BMS Buys Into BioNTech Bispecific Antibody, Putting Up $1.5B to Collaborate in Multiple Cancers
BioNTech’s oncology strategy centers on a bispecific antibody that the company envisions as the backbone of many potential drug combinations for many types of cancer. Bristol Myer Squibb is buying into that strategy, paying $1.5 billion up front to partner on the clinical-stage asset, which could have applications as part of combinations with the pharmaceutical giant’s own immunotherapies and other cancer drugs.
The deal announced Monday calls for both companies to share in the development and manufacturing of the bispecific antibody, BNT327, as a monotherapy and in combination with other drugs. Each company retains the right to independently develop BNT327 independently in more indications and drug combinations, including combinations with their respective drug assets.
A bispecific antibody binds to two targets simultaneously, offering two different disease-fighting mechanisms in a single drug. The first target of BNT327 is PD-L1, a so-called checkpoint protein that keeps immune cells from recognizing cancer cells. The drug also blocks VEGF-A, a protein key to the formation of blood vessels that support tumors. BNT327 was originally developed by China-based Biotheus; BioNTech completed its $800 million acquisition of the biotech in February, gaining full control of the bispecific antibody.
Bispecific antibodies addressing PD-L1/PD-1 and VEGF have become a hot commodity to drug developers. Summit Therapeutics, Merck, Instil Bio, and Pfizer are among the companies developing bispecific antibodies for these targets — each with a drug from a China-based biotech. Summit’s drug, ivonescimab, has been closely watched due to preliminary data last year showing it beat Merck’s blockbuster checkpoint inhibitor, Keytruda, in a head-to-head Phase 3 test. Those results were only in China.
New data from the Summit drug was not part of the annual meeting of the American Society of Clinical Oncology in Chicago this weekend, but it was still part of the conference buzz. Last Friday, Summit announced preliminary results from a Phase 3 study that compared its drug and chemotherapy against chemotherapy alone in advanced cases of non-small cell lung cancer. The company reported statistically significant and clinically meaningful benefit in progression-free survival. But on overall survival, Summit reported only a positive trend. Falling short in overall survival matters because the FDA has made a statistically significant result on this measure a requirement for regulatory approval. Summit said it plans to seek regulatory approval of ivonescimab, but is uncertain of the timing.
There’s precedent for the FDA rejecting drugs with China-only data. The new data for Summit’s drug are important because they include patients recruited from North America. It’s this aspect of the results that hearten BioNTech Chief Commercial Officer Annemarie Hanekamp. In an interview at the ASCO meeting prior to announcement of the BMS partnership, Hanekamp said the Summit data are important to BioNTech because they show that a bispecific antibody’s positive results in China can be replicated in a non-Asian population. Hanekamp acknowledged that the overall survival still data needs to mature, but she said these early results bode well for BioNTech’s bispecific drug.
“You could see that it was very close to significance and it actually boosted our confidence to see we’re on the right trajectory as well,” she said.
Immunomodulating drugs, such as the PD-L1 and VEGF bispecific antibody, make up one of three pillars of BioNTech’s oncology strategy, Hanekamp said. The other pillars are the messenger RNA technology that was the foundation of BioNTech, and targeted therapies, which encompasses antibody drug conjugates (ADCs). Business deals have expanded BioNTech’s presence in ADCs, via deals with Duality Bio and MediLink.
While the ADCs from these deals were initially developed as monotherapies, Hanekamp said BioNTech believes greater potential will be realized by incorporating them in drug combinations. She added that one objective of BioNTech’s dealmaking was to give it the ability to explore many different combinations with the modalities it has assembled. Combinations expand checkpoint inhibition to tumors that are considered “cold,” meaning they don’t trigger a strong immune response. Pairing ADCs with checkpoint inhibition could bring additional benefit over blocking checkpoint proteins alone, Hanekamp said.
Leerink Partners analyst Daina Graybosch said in a research note that more than bringing its cancer drugs for potential combinations, the BMS brings to BioNTech its deep experience in clinical trials. The German company’s relative inexperience in late-stage oncology development was considered “a major risk” before the BMS partnership.
“The deal also reinforces our confidence in BioNTech’s management team’s ability to make incisive business decisions that spread risk, preserve their balance sheet, and protect their organization to grow internal capabilities pragmatically,” Graybosch said. “We often hear the bear case from investors that they worry about investing in a company led by physician scientists, and while we agree with this as a general risk, BioNTech’s CEO, Uğur Şahin, and his senior management team have repeatedly shown business acumen and strong leadership that negates the criticism.”
The alliance calls for the companies to develop BNT327 across multiple types of solid tumors. BioNTech’s broad clinical development program for the drug currently spans several types of lung and breast cancers as well as other types of tumors; three of the studies are global pivotal studies in triple negative breast cancer, small cell lung cancer, and non-small cell lung cancer. Analysts say BNT327 could become the second PD-L1/PD-1 and VEGF bispecific antibody to market behind Summit’s drug. The BioNTech drug is also being evaluated as part of a combination with BNT3213, an antibody designed to block two checkpoint proteins. A China-only Phase 1/2 study is underway evaluating this combination in hepatocellular carcinoma.
Beyond the upfront payment, the deal calls for BMS to pay $2 billion in non-contingent anniversary payments through 2028. BioNTech is also eligible to receive up to $7.6 billion in milestone payments. If the bispecific antibody secures regulatory approval, the two companies will co-commercialize it; BioNTech will book sales in the U.S. while BMS will record them in the rest of the world.
Illustration: Thom Leach/Science Photo Library, via Getty Images
