Moderna shares more than doubled on Wednesday, surging roughly 131% to touch $163 intraday before settling near $148, after the company and Merck announced that their personalized mRNA cancer therapy had met both primary endpoints in a Phase 3 trial. It was a record one-day gain for the stock, and it came with a brutal side effect for traders who had bet against the company.
The trial, called INTerpath-001, tested intismeran autogene — also known as V940 or mRNA-4157 — combined with Merck's blockbuster immunotherapy Keytruda in patients with surgically removed stage IIB-IV melanoma. According to the companies' joint announcement, the therapy hit both recurrence-free survival and distant metastasis-free survival endpoints, marking the first positive Phase 3 result ever recorded for both a personalized neoantigen therapy and an mRNA-based cancer treatment.
How the Therapy Works
Unlike a conventional vaccine, intismeran autogene is built individually for each patient. Doctors sequence a patient's tumor, map its unique mutations, and use that data to design a personalized mRNA sequence that trains the immune system to recognize and attack the specific neoantigens — protein fragments unique to that patient's cancer cells — produced by the tumor. The Phase 3 readout builds on earlier Phase 2b data, which had shown the combination cut the risk of recurrence or death by 49% and the risk of distant metastasis or death by 59% compared to Keytruda alone, results strong enough that Wednesday's confirmation was widely anticipated by biotech investors even if the scale of the stock reaction wasn't.
A Short Squeeze on Wall Street
The move caught a heavily shorted stock off guard. With short interest sitting at 13.5% of Moderna's free float heading into the announcement, traders betting against the company faced an estimated $4.8 billion in mark-to-market losses as shares rocketed higher. "With each shorted share now down almost $100, that is exactly the kind of pressure that can trigger a squeeze," ORTEX co-founder Peter Hillerberg said of the move.
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Merck shares also climbed on the news, given its role supplying Keytruda to the combination therapy, and at least one Wall Street analyst moved quickly to reflect the new data: Morgan Stanley raised its price target on Moderna to $209 from $170 following the announcement.
What Happens Next
Moderna and Merck said they plan to present the full trial data at an upcoming international medical meeting and will begin engaging with regulators on filing submissions for intismeran autogene in combination with Keytruda. A regulatory filing would set up what could become the first approved personalized mRNA cancer therapy, a milestone that would extend mRNA technology's reach well beyond the infectious-disease vaccines that first made it famous.
