Moderna, Inc. (NASDAQ: MRNA) witnessed a record-breaking surge in its stock price on Wednesday, delivering a severe financial blow to short sellers who had wagered on the company's prolonged downturn. The dramatic rally followed promising results from a late-stage melanoma trial for its personalized cancer vaccine, developed in partnership with Merck & Co., Inc. (NYSE: MRK), which demonstrated a reduction in the rate of cancer recurrence.
According to data from S3 Partners LLC, this single-day spike resulted in approximately $5.5 billion in mark-to-market losses for short sellers, bringing their total year-to-date losses to roughly $7.7 billion. The trial results suggest the vaccine could offer a new treatment avenue for melanoma, the most severe form of skin cancer, which afflicts about 112,000 Americans annually and claims around 8,500 lives, based on American Cancer Society statistics.
In a joint statement, both companies indicated their intention to discuss regulatory submission plans with health authorities and to unveil the detailed data at an upcoming medical conference. Moderna, Inc. Chief Executive Officer Stéphane Bancel noted in an interview that, depending on regulatory review timelines, the product could potentially receive approval as early as 2027.
Matthew Unterman, Managing Director at S3 Partners, described the move as "an extraordinarily painful move for Moderna short sellers," adding that "today's action fundamentally changes the risk-reward for anyone maintaining a bearish position."
Prior to the melanoma trial announcement, Moderna, Inc. shares had already climbed 114% this year, fueled by investor optimism that its influenza vaccine pipeline could help diversify the company's revenue streams away from its shrinking COVID-19 vaccination business. This optimism stands in stark contrast to the preceding four consecutive years of share price declines, which left the stock nearly 94% below its 2021 peak as demand for COVID shots waned.
Wall Street analysts have widely praised the trial results as a substantial potential catalyst for Moderna, Inc. Needham analyst Joseph Stringer called the melanoma study a "milestone victory" for the company, suggesting it could transform its oncology franchise into the next major growth driver. Concurrently, William Blair's Myles Minter upgraded the stock from "Market Perform" to "Outperform," telling investors that Moderna, Inc. now possesses a clearer vision for revenue diversification beyond its COVID franchise.
Interestingly, the pain for short sellers could have been even more severe. S3 Partners data indicates that short interest as a percentage of Moderna, Inc.'s float—a measure of tradeable shares—had reached as high as 20% earlier this year, before receding to around 14% as some traders closed out bearish positions. Unterman elaborated, "Today's impact is more profound because shorts were already covering—roughly 20 million shares, or about a quarter of the positions, had been bought back in 2026. This magnitude of a move will force other shorts to reassess or cut their positions."
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