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Good afternoon, and welcome to Verastem Oncology's Fourth Quarter and Full Year 2025 Earnings Conference Call. My name is Desiree, and I will be your call operator today. Please note this event is being recorded. [Operator Instructions] I will now turn the call over to Julissa Viana, Vice President of Corporate Communications, Investor Relations and Patient Advocacy at Verastem Oncology. Please go ahead.

Thank you, operator. Welcome, everyone, and thank you for joining us today to discuss Verastem's Fourth Quarter and Full Year 2025 financial results and recent business updates. This afternoon, we issued a press release detailing these results along with a slide presentation that we will reference during our call today. Both are available on the Investor Relations section of our website. Before we begin, let me point out that we'll be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially. We encourage you to consult the risk factors discussed in our SEC filings for additional detail. Additionally, today, we will be discussing certain non-GAAP financial measures. Reconciliations to the most directly comparable GAAP measures are provided in the press release we issued today. Joining me on today's call to deliver prepared remarks and take your questions are Dan Paterson, President and Chief Executive Officer; Mike Crowther, Chief Commercial Officer; Dr. Michael Kauffman, President of Development; and Dan Calkins, Chief Financial Officer. I will now turn the call over to Dan.

Thank you, Julissa. Good afternoon, and thanks for joining our call today. 2025 was a truly transformative year for Verastem as we transition to a commercial stage company following our FDA approval of the first treatment specifically for KRAS-mutated recurrent low-grade serous ovarian cancer, nearly two months ahead of our PDUFA date. For the launch period of May through December 2025, we delivered $30.9 million of net product revenue and $17.5 million for the fourth quarter. I'm pleased to report that the strategies we put in place to guide our commercial launch continue to yield meaningful results. We continue to see steady growth driven by consistent adoption among both academic centers and community oncologists. Before I continue, I want to address the updated NCCN ovarian cancer guidelines that were released last week and mentioned in our press release today. The guidelines did not expand the recommendation for avutometinib plus defactinib to include patients with the recurrent LGSOC, without a KRAS mutation. This does not change our launch trajectory. Everything we've been doing for the launch has been based on the guidelines that include the combination as a category 2A recommendation for KRAS-mutated recurrent LGSOC. We're disappointed for the patients with KRAS wild-type recurrent LGSOC, who currently have no targeted FDA-approved treatment options specifically for their disease and face a particularly poor prognosis. Across three separate clinical trials, the FRAME study, RAMP 201 and RAMP 201J, we've observed what we believe are robust objective response rates for patients with recurrent LGSOC, with and without KRAS mutations. We remain committed to advancing the clinical evidence through longer-term follow-up analyses from the RAMP 201 study in 2026 and completing our ongoing confirmatory RAMP 301 Phase III clinical trial, which includes patients with and without KRAS mutations and look forward to sharing these data next year with the NCCN and the medical community to support future guideline consideration. This clinical conviction and our confidence in our data is what underpins our commercial execution. As Mike will share with you shortly, we have an opportunity to continue to drive more growth through the expansion of our prescriber base and increasing their comfort to use AVMAPKI FAK

Thank you, Dan. I'll cover our commercial performance for the quarter, our launch progress in 2025 since our FDA approval in May and some perspective on how we see the launch progressing in 2026. As we have shared, a diagnosis of LGSOC is a life-changing event. LGSOC can affect women as young as in their 20s and the vast majority of these women about 80% to 90% experienced recurrence highlighting the urgent need for more effective therapies. In May of 2025, AVMAPKI FAK

Thank you, Mike. When I moved from Lead Director on the Board to Head of Development at Verastem last year, it was because I see significant promise in our pipeline and specifically believe that what we're building here with VS-7375 as the potential to significantly change outcomes for people living with KRAS-C12D-driven cancers. I'm proud of the progress our team has made in such a short amount of time. Let me start by recapping where we ended the year with avutometinib plus defactinib because 2025 was a defining year across our portfolio. Our team completed enrollment ahead of schedule in our two avutometinib and defactinib clinical trials, RAMP 301 in LGSOC and RAMP 205 in pancreatic cancer. This positions us well for the catalysts ahead. On RAMP 301, because we completed enrollment early, we expect to report the top line primary analysis in mid-2027. As a reminder, this is our randomized international Phase III trial of avutometinib plus defactinib against standard therapy in recurrent LGSOC, with or without a KRAS mutation. It will serve as a confirmatory study for the initial indication and has the potential to expand the indication regardless of KRAS mutational status and to support future regulatory filings outside of the United States. Turning now to some of our progress. For our Japan-specific RAMP 201J study in LGSOC, in collaboration with Japan's GOG, we shared an update of all 16 patients enrolled by investigator assessment that demonstrated a 57% overall response rate with KRAS mutant and a 22% overall response rate with KRAS wild-type recurrent LGSOC. This is the first ever study conducted in Japan for this disease. We look forward to sharing more data from that trial in the future. And in Europe, we received growth in drug designation in ovarian cancer last year from the European Commission. We continue working through the steps needed for our future regulatory application once we have the RAMP 301 results in hand. For RAMP 205, our first-line metastatic pancreatic cancer study of avutometinib plus defactinib in combination with [ GEM ABRAXANE ]. At ASCO last year, recall we reported a confirmed response rate in 10 of 12 patients for an overall response of 83%. We completed enrollment of the expansion cohort and expect to share an update on the additional patients enrolled in the trial in Q2 of this year. We're excited with the progress we've made with our avutometinib plus defactinib combination trials which we believe has the potential to expand the franchise into new and larger markets. Now turning to VS-7375. We moved quickly after licensing the product to secure FDA IND clearance and Fast Track designation, and we dosed our first patient in June of 2025, following the very promising early results from our partner in their trial in China and we've continued to build momentum since. Here's why the program matters so much. KRAS G12D is an important mutation in pancreatic, colorectal and lung cancers along with lower prevalences in a variety of other difficult-to-treat cancers. There are no FDA-approved therapies targeting this mutation. We have taken a broad approach to generate data not only in these larger tumor types but also across other KRAS G12D cancers, such as biliary tract cancer. We've made some exciting progress in a short time. We recently cleared the oral dose of 900 milligrams once daily in our dose escalation phase, and we're evaluating the 1,200-milligram daily dose. Our partner GenFleet selected the 600-milligram daily dose as their go-forward dose in China due to a strong efficacy signal. While we are advancing some of our cohorts using the 600-milligram dose, we're continuing on our dose escalation to the 1,200-milligram dose level to further interrogate the dose range and characterize the safety, tolerability and efficacy profile of our agent. In addition, based on a preclinical synergy with dual RAS EGFR blockade, we are evaluating the combination of VS-7375 with cetuximab. We recently cleared 600-milligram daily dose level in combination with [ secure ] dose cetuximab, and we'll continue to evaluate higher doses in this combination. I'm also pleased to share that the FDA recently provided feedback on our Phase I/II protocol. Per the agency's request, we are changing our initial Phase I/II trial, which had multiple expansion cohorts and breaking out several disease-specific Phase II registration-directed trials for KRAS G12D mutated cancers, including second-line pancreatic ductal carcinoma, second and third-line non-small cell lung cancer and with VS-7375 in combination with cetuximab in second line plus colorectal cancer. Now let me move to discuss our recent PK analysis that we did. Doses of 600-milligrams daily and above with feeding and antiemetic prophylaxis yielded similar exposures to that observed in China with faster patients. And exposures achieved cover the exposures to preclinical models necessary for maximal antitumor efficacy. From a safety perspective, we continue to be pleased with the profile we see emerging. We have the benefit of hindsight of our partners' trials in China, and we adjusted our protocols to directly address some of the tolerability issues that our partner has seen early on. As noted, the overall tolerability of VS-7375 in the United States appears to be better than that which was observed in China as we're able to escalate beyond 600-milligrams and now beyond 900-milligrams. No drug-related liver function test abnormalities have been reported in any patient across any of the dose levels to date. No drug-related neutropenia in Grade 2 has been reported. And we included in the protocol strong recommendations for standard prophylactic anti-nausea agents and rapid institution of over-the-counter antidiarrheal agents as needed. As a result, rates of nausea, vomiting and diarrhea are lower than those reported by our partner in China. The differentiation we are seeing from the data and our partner in China as well as early signals from our own trial give us strong confidence that potential of this asset to treat multiple difficult-to-treat cancers where there's a high end of medical need with a highly targeted once-a-day oral agent. Looking ahead to this year, our goal is to generate a meaningful data set in each of these tumor types, both as single agents as well as in selective cancers in combination with other treatments. Initially, we plan to share an update on preliminary data in the first half of 2026. But as I said, because of our success to date, we're able to continue with the dose escalation and also enrollment into our various tumor cohorts. And this is really important, getting the optimal dose, of course, matters greatly. We plan to share a more fulsome data at our go-forward dose in the second half of this year. Now I'll turn the call over to Dan Calkins.

Thank you, Michael. Our full financial results are included in our press release, so I'll focus on the highlights here. I'm also pleased to reiterate that we reported $17.5 million in net product revenue for the fourth quarter of 2025 and $30.9 million for the full year, which includes the launch period of May through December. Cost of sales were $2.6 million for the fourth quarter of 2025 and $4.6 million for the full year 2025 period. Cost of sales increased in the fourth quarter in line with the increase in net product revenue for the quarter. As we've previously communicated, we're not providing detail on gross to net other than to say that expectations should be consistent with other oncology small molecule therapeutics. Turning to Research and Development expenses. They were $31.7 million for the fourth quarter of 2025 and $114.6 million for the full year. R&D expenses were driven by both the ongoing global confirmatory Phase III or RAMP 301 clinical trial and the ongoing VS-7375 Phase I/II clinical trial as well as higher costs associated with drug substance production activities related to 7375. SG&A expenses were $24.4 million for the fourth quarter and $81.1 million for the full year. The expenses were driven by commercial activities and operations, including personnel-related costs to support the ongoing CO-PACK launch. Directionally, for 2026, we would expect SG&A expenses to remain roughly the same on a quarterly basis as we continue to be disciplined in our expense management, making the right investments at the right time to support the ongoing commercial launch efforts while simultaneously advancing our pipeline. For the fourth quarter of 2025, non-GAAP adjusted net loss was $39.8 million or $0.48 per share diluted compared to non-GAAP adjusted net loss of $29.3 million or $0.60 per share diluted for the fourth quarter of 2024. For the full year, non-GAAP adjusted net loss in 2025 was $163.1 million or $2.35 per share diluted compared to non-GAAP adjusted net loss in 2024 of $107.4 million or $3.01 per share diluted. Please see our press release for a full reconciliation of GAAP to non-GAAP measures. Moving to the balance sheet. We ended the fourth quarter of 2025 with cash, cash equivalents and investments of $205 million including the proceeds of the expiring cash warrants, which were exercised in January of 2026, our pro forma cash balance as of December 2025 was $234.4 million. We believe our current cash, combined with the future revenues from AVMAPKI FAK

Thanks, Dan. Before we open the call to Q&A, I'll spend a few minutes on 2026 priorities. 2025 has given us a solid foundation for the remainder of 2026, we'll stay laser-focused on 4 key strategies: first, maximize the commercial launch execution of AVMAPKI FAK

[Operator Instructions] Our first question comes from the line of Eric Schmidt with Cantor.

Congrats on all the progress. Maybe on the NCCN non update, do you guys have any visibility into the thought process behind why wild-type patients weren't included? And then if you could comment on your confidence that wild-type patients can continue to gain reimbursement? I know they've been a meaningful cohort for you in the commercial setting to date.

Eric, thanks for your question. Look, we were -- it was disappointing, and we're a little surprised. We've not gotten any direct feedback. We're not really going to speculate. We suspect it might have had something to do with the imminent Phase III readout coming. We know they don't like to change things once they do add something. We don't see any difference to how we've been running our business and to the trajectory. I've said a number of times, it would be nice to have NCCN because it's kind of like air coverage and we're fighting a ground war right now on the reimbursement side. But our team has been doing a wonderful job securing reimbursement regardless of KRAS mutation status, and we'll continue to do the same thing. So our message to our team to physicians and to patients is we're going to continue to do what we've been doing before. Ultimate adoption likely to be very much driven by the results of the confirmatory study because then we can actively promote, which even with the NCCN guidelines, we can't actively promote although we are allowed to share the publications that we have and both the FRAME study and the RAMP 201 study have results in both wild-type and mutated that we believe show benefit to patients, and we'll continue to share those publications.

The next question comes from the line of Michael Schmidt with Guggenheim Partners.

I had a couple on 7375. Obviously, the safety now looks very good in the U.S. study based on the detailed table that's included in the slide deck this quarter. Could you comment on what you've seen or if you have seen any dose modifications or perhaps discontinuations? So I'm just curious if you've seen any of those? And then question on how you're approaching dose selection. I believe you've been enrolling patients and expansion cohorts at 600 mg QD, but obviously escalating further up to 1,200 now. So how do you think about dose selection for these planned Phase II studies? And then lastly, just thinking about your combination strategy, maybe just comment on how you're thinking about the longer-term positioning of 7375 in the landscape -- in the RAS space. I know you've planned combination cohorts with approved center of care and various indications, but would it make sense perhaps to also consider combining with other novel agents, for example, pan-RAS inhibitors or other agents that are out there?

Michael, thanks for your question. I'll let Michael Kauffman address the questions for you.

Sure. I'll try to remember all of them and come back to me if I missed something. I think -- first of all, the number of dose modifications is low and slower than typically that I expect in various trials. And remember, these are heavily pretreated refractory tumors and the patients are doing well, the drug. So the tolerability is consistent with the data you saw on the table and then consistent with any modifications, the dropout rate is very low for the patients. So we're really pleased with what we're seeing. And that includes both the 600 and the 900-milligram cohort. The second issue is how we think about escalation and evaluation of these doses because what we're really doing is kind of a 2-dimensional matrix here with dose escalation where we're increasing the dose now up to 900 and now beyond that. At the same time, we have to determine longer-term tolerability because that's the name of the game now with chronic cancer medicines and longer-term disease control and responses where we're looking for durable antitumor responses. So it's a 2-dimensional matrix for sure. We believe we can identify the proper doses evaluating 10 to 15 patients in each of these areas. And this is not going to be a long-term commitment. I mean these drugs tend to work quickly. Our drug, in particular, works quickly. and we're able to discern a lot of this stuff in several months. But the other -- just to remember, it does take -- it still takes at least two CT scans to determine if someone has a confirmed response and sometimes the responses take more than the first CT scan. So we'll be looking at multiple months. The last point on that is that the important achievements really are after 6 months because in all cases, we need to see prolonged disease control. And as you all know, thankfully, the minimum kind of numbers that we all want to see now even in these difficult-to-treat tumors is north of 6 months. So that's -- it will just take 6 months at least to affect this and understand it better, but we think we're going to be there in the not-too-distant future. The last bit is the combination strategy. Yes, I mean, there's two goals here. One is regulatory, clearly, and the second goal is where is the puck going to sort of -- Wayne Gretzky quote of how to predict the future. And we'll be looking at both. But the primary goal here is to move these drugs initially into the second and third-line setting through these accelerated approval pathways, which the FDA has helped pave the way aggressively with us to do that and then to run into frontline studies with standard of care so that we can achieve regulatory approvals but then to start to investigate -- probably through investigator-sponsored trials, some of the novel combinations.

Our next question comes from the line of Clara Dong with Jefferies.

Congrats on all the progress. Just on the NCCN guideline update, do you have any plan to maybe reengage with the NCCN in the future with longer term data, maybe RAMP 301 data or on additional Japan data as well. And then for the FDA feedback at G12D, can you walk us through what specifically trigger feedback to separate the study into disease-specific and registration directive Phase II trials for the three indications?

Clara, thanks for your questions. I'll take the NCCN one and then turn it over to Michael for the FDA question. Yes, we intend to continue to develop evidence on the use of this molecule in both wild-type and mutated. We have a number of activities ongoing that I won't get into details on right now. And then, obviously, as I mentioned, when we have the readout from 301, that's kind of the penultimate randomized readout that will help with both NCCN and hopefully, with the label expansion at the FDA. Michael, do you want to address the question on 7375?

Sure. We modified our protocol, our initial 101 protocol based on initial results that we were quite pleased with to expand the cohorts in each of the three major diseases as well as in a sort of tumor-agnostic cohort basically taking a page from the playbook of KEYTRUDA, where they use the Phase I trial to expand into lots of different places. The FDA since then, since the KEYTRUDA really has split the solid tumor divisions into multiple divisions. And based on that, pretty much was the driver for the FDA is saying, "Hey, we like your plan. But in general, cohorts that are going to be used for marketing authorization should be included in separate protocols." We didn't explicitly ask them for the marketing authorization, but we got the answer very clear in black and white, which was really gratifying. I mean they knew what we were trying to do. And when you put 80 to 100 patients in an expansion cohort, they know where you're going with this. And I think they were extremely supportive with us and excited about the kinds of data that we have provided both from China and the initial safety data from the U.S.

The next question comes from the line of Graig Suvannavejh with Mizuho.

Congrats on continued progress. I was hoping to get maybe some color on -- a little bit more color just on the prescribing dynamics for CO-PACK right now? I might have missed it in your prepared remarks, but usage between -- in the academic center versus the community setting and color on refills? And then the second question, if I could, is just a question on financing and I'm wondering with things at your disposal, how are you thinking about future financing for the company to extend the cash runway beyond first half of 2027?

Yes, Graig. Thanks for your question. I'll take the second one first and then ask Mike to address your question on uptake. As we've said, and we think this is really important. We believe that launch for the [ A+F ] franchise will be self-sustaining by the second half of the year and won't require additional fundraising. So any additional capital that we have to access will be based on good data coming out of the G12D program. We're looking very carefully at prioritizing what we need to do, looking at different vehicles to raise money. Obviously, going out and doing straight equity raises, creates dilution, and we like to avoid that as much as possible, especially at current stock prices and are looking at a number of different ways to stage things over time to make sure we've got enough runway, but we're being prudent in how we raise that money. Non-dilutive approaches are ones we're spending a lot of time looking at. We have had a lot of strategic interest, not saying that there's anything imminent or that we're going to go ahead and out-license the program, but there's a lot of flexibility when you have a lot of interest from folks. And I think there is a growing consensus that this is probably a best-in-class molecule, and I think that gives us a lot of degrees of freedom. And so we'll continue to look at different ways to fund it, and we'll be prudent in doing it over time. Mike, maybe if you want to address the other part of the question?

Sure, Dan. Thanks for the question. We're not giving specific guidance on patient numbers or refill rate yet since we're still early in the launch. But I can certainly give some color about the prescribers and some other factors. So we've continued to grow the number of new prescribers through February. There have been nearly 300 total new prescribers. Month over month, our field team is making some really good headway with our top accounts. Our top institutions include both academic and community centers and around 75% of these organizations have either introduced or adopted the CO-PACK reflecting growing penetration across the providers. The split of prescriptions remains roughly 60-40 between GynOncs and MedOncs, which is consistent with our previous reports. More than half the prescriptions are coming from the academic center. We expect that split to be consistent with the community over time. And importantly, as we talked about our Verastem Cares program, has continued to perform incredibly well with short times for reimbursement and fills between 12 to 14 days and about 60% of our commercially eligible patients are using our co-pay program.

The next question comes from the line of Leonid Timashev with RBC Capital Markets.

I want to ask on 7375's safety. Just to ask you guys to elaborate a little bit more on that. I've got three questions, but hopefully, they're all related. I guess the new cut of data looked quite encouraging, but I was just trying to better understand how much we can lean on that versus what we saw coming out of China. I guess if you have any insights into what might be different across those two populations to lead to such a different safety profile. And then if you could also remind us on the kinetics of when some of these events might occur, particularly via the heme events or the liver signals just given that these patients have been followed for just -- only about 1.6 months, I think, it said. And then lastly, I know you guys were also working at some point on some potential formulation improvements that you were going to effect later on. I'm just curious how much further those could potentially improve some of the GI tolerability?

Michael, do you want to address those questions?

Sure. The data that we provided to you that are all in the database and cleaned and all that, pretty clean, they're not completely clean, but they're representative for sure. and they're very consistent with what we're hearing ongoing now even -- these data were with a date cut off more than a month ago. So I think we've not heard of anything new and the drug is behaving very well, including at the higher dose of 900 milligrams. The cadence of these side effects are pretty straightforward. The nausea and diarrhea and vomiting, as you know, are all pretty fast, and we've really taken them down to pretty much Grade 1 and a lot of the Grade 1 goes away over the first week or two with the proper use of antinausea agents like standard

The next question comes from the line of Yuan

Can you expand on the impact of this protocol update on your clinical development? What's the real impact or change there? Was it narrowed patient enrollment criteria or fewer doses to be tested there?

Thanks for the question. I I'll let Michael elaborate, but it's essentially an administrative change where we're just breaking out into separate protocols and working to streamline things to get the new protocols in place at our current institutions. Anything more you want to say, Michael?

No, that's -- I don't think there's going to be a significant time line hit. We're going to be going -- we'll be sending the protocols in with a cover letter that basically explains is, as Dan said, this is administrative, there's no new safety change. There's no informed consent change. It's just a different protocol basically so that each of these can go to the proper part of the FDA.

Got it. On the dose selection part, do you see a possibility to do maybe a [ titration ] meaning starting at 900 or 1200 milligrams and then using 600-milligram as maintenance dose if needed?

Michael, do you want to address that?

Sure. Look, it's -- one thing we've learned about most cancer therapies, not all, but most, over the years is that starting high and blasting the tumor because it's really a vicious war, getting it under control and shrinking it. And as you suggest, which is sort of an induction, if you will, followed by maintenance is probably okay. Honestly, we have any reason to believe yet that we're going to need to lower the dose. It's fairly early with our U.S. experience. And I'll remind folks that in China, they were not able to get to 900 milligrams. So we have a number of patients ongoing now with 900 milligrams over many, many weeks and there doesn't seem to be a major issue. That said, of course, there will be time for patients to reduce their dose. But I'm not sure it doesn't seem like it at this point that we're going to need to reduce the dose.

[Operator Instructions] And we'll take our last question. It comes from the line of James Molloy with AGP, Alliance Global Partners.

Matt on for Jim today. Congrats again on the continued progress. So firstly, I wanted to ask about the RAMP 201J trial. The updated data look positive to us. But can you just take us through the next steps in Japan for the [ A+D ] combo?

Sure. There's a couple of things going on in parallel. One is all of the institutions that participated in the 201J study have now been converted over to the confirmatory study. Although we've completed accrual in the rest of the world, we do want to have enough Japanese patients on there so that we can have final approval in Japan. But the intent is to meet with the PMDA and discuss using the bridging study for conditional approval. And steps are underway for that right now. And I think we've guided that we'll probably file early next year when we have enough follow-up.

Got it. And then in terms of the U.S. launch, is there any specific insight into the payer coverage of KRAS wild-type patients? Do you have any number or like ballpark of how many of these cases have been covered since launch?

We don't have specific numbers on the number of cases. What I will say is our most common group of patients are of the KRAS mutant. The second biggest group is KRAS unspecified. We're seeing a lot of prior [ auths ] put in, where they're not putting the status, and those seems to be going through pretty smoothly. And then the third group is the KRAS wild type, where we've said a number of times, we're having really good success getting those paid for too. And I think it's an indication of the high unmet need. And then if you look at the totality of the data in the publications that we use and submit to the payers, these patients do appear to be benefiting where we have gotten some tightening in the last quarter or so is what I would call the totally off-label. So brain, lung, PDAC, we have seen a little pushback from payers on those. And that's not to be unexpected. I think in the early days, you sometimes get a bit of a honeymoon period. And in PDAC, we're talking the data set of 12 patients. And then in -- some of these other diseases that it was slipping through really not a lot of support. And so we're very pleased with what we're seeing to date. I think our specialty pharmacy and our hub are doing a great job, and we're hoping to see that continue.