KRAS G12D Inhibitor Shows Multi-Cancer Activity; Gilead and Zealand Strike Major Deals | Industry News
Three industry developments: Verastem's KRAS G12D inhibitor VS-7375 posted a 50% confirmed ORR in 2L pancreatic cancer; Vir and Gilead struck an up-to-$1.875B PRO-XTEN dual-masked T-cell engager pact; Zealand and Generate Biomedicines signed a near-$1.2B AI protein-drug collaboration.
Several biopharma developments stood out this week: a potential best-in-class oral KRAS G12D dual ON/OFF inhibitor reported multi-cancer clinical data, and two major partnerships around next-generation T-cell engagers and AI-designed protein drugs were announced.
KRAS G12D inhibitor VS-7375 reports multi-cancer data; 50% confirmed ORR in 2L PDAC
Verastem Oncology reported updated data from the Phase 1/2 TARGET-D 101 study of oral KRAS G12D inhibitor VS-7375 in advanced KRAS G12D-mutant solid tumors. Among second-line pancreatic ductal adenocarcinoma (PDAC) patients receiving 900 mg once-daily monotherapy, the confirmed objective response rate (ORR) reached 50% (4/8); across the 2L and later-line population the confirmed ORR was 41% (9/22), with two complete responses. TARGET-D 101 is a multicenter, open-label, dose-escalation and expansion Phase 1/2 study that has enrolled over 200 patients. In 22 2L/later-line PDAC patients, disease control rate was 86%, 6-month progression-free survival 67%, and 6-month overall survival 80%. VS-7375 is a potential best-in-class oral KRAS G12D dual ON/OFF inhibitor binding both active and inactive KRAS G12D; among 48 patients on 900 mg daily, discontinuation due to adverse events was 2% and grade-3 treatment-related events 10%, with no clinically meaningful cumulative toxicity. Verastem aligned with the FDA on a Phase 3 design in first-line metastatic PDAC and plans to start by end of 2026.
Up to $1.875B: Gilead enters dual-masked T-cell engager collaboration
Vir Biotechnology announced a collaboration and license agreement with Gilead Sciences to discover and develop three dual-masked T-cell engagers (TCEs) targeting solid-tumor-associated antigens. Vir will receive $90M upfront and equity investment, up to $450M in near-term preclinical milestones, and up to $1.74B in downstream development, regulatory and commercial milestones. The collaboration leverages Vir's PRO-XTEN dual-masking technology and AI-based dAIsY platform. Conventional TCEs bind tumor antigen and CD3 to redirect T cells, but in solid tumors are limited by systemic immune activation and toxicity. PRO-XTEN keeps the TCE relatively inactive in circulation; tumor-associated proteases cleave the mask in the tumor microenvironment to release activity, and the platform can also extend half-life, broadening the therapeutic window. Vir leads discovery and design optimization of the three candidates; Gilead gets nomination and exclusive rights to advance them, and is responsible for clinical development, manufacturing and commercialization.
Nearly $1.2B milestones: Zealand and Generate sign AI protein-drug pact
Zealand Pharma announced a multi-target strategic collaboration and license agreement with Generate Biomedicines, combining Zealand's obesity and metabolic-disease expertise with Generate's generative-AI platform to design and develop multi-specific protein drugs for obesity and other metabolic diseases. Generate will receive $30M upfront and up to $35M in near-term preclinical milestones; across the two initial programs it is eligible for approximately $1.2B in milestones spanning development, regulatory and commercial stages. Generate's platform pairs generative AI with large-scale experimental validation to design proteins to predefined biological functions and optimize them iteratively; Generate leads discovery through lead candidate selection, and Zealand handles clinical development, regulatory filing and global commercialization.
