Mersana Therapeutics at TD Cowen Summit: Strategic Updates on Oncology Innovations

Mersana Therapeutics presented at TD Cowen’s Oncology Innovation Summit, focusing on their EMILI drug for B7-H4 expressing tumors. EMILI showed a 31% overall response rate (ORR) across all tumor types in the intermediate dose range, and the company is implementing Protocol Amendment 5 to mitigate proteinuria, a common side effect. Future pivotal trials will likely favor a randomized design to expedite time-to-event analysis and include a control arm, with the company aiming for a response rate above 20% in upcoming trials to demonstrate clinical benefits, compared to a 5% rate in the control arm.

Analysis

Mersana Therapeutics (NASDAQ:MRSN) presented an update on its oncology drug candidate, EMILI, targeting B7-H4 expressing tumors, at TD Cowen’s 6th Annual Oncology Innovation Summit. The company reported a 31% overall response rate (ORR) across all tumor types in the intermediate dose range for EMILI, an encouraging signal for its Dolasynthen platform, designed for a differentiated safety profile by avoiding common ADC-related toxicities like neutropenia and neuropathy. A key operational development is Protocol Amendment 5, aimed at mitigating proteinuria—a side effect observed, particularly at high doses, and attributed to the auristatin payload class—by allowing treatment continuation with ACE inhibitors/ARBs for asymptomatic patients; early physician feedback is reportedly positive. Mersana is strategically adjusting its B7-H4 expression assay to establish a commercial standard for patient selection. For future pivotal trials, the company is contemplating a randomized design with a control arm, pending FDA discussions, which could expedite time-to-event analysis and potentially negate the need for a separate confirmatory trial. The target population for these trials includes TNBC patients with one to four prior therapies, notably those post-topoisomerase (topo) based ADCs, a segment with significant unmet need, especially as drugs like Gilead's Trodelvy move into earlier lines of therapy. Mersana aims for an ORR exceeding 20% against an anticipated 5% in the control arm. The upcoming ASCO presentation will provide further data on non-breast cancer patients using the same March data cutoff as the ESMO breast presentation, while more definitive data on high-dose regimen efficacy and proteinuria mitigation is expected in the second half of the year. The company clarified that the 31% ORR was observed in B7-H4 high evaluable patients at intermediate doses, and the focus for ASCO will be these intermediate dose patients, with some high-dose backfill patients treated under the original proteinuria protocol also included.

Key Decisions for Investors

• Monitor Mersana's upcoming ASCO presentation for detailed data on EMILI in non-breast cancer cohorts and the subsequent H2 2024 update for crucial insights into high-dose efficacy and the effectiveness of proteinuria mitigation strategies.
• Evaluate the company's progress with Protocol Amendment 5, as successful management of proteinuria is critical for optimizing EMILI's therapeutic window, particularly at higher, potentially more efficacious doses.
• Closely track communications regarding FDA feedback on the proposed randomized pivotal trial design, as this strategy could significantly de-risk and accelerate the path to market if aligned upon.
• Consider the growing unmet need in post-topo ADC settings for TNBC, where EMILI's 23% response rate in late-line, highly refractory patients who had seen a prior topo payload (rising to 29% in the specific pivotal trial target population) presents a competitive differentiator if sustained in larger trials.
• Assess the risk-reward profile, balancing promising early-stage ORR data and strategic clinical development adjustments against the inherent uncertainties of oncology drug development, including final pivotal trial outcomes and regulatory approvals.