Verastem, Inc.

Good afternoon and welcome to Veristem 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. All participants will be in a listen-only mode. After today's presentation, there will be an opportunity to ask questions. I will now turn the call over to Julissa Viana, Vice President of Corporate Communications, Investor Relations, and Patient Advocacy at Veristem Oncology. Please go ahead.

Thank you, operator. Welcome, everyone, and thank you for joining us today to discuss Verisim'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'll 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 Patterson, President and Chief Executive Officer, Mike Crowther, Chief Commercial Officer, Dr. Michael Kaufman, President of Development, and Dan Calkins, Chief Financial Officer. I will now turn the call over to Dan. Thank you, Delisa.

Good afternoon, and thanks for joining our call today. 2025 was a truly transformative year for Veristem 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. 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 rudimentinib 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, RAMP201, and RAMP201J, we've observed what we believe are robust objective response rates for patients with recurrent LGSLC with and without KRAS mutations. We remain committed to advancing the clinical evidence through longer-term follow-up analyses from the RANF 201 study in 2026, and completing our ongoing confirmatory RANF 301 phase three 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 AvMapKey Faxinja Copac as first recurrence. With this approval, we've proven that precision targeting of RASMapK pathway with the combination of Arutamate and Plus-Defactonate 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 anti-cancer activity. The cancer will compensate by activating other signaling proteins within the RAS pathway or in parallel pathways. This is what differentiates azimutinib plus defactin 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 avutametinib plus defactinib has shown promising anti-tumor activity in pancreatic cancer, a highly KRAS-driven cancer. And our RAMP205 trial in first-line metastatic pancreatic cancer we're combining avutametinib and difactinib with standard of care chemotherapy to improve response rates and other outcomes. Avutametinib can help to inhibit tumor growth, while difactinib works to inhibit SAC to reduce the stromal density in the pancreatic cancer tumor and address adaptive resistance to avutametinib. 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 Ibutametinib-Defactinib combination, we're targeting RAS-driven cancers with other novel therapies. This includes our other exciting pipeline program, VS7375, 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 VS7375 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 out disease-specific Phase II registration-directed trials. This added clarity will help us move this program toward a potential accelerated approval pathway. Given the early results, we believe VS7375 has the strong potential to be the preferred agent in treating KRAS G12D-driven cancers like 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 our glutamate plus defactant program in lung cancer in light of an evolving treatment landscape despite an interesting clinical signal. We have a wealth of opportunity but limits to our resources and will 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 COPAC revenues funding both the commercial operations and any ongoing clinical trials for A plus 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?

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 LGS-OC is a life-changing event. LGS-OC 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, Avmapke-Faxinger-Kopak became the first-ever treatment specifically approved for KRAS-mutated recurrent LGS-OC, forever changing the treatment landscape for this disease. Let me give you an example of the impact of the COPAC 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 on the COPAC, and her most recent scans have shown a complete response to treatment. This incredible outcome underscores the benefit of using the COPAC. 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 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 abmapkifaxin jacopak. 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 healthcare 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 at the COPAC. 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 Avamaki, Faxinger, Copac 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 are starting to incorporate the therapy of 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 time to kill 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 VeriSTEM CARES program has been effective in helping patients manage their 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 healthcare 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 for side effects management to help both prescribers and patients stay on the treatment and realize the benefits of the COPAC. 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 with LGSOC and appreciate support for patient management. From a patient perspective, we continue to see high engagement in our brand of website. Patients are opting in to receive more information about the COPA 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 Veristem 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 COPAC is often in later lines, we will continue to focus on driving use of first recurrence so patients can receive the full benefits of ADMAP-Kefaxinja Copac. In the next quarter, we will be launching a new promotional campaign to help 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 treatments 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 reach in new patient staffs. We are deploying our sales reps and nurse 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 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 sustain 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 moved from lead director on the board to head development at Veristem last year, It was because I see significant promise in our pipeline and specifically believe that what we're building here with BS7375 has 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 avutamatinib plus defactinib, because 2025 was a defining year across our portfolio. Our team completed enrollment ahead of schedule in our two avutamatinib and defacto clinical trials, RAMP301 in LGSOC and RAMP205 in pancreatic cancer. This positions us well for the catalyst ahead. On RAMP301, 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 three trial of abutamentinib plus defactative 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 RAMP201J 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 orphan drug designation in ovarian cancer last year from the European Commission. We continued working through the steps needed for a future regulatory application once we have the RAMP 301 results in hand. For RAMP 205, our first-line metastatic pancreatic cancer study of avudimetinib plus dipactinib in combination with gemobrachate. At ASCO last year, we called, 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 avutamatinib plus diffractin 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 IMD 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 in other KRAS T12B 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, GenFleece, 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 agents. In addition, based on Mark's preclinical synergy with dual RAS-EGFR blockade, we are evaluating the combination of VS-735, 7375 with cetuximab. We recently cleared 600 milligram daily dose level in combination with standard 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 1-2 protocol. Per the agency's request, we are changing our initial Phase 1-2 trial, which had multiple expansion cohorts, and breaking out several disease-specific Phase 2 registration-directed trials for KRAS G12V mutated cancers, including second-line patriotic ductal carcinoma, second- and third-line non-small-cell lung cancer, and with VS7375 in combination with Cetuximab in second-line plus colorectal cancer. Now let me move to discuss a recent PK analysis that we did. Doses of 600 milligrams daily and above with feeding and anti-emetic prophylaxis yielded similar exposures to that observed in China with fasted patients. And exposures achieved cover the exposures in preclinical models necessary for maximal anti-tumor efficacy. From a safety perspective, we continue to be pleased with the profile we see emerging. We have the benefit of hindsight of our partner's 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 intrapenia in grade two has been reported. And we included in the protocol strong recommendations for standard prophylactic anti-nausea agents and rapid institution of over-the-counter anti-diarrheal 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 in our partner in China, as well as early signals from our own trial, give us strong confidence in the 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 set at our go-forward dose in the second half of this year.

Now I'll turn the call over to Dan Cochran. 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 previously communicated, we're not providing detail on gross to net other than to say that expectation 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 Ramp 301 clinical trial and the ongoing BS 7-375 Phase I-II clinical trial, as well as higher costs associated with drug substance production activities related to 7-375. 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 COPAP 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 48 cents per share diluted compared to non-GAAP adjusted net loss of 29.3 million or 60 cents 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 that Matthew Faxinger co-pass 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 COPAP's 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 COPAP revenues funding both the commercial operations and any of our abutamentinib 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 the FMAP-D Fexsingicopax 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, continue execution of the RAMP 301 confirmatory phase three trial in recurrent LGSOC. And fourth, maintain proven capital management through our key catalyst and a strong balance sheet. In support of these strategies, we set several goals by which to measure our success. We want to maximize adoption of the COPAQ 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 VS7375 trial, we expect to further demonstrate the breadth of our RAS MAP-K 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 RASMAPK-driven cancers. As we enter 2026, we're well positioned to continue to deliver on our milestones.

With that, we'll open up the calls for questions. Operator?

Thank you. We will now begin the question and answer session. If you have dialed in and would like to ask a question, please press star 1 on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star 1 again. If you are called upon to ask your question and are listening via speakerphone in your device, please pick up your handset to ensure that your phone is not on mute when asking your question. Again, press star 1 to join the queue. Our first question comes from the line of Eric Schmidt with Kantor. Your line is open.

Thanks for taking my question. 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. Thank you.

Eric, thanks for your question. Look, it was disappointing and we were a little surprised. We've not gotten any direct feedback. We're not really going to speculate. You know, we suspect it might have had something to do with the imminent phase three 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. You know, 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, you know, 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, you know, 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 RAMP201 study have results in both wild-type and mutated that we believe show benefit to patients and will continue to share those publications.

Thank you very much.

Next question comes from the line of Michael Smith with Guggenheim Partners. Your line is open.

Hey, good afternoon. Thanks for taking my questions. I had a couple on 7375. Obviously, the basically now looks very good in the US study based on the table, 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? 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 in expansion courts at 600 mid to QD, but obviously escalating further up to 1200 now. So how do you think about dose selection for these planned phase two 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 courts 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? Thanks so much.

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

Sure. I'll try to remember all of them and come back to me if I missed something. I think that, 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 on the drug. So the tolerability is consistent with the data you saw on the table and consistent with any modifications. The dropout rate is very low for the patient. 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 two-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 anti-tumor responses. So it's a two-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. 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 six 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 six months. So it'll take six 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. Yeah, I mean, there's two goals here. One is regulatory, clearly. And the second goal is, where's the puck going? The sort of Wayne Gretzky quote of how to predict the future. And we'll 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 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 to investigate responsive trials, some of the novel combinations.

Great. Thanks, Mike. Appreciate it.

Sure. Our next question comes from the line of with . Your line is open.

Hi. Good afternoon. Thanks for taking my question, and congrats on all the progress. So 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 REMS 301 data or additional Japan data as well. And then for the FDA feedback on G12D, can you walk us through what specifically triggered the feedback to separate the study into disease-specific and registration-directed phase of trials for the three indications? Thank you.

Clara, thanks for your questions. I'll take the NCCN1 and then turn it over to Michael for the the FDA question. Yeah, 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, 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 a label expansion at the FDA. Michael, 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 playbook page from the playbook of Keytruda, where they use the phase one 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 saying, hey, we like your plan, but in general, cohorts that are gonna 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, you know, 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 had provided both from China and the initial safety data from the U.S.

Thank you.

Next question comes from the line of Craig Suvanovich with Mizzou. Your line is open.

Good afternoon. Thanks for taking my questions. Congrats on continued progress. I was hoping to get maybe some color on, a little bit more color just on the prescribing dynamics for COPAC 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 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? Thank you.

Yeah, great. Thanks for your question. I'll take the second one first and then ask Mike to address your question on uptake. You know, as we've said, and, you know, we think this is really important, we believe that the launch or the A plus 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, you know, 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. We'll continue to look at different ways to fund it and we'll be prudent in doing it over time. Mike, maybe if you want to address the other part of the question.

Sure, Dan. Thank you 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 COPAC. 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 centre. We expect that split to be consistent with the community over time. And importantly, as we talked about, our Veristem 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.

Okay, thank you.

Next question comes from the line of Leonard Dimenev with RBC Capital Markets. Your line is open.

Hey guys, thanks for taking my question. I want to ask on 7375 safety, just 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 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 affect later on. I'm just curious how much further those could potentially improve some of the GI tolerability.

Thanks. Michael, you want to address those questions?

Sure. Yeah, the data that we provided 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 one. And a lot of the grade one goes away over the first week or two. with the proper use of anti-nausea agents like standard Zofran or Pelinosatron 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 to have any nausea, then 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 cytokine. 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 once, 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's aware, that patients in China tend to use a lot of natural products and they are very, you know, inconsistent quality that have all kinds of liver abnormalities as well as other abnormalities associated with them. And we 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, with, 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 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, 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 anti-nausea agents, we'll be able to make some decisions on formulation.

But I think there is some room for a formulation to help things.

Question comes from the line of U1Z with B Riley Securities. Your line is open.

Thank you for taking our questions. 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'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 right. 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, 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 they can go to, 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 titration? meaning starting at 900 or 500 mg and then using 600 mg as maintenance dose if needed.

Michael, 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 haven't any reason to believe yet that we're going to need to lower the dose. It's fairly early yet with our U.S. experience, and I'll remind folks that in China, they were not able to get to 900 milligrams, but 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 times 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.

Got it. Thank you for taking our questions.

And everyone, again, if you would like to ask a question, press star, then the number one on your telephone keypad. And we'll take our last question, comes from the line of James Molloy with AGP Alliance Global Partners. Your line is open.

Hi guys, Matt on for Jim today. Thank you for taking our questions and congrats again on the continued progress. So first we wanted to ask about the RAMP201J trial. The updated data looked positive to us, but can you just take us through the next steps in Japan for the A plus D combo?

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

Got it. And then in terms of the US 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, you know, our most common group of patients are the, 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 seem to be going through pretty smoothly. And then the third group is the KRAS wild type where, You know, 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, you know, these patients do appear to be benefiting. You know, where we have gotten some tightening in the last quarter or so is what I would call the totally off label. 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, you know, in PDAC, you know, we're talking data set of 12 patients. And then in some of these other diseases that it was slipping through, really not a lot of support. 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.

Great. Thank you, guys. Thanks for taking our questions.

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

Thank you. Bye. Bye.