There was a stock trading day like any other Wednesday and a single-day valuation swing of one of the most dramatic in biotech in years. In a Phase 3 study, Moderna and Merck's blockbuster immunotherapy Keytruda were used together to treat patients with high-risk melanoma who have already had surgery to remove their tumors and resulted in a personalized mRNA vaccine. Moderna's stock settled 177% higher, nearly tripling the value of its shares in one day. A firm over ten times as big as Moderna, Merck, increased by a relatively small 12%. The two moves are a decade-long, scientific wager that is more than a stock chart: A wager that messenger RNA can outwit a virus, and even a cancer.

INTerpath-001 was a trial of 1,137 patients who had been diagnosed with stage IIB to IV melanoma and had had their tumors surgically removed. The half that got Keytruda alone was treated for 1 year and the other half was treated with both Keytruda and intismeran autogene, a vaccine developed using a genetic profile of each individual's own tumor. As each cancer is unique, the treatment is also tailored to each individual identifying the mutations (neoantigens) in that person's cancer and educating the T cells to target those specific mutations. Keytruda releases the brakes that allow cancer to evade the immune system; the vaccine's role is to provide the immune system with a list of targets. The combination achieved a primary objective, recurrence-free survival, and a key secondary objective, delaying spread of the cancer to distant organs, versus Keytruda alone.

This is not just an incremental drug update, but a precedent that is set. It's been almost 20 years since neoantigen vaccines started to be developed as a cancer therapy, but there has never been an unambiguous late-stage, randomized trial that showed they work. Previous results of the companies' Phase 2b trial itself, which took place over five years, had already demonstrated that the vaccine reduced the risk of recurrence or death by 49% when combined with Keytruda. Three-year survival data were also released previously, where the combination was found to extend the time without recurrence or death to around 75% compared to around 56% for Keytruda alone. Wednesday's Phase 3 readout follows on the heels of positive earlier results, but this time in a trial that is designed and powered to be this time definitive. The outcome was a landmark for adjuvant melanoma treatment, said Georgina Long, principal investigator of the study and a melanoma specialist at the University of Sydney, and external experts were equally vocal. The discovery marks a new era in the field of immunotherapy for solid tumors, not just for melanoma, said Karen Knudsen, head of the Parker Institute for Cancer Immunotherapy.

That's where the true economic article is. Melanoma is just the beginning sign. Eight distinct Phase 2 and 3 trials of the personalized-vaccine architecture for other tumors, such as non-small-cell lung cancer, bladder cancer and renal cell carcinoma, are underway for both Moderna and Merck. Analysts have emphasized that Wednesday's share reaction was not only about melanoma's estimated 1.5 million patients in the United States, but about whether this can be a platform technology that is added to dozens of kinds of tumors that are treated with checkpoint inhibitors. Jessica Fye from JPMorgan commented that prior to the announcement, a lot of melanoma was already built into the valuation of Moderna, and the hefty move will be driven by the "read across" effects to the other cancers. Jefferies identified knock-on beneficiaries within the bioprocessing and life-sciences tools supply chain who would need to ramp up to produce individual doses at scale. For Bank of America, it's a turning point that enables Moderna to break free of an infectious-disease image that the company has long tried to sever ties with due to the flattening demand for COVID-19 vaccines.

The word of caution under the word euphoric can't be ignored. But neither company published the actual hazard ratios or confidence intervals or the actual efficacy numbers the latter are being awaited at a medical conference and regulatory filings, and the market jumped on a topline summary, not the numbers. Wednesday's rally was probably fueled by short sellers, who had already piled into Moderna at about 13.5% of its free float, which tend to drive rallies in either direction. And personalised manufacturing has a fundamentally different cost structure to mass-produced shot: each dose would need to be sequenced, designed and produced for one patient, raising real questions about turnaround time, production capacity and whether it would ever be affordable by the healthcare systems in other markets. That's a treatment that is so personalized that the luxury of it is available in Boston and Zurich long before it hits Lagos or Manila and that disparity needs to be examined just as much as the science.

Nevertheless, the scientific bar that is raised here isn't a small one. For the first time, a late-stage, randomized, controlled trial has demonstrated that a vaccine designed based on a specific tumor's own mutations has the potential to make a meaningful difference in the treatment of cancer and not just a model of cancer in a laboratory setting. Now it won't be a matter of how quickly that discovery turns into treatment for regulators in the United States, and probably parts of Europe and Asia. Regardless of the ultimate figures that emerge upon publication, this Wednesday was when mRNA began to move beyond its pandemic-era status and was used for the treatment of cancer in its own right, by clinicians and investors.