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DATE

Thursday, May 7, 2026 at 8 a.m. ET

CALL PARTICIPANTS

  • President and Chief Executive Officer — Daniel Paterson
  • Chief Medical Officer — Michael Glen Kauffman
  • Chief Financial Officer — Daniel Calkins
  • Chief Communications and Investor Relations Officer — Julissa Viana

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TAKEAWAYS

  • Net Product Revenue -- $18.7 million reported for AVMAPKI FAKZYNJA CO-PACK in the quarter, contributing to nearly $50 million since launch.
  • Patient Access and Prescriber Growth -- Over 400 unique prescribers through April, with increasing new patient starts and a 60%-40% split between gynecologic and medical oncologists.
  • Reimbursement and Payer Mix -- Approximately 65% of eligible patients accessed the Verastem Cares Co-Pay Program; average co-pay for commercially insured patients remained below $30; payer mix is roughly 50% commercial and 50% Medicare.
  • Prescription Fulfillment -- Time to fill initial prescriptions remained consistent at 12-14 days due to rapid prior authorization approvals.
  • Commercial Optimization -- Leadership realignment included appointing a new Chief Commercial Officer and expanding the field force by two sales personnel as part of targeted commercial execution changes.
  • Cost Structure -- R&D expenses were $38.2 million, driven by continued Phase III (RAMP-301) and Phase I/II (VS-7375 Target-D 101) clinical activity and increased supply spending; SG&A expenses were $22.3 million, and are expected to remain roughly stable each quarter for the year.
  • Adjusted Net Loss -- Non-GAAP adjusted net loss of $42.7 million ($0.43 per share diluted) compared to $42.9 million ($0.79 per share diluted) a year prior.
  • Cash Position -- Ended the quarter with $181.7 million in cash, cash equivalents, and investments; management projects cash runway into the first half of 2027.
  • Self-Sustaining Franchise -- Management reiterated expectations for the LGSOC franchise to become self-sustaining in the second half of 2026, with CO-PACK revenue covering commercial and clinical operations.
  • VS-7375 Clinical Program -- Phase I/II trial is progressing with enrollment at 1,200-milligram dose; three Phase II registration-directed trials are underway in pancreatic, non-small cell lung, and colorectal cancers, each designed with overall response rate by blinded independent central review as primary endpoint.
  • Dose Rationale and PK Data -- Updated pharmacokinetic analysis shows 900 milligrams achieves serum levels at or above the company’s target and is well tolerated; higher doses (1,200 milligrams) are being tested with formulation constraints described.
  • Upcoming Clinical Milestones -- First patient enrollment in all three Phase II trials is anticipated by mid-year or earlier; a more comprehensive data set with double-digit patient numbers at go-forward dose is expected in the second half of the year.
  • AVMAPKI FAKZYNJA CO-PACK Launch Dynamics -- Early patient discontinuations reflected use in more advanced patients; seasonal insurance turnover and weather were cited as temporary Q1 headwinds.
  • Physician Preferences -- Recent ATU survey indicated most physicians select the CO-PACK as their first choice at patients’ next recurrence.
  • Clinical Operations -- RAMP-301 trial achieved full accrual in December 2025, supporting management's expectation that related R&D spending may decline going forward.

SUMMARY

Verastem (VSTM 13.60%) reported quarter-over-quarter revenue growth for its lead product, AVMAPKI FAKZYNJA CO-PACK, and expects this franchise to fund its commercial activities and ongoing clinical development efforts by the second half of the year. Management attributed temporary Q1 impacts on patient starts and refills to seasonality and weather, while highlighting actions taken to expand sales resources and sharpen commercial execution. Pipeline progress includes ongoing dose escalation in the VS-7375 Target-D program, with pivotal Phase II trials advancing for registration-directed indications and confirmation that larger capsules are in development to address dosing logistics. Company leadership projects its current cash reserve, augmented by future product sales, will support operations beyond the next year and notes that ongoing R&D and SG&A expenses are expected to remain disciplined.

  • Leadership noted that in-market physician feedback and survey data support continued adoption of the CO-PACK, with active prescribers and new patient initiations both increasing after early-year volatility.
  • New commercial leadership and targeted promotional campaigns have been implemented to drive earlier utilization at first recurrence and reinforce the importance of therapy duration management.
  • In clinical operations, separate Phase II protocols for pancreatic, non-small cell lung, and colorectal cancer have been established as registration-directed studies, following prior FDA guidance, with initial patient enrollment imminent and updated data sets expected throughout 2026.
  • Ongoing evaluation of higher VS-7375 dose levels is fueled by updated PK data and observed tolerability, with 900 milligrams chosen as the planned registration dose unless larger pill sizes enable further escalation.

INDUSTRY GLOSSARY

  • LGSOC: Low-grade serous ovarian cancer, a type of epithelial ovarian cancer targeted by AVMAPKI FAKZYNJA CO-PACK.
  • RAMP-201 / RAMP-301 / RAMP-205: Clinical trial identifiers for avutometinib plus defactinib in ovarian and pancreatic cancers, with distinct phases and target populations.
  • Target-D: The clinical trial program for VS-7375, an oral KRAS G12D ON/OFF inhibitor under evaluation for several solid tumor types.
  • BICR: Blinded Independent Central Radiological Review, a trial endpoint assessment ensuring objectivity in measuring response rates.
  • ATU: Attitudinal tracking studies capturing physician prescribing intent and preferences regarding new therapies.
  • PDAC: Pancreatic ductal adenocarcinoma, the predominant form of pancreatic cancer included in clinical studies.
  • EGFR inhibitor: A class of drugs targeting epidermal growth factor receptor, used in combination regimens to overcome resistance mechanisms in solid tumors.

Full Conference Call Transcript

Daniel Paterson: Thank you, Julissa. Good afternoon, and thank you for joining our call today. Tomorrow marks 1 year since the accelerated approval of AVMAPKI FAKZYNJA CO-PACK, a practice-changing medicine approved for patients with KRAS-mutated recurrent low-grade serous ovarian cancer. Since our launch in May 2025, we've seen steady growth quarter-over-quarter, achieving $18.7 million in net product revenue in Q1 with nearly $50 million in total net product revenue to date. While we're pleased with the growth we've seen, we believe there's meaningful opportunity to build on the foundation we've established. New patient starts remain consistent month-over-month. Our prescriber base continues to grow and the reimbursement environment is favorable.

As part of our ongoing commitment to optimize our launch, we conducted a focused review of our launch performance and execution and implemented targeted changes to our commercial organization and leadership. I'll walk through these details in a few minutes. I want to underscore that our confidence in the underlying demand and overall opportunity for the CO-PACK remains unchanged. Moving to R&D. We've made significant progress with our clinical trials for VS-7375, our potential best-in-class oral and selective KRAS G12D ON/OFF inhibitor, now branded as the VS-7375 Target-D clinical trial program. The Target-D-101 Phase I/II dose escalation and expansion trial is already underway, and we continue to enroll patients and evaluate higher dose levels.

In addition, we've also initiated our Phase II registration-directed clinical trials in second-line pancreatic cancer, second and third-line non-small cell lung cancer and second-line plus metastatic colorectal cancer. Michael will share more about our progress and strategies with these trials. We continue to closely manage our expenses and remain on track for the LGSOC franchise to be self-sustaining in the second half of the year, meaning CO-PACK revenues will support both commercial operations and any ongoing clinical trials for avutometinib plus defactinib. As we look to the balance sheet, our focus remains on identifying value-creating nondilutive opportunities as we advance our pipeline and deliver for patients and shareholders. With that, let me turn to our commercial update.

With almost a year into the launch, we're continually monitoring our progress. As with any launch, there's a natural evolution as we learn more about the market dynamics. We took a comprehensive look at our commercial execution and have taken decisive actions to strengthen it and position the business for the next phase of growth. Most notably, we've appointed a new Chief Commercial Officer, Dan Lyons, who has deep and relevant experience in oncology and rare diseases. He has a strong track record of leading global commercialization strategies across solid tumor cancers, including 2 successful rare disease and oncology launches at SpringWorks.

Dan's leadership will be instrumental as we evolve our launch and bring AVMAPKI FAKZYNJA CO-PACK to all patients who could benefit from this important treatment. While Dan will not be joining us on the call today, he's already actively engaged with the team driving new and existing initiatives forward. Turning to the first quarter results. We were impacted by the seasonal headwinds many companies experienced, namely insurance turnover and reverifications as well as more severe weather, which affected patient access. This impacted both new patient starts and refills.

On closer examination, we also observed a specific dynamic where some patients prescribed the therapy by early adopters were much further along in their disease and treatment journey than we would have anticipated and therefore, discontinued the treatment earlier than expected. This is not surprising as in many cases, these patients likely had no other alternative therapeutic options with proven clinical benefit. Since January, we've seen a rebound with a strong number of new patients through the end of the first quarter. There also continues to be strong physician conviction with the majority of physicians surveyed at our most recent ATU indicating that the CO-PACK would be their first choice at their patient's next recurrence. Now on to the numbers.

Active prescribers continue to expand and through April, there have been more than 400 unique prescribers to date. And consistent with previous quarters, we continue to see prescriptions split between GynOncs and MedOncs at a 60-40 percentage. Separately, our active patient pool has grown over recent months, indicating patients are staying on therapy longer, but it's too early to provide duration of therapy as it continues to evolve. It's also too early to give an average number of refills, but the trend we are seeing is consistent with what we would expect at this point in the launch. Approximately 65% of commercially eligible patients are using our Verastem Cares Co-Pay Program.

The remaining patients did not require co-pay assistance and the average co-pay for commercially insured patients is less than $30. Time to fill initial 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 at about half commercial and half Medicare. As we look ahead and consider our recent learnings, we focused on 3 key drivers in our business to help patients realize the full benefit of the CO-PACK. The first key driver is to maintain the consistent level of demand of new patient starts. This starts with identifying the right patient for treatment.

Without an ICD-10 code specific to LGSOC, we've identified other proxy measures within EHRs, including mutational status, AI or MEK use that may indicate an appropriate patient for the CO-PACK. Our team is actively working with prescribers when these proxy measures are identified in a patient file. Additionally, we've now added incremental personnel to continue to drive demand and support patient adoption. The second key driver is to drive earlier use at first recurrence. Over the course of the launch, we've observed discontinuations that in part reflect use outside of the attended approved patient population and in LGSOC patients who are much sicker than the patient population in RAMP-201 that was the basis for FDA approval.

In fact, in some cases, patients were heading into hospice. As multiple physicians have noted, disease progression and complications can make it harder for patients to tolerate and absorb oral therapies, underscoring the importance of using the CO-PACK early at first or next recurrence when patients have the best opportunity to realize its full benefits. Our recently launched Reimagine Recurrent LGSOC direct-to-physician and patient campaign is focused squarely on this shift. The third key driver is to help patients stay on therapy.

Recent long-term data from the RAMP-201 trial presented at the Society of Gynecologic Oncology showed that after 2 years of follow-up, patients on the CO-PACK achieved durable benefit with discontinuation rates consistent with the package insert, findings that physicians view as clinically meaningful. Our recent exposure response analysis also demonstrated that early side effects can be effectively managed with dose interruptions after which patients resume at the approved dose and schedule. Setting expectations with both patients and physicians around the AE profile and how to manage through it is a key initiative for the remainder of 2026.

We continue to see a substantial market opportunity for the CO-PACK with growth potential coming from multiple directions, expanding reach among prescribers who ever prescribed the CO-PACK, deepening experience among current prescribers by identifying additional patients in their practices and shifting entrenched prescriber behaviors to starting CO-PACK on their first occurrence when appropriate. LGSOC is a relatively slow growing but unrelenting cancer where patients stay on their first treatment for several years. Therefore, achieving peak share at first occurrence will take time. But we believe the earlier use of the CO-PACK drives deeper adoption, produces real-world outcomes that mirror our trial experience and establishes the CO-PACK as the new standard of care at first reoccurrence.

We remain focused on our core product launch priorities and sustaining steady growth throughout the year. I'll now turn the call over to Michael.

Michael Glen Kauffman: Thank you, Dan. We continue to make good progress across our pipeline programs, and I'll spend the next several minutes with an overview of our VS-7375 oral KRAS G12D inhibitor program. As Dan mentioned, we've named our VS-7375 trials Target-D. Target-D 101 is our ongoing Phase I/II dose escalation, dose expansion and combination evaluation trial. In the dose escalation portion, we are now evaluating the 1,200-milligram daily dose to fully characterize the dose range available. We will complete enrollment across the various expansion cohorts shortly as well as the current cohorts evaluating combinations with chemotherapies. And importantly, we are moving to enroll patients into each of our Phase II trials, which I'll describe in more detail.

As we mentioned last quarter, the FDA requested that we develop separate Phase II protocols for any trials where we are seeking marketing authorization. Thus, we have developed 3 Phase II registration-directed trials in pancreatic cancer or PDAC, non-small cell lung cancer, or NSCLC, and colorectal cancer or CRC. I'll now provide some detail on each of these. Target-D 201 is our second-line PDAC study. This Phase II open-label study is designed to evaluate VS-7375 at the 900-milligram daily dose, both as monotherapy and in combination with cetuximab.

Based on strong preclinical rationale showing EGFR pathway activation in pancreatic cancer and its role as a potential resistance mechanism to RAS inhibition, we are studying the combination of VS-7375 and anti-EGFR antibodies to potentially deepen and prolong responses. We're also taking the opportunity to evaluate VS-7375 and anti-EGFR antibodies in first-line pancreatic cancer where we believe we can generate compelling data. It is worth noting that because VS-7375 has not been associated with skin rash to date, combination with EGFR inhibitors is expected to be clinically feasible and growing tolerability data to date support this.

In addition, we are currently studying the combination of VS-7375 and gemcitabine nab-paclitaxel or GNP in patients with PDAC looking towards a frontline treatment regimen. Target-D 202 is our advanced non-small cell lung cancer study. This Phase II open-label study is designed to evaluate VS-7375 at the 900-milligram daily dose in patients who have received 1 or 2 prior lines of therapy, including a platinum-based chemotherapy and a PD-1 or PD-L1 blocker. We are currently evaluating VS-7375 at 600 milligrams daily in non-small cell lung cancer in our 101 trial, and this will provide information at this lower dose.

But as in PDAC, we anticipate that the 900-milligram daily dose will be our go-forward monotherapy dose in previously treated non-small cell lung cancer as we look towards potential marketing authorization. We are also evaluating VS-7375 monotherapy in patients with non-small cell lung cancer and asymptomatic brain metastases where there remains a significant unmet medical need and an opportunity to improve outcomes. And as previously noted, we are evaluating the combination of VS-7375 plus pembrolizumab without or with platinum pemetrexed chemotherapy in the 101 study looking towards a frontline treatment regimen. Lastly, we have our Target-D 203 metastatic colorectal cancer study.

This Phase II open-label study is designed to evaluate VS-7375 at the 900-milligram daily dose as both monotherapy and in combination with EGFR inhibitors, including cetuximab or panitumumab in patients with previously treated colorectal cancer. While we do not expect to see meaningful responses for VS-7375 as a single agent, this will be critical to showing the contribution of PARs for potential combination therapy regulatory submission. We're also going to evaluate VS-7375 in combination with anti-EGFR antibodies and the modified FOLFOX6 regimen in the first-line setting, again, to expand the opportunity and help us improve outcomes in patients with colorectal cancer with the goal to develop a frontline combination regimen.

Importantly, across all 3 Phase II trials, the primary endpoint is overall response rate by blinded independent central radiological review or BICR, with BICR determined duration of response or DOR as the key secondary endpoint, supporting potential accelerated approvals in each of these 3 indications. The protocols have been sent to clinical trial sites, and we anticipate the first patient in each of these studies to occur mid-year, if not sooner. We continue to enroll patients and evaluate the 1,200-milligram dose, which is the highest practical dose that we can administer to define the upper end of the dosing range.

We now have updated PK data that show that the 900-milligram dose delivers serum levels of VS-7375 at or above our target level and provides clear separation from the 600-milligram dose. While we are seeing good responses at 600 milligrams, these data, along with good tolerability, support our enthusiasm for advancing the 900-milligram dose in our Phase II trials. As additional data emerge, we expect to finalize the go-forward dose across tumor types and combination settings.

As we shared last quarter, our goal is to generate meaningful data sets in these tumor types, both as single agent as well as in combination with other treatments with the goal of potential accelerated approvals in previously treated cancer as well as developing combination strategies to position our regimens in the frontline setting across all 3 tumor types. Now let me briefly set expectations for our first half update from the Target-D 101 trial. In terms of patient numbers, the safety data set will include a broad set of patients across Target-D 101. However, the number of patients evaluable for efficacy will still be relatively small.

Recall that response evaluations require a minimum of 2 baseline scans, which are typically 6 to 8 weeks apart and not all responses occur at the first scan. And of course, duration of response requires follow-up for months after the initial response determination. We note again that meaningful response duration is typically about 6 months. As we've discussed previously, we believe that administering the highest well-tolerated dose of VS-7375 will maximize the chances for each patient to have a meaningful antitumor effect. And because the 900-milligram dose has been well tolerated to date in over 20 patients in the U.S., our results of this dose will require several additional months over what was originally projected for the 600-milligram dose.

At this time, we can also add that the 400 and 600-milligram doses of VS-7375 in combination with cetuximab are well tolerated and that we are currently evaluating the 900-milligram dose in this combination. To reiterate, we will only be able to provide a preliminary view on activity overall because we've been able to utilize higher doses in our patients in the United States. That said, we see this first half update as an early checkpoint and believe the data set will be meaningful in terms of demonstrating our progress in enrollment, along with a more mature safety update and more PK data. We do plan to include some patient cases across tumor types and combinations in the update.

Later this year, we expect to provide a more comprehensive data set, including tumor-specific breakdowns and more mature efficacy data as we enroll in our Phase II trials for potential marketing applications. Finally, switching gears for a minute to our avutometinib plus defactinib program. We remain on track to report an update on our RAMP-205 study in first-line PDAC before the end of the second quarter of this year. Now I'll turn the call over to Dan Calkins.

Daniel Calkins: Thank you, Michael. Our full financial results were included in our press release, so I'll focus on the highlights here. For the first quarter of 2026, we recorded $18.7 million in net product revenue and $2.8 million in product cost of sales. Cost of sales increased in the first quarter in line with the percent increase in net product revenue for the quarter. Research and development expenses were $38.2 million for the first quarter of 2026.

R&D expenses continue to be driven by both the ongoing global confirmatory Phase III RAMP-301 clinical trial with the CO-PACK and the ongoing VS-7375 Target-D 101 Phase I/II clinical trial in the U.S. as well as higher costs associated with clinical supply and drug production activities related to our expanded VS-7375 program. SG&A expenses were $22.3 million for the first quarter of 2026. The expenses were driven by commercial activities and operations, including personnel-related costs to support the ongoing CO-PACK launch.

I can reiterate that we expect SG&A expenses to remain roughly the same on a quarterly basis throughout 2026 as we remain disciplined in our expense management, making the right investments at the right time to support the ongoing commercial launch efforts. For the first quarter of 2026, non-GAAP adjusted net loss was $42.7 million or $0.43 per share diluted compared to non-GAAP adjusted net loss of $42.9 million or $0.79 per share diluted for the first quarter of 2025. Please see our press release for a full reconciliation of GAAP to non-GAAP measures. Moving to the balance sheet. We ended the first quarter with 2026 with cash, cash equivalents and investments of $181.7 million.

We believe our current cash, combined with the future revenues from the AVMAPKI FAKZYNJA CO-PACK sales will provide cash runway into the first half of 2027. We remain encouraged by the initial launch and look forward to building on the CO-PACK's growth in 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 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, our focus for the remainder of 2026 is very clear, and that's to drive strong execution across our commercial launch, move our 3 Phase II trials expeditiously towards potential registrations, determine appropriate VS-7375 combinations for frontline strategies and maintain disciplined capital management while identifying nondilutive financial opportunities to deliver for patients and our shareholders. Overall, we believe we're well positioned to deliver on our key milestones this year and continue building a leading oncology franchise in RAS/MAPK-driven cancers. With that, we'll open up the call for questions. Operator?

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

Eric Schmidt: Maybe one on each of the 2 programs. On 7375, what do you think potential partners need to see from either your Phase I or early Phase II data sets in order to be very interested in the asset? And then 2 for Dan in terms of the self-sustainability of the CO-PACK franchise. Can you be a little bit more granular in terms of the revenue that gets you to that sustainability?

Daniel Paterson: Sure. Eric, thanks for the question. Just to comment on potential partners, we have had a fair amount of interest. And what typically happens in situations like this, it tends to come down to the competitiveness. I think if there's one party interested, it can go on forever. I do think the fact that we've got significant data out of China that aligns well with the preclinical profile, it's really seeing enough data from the U.S. where we show that we can give it in a tolerable way in a way that can be combined and that we start to recapitulate efficacy that puts us in the ballpark of still being potentially best-in-class.

And Michael, I don't know if there's anything more you want to add there, but why don't you comment and then we can have Dan C talk about the expenses second half of the year and kind of what we're talking about being covered.

Eric Schmidt: I think you covered it real well, Dan. We need U.S. data, and we need a lot of detail on the patients and their prior therapy, and we're quite optimistic that we'll be able to deliver on that.

Daniel Calkins: Yes. Eric, this is Dan C. So yes, just in terms of the self-sustaining question, obviously, we haven't given guidance in terms of the revenue for the remainder of the year. But just in terms of the expenses, if you look at SG&A expenses from -- on a quarterly basis from when we were pre-commercial to where we are now, that increase has typically been around $10 million to $15 million per quarter. And then from an R&D perspective, if you look specifically at the A+ related programs, that spend has typically been about $10 million to $15 million per quarter as well.

And the majority of that spend is really coming from the RAMP-301 trial, which we announced reached full accrual back in December of 2025. So that's now at full accrual. So I don't expect that, that will increase more likely be coming down. So that would give you a good sense of what it would take to be self-sustaining within that program.

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

Michael Schmidt: I had a couple on 7375. Maybe one for Michael first. You talked about the Phase I update in the first half of this year. And maybe if you could just comment a little bit more about how the patients perhaps in the U.S. study compared to the GenFleet Phase I study that we saw last year. And also, you mentioned different follow-up with -- depending on which dose was used. And so how comparable will the U.S. update be perhaps to the GenFleet data from last year?

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

Michael Kauffman: Sure. Yes. Sure, Dan. So PDAC is generally treated the same way across the world. And frankly, these days, lung cancer, I mean, KEYTRUDA may or may not be the immunotherapy, but it's generally treated with a platinum agent, typically carbo and since these are adenocarcinomas of pemetrexed. And again, colorectal cancer, it's pretty standard, whether they're getting FOLFOX or FOLFIRI and some people are getting FOLFIRINOX, it's all pretty similar. The patients are fairly similar. I think the most important difference and the reason we want to continue to study our drug is because the tolerability in the U.S. has been substantially better than what was reported in China.

We are not seeing any significant level at all of liver dysfunction. We haven't seen any significant hematologic issues at all. And we continue to see that even with patients now who are on for many months. Some who are on for more than 6 months. We're just not seeing that. We're also not seeing cumulative toxicities, which is really great for a drug that can be given chronically. We have really not seen anything major with this drug to date, and it's -- the numbers are starting to climb. So the 600-milligram dose has been studied for a little bit of a while now, but across a whole bunch of different cancers. It was an open study.

We'll have a little bit more specifics on it. But I think the points I made in the call were that it takes a while to get responses here. I mean you can't even assess the first response until 6 to 8 weeks after initiation of dosing. And remember, when we open a trial, we don't accrue everybody at the beginning. So this is a staggered accrual, of course, with staggered dosing. We all wish this could happen immediately. But the first scan is 6 to 8 weeks and then a confirmatory scan is another 6 to 8 weeks.

And then if like in PDAC when many of your responses are going to occur in the second scan after the first scan because these are tough tumors and they have a lot of scar tissue. It's going to take a while, and that's okay, and that's very good. We absolutely have responses in the first scans after dosing starts, and we've seen responses at second, and we've seen patients who've done really well, have shrinkage of tumors and cross the important 30% threshold for a PR in scan 3 or 4. I don't want to go into any detail, but we're quite pleased with what we're seeing, and we believe that 900 milligrams will be the go-forward dose.

So that won't be -- the 900-milligram details will not come until the second half of the year, as we said. And we'll be able to give a little bit of data on the 600 milligram. But we would far prefer to give you guys substantial data sets in the 20 to 30 patient range with reasonable durability so that we can make some -- you and we can make some intelligent decisions on how this drug is stacking up against others. All of that said, we remain very, very excited about the potential for this to be a best-in-class agent.

And I would lastly point out that this drug does not carry rash with it at all nor does it carry stomatitis. And these are really important considerations for patients who could spend a year or more on these drugs.

Michael Schmidt: Okay. Understood. And maybe a question on your Phase II program. Specifically the 201 study on Slide 12 is schematic and just wanted to ask, so you have Part A and Part B. And I'm just curious what the decision process is for either selecting 1 of the 2 cohorts, monotherapy or combination and then whether the Part A and B patients will be pooled at the respectively selected cohort. Will this be a 100-patient type -- actually 80 patient type registration cohort? Or how should we think about the decision path as you have sort of multiple steps in these Phase II studies?

Daniel Paterson: Right. Well, beautiful way to put it, and you correctly figured out what we're really doing here, which is to expect that based on what's going on right now at the 900-milligram dose currently in our Phase I, we do think 900 milligrams will be good as both a monotherapy and in combination. We think both of these cohorts are going to be important. And we do intend to pull Parts A and B. This is sort of a 2-step.

It's almost sort of a baby and 2-step trial, but we're just putting it in here this way so that we can review this in case there's some unexpected findings here, which frankly, would be different from what we're finding already in the 101 study. We don't believe that's going to happen, but this was -- we discussed it with our statisticians, and we thought this was the most appropriate way to do this. It doesn't really affect our time lines at all because we think both cohorts are going to go through, and we'll have both a monotherapy and a combination.

I'll just add one more thing, and that is that these are important cohorts, assuming cetuximab can add efficacy, but it also remember, cetuximab brings about an 80% burden of it. It's a different kind of a rash than you see with some of the pan-RAS inhibitors. The cetuximab rash is so-called acneiform, and it's actually really well controlled with, frankly, standard acne medicines plus steroids. So a lot of the patients will go on prophylactic minocycline or doxycycline, and that can really mitigate these rashes. But it still comes with a rash. And there are patients even with pancreatic cancer who don't want that.

So we think both of these options will be important, and we think we can deliver very significant response rates, which will be correlated with durability with this kind of a drug because it doesn't have cumulative toxicities for both of these cohorts, and we'll have 2 different options for patients.

Michael Schmidt: Okay. And then cetuximab is clearly an interesting choice, I think, in PDAC, but any plans to potentially evaluate combination of 7375 with an investigational pan-RAS inhibitor?

Daniel Paterson: We're absolutely considering that, and we're in discussions with folks. We have generated and continue to generate some interesting data in that regard. So we're absolutely looking into that. That said, frankly, there's a lot of different pathways that deserve study in now that we seem to have made a dent in pancreatic cancer, and we're considering multiple other options as well.

Operator: Our next question comes from Faisal Khurshid with Jefferies.

Faisal Khurshid: I wanted to ask about the GenFleet partnership. So when you guys did the partnership, I think you had 3 RAS programs that you were eligible to in-license. And if you look at the GenFleet pipeline, they have the G12D, the G12C and the multi-RAS. Can you confirm if you guys are able to license the multi-RAS and what the considerations around that could be?

Daniel Paterson: Yes. This is Dan. So those 3 molecules were not -- well, except for the G12D, which we developed together with them and chose the lead. The other 2 programs were not officially part of the original collaboration. We continue to have discussions for us to jump into the pan-RAS space right now. We'd have to be convinced that it was a differentiated molecule and that, frankly, that combining G12D and pan-RAS is actually the preferred path we might want to go down. And we think we have so many other options. We're still considering it, but there are a lot of other options to look at for combination.

Faisal Khurshid: Got it. But you do have 2 more molecules that you can get from GenFleet under the current deal?

Daniel Paterson: We do, and we've not disclosed those targets yet.

Operator: Our next question comes from Leonid Timashev with RBC.

Leonid Timashev: I wanted to pivot maybe to the commercial side of A+F. Really appreciate the color on sort of how you see the commercial strategy evolving. But I guess I'm curious if you could provide more details on how you'll actually affect those changes. I mean is there a different way the sales force is going to message? Are the promotional materials going to be different? Are the regions going to shift? I guess how do you actually drive towards those goals that you laid out?

Daniel Paterson: No, that's a great question. And the short answer is I'll accept the last one. So we did add 2 additional sales positions, and that was really driven by the fact that 2 of the regions were just too big. And so we said all along we were going to rightsize the launch. We were in the process of doing a deep dive. We're about 6 months in when we got to the end of the year.

We had that seasonal issue, which frankly, impacted refills more than initial scripts, and it was reauthorizations and things like that, that would push things from January into February We actually had some patients we had to put on free drug for a month until things got sorted out. And so when I -- when we talk about the focus for 2026, some of it was just additional training. Some of it is making sure that we're putting the right amount of effort into the visits after the first prescription and not putting all our effort into getting a prescription.

And then implemented a number of different steps with information flow between the specialty pharmacy and really our integrated force, which is both the sales team and the med affairs team to make sure that when there's a delay, and we increased the number of calls to patients so that we are in touch with what's going on with the patient. But also a very deliberate link where if there's a dose delay, somebody is calling on the practice, whether it's med affairs or the sales rep to both find out what's going on and then reinforce the messaging that came out of the SGO meeting recently.

We had 2 big events at the SGO meeting, which that and IGCS tend to be our 2 big meetings of the year. We had the long-term update to RAMP-201, which showed durability and no increase in side effects with cumulative use over a long period of time. But also, we had a poster on the importance of dose intensity. And one of the things that you're able to do in a clinical trial when you're interacting in a very regular basis is make sure you're reinforcing the protocol rules, which is if there's a side effect, you delay the dose and you restart at full dose. That works really well with this drug.

I think we were finding with MedOncs in particular, who are used to the dynamics for chemotherapy are a little different where you may get a response earlier and side effects are cumulative, where with this treatment, you tend to get early side effects, and they tend to be predictable things and things that the patient knows they're coming can be dealt with and then the response becomes later. And so really reinforcing the messaging and really the sharing of data on how important it is to get the patient through that first 3 months or so, so they get the benefit of the treatment. And then we talked about the new campaign that we rolled out.

That's something that had been in the works for a little over 6 months. When you launch with accelerated approval, you're limited in what you can talk about in the early days. And so this was really our next wave of the promotional campaign that had been planned from the beginning and really reinforces the importance of getting on this treatment early. I think there's another dynamic going on is also at SGO, there was an early report of a frontline LGSOC study that compared platinum-containing chemotherapy followed by as part of the same regimen, an AI versus an AI only. And the combination won out.

And I think you're going to start seeing patients as standard of care based on the data that just came out that will get the platinum-based chemotherapy followed by AI as frontline therapy. And I think that really sets us up very nicely to be the next therapy that patients get after that.

Operator: Our next question comes from Graig Suvannavejh with Mizuho.

Samuel Lee: This is Sam on for Graig. Congrats on the quarter. Maybe one on 7375. So how should we be thinking about the cadence in terms of the timing of readouts? Is there a specific program or indication that you see as, I guess, the most likely path for successful registration-enabled readout and data?

Daniel Paterson: Sam, thanks for the question. I'll start, and then I'll turn it over to Julissa to give more specifics on what we'll have when. We believe all 3 of those indications are important for patients and places where our drug, we believe, will work quite well based on preclinical data. So they're all moving forward in parallel. Our goal is to have those Phase II studies largely accrued by the end of this year and then move forward as quickly as possible. Obviously, there's a lot of movement in PDAC. We're going to have to monitor.

We are in an enviable position as a company of our size that we have multiple programs in PDAC, and we're going to have to see how both of those develop to make some decisions on how best to prioritize things while staying right on top of what's going on in the competitive space because obviously, there's a lot going on in PDAC. And then for CRC and lung cancer, again, the preclinical data is really exciting. If you look at the GenFleet data in second-line lung cancer, 50 -- or 69% response rate we're seeing unprecedented response rates as a single agent. We're starting to see that we can combine nicely with other agents.

And so we've got a lot of choices to make around the frontline path in a very short period of time. But while we do that, and we will be doing frontline Phase III studies, we will continue to push forward very aggressively on those potential accelerated approval paths.

Julissa Viana: I'll just add just with that. Yes. I think just to reiterate what we said on the call about the timing, again, the update in the first half will show progress on enrollment. We'll share some more mature safety profile data since the one that we provided back in March. And we'll provide some patient cases so that you can get a sense of the efficacy that we're seeing. And then in the latter half of the year, again, the goal is more comprehensive data set, double-digit patient numbers across the tumor types, ideally at the go-forward dose, looking both at mono and combo data sets.

So we can make some decisions at that point, looking at all of the variables that were just mentioned.

Daniel Paterson: Yes. In the first half data release, we'll have much -- we'll have more data on PK. And as Michael mentioned during his prepared remarks, this is the first time we've disclosed that in the U.S., we are seeing better PK at 900 than 600. And that's both AUC, which is kind of, I guess, the standard measure folks would normally use. But because of the residence time or time on target, being about 24 hours, we actually think Cmax matters a lot. So it can come out of the blood and still be actively blocking the target, and Jon Pachter presented some really elegant work at AACR last meeting recently.

And so we think by seeing that PK going up with the dose, we think it just further strengthens the case for pushing that 900-milligram dose, especially since we are seeing that it's tolerable.

Operator: Our next question comes from Andres Maldonado with H.C. Wainwright.

Andres Maldonado: Congrats on the progress. Two for me for 7375. First, so in the non-small cell lung cancer, you're including an asymptomatic untreated brain metastases cohort. So curious there, is the goal mainly to show systemic activity in a difficult subgroup? Or is there potential to -- do you guys think you have enough CNS exposure to support a differentiated intracranial profile that extends beyond that tissue type? And then second question, kind of a macro question. So earlier this quarter, we saw a pan-RAS program report a Grade 5 pneumonitis given the historical trends also seen with approved G12C, how should we be thinking about these events through the lens of an on-off G12D or other strategies targeting G12D?

Daniel Paterson: Michael, do you want to take those?

Michael Kauffman: Sure. So first on the question of the brain mets. The systemic activity of the drug will be in lung cancer generally is being evaluated now at 600 in the ongoing Phase I, and we will be doing the 900 in the Phase II, as you see, as you saw from the deck that we had along with the prepared remarks. There is a separate cohort because, obviously, when you're trying to ascertain the value of the drug, systemically, you tend not to pick patients with metastatic brain disease. That said, lung cancer frequently goes to the brain, unlike colorectal and unlike pancreatic cancer. And so in lung, it's especially important to try to see if there's substantial brain activity.

The drug does penetrate the brain. I believe GenFleet reported that 2 out of the 5 patients that they had who had asymptomatic brain mets had systemic responses to the drug. We haven't been able to ascertain exactly how much the brain mets may have shrunk, but the brain mets clearly did not progress because they wouldn't have been responsive if they had. So this cohort of about 25 patients will be treated at 900, which is a higher dose than GenFleet is able to obtain to see if we can control the brain mets.

And you all know about avutometinib and some of the other amazing therapies that also cross the blood-brain barrier and really can help these patients do very well over time by preventing or treating brain mets. So that's a starting point for potential for this drug that may differentiate it from others. And to reemphasize what Dan said, the fact that we're able to deliver such good systemic levels that are very tolerable so far with the 900 gives us a good shot at being able to drive enough of the drug into the brain and do something about this.

As far as pneumonitis is concerned, we have not seen any cases of pneumonitis that were believed to be caused by the drug. I believe that they -- that we may have a treatment unrelated pneumonitis case in a patient who already received radiation and it was thought to be a radiation associated, but it was grade 1, and it had 0 impact at all on anything we've seen. We've certainly not seen any kind of pulmonary symptoms with our drug that give us any pause.

That said, we'll be treating a large number of patients with previously treated lung cancer, many of whom have received chest field radiation, many of whom have had one or more infections, all of which predispose you to downstream lung events. We're obviously hopeful we're not going to see that. And lastly, we do not believe, based on our tox studies, there's any drug-related risk of pneumonitis, but that remains to be seen, but nothing important so far.

Daniel Paterson: And just to amplify Michael's comments about pneumonitis, we do have access to the entire PV database at GenFleet. And when we heard these events with some of the other drugs, we did a deep dive. And so his comments are informed by that work that's been done.

Operator: Our next question comes from Yuan Zhi with B. Riley.

Yuan Zhi: Maybe one question on the combination of 7375 plus EGFR inhibitors in the PDAC indication. So with this incremental addition of EGFR inhibitor, which normally patients cannot get because of baseline KRAS mutation, what kind of incremental efficacy you guys are looking to justify the addition of this agent considering the safety liability with this EGFR inhibitor?

Daniel Paterson: Michael, do you want to take that one?

Michael Kauffman: Sure. There's 2 components to this. One is the overall response rate, of course. And the second very important one is durability. It is -- we do believe, and we have some early data that could support that hypothesis that we could deliver a higher response rate. We -- it's too early yet to say whether we would have an increased durability of response. That said, the mechanism of action of cetuximab is to block -- specifically block not only a growth pathway. It's an accessory growth pathway for sure, for RAS-driven cancers. It's not the primary one.

But when you block RAS in these cancers, including pancreatic and colorectal and probably some of the other gastrointestinal tumors, the EGFR pathway becomes much more important and blockade of that can be helpful, again, upfront, but also to prevent the development of resistance and running growth pathways through the EGFR pathway. So this could have impact on both sides of this. We will know fairly soon what kind of incremental we'll have. I can't give you a real number. I think what we'd like to do is say that if there are probably patients who would benefit from cetuximab from the get-go. We don't know who they are.

And there'll be other patients who might benefit from down the road after, say, 8 or 9 or 12 months on our drug, if they started to develop resistance, one could imagine adding cetuximab. We think that this development plan that we expect could support accelerated approvals could lead to availability of this combination regimen, maybe not upfront in everybody, but certainly as an option for patients if they start to see progression of their tumor as well as for some patients upfront. So I think this provides a lot of flexibility. This is not an option for most of the pan-RAS inhibitors because the strong concerns about added rash here.

And I think for the 40% of patients who have PDAC that's G12D and the 20% of patients that have colorectal cancer that's G12D that this could be a really important addition either upfront or down the road.

Operator: Our next question comes from Jeet Mukherjee from BTIG.

Jeet Mukherjee: Two for me. You certainly mentioned that 900 mg is looking like a very suitable go-forward dose. But I was just wondering if you could elaborate a bit further on why this hits the sweet spot. It looks like 1,200 mg is certainly still under evaluation. Was there some limiting factor with that dose perhaps? And then the second question was just related to the target studies. I think you've definitely mentioned that these are designed to be supportive of approval. Have you reached some degree of alignment with the agency on what the bar for approval is? It looks like ORR is a primary endpoint across several of the studies. Is there some threshold you need to exceed?

Any details there would be helpful.

Daniel Paterson: Michael, do you want to take those?

Michael Kauffman: Sure. So just to be really -- it's a simple answer for 1,200. The capsules that we have right now -- I'm sorry, the pills that we have right now are 100-milligram pills. Asking patients to take 9 of these to give you 900 mg is the upper limit of what they can really handle in one swallow, if you will, or one session, if you will. For the 1,200, we're going to a split session of 6 and 6 split by about 30 minutes because we ask people to take it with food and plenty of water and so on to make sure it gets down there and everything.

So it's just impractical to go much above 1,200 with the current pill size. That said, we are certainly in the midst of constructing larger pills, which we'll update you guys on when we have that to a point where we think it's real. And hopefully, we won't be -- we don't expect to be marketing this as 100-milligram pills. We expect to be marketing it with higher pill sizes so that we don't have to give people that much. So it's pretty simple and straightforward. Once we have the larger pills, depending on what we see with 1,200, we may consider going higher. But right now, 1,200 is it.

As far as FDA's threshold, I mean, we have not had any discussions with them specifically about what this is. But thankfully, and I think the oncology division of the FDA has been superb about this, particularly for molecularly defined subsets of cancers. They have routinely approved drugs as low as 25%. Typically, the 25% to 30% ORR range is what's approvable as a single-arm study, provided there is sufficient durability. If you go to ASCO, most experts will tell you they want to see at least 6 months duration of response. You all keep in mind that, that's 6 months plus the 1.5 months minimum, it takes to get to a response.

So you're talking 7.5 to 8 months at least on the drug, which for these kinds of tumors is pretty impressive, particularly in heavily pretreated patients. I think those are kind of the thresholds you should be thinking about 30% on the ORR number and 6 months durability, but those are general numbers, and it's always a review issue with the FDA.

Operator: And our final question comes from James Molloy with Alliance Global Partners.

Matthew Venezia: This is Matt on for Jim today. Just 2 from us. In terms of the launch for A&F, the reimbursement for KRAS undefined and KRAS wild type, is that continuing at similar rates from previous quarters?

Daniel Paterson: Yes, we've seen no change.

Matthew Venezia: Okay. Excellent. And then do you guys have any anecdotes from treating doctors whose patients have been on treatment for over 8 or 9 months at this point? And if you could share, that would be very helpful.

Daniel Paterson: Sure. I mean it's anecdotal at this point, given the fact we've only been out for just a year now. But there are patients that have done quite well that are both wild-type and mutant. And we also continue to interact with the sites on RAMP-201. And I recently spent some time with a patient that's been -- never achieved a PR with stable disease, but had a really transformational change in her ability to do things. She went from not being able to vacuum or living room to running a 5k and has been on our drug for, I believe, 3 to almost 4 years now.

And so we do have a lot of anecdotal information, even going back to the FRAME study, we had a number of patients staying on for a long time. So we do think when it's the right patient that we'll recapitulate what we saw in the clinical trial. As you may recall, in RAMP-201, we had patients from anywhere from 1 prior therapy to 10 prior therapies. And it tends to be less, I think -- of course, the more prior therapies you have, the more challenged the patient has. But I think the big difference in the real world versus the clinical trial will be performance status. In most clinical trials, you're limited to performance status 01.

And obviously, in the commercial setting, you take anybody who wants to come on the drug. And even though we did hear instances of patients going on cycle and coming off and then you can say, well, they probably shouldn't have gone on the therapy. We've also heard anecdotal stories of patients that were pulled out of hospice put on the drug and did well for a number of months and got a number of months with good quality of life they wouldn't otherwise wouldn't have had. And so those are great stories to hear, and we continue to monitor those. And we're very excited about the franchise.

I think we've uncovered some things from seasonality, plus you learn as you go through the launch, and I think we've made some course corrections that it may take a couple of months to see the full benefit of. But I will say with confidence, we already are sure that we will see an increase from Q1 to Q2 that was bigger than the Q4 to Q1.

Operator: Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.