGSOC, that's across both. KRAS mutant, it's actually 12 years, and KRAS wild-type, it's seven years, and that's regardless of therapy. That's kind of across the board, and so it really is a prognostic factor. Frankly, that was part of the challenge in trying to do an accelerated approval in KRAS wild-type because arguably, if you look at the accelerated approvals that you've seen across the board, that would be a low number, 17%. There weren't good comparators because there have not been studies done that prospectively identified KRAS status upfront and stratified by it. We're doing that in our confirmatory study, and that will be the first study it's actually been done in. Looking directly at the population. Yes. So from the accelerated approval perspective, how do you think the agency is going to look at that wild-type data? Do you expect that to be sufficient from the phase two? No. No. No. I mean, we'll try, and we're continuing, and our NDA has all the data, but all the signals we've had, it really is focused around mutant. It looks very impressive. You know, but I would be surprised if we were able to get an initial approval in wild-type. I do believe we'll eventually get one. The confirmatory study. Yeah, the confirmatory study has the entire population. And I think one of the things that gives us some confidence in wild-type in the confirmatory study is the primary endpoint is PFS. If you look at even the data from our RAMP-201 study, the clinical benefit rate, which is CR plus PR plus stable disease of at least six months, was 50% even in the wild-type. And so we believe that bodes well for a good PFS result. I think it's also important to remember when you compare the data from the RAMP study to the other data that's available. First of all, the other studies had less prior lines of therapy. So these patients were, you know, more heavily pretreated, which, you know, pretty clearly in oncology, the more lines of therapy you have, the worse you do, unfortunately. The other big issue is about half of the patients in our study had prior bevacizumab. In the prior phase three studies, there was almost no bevacizumab, and even in the FRAME study, which is our original one, the difference in response rate between the FRAME study and what we're seeing in RAMP is likely due to Bev usage because patients do worse when they've had prior Bev, and there was almost no prior Bev in any of those studies, so this is a very different patient population, and so the reason we're so excited about the phase three is it's the first time that we'll be comparing our therapy on an equal footing. Right. So, you know, randomized, same number of prior therapies, stratifying by KRAS, stratifying by prior MEK or not. And so it'll give it the first time kind of an even chance, if you will. Yeah. Well, I think we've touched on this in the past couple of questions here, but the NDA filing is in. You're expecting acceptance of the filing by the end of the year. But what are the key regulatory questions that you think are still on the agency's mind? What are they looking at? You know, you say you expect a KRAS mutant label, not a KRAS wild-type label. What do you think might be their hang-ups? What do you think that they're going to be focused on? I mean, I think it's a relatively clear path forward in KRAS mutant. You know, we've had quite a bit of interaction. You know, I was talking to the team yesterday. We've had, you know, a couple of information requests in the last week. You know, they're digging in and digging in deep. You know, I think on the wild-type, again, if you look at the current environment when there's been a number of accelerated approvals where either there wasn't the follow-through in the confirmatory study or the confirmatory study was negative, I think they're more cautious than they probably were a year or two ago. And so when you take something that on the face of it has, you know, a 17% response rate, which I think if you look at the totality of the data, the majority of patients had some level of tumor shrinkage. Disease control seems pretty good. The things that matter to the treating physicians, I think, come through here. And again, I think it'll come through in the confirmatory study. For an accelerated approval, you really have to have a response rate that I would say is probably north of 20%. Sure. Obviously better than available therapy. I think a key test they use is the likelihood of confirming clinical benefit when you do the confirmatory study. You know, the fact that, you know, they agreed with us, as did our steering committee from GOG and ENGOT, that we should continue to have the wild-type in the phase 3 really speaks to, you know, I think there's a good chance there. I think this will. Maybe not for accelerated approval, but a good shot on. Yeah. And, you know, we've said this, you know, quite a bit. You know, we do think, especially in this disease where nothing else has a label, being on the NCCN guidelines is really important for insurance payment. I mean, doctors can do whatever they want. It's not going to get paid for it. It's not going to get paid. That doesn't help. That's where the NCCN guidelines come in. Especially for a slower-progressing disease where you expect a long duration. A long duration, yeah. I mean, you wouldn't want to put that burden on patients. And, you know, frankly, in our industry, not a lot of us are fans of the IRA, and I'm not either. But one of the best parts of the IRA is limiting the patient out-of-pocket costs, which was always a big issue with Medicare patients because we could help commercial patients and uninsured. We could never do anything to help the Medicare patient. And I think having that come in in 2025 is huge for everybody. Okay. You've mentioned a couple of times trying to disambiguate the LGSOC population from a high-grade population. You've been very active in that space already. How's progress in talking to the physicians and getting that message across to the practicing population? Yeah. So we measure that. So, you know, one of the goals that our field team, our MSLs have is really the awareness of the disease. And we think it's gone up quite a bit. There's a lot more awareness on patients as well. I do think out in the community, until you have a specific therapy and a new therapy for the disease, they're juggling a lot of information. So why do I care whether this patient is low-grade or not if I'm going to treat him the exact same thing? And so, you know, we started an unbranded campaign for HCPs back last year where we're just literally the message is LGSOC, it's distinct and different. And if we can get that in the minds and they know when they get a patient with LGSOC, they're going to go look up what they could use. And then the good news is a lot of the physicians in the community who may not see a lot of these patients are affiliated with the large practices that have electronic medical record systems and have their guidelines embedded. And so that's the way to educate them. And then really working with those groups to do their in-services and things because that's not the setting where you're going to go detail individual physicians. They don't want you in the practice, but it's just not cost-effective. And so we use those methods there. And we'll focus our sales force on the large centers. Roughly 100 centers treat half of the patients. And that's really where our target needs to be. Well, that was going to be my next question. You know, looking forward to commercialization here, what do you need to successfully commercialize both from a manufacturing and a sales perspective? It is a smaller indication, but it's not fully centralized in the way that some, you know. Correct, and you know, on the manufacturing side, you know, the good news, I guess, about a relatively small indication is the drug we have to make for our validation batches because you have to do three validation batches is enough to supply us for a couple of years. Sure. So there's going to be no supply issues. And we do have backup manufacturers and all of that in place. You know, a lot of it's the pre-work we've been doing over the last couple of years, educating patients and HCPs so that they understand it's a different disease. Then it's a matter of getting out to those 100 centers that see half the patients and making sure. Now, a lot of those centers are our clinical trial sites. So they already, we've got people there using the drug already. You know, and then the challenge becomes those physicians out in the community that see one or two. And again, we work through the organizations they belong to because it's not effective to have salespeople call one-on-one. It is literally get on their guidelines. And the way these practices work, they literally have an oncology-specific electronic medical record. And the guidelines, which are typically based on NCCN guidelines, and then they build on it a little, are actually embedded in there. And they'll put it in and it'll pop up, this is what you should use. So as long as when the treating physician says, "Oh, geez, I haven't seen a patient like this in five years," when they look it up, it's you. Yeah. And it's unfortunate that for ovarian cancer overall, they sometimes go through a tortuous diagnostic journey. It's not obvious. You know, there's no blood test and, you know, so they go through a lot. And then with the LGSOC patients, they may not recognize the fact they have low-grade serous ovarian cancer until they've been on one or two therapies that didn't work for them. And then they go back and say, "Something's not right here." And then they'll say, "It's different." And so we're also doing a fair amount of work in the community educating pathologists so they can use their voice when there's a new drug to say, "Hey, pay attention to this. This is different than what you normally see. Okay. We've talked about a couple of different market segments, maybe just in the last couple of minutes here. We've talked about KRAS mutant versus wild-type, but there's also multiple lines of therapy relevant to how early patients manage to get diagnosed with low-grade. Can you walk us through some of the market potential in these various segments? Sure. Sure. Where do you think the low-hanging fruit? Yeah. We would say the total addressable market is, you know, north of $3 billion. And part of that is long therapy. And, you know, when you have a relatively rare disease, pricing is probably going to be relatively premium. We look at the market. All low-grade. Yes. All low-grade. Now, the way we look at the market is really in four quadrants. You know, you have the mutant versus wild-type. And then you have the incidence population, so patients who are newly relapsed. And that would typically be when you size an oncology market, you usually look at incidence because unfortunately, patients aren't around for very long. With LGSOC, since they live for so long and they cycle through therapies continually the whole time, we're also looking at the prevalent population. So everybody that's out there diagnosed with LGSOC who's relapsed on their first therapy is an available patient for us. And based on the market research we've done, based on the product profile, it's likely the next thing they'll use when the patient relapses. Great. Well, we are basically out of time, but maybe just last question. Sure. We didn't get a chance to talk much about beyond ovarian, but can you just briefly run us through what we should be expecting from lung cancer, from KRAS combos, from the beyond? Yeah. It's an incredibly exciting time for us. You know, as I said, being able to get a drug approved for the first time in an indication is something you don't get to do in your career very much. But we do have very exciting programs in lung cancer, the combination with G12C, so our sotorasib combination. We have recently added defactinib back in there. And the triplet was always the end game based on the preclinical data and frankly, based on what we saw in low-grade serous ovarian cancer. Adding FAK made it a lot better. And then the early data we presented on pancreatic cancer last year. Again. Did you mention the response rate? Unprecedented response rate. Small number of patients, but we'll have a bigger data set that we'll give an update on early next year. The lung cancer we'll give a bit of an update before the end of the year and then present some data next year. But as I said, you know, really trying to get patients onto the triplet because that's the really exciting part. And then our oral G12D inhibitor, which based on the preclinical profile that we presented at AACR, has the potential to be best in class. It's an on-off inhibitor, quite potent, quite selective. It's in phase 1 in China. Our partner started in July because we could go much more quickly with the dose escalation there. We'll file an IND here in the U.S. early next year and get it into the clinic and build off of what they've already done. Okay, so multiple data catalysts and a launch. Yes.