BioNTech pays $800M to take control of potential Keytruda killer

BioNTech is upping its bet on a PD-L1xVEGF-A bispecific, paying $800 million upfront to buy its Chinese partner Biotheus and secure full rights to a leading prospect in the white-hot immuno-oncology space.

Germany-based BioNTech got into the space before the gold rush that was unleashed in September by the news that Akeso and Summit Therapeutics’ PD-1xVEGF-A prospect ivonescimab had beaten Merck & Co.’s Keytruda. BioNTech secured a leading candidate in the race one year ago by paying Biotheus $55 million upfront for the rights to PM8002 outside of greater China.

Now, the biotech has struck a deal to gain full control of PM8002, a bispecific also known as BNT327. BioNTech is paying $800 million and committing up to $150 million in milestones to buy Biotheus. The original PM8002 licensing deal included more than $1 billion in milestones.

BioNTech’s willingness to significantly increase its upfront bet on BNT327 reflects a belief the candidate could set a new standard of care in multiple cancer indications. If, as ivonescimab’s victory over Keytruda suggested, PD-(L)1xVEGF-A bispecifics are more effective than traditional checkpoint inhibitors, the new class of molecules could replace blockbusters that currently form the spine of many cancer regimens.

The opportunity is enormous: Keytruda alone generated $25 billion last year across multiple indications. That still left room for rivals to generate blockbuster sales, with Bristol Myers Squibb’s Opdivo and Roche’s Tecentriq pulling in around $9 billion and $4 billion, respectively.

Akeso and Summit are leading the race, but BioNTech is well placed, with multiple registrational trials of BNT327 scheduled to start in 2024 and 2025. The trials will assess the bispecific antibody in combination with chemotherapy in solid tumors including small cell lung cancer, non-small cell lung cancer and triple-negative breast cancer. BioNTech is also exploring combinations with antibody-drug conjugates.

Ivonescimab is entering a similarly sweeping late-phase program. BNT327 and ivonescimab are designed to unleash T cells against tumors, like standard checkpoint inhibitors do, while also neutralizing the  immunosuppressive VEGF-A in the tumor microenvironment. The main difference is BNT327 targets PD-L1 while ivonescimab engages PD-1.

On an earnings call last week, BioNTech CEO Ugur Sahin said the design of BNT327 “comes with the potential advantage of being further enriched in the tumor microenvironment by binding to PD-L1, or vice versa enabling or adding to the binding of VEGF in the tumor microenvironment.” Whether that will affect efficacy remains to be seen.

“The data that we have so far ... look similar,” Sahin said. “[We] have to see whether this potential mechanistic difference could translate into better response rate and better durability, particularly in PD-L1-positive tumors. There is a slight trend in this direction, but it's too early to validate that.”

Buying Biotheus will give BioNTech assets beyond BNT327. The biotech’s pipeline features bispecifics against a range of targets, including one candidate that hits PD-L1 and TGFβ and another that inhibits TIGIT and PVRIG. Biotheus also has antibody-drug conjugates in preclinical development.

BioNTech will also acquire the capabilities and infrastructure that Biotheus has built up to discover and advance the candidates. Buying Biotheus will provide BioNTech with a R&D hub to conduct clinical trials in China. The acquired biotech has more than 300 employees in R&D, manufacturing and enabling functions. BioNTech expects the Biotheus staffers to join its workforce.