Moderna shares surged 177% Wednesday — the largest one-day gain for an S&P 500 company in over two decades — after the company and partner Merck reported positive late-stage trial results for their personalized mRNA melanoma vaccine. The trio of Moderna, Merck, and BioNTech added roughly $80 billion in market value in days, pushing Moderna’s valuation near $60 billion from $25 billion pre-announcement. The trial showed patients receiving the personalized vaccine alongside Keytruda had significantly lower melanoma recurrence rates, marking the first late-stage validation of an mRNA cancer vaccine.

Yet analysts caution the financial upside may be overstated. Leerink Partners’ David Graybosch models the therapy generating only low-single-digit billions in annual sales by 2032. Even a bull-case $10 billion peak would justify roughly $40 billion in combined added value — less than the single-day market gain. Melanoma’s high mutation count and immunotherapy sensitivity make it unusually suited for this approach; kidney, bladder, and pancreatic cancers present tougher challenges.

Manufacturing each vaccine requires tumor sequencing and custom mRNA production, a vastly costlier process than bulk drugs. Treatment could cost around $300,000, but pricing pressure in Europe and U.S. policy moves to align American prices with international reference pricing may compress margins to 50–80%, well below the 90%+ typical for conventional drugs. RBC Capital Markets’ Brian Abrahams notes the market is pricing in broader success that remains unproven.