H.C. Wainwright initiated coverage of Verastem (NASDAQ:VSTM) with a Buy rating and set a price target of $18.00, according to a research note released on Wednesday. The firm’s analyst, Andres Maldonado, placed particular emphasis on the company’s KRAS G12D program and its MAPK CLAMP approach following consultations with academic MAPK pharmacology experts and medical oncologists.
The research note singled out VS-7375 as what the firm described as "one of the most underappreciated aspects of the Verastem story," saying it could emerge as the larger long-term value driver for the company. H.C. Wainwright highlighted the biology underlying VS-7375, noting that the compound is designed to bind both the active GTP-bound and the inactive GDP-bound conformations of KRAS. By engaging both states, the firm said, VS-7375 may enable suppression of the MAPK pathway across the full cycle of KRAS activation rather than relying on transient shifts in equilibrium.
Early clinical data were presented as supportive evidence. H.C. Wainwright cited monotherapy overall response rates of roughly 41% in pancreatic ductal adenocarcinoma (PDAC) across dose levels and about 58% across non-small cell lung cancer (NSCLC) dose levels. The note emphasized particularly strong activity in second-line PDAC patients, where an overall response rate of 58.3% was reported. In NSCLC, the 600 mg dose level showed an approximate 69% overall response rate, including responses in patients with brain metastases and those with adverse co-mutations, according to the research team’s summary.
Beyond VS-7375, H.C. Wainwright framed Verastem’s commercial base around its approved co-pack of avutometinib and defactinib. The firm characterized that co-pack as delivering a more tolerable and durable RAF/MEK clamp combined with a FAK strategy, and suggested it has meaningful adoption potential that could extend beyond low-grade serous ovarian cancer (LGSOC).
In a strategic pivot, Verastem announced it will discontinue the RAMP 203 trial, which had focused on advanced KRAS G12C-mutated NSCLC. The company said that decision followed evaluation of interim data and a reassessment of the evolving competitive landscape for KRAS G12C inhibitors. Verastem intends to reallocate resources to the clinical development of VS-7375, an oral KRAS G12D inhibitor, with plans to target advanced NSCLC and other solid tumors.
To support those development efforts, the company has implemented leadership changes. John Johnson has been appointed chairman of the board, and Michael Kauffman, M.D., Ph.D., has been named president of development. Verastem described these moves as part of a broader push to accelerate its clinical programs.
Separately, Mizuho reiterated an Outperform rating on Verastem and maintained a $15.00 price target following release of interim Phase 1/2 RAMP 203 study data. Mizuho’s commentary noted the study evaluated combinations of avutometinib, defactinib, and Amgen’s Lumakras (sotorasib). While the combination showed efficacy, Mizuho stated it was "not as competitive" when compared with other next-generation G12C inhibitors.
The information in the research notes and company announcements frames a clear near-term strategy for Verastem: concentrate development on VS-7375 and leverage the approved avutometinib/defactinib co-pack as a commercial anchor while senior leadership shifts aim to expedite execution.