IO Biotech eyes FDA nod for skin cancer vaccine despite narrow trial miss

IO Biotech’s Cylembio plus Merck’s Keytruda narrowly failed to meet statistical significance in its Phase 3 melanoma trial, showing a 23% lower risk of progression or death versus Keytruda alone. Certain subgroups, like PD-L1 negative patients, saw bigger benefits (46% risk reduction).

Why it matters: Despite the miss, the company believes the close result, especially in pre-specified subgroups, could still support U.S. approval, potentially making Cylembio one of the few “off-the-shelf” cancer vaccines to market.

Big picture: Cylembio uses engineered peptides to trigger immune attacks on PD-L1 and IDO1, immune checkpoints linked to tumor defense. Unlike personalized mRNA cancer vaccines from Moderna or BioNTech, this off-the-shelf drug could be faster and cheaper to produce. The razor-thin miss underscores oncology’s statistical hurdles and how clinical benefits appearing in subgroups aren´t enough to get the FDA green light.

The trial: The trial enrolled 400+ newly diagnosed, unresectable or metastatic melanoma patients randomized to Keytruda alone or Keytruda with Cylembio. Apart from the missed primary endpoint, patients negative for a key biomarker saw a 46% reduction, while patients new to immunotherapy saw a 26% reduction.

Next step: IO Biotech is set to meet with the FDA in Q3, with the aim of filing for approval by the end of the year.

• While the company has cash reserves of $28 million, which will see it through to the end of Q1 2026, it needs FDA approval to unlock a $17.4 million loan tranche from the European Investment Bank, which would give it a longer development runway.

• IO’s shares fell 20% on Monday and the company has lost most of its value since its 2021 IPO.