Verastem (VSTM) Q4 2025 Earnings Call Transcript

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DATE

March 4, 2026, 8:00 a.m. ET

CALL PARTICIPANTS

• President and Chief Executive Officer — Daniel Paterson
• Chief Commercial Officer — Michael Crowther
• Head of Development — Michael Glen Kauffman
• Chief Financial Officer — Daniel Calkins

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TAKEAWAYS

• Net product revenue -- $17.5 million in the fiscal fourth quarter ended Dec. 31, 2025, and $30.9 million for the launch period of May through December, from AVMAPKI FAKZYNJA CO-PACK sales.
• Prescription penetration -- Nearly 300 prescribers through February, with about 75% of academic and community target institutions introducing or adopting AVMAPKI FAKZYNJA CO-PACK.
• Payer coverage -- Coverage remains strong for all LGSOC prescribed patients, regardless of mutational status; approximately 60% of commercially eligible patients utilize the co-pay program.
• Prescribing patterns -- GynOncs and MedOncs prescription split holds near 60%-40%, and more than half of prescriptions originate from academic centers.
• Clinical trial milestones -- Early completion of enrollment in both the RAMP 301 LGSOC and RAMP 205 pancreatic cancer clinical trials positions the company for upcoming catalysts.
• Japan RAMP 201J data -- Reported 57% overall response rate for KRAS mutant and 22% for KRAS wild-type LGSOC patients (16 enrolled) by investigator assessment.
• Pancreatic cancer study response -- RAMP 205 showed an 83% confirmed response rate in 10 of 12 patients using avutometinib plus defactinib with GEM ABRAXANE; expansion cohort enrollment completed, with an update expected in Q2.
• VS-7375 dose escalation -- Cleared 900-milligram daily oral dose in U.S. trials, with ongoing 1,200-milligram dose assessment, and lower reported rates of nausea, vomiting, and diarrhea than in Chinese partner data.
• R&D and SG&A expenses -- Fiscal R&D expenses reached $31.7 million in the fourth quarter and $114.6 million for the year ended Dec. 31, 2025, while SG&A expenses were $24.4 million in the fourth quarter and $81.1 million for the year, driven by commercial and pipeline activities.
• Cash position -- Cash, cash equivalents, and investments stood at $205 million at quarter end, with a pro forma December 2025 balance of $234.4 million, projecting runway into the first half of 2027.
• Non-GAAP adjusted net loss -- Fiscal fourth quarter non-GAAP adjusted net loss was $39.8 million ($0.48 per share diluted); full-year loss reached $163.1 million ($2.35 per share diluted).
• FDA and protocol updates -- The FDA recently provided feedback, prompting division of VS-7375-101 trial into several disease-specific, registration-directed Phase II trials for KRAS G12D-mutated cancers.

SUMMARY

Verastem (NASDAQ:VSTM) marked its transition to a commercial-stage entity with $30.9 million in product revenue for the initial launch period, supported by the rapid adoption of AVMAPKI FAKZYNJA CO-PACK across both academic and community centers. Strategic pipeline momentum was evidenced by the completion of enrollment in Phase III RAMP 301 (LGSOC) and RAMP 205 (pancreatic cancer) trials, as well as the advancement of VS-7375 into higher dose cohorts in U.S. studies. Management reported a strong cash position and emphasized extending runway through disciplined expense management and the anticipated self-sustaining performance of the LGSOC franchise in the second half of 2026.

• The company described negotiations with the Japanese PMDA to leverage bridging data from RAMP 201J for potential conditional approval and indicated plans to file early next year upon reaching sufficient follow-up.
• Feedback from the FDA resulted in administrative changes, leading to the separation of VS-7375-101 into multiple disease-focused Phase II protocols without impacting clinical timelines or safety procedures.
• The current payer environment is favorable for both KRAS mutant and wild-type LGSOC, with some tightening observed in non-ovarian off-label settings.
• Management maintained that additional capital needs will depend on G12D data milestones, highlighting flexibility in pursuing non-dilutive funding opportunities amid strategic interest.
• The company is launching new physician- and patient-focused promotional campaigns and expanding educational initiatives to further drive adoption of AVMAPKI FAKZYNJA CO-PACK, particularly at first recurrence.

INDUSTRY GLOSSARY

• LGSOC: Low-Grade Serous Ovarian Cancer; a rare subtype of ovarian cancer distinguished by slow growth and resistance to conventional chemotherapy.
• KRAS G12D: A specific genetic mutation common in pancreatic, colorectal, and lung cancers, for which there are currently no approved targeted therapies.
• AVMAPKI FAKZYNJA CO-PACK: The commercial brand name for the combination of avutometinib and defactinib, approved for KRAS-mutated recurrent LGSOC.
• RAMP: Series of clinical trials for Verastem’s drug programs; e.g., RAMP 301 for confirmatory LGSOC data, RAMP 205 for pancreatic cancer, RAMP 201J for Japanese LGSOC patients.
• PMDA: Pharmaceuticals and Medical Devices Agency—the Japanese regulatory authority overseeing drug approvals.
• GynOncs/MedOncs: Gynecologic oncologists/Medical oncologists; physician specialties responsible for cancer therapy prescriptions as referenced in the call.

Full Conference Call Transcript

Daniel Paterson: 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 FAKZYNJA CO-PACK at first recurrence. With this approval, we've proven that precision targeting of RAS/MAPK pathway with the combination of avutometinib and plus defactinib can deliver meaningful outcomes for patients. Cancer is highly dependent on this pathway for its growth and approaches [ that block ] just a single node in this pathway are generally insufficient for deep and durable anticancer activity. The cancer will compensate by activating other signaling proteins within the RAS pathway or in parallel pathways.

This is what differentiates avutometinib plus defactinib and is defining our success in the market in the clinic. The team's execution through the early phases of the launch has enabled us to quickly deliver this medicine to patients living with a rare ovarian cancer who previously had no approved treatment options specifically for their disease. Likewise, our R&D team has made great strides in advancing key strategic clinical trials. As with LGSOC, the combination of avutometinib plus defactinib has shown promising antitumor activity in pancreatic cancer, a highly KRAS-driven cancer and our RAMP 205 trial in first-line metastatic pancreatic cancer where combining avutometinib and defactinib with standard of care chemotherapy to improve response rates and other outcomes.

Avutometinib can help to inhibit tumor growth while defactinib works to inhibit FAP to reduce the stromal density in the pancreatic cancer tumor and address adaptive resistance to avutometinib. The updated data we shared at ASCO last year demonstrates the potential for this combination in treating one of the most challenging cancers. In addition to the avutometinib defactinib combination, we're targeting RAS-driven cancers with other novel therapies. This includes our other exciting pipeline program VS-7375 which has the potential best-in-class oral KRAS G12D ON/OFF inhibitor. Building on the unprecedented data from our partner in China, we moved VS-7375 into the clinic last year with a multi-indication trial strategy.

Recent feedback from the FDA has given us a clear strategic path forward for clinical development. As a result, we'll be amending our existing VS-7375-101 trial protocol and separating our disease-specific Phase II registration-directed trials. This added clarity will help us move this program towards a potential accelerated approval pathway. Given the early results, we believe VS-7375 has the strong potential to be the preferred agent in treating KRAS G12D driven cancers on pancreatic, lung and colorectal. Michael will provide a more fulsome update shortly. With all our clinical studies, we've made disciplined data-driven decisions to prioritize those with the greatest potential impact for patients living with RAS-driven cancers.

This was demonstrated in our decision to accelerate the VS-7375 program towards registration-directed studies and with the discontinuation of avutometinib plus defactinib program in lung cancer in light of an evolving treatment like landscape despite an interesting clinical signal. We have a wealth of opportunity but limits to our resources, and we'll continue to prioritize the opportunities with the highest value. We'll continue to closely manage our expenses and with our last financing and the exercise of the remaining cash warrants, we've extended our cash runway into the first half of 2027, giving us what we need to advance our near-term milestones.

In fact, we believe the LGSOC franchise will be self-sustaining in the second half of this year with CO-PACK revenues funding both the commercial operations and any ongoing clinical trials for [ A+D ]. Our focus remains on identifying value-creating non-dilutive opportunities in this challenging environment as we advance our clinical programs and deliver for patients and shareholders alike. With that, I'll turn the call over to Mike. Mike?

Michael Crowther: 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 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 4 months ago, she started in the CO-PACK and her most recent scans has 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 3 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 continues 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 physician's first experience with the CO-PACK is often in later lines, we will continue to focus on driving use of first recurrence that 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 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 educates 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.

Michael Glen Kauffman: 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.

Daniel 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.

Daniel Paterson: 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 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 reoccurrence. 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?

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

Eric Schmidt: 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.

Daniel Paterson: 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.

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

Michael Schmidt: 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?

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

Michael Glen Kauffman: 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.

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

Yuxi Dong: 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?

Daniel Paterson: 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?

Michael Glen Kauffman: 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.

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

Graig Suvannavejh: 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?

Daniel Paterson: 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?

Michael Glen Kauffman: 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.

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

Leonid Timashev: 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?

Daniel Paterson: Michael, do you want to address those questions?

Michael Glen Kauffman: 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 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.

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

Yuan Zhi: 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?

Daniel Paterson: Thanks for the question. 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?

Michael Glen Kauffman: 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.

Yuan Zhi: 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?

Daniel Paterson: Michael, do you want to address that?

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

Matthew Venezia: 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?

Daniel Paterson: 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.

Matthew Venezia: 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?

Daniel Paterson: 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.

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

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