Verastem (VSTM) investor relations material

Study overview and development

• TARGET-D 101 Phase 1/2 enrolled >200 patients with advanced KRAS G12D-mutated solid tumors; 900 mg QD is advancing across tumor types, with 1,200 mg QD evaluation ongoing. Efficacy cutoff was Oct. 7, 2026.

• VS-7375 is an oral, selective KRAS G12D on/off inhibitor; 900 mg exposures reached or exceeded preclinical efficacy targets, with dose-proportional exposure reported in the U.S. update.

• FDA-aligned 1L mPDAC Phase 3 design has three arms: 900 mg QD plus anti-EGFR, 900 mg QD plus gemcitabine/nab-paclitaxel, or chemotherapy; PFS and ORR are dual primary endpoints, OS secondary, with crossover after progression.

• Phase II enrollment in PDAC and CRC was expected to complete by end-2026; initial 2L PDAC data were expected in Q2 2027, with NSCLC and CRC data in 2H 2027.

• The 1L mPDAC Phase 3 trial was planned to open by year-end 2026; 1L NSCLC and CRC pivotal trials were planned for H1 2027, subject to FDA discussions on trial designs. Fast Track Designation was granted in advanced/metastatic PDAC and NSCLC.

Pancreatic cancer

• At 900 mg QD, confirmed ORR was 41% (9/22) in 2L+ mPDAC, including 50% (4/8) in 2L and 36% (5/14) in 3L/4L; the 2L+ cohort included two complete responses, one confirmed and one unconfirmed.

• In 2L+ PDAC, DCR was 86%, 6-month landmark PFS was 67%, 6-month landmark OS was 80%, and 16/22 patients remained on treatment; median follow-up was 6.4 months.

• Among 12 evaluable patients with detectable baseline ctDNA, all had ≥50% KRAS G12D VAF reductions, 11/12 had ≥90% reductions and 7/12 cleared detectable ctDNA by cycle 3 day 1; 15/17 with elevated baseline CA19-9 had >50% reductions.

• An investigator-reported patient had pain relief within one week; a separate heavily pretreated patient stopped morphine and later achieved a confirmed partial response exceeding 50%.

Colorectal and lung cancer

• In 3L+ mCRC, 900 mg QD plus cetuximab produced a 33% ORR (2/6), including one confirmed and one unconfirmed response; five patients remained on treatment, and Phase 2 enrollment was ongoing.

• In 2L+ NSCLC, 600 mg QD monotherapy produced a 43% confirmed ORR (10/23); 6-month landmark PFS was 72%, median PFS was not reached, and 17/23 patients remained on treatment.

• In 1L KRAS G12D lung adenocarcinoma, 600 mg QD with platinum-pemetrexed, with or without pembrolizumab, showed a 75% ORR (6/8); six patients remained on treatment.

• All five evaluable 2L+ NSCLC patients with detectable baseline KRAS G12D ctDNA achieved complete ctDNA clearance on 600 mg QD monotherapy.