BMS buys Biontech Bispific antibody for multiple cancer collaborations at $1.5B
Biontech's tumor strategy focuses on bispecific antibodies that envision it as the backbone of many potential drug combinations for many types of cancer. Bristol Myer Squibb is adopting the strategy, paying $1.5 billion on the clinical-stage asset, which could be part of a merger with the drug giant's own immunotherapy and other cancer drugs that could be applied to the clinical-stage.
The deal announced Monday that it called on both companies to share as a monotherapy in the development and manufacture of the bispecific antibody BNT327 and use it in combination with other drugs. Each company reserves the right to independently develop BNT327 with more signs and drug combinations, including combinations with their respective drug assets.
Bispecific antibodies bind to two targets simultaneously, providing two different anti-pathogenic mechanisms in one drug. The first target of BNT327 is PD-L1, a so-called checkpoint protein that prevents immune cells from recognizing cancer cells. The drug also blocks VEGF-A, a protein bond that supports the formation of blood vessels in the tumor. BNT327 was originally developed by China-based Biotheus; Biontech completed a $800 million biotech acquisition in February and gained full control of bispecific antibodies.
Bispecific antibodies against PD-L1/PD-1 and VEGF have become popular products for drug developers. Summit Therapeutics, Merck, Intil Bio and Pfizer are one of the companies that develop bispecific antibodies to these targets, each with a drug from China Biotech. Summit's drug Ivonescimab has attracted attention for last year's preliminary data, suggesting it beat Merck's blockbuster checkpoint inhibitor KeyTruda in a positive phase 3 test. These results are only in China.
New data on Summit’s drug are not part of the annual meeting of the American Society of Clinical Oncology in Chicago this weekend, but it remains part of the conference buzz. Last Friday, Summit announced preliminary results from a Phase 3 study that compared its drugs and chemotherapy with chemotherapy in advanced cases of non-small cell lung cancer only. The company reported no statistically significant and clinically progression-free survival benefits. But in terms of overall survival, Summit reported only positive trends. As the FDA achieved statistically significant results on this measure, there was a lack of overall survival matters. Summit said it plans to seek regulatory approval from ivonescimab, but it is uncertain about the timing.
There is a precedent for the FDA to refuse to use drugs with Chinese data only. New data on Summit drugs are important because they include patients recruited from North America. The result of the heart-wrenching Biontech chief commercial officer Annemarie Hanekamp is this aspect. Hanekamp said in an interview at the ASCO meeting before the announcement of the BMS partnership that the summit data are important to Biontech because they show that the positive outcomes of bispecific antibodies in China can be replicated in the non-Asian population. Hanekamp acknowledges that overall survival still needs to be mature, but she says these early results signs of Biontech’s bispecific drug.
“You might find it very close to meaning, and actually seeing us on the right track, it actually strengthens our confidence,” she said.
Hanekamp said immunomodulatory drugs, such as PD-L1 and VEGF bispecific antibodies, form one of the three pillars of Biontech's oncology strategy. Other pillars are Messenger RNA technology, which is the basis and targeted therapy for Biontech, including antibody drug conjugates (ADCs). Commercial transactions have expanded Biontech's presence in ADCs through transactions with Duality Bio and Medilink.
Although the ADCs in these deals were initially developed as monotherapy, Hanekamp said Biontech believes it will achieve greater potential by incorporating them into the drug combination. She added that one purpose of the Biontech deal is to enable it to explore many different combinations from how it assembles. The combination expands checkpoint inhibition to tumors considered “cold”, meaning they do not trigger a strong immune response. Hanekamp said pairing ADCs with checkpoint inhibition can bring more benefits to blocking only checkpoint proteins.
BMS not only uses its cancer drugs for potential combinations, but also brings deep experience in clinical trials by Biontech, said in a research note. The relative inexperience in late-stage tumor development of the German company is considered a “main risk” before the BMS partnership.
“This deal also enhances our ability to make keen business decisions about the Biontech management team to spread risks, retain balance sheets and protect their organizations to develop their internal capabilities practically,” Graybosch said. “We often hear bear cases of investors who are concerned about investing in companies led by physician scientists, and while we agree that this is a common risk, Biontech CEO Uğurisahin and his senior management team repeatedly demonstrated business acumen and strong leadership talent that negated the criticism.”
The alliance calls on companies to develop BNT327 in multiple types of solid tumors. Biontech’s extensive clinical development program for the drug currently covers several types of lung and breast cancers, as well as other types of tumors. Three of these studies are globally critical studies in triple-negative breast cancer, small cell lung cancer and non-small cell lung cancer. Analysts say BNT327 could be the second PD-L1/PD-1 and VEGF bispecific antibodies in the market behind Summit drugs. The Biontech drug was also evaluated as part of a combination with BNT3213, an antibody designed to block two checkpoint proteins. Only the Phase 1/2 study in China is evaluating this combination in hepatocellular carcinoma.
In addition to upfront payments, the transaction requires BMS to make $2 billion in non-anniversary payments by 2028. Biontech is also eligible for milestone payments of up to $7.6 billion. If the bispecific antibodies are approved for regulatory approval, the two companies will be jointly business; Biontech will pre-order sales in the United States, while BMS will record them in the rest of the world.
Illustration: Thom Leach/Science Library, by Getty Images
