BioNTech's BNT113 Fails Key Goal in Head and Neck Cancer Trial

BioNTech announced on Tuesday that its experimental mRNA cancer immunotherapy BNT113 failed to meet its primary endpoint in a Phase 3 head and neck cancer trial. The combination of BNT113 and Merck's blockbuster drug Keytruda (pembrolizumab) did not produce a statistically significant improvement in progression-free survival compared to Keytruda alone.

The Phase 2/3 Ahead-Merit trial evaluated the drug combination as a first-line treatment for patients with advanced head and neck squamous cell carcinoma linked to the HPV16 virus. An interim analysis of the late-stage study showed the combination did not extend progression-free survival, the trial's first main goal. BioNTech's US-listed shares fell nearly 3% in early trading following the announcement, heading for their fifth decline in six sessions.

Company and analysts recommend continuation

Despite the setback, BioNTech's leadership and an independent data monitoring committee support continuing the trial. The committee recommended proceeding to evaluate overall survival, which is the study's second primary endpoint. Overall survival is considered the gold-standard measure in oncology, and other immunotherapies have won approval after missing progression-free survival but achieving a survival benefit.

BioNTech Chief Medical Officer Özlem Türeci said the early results support continued testing. Özlem Türeci said: "The early results 'support continued evaluation' and show the drug combination is 'engaging its intended therapeutic mechanism'." She added that immune responses may take time to produce lasting benefits.

Market and analyst reaction reflects skepticism

BioNTech's stock declined sharply after the announcement, falling more than 5.5% on Tuesday. The stock is down more than 6% so far this year. Citi maintained its 'Buy' rating and $125 price target, which implies a 39% upside potential from current levels. The bank noted that head and neck cancer can be difficult to treat with immunotherapy and that it is challenging to demonstrate additional benefits over Keytruda alone.

Citi analyst Geoffrey Meacham commented on the trial’s results, noting challenges due to tumor heterogeneity and immunosuppression. The bank highlighted that the trial could still be successful if overall survival is significantly improved, preserving a meaningful development path. Leerink Partners analyst Daina Graybosch wrote in August that the evidence supporting BNT 113's activity in head and neck cancer was sparse when the Phase 3 study launched. Daina Graybosch said: "The evidence supporting BNT 113’s activity in head and neck cancer was 'sparse' when the Phase 3 study was launched." Her team expected a negative outcome partly due to enrollment of patients with lower PD-L1 levels.

Broader pipeline and strategic shift underway

The outcome occurs as BioNTech advances its oncology focus, its original area of research from nearly two decades ago. The company developed the COVID-19 vaccine Comirnaty with Pfizer, which became one of the most lucrative pharmaceutical products in history. Sales have since fallen significantly due to dwindling demand. BioNTech and Moderna have reduced resources for infectious disease research, and mRNA technology has become a political target.

BioNTech is now pivoting back to cancer. The company acquired a bispecific cancer treatment now called pumitamig, which it is developing through a partnership with Bristol Myers Squibb. Pumitamig is involved in multiple advanced clinical trials. Leerink's Graybosch noted in August that BioNTech is leaning ever more on this candidate. BioNTech reported a colorectal cancer study setback earlier this year. The company has 14 oncology trials underway as of August and its pipeline also includes antibody-drug conjugates. BioNTech reported about €16.63 billion in cash, cash equivalents, and security investments as of June 30, equivalent to $18.62 billion.

What’s next for BNT113

The Ahead-Merit trial will proceed to assess whether the BNT113 and Keytruda combination can deliver a meaningful improvement in overall survival. This gold-standard endpoint will determine the future of the investigational mRNA-based cancer immunotherapy in HPV-associated head and neck cancer.