Mersana Therapeutics Narrows Focus to B7-H4 ADC, Cuts Workforce by 55%

Mersana Therapeutics, a Massachusetts-based biotech company, has announced a significant restructuring plan to extend its cash runway and focus on its lead antibody-drug conjugate (ADC) program, emiltatug ledadotin (Emi-Le). The company will lay off 55% of its workforce and reduce internal research and development efforts to prioritize the development of Emi-Le, which targets B7-H4.

Strategic Realignment and Workforce Reduction

Mersana's decision to streamline operations comes as the company seeks to extend its cash runway into mid-2026. The restructuring will involve:

• Laying off 55% of employees by the end of the third quarter of 2025
• Reducing research activities and eliminating internal pipeline development efforts
• Focusing resources on generating safety, tolerability, and clinical activity data for Emi-Le in breast cancer
• Continuing dose escalation for XMT-2056, a HER2-directed ADC optioned by GSK
• Maintaining support for existing collaborations with Johnson & Johnson and Merck KGaA

This move marks a significant shift for Mersana, which ended 2024 with 102 full-time employees. The company had previously halved its workforce less than two years ago following the failure of its former lead candidate.

Emi-Le: Mersana's New Focal Point

Mersana's restructuring centers around the development of Emi-Le, an ADC targeting B7-H4. Key aspects of the program include:

• Initial phase 1 data shared in January 2025
• Ongoing expansion portion of the study in triple-negative breast cancer patients
• Potential differentiation from competitors due to its proprietary dolasynthen payload

The B7-H4 space is highly competitive, with companies like AstraZeneca, BeiGene, and GSK also developing ADCs in this area. However, most rival candidates use topo-1 payloads, potentially allowing Emi-Le to carve out a niche in patients previously treated with topo-1 ADCs.

Pipeline and Collaboration Updates

While focusing on Emi-Le, Mersana will continue to advance other key programs:

• XMT-2056: GSK paid $100 million upfront in 2022 for an option on this HER2-directed ADC. Mersana must complete dose escalation with enrichment for breast cancer patients in a phase 1 single-agent trial to support GSK's opt-in decision.
• Ongoing collaborations: The company will continue to support partnerships with Johnson & Johnson and Merck KGaA, although specific details were not provided.

Mersana's 2025 timeline includes anticipated data readouts from Emi-Le dose escalation and backfill cohorts, as well as initial clinical pharmacodynamic STING activation data for XMT-2056. These results will be crucial in revitalizing interest in the company, whose share price has dropped to $0.36.