Verastem (VSTM) 8th Annual Wolfe Research Healthcare Conference summary

Drug differentiation

• VS-7375 is positioned as a potent, highly KRAS G12D-selective dual on/off inhibitor with a long residence time; speakers said selectivity supports tolerability and sustained target coverage during dose interruptions for GI adverse events.

• Speakers said maximal target inhibition and stronger KRAS G12D variant allele frequency reduction distinguish the drug, alongside single-agent activity they view as important for durable responses.

• Speakers see the field shifting toward variant-selective agents; they argued that single-agent activity matters even when combinations are planned, since chemotherapy doses may be reduced or stopped over time.

Dose and clinical benchmarks

• Disclosed data show a dose-response relationship from 600 to 900 mg, with dose-proportional PK and identical tolerability; 900 mg is the go-forward dose across cancer indications.

• In waterfall plots, speakers said 900 mg showed no tumor-growth best responses across indications, unlike occasional cases at 600 mg.

• For previously treated PDAC, the 900 mg benchmark is >40% single-agent activity and PFS north of 7-9 months; PFS follow-up for the disclosed 22-patient dataset is planned for a future medical conference.

• In lung cancer, 600 mg showed a 43% confirmed response rate; KOLs view an approximately 15-point ORR difference with longer PFS as clinically meaningful, while the stated goal is best-in-class efficacy at 900 mg.

Combination strategy

• TARGET-D 301 includes chemotherapy-based gemcitabine/nab-paclitaxel and chemo-free cetuximab regimens; either arm can be positive, and speakers said the trial does not require both to succeed.

• Cetuximab has preclinical rationale and early clinical signals in PDAC, including responses at subtherapeutic doses and faster, deeper responses at higher doses; comparative evidence is expected before the main TARGET-D 201 cohort reads out.

• DLTs have been cleared for 900 mg with anti-EGFR and gemcitabine/nab-paclitaxel; dose clearing with frontline colorectal and lung chemotherapy or chemo-IO combinations is ongoing.

• A clinical trial combining VS-7375 with Erasca's pan-RAS inhibitor is expected to start in 2027; discussions on a PRMT5 combination are advanced, with MTAP-deleted G12D PDAC a potential focus.