Verastem (NASDAQ:VSTM) executives highlighted commercial momentum for the company’s newly launched ovarian cancer therapy and laid out near-term clinical catalysts across its RAS-pathway pipeline during a fireside chat hosted by Guggenheim Senior Biotech Analyst Michael Schmidt. President and CEO Dan Paterson and Chief Scientific Officer Jonathan Pachter discussed uptake of the company’s low-grade serous ovarian cancer (LGSOC) regimen and provided updates on the confirmatory RAMP 301 trial, pancreatic cancer program RAMP 205, and the company’s KRAS G12D inhibitor program, VS-7375.
Commercial launch: early growth and broad adoption in LGSOC
Paterson said Verastem’s commercial product launch has been “successful” through its first three quarters on the market. He stated the company beat analyst consensus “three quarters in a row” and reported that sales increased by more than 50% from Q2 to Q3 to Q4. While questions around seasonality remain, he said the company does not yet have enough history to determine whether seasonality is a factor.
On prescribing dynamics, Paterson said the company is seeing “pretty broad adoption” across major academic centers and large practices as well as community settings. He described a commercial approach focused on large national practices and their infrastructure, with outreach to key gynecologic oncologists and engagement through group purchasing organizations (GPOs).
Reimbursement and on-label vs. off-label use
Paterson said Verastem has been “relatively pleased” with reimbursement trends for a new-to-market product that generally requires prior authorization. He noted reimbursement has occurred for both on-label use (KRAS mutant) and off-label use (KRAS wild type). He added that early in launch the company saw some “really off-label” use in pancreatic, lung, and brain cancers, though he said that has declined and was not included in the company’s model; he also said those patients tend not to remain on therapy as long as on-label LGSOC patients.
Regarding KRAS wild-type LGSOC specifically, Paterson said it is difficult to quantify the mix because prior-authorization information may list KRAS mutant, KRAS wild type, or KRAS “unspecified,” with the unspecified portion running higher than expected. He said the company is seeing reimbursement for unspecified and wild-type cases.
He also described an evolution in distribution strategy: Verastem initially launched through specialty pharmacies, which Paterson said are “really, really good at getting reimbursement,” and later opened specialty distributors tied to GPOs and large practices. He said the company is advising practices to use specialty pharmacy for an initial prescription and then transition to the practice’s own pharmacy workflow.
Paterson added that following the initial period after accelerated approval, Verastem is launching a new campaign centered on positioning the regimen as the “preferred therapy” after frontline progression.
NCCN guidelines and RAMP 301 confirmatory trial timing
Asked about potential inclusion in NCCN guidelines, Paterson said Verastem has been told to expect it “early this year,” but noted the company is not permitted to ask for timing. He said NCCN inclusion could provide incremental benefit, but framed the primary focus as delivery of confirmatory trial results.
Paterson said the randomized confirmatory trial, RAMP 301, has completed accrual and is designed against standard-of-care therapy. The trial includes both KRAS mutant and KRAS wild-type patients, with progression-free survival (PFS) as the primary endpoint and an overall survival endpoint as well. He anticipated a readout “around mid-next year, maybe even a little earlier.”
He also noted Verastem has two publications that include both KRAS mutant and wild-type data, and said the earlier FRAME study used to support FDA Breakthrough Therapy Designation showed a higher response rate in wild-type patients than the RAMP study, which he said makes the company feel “pretty good” about the confirmatory effort.
RAMP 301 enrollment increase and Japan bridging study
Paterson addressed prior scrutiny related to an enrollment increase in RAMP 301. He said the trial was designed with a pre-specified ability to resize based on actual results because the study began before final RAMP 201 results were available and because historical comparators involved different patient populations without prospective separation by KRAS status.
Because enrollment proceeded faster than expected, Paterson said Verastem conducted the interim assessment earlier than the originally planned 50% of events to avoid pausing the trial and risking site disengagement. To maintain a conditional power of 85% despite having fewer events at interim, he said the company added roughly 30 patients, increasing enrollment from 270 to 300. Paterson said the data monitoring board recommended adding patients to both the wild-type and mutant groups, which he described as indicating both were in a “zone of goodness.”
Paterson also referenced a Japanese bridging study conducted in “all comers” and said the company was “really happy” the results were consistent with the larger study. He said the company plans to add additional Japanese patients so that Japan represents about 15% of the confirmatory population. Paterson said Verastem expects to pursue conditional approval in Japan based on the bridging study and full approval based on the confirmatory trial, adding that conditional approval should not create reimbursement differences once obtained.
Pipeline expansion: pancreatic triplet and KRAS G12D program
In pancreatic cancer, Paterson discussed RAMP 205, which evaluates avutometinib and defactinib in combination with gemcitabine and nab-paclitaxel in frontline metastatic pancreatic ductal adenocarcinoma. He emphasized a key operational finding across five cohorts: maintaining full-dose gemcitabine/nab-paclitaxel on the full schedule materially impacted response rate, while modifying chemotherapy dosing reduced responses. Paterson cited an 83% confirmed response rate presented at ASCO based on 12 patients, which he called “unprecedented” in PDAC. He said the cohort has since been expanded to 29 patients, with a mid-year update expected to include durability, with more than six months of follow-up for all patients.
On the KRAS G12D inhibitor program, Pachter highlighted VS-7375 and described data generated by partner GenFleet in China, where he said more than 200 patients have been enrolled. He cited GenFleet-reported response rates of 58% in second-line pancreatic cancer and 69% in advanced metastatic lung cancer. Pachter attributed differentiation to three factors he said are important for this class: a “dual on/off profile,” strong bioavailability, and a long target residence time.
Addressing tolerability concerns discussed previously in the market, Pachter said Verastem’s goal in the U.S. trial is to maintain best-in-class efficacy while improving tolerability, and he said early U.S. dose-escalation cohorts did not show nausea, vomiting, or diarrhea above grade one. He said tolerability in the U.S. study appears better than what was reported in the Chinese trial, potentially enabling higher dosing; while GenFleet advanced 600 mg once daily, Pachter said Verastem is considering whether 900 mg once daily could be feasible.
Executives said Verastem has completed single-agent dose escalation at 400 mg, 600 mg, and 900 mg once daily without dose-limiting toxicities. The company has taken 600 mg into single-agent expansion cohorts in second-line pancreatic cancer, advanced lung cancer, and a tumor-agnostic cohort that includes biliary tract cancers, and is advancing a cetuximab combination strategy for second- and third-line colorectal cancer. They also described longer-term plans to evaluate frontline settings, including combinations with chemotherapy (and pembrolizumab in frontline lung) and the potential inclusion of a single-agent arm.
For upcoming disclosures, management indicated it expects to share additional mid-year data from the RAMP 205 pancreatic program and VS-7375 U.S. phase I work, likely via a company-sponsored event, with updates dependent on enrollment and data maturation.
About Verastem (NASDAQ:VSTM)
Verastem Oncology, Inc is a clinical-stage biopharmaceutical company focused on the discovery and development of small molecule therapies that target cancer stemness and resistance pathways. Established in 2010 and headquartered in Needham, Massachusetts, Verastem Oncology applies a precision-medicine approach to identify key signaling nodes responsible for tumor growth and relapse, with an emphasis on hematologic malignancies and solid tumors. The company’s research platform integrates insights into complex signaling networks to advance novel compounds from early discovery through clinical proof of concept.
The company’s lead marketed product is COPIKTRA (duvelisib), an oral inhibitor of PI3K-delta and PI3K-gamma, which received U.S.
