Here’s a tough day in biotech: Replimune Group Inc. (REPL) got a formal rejection from the U.S. Food and Drug Administration on Friday for its melanoma therapy. But the company isn’t just taking the "no" quietly—it’s pushing back, hard, and questioning how the FDA played the game.

The agency sent a Complete Response Letter for the Biologics License Application seeking approval of RP1 in combination with nivolumab. Replimune, however, is challenging the assessment. The company argues that the dataset which previously earned it a breakthrough therapy designation should have been enough for an accelerated approval. It’s pointing to results from its IGNYTE trial, where patients who had progressed on prior anti-PD-1 therapies showed a 34% response rate when treated with the RP1 combo. The median duration of response was 24.8 months, and the company says the safety profile was favorable.

Replimune Says the Goalposts Moved

Replimune is flagging what it describes as inconsistencies in the FDA’s review process. According to the company, a new review team was assigned during the resubmission phase, replacing the original team that had been engaged earlier. The new team, Replimune says, did not meet with management during the review despite outreach efforts. The company also points to prior statements from a senior reviewer indicating the clinical team had supported the evidence package, though leadership disagreed.

It’s essentially an argument that the rules changed mid-process. The company says the CRL contradicts earlier FDA feedback, particularly from a meeting back in September 2025. At that time, the agency had not raised additional concerns about patient heterogeneity and acknowledged challenges in conducting randomized trials in this setting, according to Replimune.

The company also submitted additional analyses, including data showing median progression-free survival of 30.6 months with RP1 plus nivolumab versus 4.4 months on prior therapies. It claims the FDA did not respond to requests for feedback before accepting the resubmission. So you have a company that thought it was having one conversation, and now feels like it’s being judged by a completely different set of criteria.

Wall Street Reacts With a Sharp Pencil

While Replimune argues its case, Wall Street analysts are reacting to the cold, hard reality of the rejection. They’ve turned sharply bearish, cutting ratings and price targets across the board.

HC Wainwright downgraded the stock from Buy to Sell. Analyst Robert Burns sees a "significantly longer path" for RP-1 to reach the market, "if at all." He added, "It may take until late in this decade to furnish the agency with the data that it appears to be demanding. There can be no assurance that Replimune would be able to accomplish this. As such, the company is facing a significant crisis and may not be able to pivot successfully."

That’s a pretty stark assessment. He’s not just saying it’s delayed; he’s questioning whether it can ever get there.

The downgrades kept coming. Jefferies moved from Buy to Hold and slashed its price forecast from $13 to $2. Wedbush went from Outperform to Neutral, cutting its target from $19 to $2. JP Morgan shifted from Neutral to Underweight. Leerink Partners downgraded from Outperform to Market Perform and lowered its target from $11 to $2. Cantor Fitzgerald also moved from Overweight to Neutral.

When you see price targets getting cut to $2 from the teens, that’s the market pricing in a fundamental reset of the company’s value and prospects.

And the market agreed. Replimune Group shares were down 63.97% at $1.71. The stock is trading at a new 52-week low.

So, what you have here is a classic biotech story with a twist. It’s not just a clinical setback; it’s a regulatory dispute. Replimune believes it had the data and followed the process, only to have the FDA say it’s not enough. Now the company is in a tough spot: it needs to convince regulators, reassure investors, and potentially design new trials—all while its cash clock is ticking and its stock price is in the gutter. It’s a high-stakes argument over what constitutes enough evidence, and for now, the FDA has the final say.