BioNTech's mRNA immunotherapy BNT113 misses progression goal in Phase 3 head and neck trial

BioNTech said on 13 October 2026 that its off-the-shelf mRNA cancer immunotherapy BNT113, given with Merck's Keytruda, did not lengthen progression-free survival over Keytruda alone in the Phase 3 portion of the AHEAD-MERIT trial in HPV16-positive head and neck squamous cell carcinoma ¹². The study stays open because overall survival, its second primary endpoint, has not yet been read out ¹².

What the trial found

AHEAD-MERIT is an open-label Phase 2/3 study comparing BNT113 plus Keytruda with Keytruda monotherapy as first-line treatment for head and neck squamous cell carcinoma driven by HPV16 ¹². At an interim analysis, progression-free survival on the combination was statistically no different from single-agent Keytruda, so the trial missed one of its two primary endpoints ². Neither report gives a hazard ratio or the size of the trial.

The independent data monitoring committee recommended that the study carry on as planned to assess overall survival ². Under the statistical design, a significant survival benefit on its own would make the trial positive ². BioNTech's co-founder and chief medical officer, Özlem Türeci, said the data show the combination is "engaging its intended therapeutic mechanism" and "support continued evaluation" ¹². Her argument is that immune-driven effects against tumours can build over time, which would show up in survival rather than early progression ².

BNT113 is designed to provoke immune responses against two HPV16 oncoproteins, E6 and E7, and to strengthen existing T-cell immunity, which BioNTech hopes will complement the T-cell activity Keytruda drives ². Unlike Moderna's intismeran autogene, which is built from antigens matched to each patient's tumour mutations, BNT113 encodes a fixed antigen set ².

What it means for the market

The result separates two approaches inside mRNA cancer immunotherapy. Fierce Biotech reports that BioNTech's shares had gained 20% after Merck and Moderna's Phase 3 data in August lifted expectations for the class, and the BNT113 miss reversed part of that ². BioNTech stock fell 5% to $91.32 before the market opened on Tuesday, from a Monday close of $95.84, and Moderna's shares slipped 3% ². BioPharma Dive put the early-trading fall at about 6% ¹.

For BioNTech the stakes are strategic. Sales of Comirnaty, its COVID-19 vaccine with Pfizer, have dropped sharply, and the company has moved resources back towards oncology, its original focus ¹. That shift has run through a series of deals, the largest being the bispecific pumitamig it now develops with Bristol Myers Squibb, which is in several late-stage trials ¹. Earlier in 2026 BioNTech also reported a setback in colorectal cancer ¹. Leerink Partners analyst Daina Graybosch wrote in August that BioNTech was relying more and more on pumitamig, and judged the evidence for BNT113 in head and neck cancer to have been thin when the Phase 3 began ¹.

Analysts at BMO Capital Markets said a slow-building immune response could still leave room for a survival gain, but that the progression-free survival miss left them much less confident of one ².

Caveats

The readout is interim, and the survival data are immature ². There is precedent on both sides: a Phase 3 trial of Keytruda in head and neck cancer missed on progression-free survival yet went on to improve overall survival, an advantage it held over five years of follow-up, but many trials that miss on progression later fail on survival too ². Leerink's team had expected a negative result partly because BioNTech enrolled patients with lower PD-L1 levels, and a number of combinations have failed over the years to beat checkpoint inhibitors such as Keytruda given alone ¹. Neither source gives a date for the overall survival analysis, which is now the result that decides whether BNT113 has a future in this setting ¹².