Mersana Therapeutics (MRSN) Goldman Sachs 45th Annual Global Healthcare Conference summary

Evolution and innovation in ADC technologies

• ADCs have significantly impacted cancer treatment, but existing platforms face tolerability and efficacy limitations, prompting the development of new payloads and platforms to address these issues.

• Two proprietary platforms, Dolasynthen (cytotoxic) and Immunosynthen (STING agonist), are being advanced to overcome current ADC drawbacks and expand therapeutic applications.

• Dolasynthen is fully synthetic, enabling homogeneous, site-specific ADCs with improved drug-like properties and reduced toxicities compared to earlier platforms.

• Clinical data show Dolasynthen avoids dose-limiting toxicities like neuropathy, neutropenia, and ocular toxicity, allowing for higher efficacy and broader target engagement.

• Immunosynthen delivers a proprietary immune stimulator to tumor and myeloid cells, aiming for targeted innate immune activation with minimized systemic effects.

Clinical programs and data insights

• XMT-1660 targets B7-H4, a biomarker with high expression in several cancers, and aims to address resistance seen with topoisomerase-based ADCs.

• Upcoming data for XMT-1660 will focus on safety, tolerability, and initial efficacy, with biomarker-driven response enrichment, though detailed biomarker cutoffs remain confidential.

• Cross-trial comparisons are limited due to differences in patient populations and prior treatments, but public benchmarks include single-agent chemotherapy and competitor ADCs.

• Combination strategies, such as pairing ADCs with platinum agents, are being explored to move into earlier treatment lines and expand patient eligibility.

• XMT-2056, targeting HER2 with a novel antibody and STING agonist payload, is back in clinical development after dose adjustments following an early adverse event.

Partnerships and business development

• Collaborations include Johnson & Johnson (Dolasynthen, three targets), Merck KGaA (Immunosynthen, two targets), and GSK (option on XMT-2056), with significant upfront payments and milestone opportunities.

• The GSK partnership could lead to a large-scale program with profit-sharing or royalties if XMT-2056 is successful.

• The company remains open to external technologies but is currently focused on advancing its lead programs.