Verastem, Inc. Q4 FY2025 Earnings Call

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. 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 transformative year for Verastem as we transitioned 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. From May to December 2025, we achieved $30.9 million in net product revenue and $17.5 million in the fourth quarter. I'm pleased to report that our commercial launch strategies continue to deliver significant results, with steady growth driven by consistent adoption among academic centers and community oncologists. I want to mention the updated NCCN ovarian cancer guidelines released last week, which did not expand the recommendation for avutometinib plus defactinib to include patients with recurrent LGSOC without a KRAS mutation. However, this will not change our launch trajectory, as our launch strategy has been based on 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 lack targeted FDA-approved treatment options and face a poor prognosis. In our 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, both with and without KRAS mutations. We are committed to strengthening the clinical evidence with 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. We look forward to sharing these data next year with the NCCN and the medical community to support future guideline considerations. Our confidence in our data drives our commercial execution. As Mike will discuss shortly, we have the opportunity to drive further growth by expanding our prescriber base and increasing their comfort with using AVMAPKI FAKZYNJA CO-PACK at first recurrence. Our approval has shown that precision targeting of the RAS/MAPK pathway with the combination of avutometinib and defactinib can lead to meaningful outcomes for patients. Cancer heavily relies on this pathway for growth, and approaches that block only a single node typically fall short of delivering deep and durable anticancer activity. The cancer compensates by activating other signaling proteins within the RAS pathway or in parallel pathways. This distinguishes avutometinib plus defactinib and underpins our success in the market and clinic. The team's execution during the early phases of the launch has allowed us to quickly provide this medicine to patients with a rare ovarian cancer who previously had no approved treatment options. Our R&D team has also made significant strides in advancing key strategic clinical trials. Similar to LGSOC, the combination of avutometinib plus defactinib has shown promising antitumor activity in pancreatic cancer, which is highly KRAS-driven. Our RAMP 205 trial in first-line metastatic pancreatic cancer involves combining avutometinib and defactinib with standard chemotherapy to improve response rates and outcomes. Avutometinib aids in inhibiting tumor growth while defactinib works to inhibit FAP, thus reducing stromal density in pancreatic tumors and addressing adaptive resistance to avutometinib. The updated data we presented at ASCO last year highlights the potential of this combination in treating one of the most challenging cancers. Alongside the avutometinib-defactinib combination, we are targeting RAS-driven cancers with other innovative therapies, including our promising pipeline program VS-7375, which could be a best-in-class oral KRAS G12D ON/OFF inhibitor. Based on exceptional data from our partner in China, we initiated the VS-7375 clinical program last year with a multi-indication trial strategy. Recent feedback from the FDA has provided a clear strategic path for clinical development. Consequently, we will amend our current VS-7375-101 trial protocol and separate our Phase II registration-directed trials for specific diseases. This clarity will help us advance the program towards a potential accelerated approval pathway. Given initial results, we believe VS-7375 has strong potential to be the preferred treatment for KRAS G12D driven cancers in pancreatic, lung, and colorectal tissues. Michael will provide a more detailed update shortly. Throughout our clinical studies, we've made strategic data-driven decisions to focus on those with the greatest potential impact for patients with RAS-driven cancers. This was evident in our decision to expedite the VS-7375 program toward registration-directed studies while discontinuing the avutometinib plus defactinib program in lung cancer due to evolving treatment landscapes, despite promising clinical signals. We have many opportunities ahead but must be mindful of our resource limits, continuing to prioritize the highest-value opportunities. We are closely managing our expenses and have extended our cash runway into the first half of 2027 with our last financing and the exercise of remaining cash warrants, supporting our ability to achieve near-term milestones. We anticipate that the LGSOC franchise will be self-sustaining in the latter half of this year, with CO-PACK revenues supporting both the commercial operations and ongoing clinical trials. Our focus is on identifying value-creating non-dilutive opportunities in this challenging environment as we continue to advance our clinical programs and deliver results for patients and shareholders. With that, I'll hand the call over to Mike.

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%—experience recurrence highlighting the urgent need for more effective therapies. In May of 2025, AVMAPKI FAKZYNJA CO-PACK became the first-ever treatment specifically approved for KRAS-mutated recurrent LGSOC, forever changing the treatment landscape for this disease. Let me give you an example of the impact of the CO-PACK therapy. Recently, we learned of a patient in her early 40s who had been diagnosed with LGSOC at age 30 and for several years, tried other systemic therapies, including chemotherapy. Following her second recurrence four months ago, she started in the CO-PACK and her most recent scans have shown a complete response to treatment. This incredible outcome underscores the benefit of using the CO-PACK. This is just one of many stories we are hearing from physicians treating people with this disease when other treatments were ineffective or a patient who experienced a recurrence, the doctor would give the difficult news that they have no other treatment to offer. This has all changed with the introduction of AVMAPKI FAKZYNJA CO-PACK. For the fourth quarter, we delivered a solid finish to 2025. The steady growth momentum since our launch speaks to the demand we continue to see. The team is executing well against all three key strategic launch imperatives, effectively reaching health care providers, ensuring seamless access to coverage, and engaging and supporting patients throughout the journey. Consistent with Q3, we saw encouraging signals in Q4 in both the breadth and depth of prescribing. The number of active prescribers continues to expand. And through February, there have been nearly 300 prescribers of the CO-PACK. Let me walk you through some of the launch dynamics we saw in the fourth quarter and have continued so far through the first quarter. More than half of total prescriptions are coming from the academic setting, and we are seeing repeat prescribers write scripts for new patients. We are making good progress with our top accounts. Our top target institutions include both academic and community centers; about 75% of these organizations have either introduced or adopted AVMAPKI FAKZYNJA CO-PACK into their ecosystems, reflecting growing penetration across prescribers. The split of prescriptions between GynOncs and MedOncs remains roughly at 60-40 consistent with previous quarters. Our GPO accounts have started to incorporate the therapy second-line use into their internal EMR pathways, and we are actively partnering with their leadership on data analytics to find eligible patients within their networks. Payer coverage continues to be strong across all LGSOC prescribed patients, regardless of mutational status. The tactical prescriptions continue to be in the range of 12 to 14 days due to rapid prior authorization approval and our payer mix remains consistent with previous quarters. Our Verastem Cares program has been effective in helping patients manage through insurance processes. Approximately 60% of commercially eligible patients are using our co-pay program. In our medical educational efforts, our medical science liaisons and oncology nurse educators have engaged in approximately 1,800 scientific exchanges and well over 700 educational engagements with health care providers through year-end. We saw high participation in multiple expert-led educational programs we supported for physicians to improve physicians' understanding of our treatment in the disease state. We provided a variety of tools to side effect management to help both prescribers and patients stay on the treatment and realize the benefits of the CO-PACK. This includes providing more education to prescribers as they gain experience and get more comfortable with the treatment. These resources are especially important where many community-based medical oncologists may see relatively few patients of LGSOC and appreciate support for patient management. From a patient perspective, we continue to see high engagement in our branded website. Patients are opting in to receive more information about the CO-PACK to facilitate further discussions with their doctor. This brings me to our plans for 2026. As the first company to develop and launch a treatment specifically for KRAS-mutated recurrent LGSOC, there were no well-established support systems in place for these patients, and we have been working to build these systems, including providing education about the disease, increased awareness of our Verastem Cares program for insurance support, and supporting patients as they learn about this new treatment option. As expected, while many physicians' first experience with the CO-PACK is often in later lines, we will continue to focus on driving use at first recurrence so patients can receive the full benefits of AVMAPKI FAKZYNJA CO-PACK. In the next quarter, we will be launching a new promotional campaign to offer physicians and patients to help them reimagine how this disease can be treated. The campaign will be supported by a comprehensive digital ad campaign to generate awareness about the availability of the first-ever treatment specifically for KRAS-mutated recurrent LGSOC and drive traffic to our product website to access more tools. We are expanding our educational plans with additional peer-to-peer programs, including a new program that directly connects physicians with an expert in LGSOC to feel confident caring for patients with LGSOC and driving optimal outcomes. In addition, we will share support tools designed to increase depth within our active accounts while continuing to expand our reach in new patient starts. We are deploying our sales reps and those educators whenever a doctor prescribes the therapy to help them understand what to expect and use the tools we have created to manage through any adverse events. We have been focused on a fit-for-purpose launch, and as such, we've added a few additional field staff, including some sales reps, nurse educators, and MSLs. Due to the nature of this disease as a slow-growing cancer where patients stay on their first treatment for several years, we know it will take time to achieve peak share of first recurrence. We remain focused on our core launch priorities and sustaining steady growth. We're encouraged by the progress we have made, and we will continue building on our momentum throughout the year. I'll now turn the call over to Michael.

Thank you, Mike. When I transitioned from Lead Director on the Board to Head of Development at Verastem last year, it was due to the significant potential I see in our pipeline, particularly with VS-7375, which I believe can greatly improve outcomes for patients with KRAS-G12D-driven cancers. I am proud of the rapid progress our team has made. Let me recap our year-end status with avutometinib plus defactinib, as 2025 was a pivotal year for our portfolio. Our team enrolled participants ahead of schedule in our two clinical trials, RAMP 301 in LGSOC and RAMP 205 in pancreatic cancer, setting us up well for upcoming developments. For RAMP 301, having completed enrollment early, we anticipate reporting the top line primary analysis in mid-2027. This is our randomized international Phase III trial comparing avutometinib plus defactinib to standard therapy in recurrent LGSOC, regardless of KRAS mutation status. It will act as a confirmatory study for the initial indication and has the potential to broaden application beyond KRAS mutational status as well as support future regulatory filings outside the U.S. Regarding our Japan-specific RAMP 201J study in LGSOC, which we conducted in partnership with Japan's GOG, we provided an update showing a 57% overall response rate for KRAS mutant patients and a 22% overall response rate for KRAS wild-type recurrent LGSOC across 16 patients. This marks the first study of its kind in Japan for this disease, and we look forward to sharing more data from that trial in the future. In Europe, we received growth drug designation in ovarian cancer from the European Commission last year and are progressing toward our regulatory application once we have results from RAMP 301. For RAMP 205, our study of avutometinib plus defactinib in first-line metastatic pancreatic cancer, we previously reported a confirmed response rate of 83% in 10 of 12 patients. Enrollment for the expansion cohort is complete, and we expect to provide updates on newly enrolled patients in Q2 of this year. We are excited about the progress in the avutometinib plus defactinib trials, which we believe can expand our presence in larger markets. Now, about VS-7375. We swiftly obtained FDA IND clearance and Fast Track designation after licensing the product, and our first patient was dosed in June 2025, following promising early outcomes from our partner's trial in China. The importance of this program cannot be overstated. KRAS G12D is a crucial mutation seen in pancreatic, colorectal, and lung cancers, with lower frequencies in other challenging cancers, and currently, there are no FDA-approved therapies targeting it. We aim to generate data across not only these major tumor types but also other KRAS G12D cancers like biliary tract cancer. We've made significant strides already. We have recently cleared the oral dose of 900 milligrams once daily in our dose escalation phase and are assessing a 1,200-milligram daily dose. Our partner GenFleet has chosen 600 milligrams as the go-forward dose in China, given its strong efficacy signal. While advancing some cohorts with the 600-milligram dose, we continue to escalate to 1,200 milligrams to further examine the dose range, safety, tolerability, and efficacy of our agent. Additionally, based on preclinical synergy with dual RAS EGFR blockade, we are testing VS-7375 in combination with cetuximab. We've recently cleared the 600-milligram daily dose with cetuximab and will explore higher doses in this combination. I am also pleased to report that the FDA provided feedback on our Phase I/II protocol. As per the agency's request, we are revising our initial Phase I/II trial to break out several disease-specific Phase II registration-directed trials for KRAS G12D mutated cancers, including second-line pancreatic ductal carcinoma and second and third-line non-small cell lung cancer. With cetuximab, we're focusing on second-line plus colorectal cancer. Now, let’s discuss our recent PK analysis. Daily doses of 600 milligrams and above with feeding and antiemetic prophylaxis yielded similar exposures to those observed in China with faster patients, covering the necessary exposures to match preclinical models for optimal antitumor efficacy. From a safety standpoint, we are pleased with the emerging profile. With insights from our partner trials in China, we've adjusted our protocols to address some early tolerability concerns. The overall tolerability of VS-7375 in the U.S. appears to be better than reported in China, allowing us to escalate beyond 600 milligrams and now to 900 milligrams. There have been no reports of drug-related liver function test abnormalities or Grade 2 neutropenia across any doses to date. We have included robust recommendations for prophylactic anti-nausea agents and prompt use of over-the-counter antidiarrheal agents as necessary, resulting in lower rates of nausea, vomiting, and diarrhea compared to our partner's findings in China. The differentiation we are observing, along with promising signals from our own trial, reinforces our confidence in this asset's potential to address multiple difficult-to-treat cancers with a targeted once-a-day oral agent. As we look to this year, our goal is to gather meaningful data across these tumor types, both as single agents and in select combinations with other treatments. We plan to provide preliminary data updates in the first half of 2026, and due to our success thus far, we will continue with dose escalation and cohort enrollment. Finding the optimal dose is critical. We intend to share more comprehensive 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 FAKZYNJA CO-PACK sales will provide cash runway into the first half of 2027. We are very encouraged by the initial launch and look forward to building on the CO-PACK growth into 2026. Given our current trajectory, I'm pleased to reiterate that we believe the LGSOC franchise will be self-sustaining in the second half of the year, with CO-PACK revenues funding both the commercial operations and any of our avutometinib plus defactinib clinical trials. With that, let me turn the call back over to Dan.

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 four key strategies: first, maximize the commercial launch execution of AVMAPKI FAKZYNJA CO-PACK for broad adoption. Second, generate monotherapy and combination data with VS-7375 to expedite the execution of our registration path in major KRAS G12D solid tumors. Third, continued execution of the RAMP 301 confirmatory Phase III trial in recurrent LGSOC. And fourth, maintain prudent capital management through our key catalysts and a strong balance sheet. In support of these strategies, we set several goals in which to measure our success. We want to maximize adoption of the CO-PACK to ensure every appropriate patient benefits from this novel treatment at their first recurrence. For our first-line PDAC study, RAMP 205, we plan to share an update on the expansion cohort in Q2. Finally, as we push to accelerate our VS-7375 trial, we expect to further demonstrate the breadth of our RAS/MAPK pathway driven approach and lay the path for expansion of our commercial product line. We plan to share an update on the 101 trial in the first half of this year. With the FDA's feedback in hand, we are creating Phase II registration-directed protocols for pancreatic, lung, and colorectal cancers. Enrollment in the 101 trial is going well, and we anticipate being able to enroll the Phase II trials quickly. Our goal is to move forward quickly and efficiently to hopefully bring this treatment to patients who currently have no FDA-approved treatments to their KRAS G12D mutated cancers. But having said that, while speed is important, we're always cognizant that bringing the best therapy to market is more important. We're privileged to have a commercial product with growing revenue and a robust clinical pipeline that addresses larger market opportunities. We're building a sustainable multi-asset oncology company to address important unmet needs in RAS/MAPK driven cancers. As we enter 2026, we're well positioned to continue to deliver on our milestones. With that, we'll open up the call for questions. Operator?

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 of questions about 7375. The safety profile now appears to be strong in the U.S. study, as indicated in the detailed table in this quarter's slide deck. Can you share if you've observed any dose modifications or discontinuations? I'm curious about that. Additionally, how are you approaching dose selection? I understand you've been enrolling patients in expansion cohorts at 600 mg QD, but are now considering increasing the dose up to 1,200 mg. What factors influence your decisions on dose selection for the upcoming Phase II studies? Lastly, regarding your combination strategy, could you elaborate on how you see 7375 fitting into the longer-term landscape, particularly in the RAS space? I know you have plans for combination cohorts with established treatments across various indications, but would it make sense to explore combinations with other novel agents, such as pan-RAS inhibitors or other treatments currently available?

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

Sure. I'll do my best to remember everything, and feel free to remind me if I overlook anything. First, the number of dose modifications is low and happening more slowly than I typically expect in various trials. Keep in mind, these are heavily pretreated refractory tumors, and the patients are responding well to the drug. The tolerability aligns with the data presented, and the dropout rate for patients is very low. We are satisfied with these findings, applicable to both the 600 and 900-milligram cohorts. The next point involves how we approach dose escalation and evaluation because we are essentially managing a two-dimensional matrix for dose escalation as we increase the dose up to 900 and potentially higher. Simultaneously, we need to assess long-term tolerability, as this is crucial for chronic cancer medications and for achieving lasting disease control and durable antitumor responses. We believe we can identify the appropriate doses by evaluating 10 to 15 patients in each area. This will not be a long-term commitment; these drugs typically demonstrate effects quickly. Our drug, in particular, shows rapid results, and we can glean significant information within a few months. However, it's important to note that it takes at least two CT scans to confirm a response, and sometimes responses can extend beyond the first scan. Therefore, we will be monitoring over multiple months. An important aspect is that significant achievements are generally observed after six months, as we need to see sustained disease control. As everyone knows, for these tough-to-treat tumors, we are looking for durations of treatment exceeding six months. So, it will take at least six months to fully understand this, but we are optimistic about reaching that point soon. Lastly, regarding the combination strategy, there are two main objectives. The first is regulatory, and the second is to anticipate future trends, reminiscent of Wayne Gretzky's insight. Our primary aim is to first transition these drugs into the second and third-line settings through expedited approval pathways facilitated by the FDA, and then to initiate frontline studies alongside standard care for regulatory approval. Following that, we plan to explore potential novel combinations, likely through investigator-sponsored trials.

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 triggered 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.

Congratulations on your continued progress. Could you provide some additional detail on the prescribing dynamics for CO-PACK at this time? I may have overlooked it in your prepared remarks, but what is the usage like in academic centers compared to community settings, and can you share any information on refills? Additionally, my second question relates to financing. With the resources available to you, how do you plan to approach future financing to extend the company's cash runway beyond the first half of 2027?

Yes, Graig. Thanks for your question. I'll address the second part first and then ask Mike to respond to your question about uptake. We believe the launch for the A+F franchise will be self-sustaining by the second half of the year and will not require additional fundraising. Any extra capital we might access will depend on solid data from the G12D program. We are carefully prioritizing our needs and exploring various options for raising funds. We prefer to avoid straight equity raises due to dilution, especially at current stock prices, and we are considering several strategies to ensure we have enough runway while being prudent in our fundraising approach. We are focusing a lot on non-dilutive strategies. There has been significant strategic interest in our program, though I am not suggesting anything is imminent or that we will pursue out-licensing. However, this interest gives us considerable flexibility. There seems to be a growing consensus that we have a best-in-class molecule, which offers us more options. We will continue to explore different funding methods over time while being cautious. Mike, would you like 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'd like to inquire about the safety of 7375. Could you provide more details on that? I have three questions that I believe are all connected. The new data looks quite promising, but I want to understand how much we can rely on it compared to what we observed in China. If you have any insights into the differences between these two populations that might explain the varying safety profiles, that would be helpful. Also, could you remind us about the timing of when some of these events might occur, especially regarding heme events or liver signals, considering these patients have only been followed for about 1.6 months? Lastly, I remember you were exploring potential formulation improvements that could be implemented later. I'm curious about how much those could enhance gastrointestinal 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 is 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 Zofran or palonosetron or one of the other 5-HT3 agents. And sometimes, patients which is typical of any drug if they don't have complete cessation of nausea. I mean, nobody wants to have any nausea, then we'll ... the docs will add a second agent and really cleans it up. So those issues have been largely dealt with diarrhea is we don't prophylax against it, but we absolutely come in and the docs have been requested to come in very quickly with over-the-counter drugs to counter that, and it's very easy to get under control. We don't expect to see much in the way of emergent heme tox. We've not seen it. We have similar entry criteria to what they required in China to get onto the trial. So I don't think this is a baseline bone marrow, I should say, baseline to cell count issue. It's probably a health of the bone marrow issue. I suspect that we're using a lot more growth factors here in America than they do in China. And so when the patients who all got chemotherapy at least once and usually multiple times coming on to our trial are probably having better bone marrow support coming in. I suspect that's the major reason. I don't expect to see much in the way of liver function abnormalities. We haven't seen that. We are aware, and I think probably everybody is aware that patients in China tend to use a lot of natural products and a very inconsistent quality that have all kinds of liver abnormalities as well as other abnormalities associated with them. And we've really tried to make sure that our patients here tell their docs about any organic or general nutrition center kind of supplements they're using and really to limit all of that. So I don't know if that's the reason we're not seeing the liver signals, but we're really very comfortable with how this drug is behaving. Lastly, as far as formulation is concerned, we are looking into whether something like enteric coating could be helpful here or not. It's really important for us to get ... obviously figure out which dose we're going to use. And my gut feel is we're going to end up at the 900, but that's just a, no pun intended, my gut feel. Once we figure out the dose and we understand better the side effect profile in the setting of standard antinausea agents, we'll be able to make some decisions on formulation. But I think there is some room for a formulation to help things.

The next question comes from the line of Yuan Zhi with B.Riley Securities.

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 timeline 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 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.

And we'll take our last question from James Molloy with AGP, Alliance Global Partners.

Matt is filling in for Jim today. Congratulations again on the ongoing progress. Firstly, I wanted to ask about the RAMP 201J trial. The updated data appears positive to us. Could you please walk us through the next steps in Japan for the A+D combination?

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 authorizations put in, where they're not putting the status, and those seem 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 a 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.

That concludes the question-and-answer session. Thank you all for joining in. You may now disconnect. Everyone, have a great day.