Mersana Therapeutics (MRSN) Study Update summary

Study background and rationale

• Emi-Le (emiltatug ledadotin, XMT-1660) is a B7-H4-targeting ADC developed using the Dolasynthen platform to address efficacy and safety limitations of current ADCs, especially in breast cancer where resistance to topo-1 ADCs is emerging.

• B7-H4 is highly expressed in TNBC, HR+ breast, endometrial, and ovarian cancers, with limited expression in healthy tissue; Emi-Le shows no target-mediated toxicities.

• Emi-Le received FDA Fast Track designation for advanced/metastatic TNBC and HER2-low/negative breast cancer post-topo-1 ADC treatment.

• WHO approved emiltatug ledadotin (Emi-Le) as the international nonproprietary name for XMT-1660.

Study design and patient population

• Phase I trial enrolled 130 heavily pretreated patients with TNBC, HR-positive breast cancer, ovarian, endometrial cancers, and ACC1 as of December 13, 2024.

• Median age was 55, with a median of 4.5 prior lines of therapy; 60% had received prior topo-1 ADCs.

• Dose escalation and backfill cohorts explored doses from 7 to 115 mg/m², with expansion at 67.4 mg/m² Q4W in post-topo-1 TNBC.

• B7-H4 expression was retrospectively assessed, with a TPS cutoff of 70 used to define high expression; 43.7% of patients with known status were B7-H4 high.

• Additional cohorts included HR+ breast, endometrial, ovarian, and adenoid cystic carcinoma.

Safety and tolerability

• Emi-Le was generally well tolerated, with no grade 4 or 5 treatment-related adverse events (TRAEs) among 130 patients.

• Most common TRAEs were transient AST increases, low-grade nausea, fatigue, and reversible proteinuria.

• Grade 3 TRAEs occurred in 30% of patients; less than 5% experienced treatment-related serious adverse events, and 2% discontinued due to TRAEs.

• Proteinuria was more frequent at higher doses but generally reversible; mitigation strategies include ACE inhibitors and ARBs.

• No dose-limiting neutropenia, neuropathy, ocular toxicity, ILD, or thrombocytopenia observed.