Tracing the Signal Beneath the Noise
A Conversation with CEO of Replimune Sushil Patel on the Edge of Immunotherapy
There is a particular kind of vertigo that happens not when science fails, but when it succeeds in ways our legacy instruments weren’t built to judge. This was the core of my recent conversation on Precision Signals with Sushil (Sush) Patel, the CEO of Replimune. Sush spent nearly two decades at Genentech, launching Tecentriq and leading the lung cancer franchise, before moving into the high-stakes world of oncolytic viruses. We traced his career from the academic bench to the boardroom, exploring what it takes to lead at the edge of a field that is constantly redrawing its own boundaries.
We focused on the unique biology of Replimune’s lead asset, RP1. Unlike traditional systemic therapies, RP1 is an engineered virus designed to invade a tumor, destroy it from the inside, and expose its contents to the immune system. The goal is to turn “immunologically invisible” tumors into targets the body can finally recognize and attack. It represents a profound shift in oncology: moving away from treating tumors as static targets to be hit, and toward reprogramming the biology of the entire microenvironment.
The conversation inevitably turned to the regulatory tension currently surrounding the company. After receiving Breakthrough Therapy Designation, Replimune was issued a Complete Response Letter (CRL) from the FDA. This wasn’t a dismissal of the science, but a question of “contribution of components”—how to attribute benefit when two agents are used together in a single-arm trial. Last summer, I wrote about this and explored what this moment reveals about the growing friction between novel biology and traditional evidentiary frameworks.
From Breakthrough to Breakdown: The $900 Million FDA Rejection Letter
We all woke up today (July 22, 2025) to a sobering reality check. The FDA's complete response letter for RP1—Replimune's oncolytic virus therapy—appears to signal the end of an era in oncology drug development, one where scientific promise and unmet medical need could occasionally trump methodological perfection.
Sush and I also discussed the FDA’s recent “Plausible Mechanism Pathway” sounding board in the New England Journal of Medicine. This new signal from the agency suggests a growing openness to using mechanistic rationale to support approvals in areas of high unmet need. As Replimune approaches its new April 10th PDUFA date, the industry is watching closely. This isn’t just about one molecule; it’s a test case for how we bring genuinely novel mechanisms forward in an era where the science is evolving faster than the rules of the road.