Mersana Therapeutics (MRSN) Leerink Global Healthcare Conference 2025 summary

Company overview and platform innovation

• Focuses on antibody-drug conjugates (ADCs) for oncology, aiming to address limitations of current MMAE and topo-based platforms.

• Developed a novel auristatin payload to avoid neutropenia, neuropathy, ocular toxicity, myelosuppression, and ILD.

• Sees opportunity to innovate with new scaffold linker payloads and target both existing and novel antigens.

Lead program (MME/B7-H4 ADC) clinical progress

• MME is the lead clinical asset, using the second-generation Dolasynthen platform, with ongoing expansion in triple negative breast cancer (TNBC) post-topo.

• Fast track designation received for breast cancer post-topo, targeting a growing patient population with limited options.

• Demonstrated a differentiated safety profile, with reversible grade 3 AST increases and manageable proteinuria, but no neutropenia, neuropathy, ocular tox, myelosuppression, or ILD.

• Achieved a 23% confirmed response rate in heavily pretreated, B7-H4-positive patients, including TNBC post-topo where standard chemotherapy yields ~5%.

Safety, efficacy, and dose optimization

• Proteinuria observed at intermediate and high doses is reversible and not associated with renal failure; mitigation includes prophylactic ACE/ARB use and protocol amendments to allow continued dosing if asymptomatic.

• High-dose cohort (>2 mg/kg) showed promising tumor reductions, but treatment interruptions due to proteinuria limited confirmed responses; ongoing efforts aim to maintain dosing and improve efficacy.

• Innovation in payload design (AF HPA) enables targeted cell killing with limited bystander effect, contributing to improved safety.

• Plans to expand to higher doses (up to 95 mg/m²) later this year, contingent on successful proteinuria management.