Investors
1 Curated Dialogues
Jorge Conde
Key Views & Dialogues
Inside Moderna’s Biggest mRNA Test Since COVID
Moderna and Merck’s personalized mRNA cancer vaccine met its Phase 3 primary endpoint in melanoma and also hit distant metastasis-free survival at the first interim analysis, with patient availability hoped for in 2027. Phase 2 showed 50% five-year recurrence-free survival versus Keytruda alone and 80% disease-free; inside-cell antigen presentation and a Marlborough facility capable of tens of thousands of doses support scale, while pricing and 20% nonresponse remain watchpoints.
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- Moderna and Merck’s personalized mRNA cancer vaccine hit its Phase 3 primary endpoint in melanoma. Bancel called it the first cancer vaccine ever proven effective; Conde framed the backdrop as more than 1,000 failed clinical trials across over 20 years. The trial met recurrence-free survival at the first interim analysis and, to Bancel’s own surprise, also hit the secondary endpoint of distant metastasis-free survival. Filing is underway with hoped-for patient availability in 2027, and the Massachusetts facility is ready.
- The Phase 2 benchmark investors should anchor on: about 50% recurrence-free survival in the comparison with Keytruda alone at 5 years, with ~80% of patients disease-free — and Bancel says oncologists consider 5 years equivalent to being cured. About 60% remain healthy after Keytruda alone, while the other 40% often develop autoimmune diseases (type 1 diabetes, lupus, Crohn’s) without benefiting.
- The moat is dual: mRNA’s inside-the-cell antigen presentation plus true individualization — “approximately 90% of antigens differ between patients,” so “the only way this can work is through personalization.” Each dose sequences the patient’s tumor versus healthy DNA “letter by letter, nucleotide by nucleotide,” an algorithm selects 34 mutations, and a bespoke mRNA is manufactured in 30 days; needle-to-needle time is currently 42 days.
- Bancel’s AI-style upgrade thesis: the algorithm used in Phases 1, 2, and 3 is 10 years old — “Moderna’s current version of intismeran autogene is the worst version you’ll see in the history of medicine.” Phase 3 blood samples and sequencing data will be analyzed to understand responders and nonresponders; the roughly 20% nonresponse figure comes from the 5-year Phase 2 data. A 2.0 algorithm could go to the FDA if the science supports it, because “you always learn more from what doesn’t work.”
- Unlike CAR-T, the process needs no patient immune cells — “the only thing we need is information… we just get the file” — making it enzymatic, aqueous, based on very small reactors, and more scalable. The Marlborough, Massachusetts, facility can produce tens of thousands of doses, which Bancel says “could easily cover the entire melanoma market”; pricing remains undisclosed pending payer discussions.
- The expansion pipeline runs on three vectors: everywhere Keytruda works (Phase 3 lung, Phase 2 kidney/bladder), early-stage disease as monotherapy (Phase 3 in stage 1 lung cancer), and where checkpoints fail outright (pancreatic and gastric), including a possible combination with Revolution Medicines’ newly approved KRAS drug. The rationale includes ASCO data showing the vaccine generates de novo T cells that recognize encoded targets not present in patients before treatment.
- The platform story extends beyond oncology: a pivotal or late-stage study in rare pediatric genetic liver disease possibly by year-end, and autoimmune disease named the “next frontier” in June — including personalized therapies that direct the immune system to attack its own malfunctioning cells, “what I’m most excited about today.”