Moderna shares hadn't done much to celebrate in years. The stock had shed roughly 94% of its value from its 2021 pandemic-era peak, and short sellers had built one of the largest bearish positions in the biotech sector. On Wednesday, all of that reversed in a single trading session, with shares surging as much as 177% — the biggest one-day move in the company's history — after a late-stage trial showed real promise for a personalised cancer vaccine developed with Merck.
What the data showed
The companies said their experimental mRNA therapy, known as intismeran autogene, met both its primary and secondary goals in a Phase 3 trial of 1,137 patients with high-risk melanoma who had already had their tumours surgically removed. Combined with Merck's blockbuster immunotherapy Keytruda, the vaccine significantly extended the time patients went without their cancer returning, compared with Keytruda alone, and also reduced the risk of the disease spreading to other parts of the body. It marks the first positive final-stage trial result for any mRNA-based cancer therapy — a milestone Moderna chief executive Stéphane Bancel called a step in turning a once-aspirational idea into reality.
The vaccine works by sequencing a patient's own tumour for mutations and building a shot tailored specifically to that individual's cancer, then pairing it with Keytruda to train the immune system to attack any remaining cells. Merck's head of oncology early development, Dr Jane Healy, described the improvement over Keytruda alone as clinically meaningful, adding that side effects were broadly comparable to routine vaccines.
The market reaction, in numbers
Because of the gap in company size, the stock moves diverged sharply: Merck, with a market capitalisation around $333 billion heading into Wednesday, rose as much as 12%, while Moderna — valued near $25 billion — soared well over 100%, briefly touching an intraday high above $160 a share. The rally forced a significant unwind among short sellers, who had already bought back roughly a quarter of their positions earlier in the year; Wednesday's move alone is estimated to have cost short positions around $5.5 billion in paper losses. The Nasdaq Biotechnology Index climbed 5.2% to a record high as the news lifted sentiment across the sector.
Wall Street analysts moved quickly to reassess both names. Needham's Joseph Stringer called the result a landmark win for the field, while William Blair's Myles Minter upgraded Moderna to outperform, citing a credible path to diversify revenue beyond the company's shrinking Covid-19 vaccine franchise. Barclays had previously estimated the therapy could generate roughly $3 billion in annual sales for melanoma alone by 2035, and analysts noted the same platform is already being tested against other cancer types, including lung cancer.
What comes next
The trial is still ongoing, and the companies have not yet released detailed overall survival data — a secondary endpoint that measures whether treated patients ultimately live longer, not just longer without recurrence. Moderna and Merck said they plan to present fuller results at an upcoming international medical meeting and have already begun early discussions with regulators, with Moderna's president, Stephen Hoge, suggesting the vaccine's breakthrough therapy designation could allow it to reach patients as soon as next year.
Manufacturing remains the open question. Because each dose is built individually from a patient's own tumour sample, scaling the therapy commercially is a fundamentally different challenge than producing a standardised vaccine — one Moderna executives say they are confident in solving but have not yet detailed publicly. For a stock that spent years defined almost entirely by its pandemic-era product, Wednesday's move gave investors the clearest signal yet that Moderna's next chapter may be written in oncology rather than infectious disease.