Moderna's $45 Billion Bet On A Sealed Number
One Tumor, One Vaccine
Merck and Moderna announced on August 19 that their Phase 3 trial of a personalized melanoma vaccine, intismeran autogene, cleared its main goals when paired with the checkpoint inhibitor Keytruda after surgery. The strange part is that no two doses of this vaccine are the same. Standard vaccines teach the immune system to recognize one fixed target, the spike protein on a coronavirus, say. This one starts by sequencing a patient's own resected tumor, hunting for the specific mutated proteins, called neoantigens, that make that patient's cancer cells look different from healthy tissue. Software then picks the mutated proteins likeliest to trigger an immune response, and an mRNA strand encoding them is manufactured to order, one batch per patient, in a process that takes several weeks. Keytruda's job is separate: it blocks a checkpoint that cancer cells use to switch off nearby T cells, so more T cells stay active. Trial INTerpath-001 tested whether adding the custom vaccine to that already-active immune system meant fewer tumors returning, in 1,137 patients with resected stage IIB through IV melanoma. Independent monitors called the result statistically significant and clinically meaningful on recurrence-free survival, the trial's primary measure, and on distant metastasis-free survival, the key secondary one.
The Number Still Sealed
None of that says by how much. Merck and Moderna have not released the size of the risk reduction Phase 3 measured, only that it cleared the bars an independent monitoring committee sets before seeing the data. That is a normal way to report a topline result, and it leaves investors to set their own estimate of the size absent the actual figure. Moderna shares closed up 177 percent on August 19, adding roughly $45 billion in market value and costing short sellers an estimated $5.5 billion, according to Bloomberg. Analysts at Evercore ISI had staked out the goalposts before the number existed: 20 percent risk reduction as a clinical floor, 25 percent or below as underwhelming, 35 to 40 percent needed to count as clearly ahead of Keytruda alone. The only public data point inside that range comes from the earlier Phase 2 trial, 157 patients, which found a 44 percent relative reduction in recurrence or death with the combination. Oncologists must decide this month whether to add the combination to a resected-melanoma patient's plan, and patients recovering from surgery must make that call now, without the number that would justify it. Both are choosing on a label, not a result, until Merck and Moderna present full data at ESMO in Madrid, October 23 to 27.
If the sealed number lands below Evercore's 35 percent bar in October, Moderna shares would reprice on that same data. Moderna and Merck are already running this same sequencing-to-injection pipeline against lung, kidney and bladder tumors. Whichever number ESMO puts on melanoma becomes the number every one of those trials gets read against, before any of them has data of its own.
Sources
- Merck.com -- Phase 3 INTerpath-001 topline results (merck.com)
- BioPharma Dive -- trial size, Phase 2 data, analyst benchmarks (biopharmadive.com)
- STAT News -- companies withheld detailed efficacy data (statnews.com)
- Bloomberg -- Moderna surge, short-seller losses (bloomberg.com)
- The Motley Fool -- Moderna 177% single-day stock move (fool.com)
- CBS News -- safety profile, trial description (cbsnews.com)