Research of Bispecific Antibodies Beyond Cancer Gains Momentum

Two recent pharmaceutical company acquisitions highlight the growing trend of research of bispecific antibodies beyond oncology, with one analyst projecting the bispecific antibodies market could reach $5.6 billion globally by 2035.

There are more than 150 bispecific antibodies in clinical trials to treat cancer, according to the most recent report on oncology trends by Institute for Human Data Science. Indications being investigated include multiple myeloma, non-Hodgkin lymphoma, non-small cell lung cancer and colorectal cancer.

Beyond cancer, bispecific antibodies are being studied in autoimmune disease either by targeting B cells or by targeting interleukin pathways. In July 2024, Johnson & Johnson completed it acquisition of Yellow Jersey, a subsidiary of Numab Therapeutics, to secure the global rights to NM26, an investigational first-in-class bispecific antibody. The transaction was valued at about $1.25 billion. NM26, which is ready to enter phase 2 studies in atopic dermatitis (AD), targets two pathways, IL-4R alpha subunit (IL-4Rα) and IL-31, which trigger Th2-mediated skin inflammation and skin itch.

Additionally, last week Merck agreed to acquire Curon Biopharmaceutical’s CN201, a novel investigational clinical-stage bispecific antibody for the treatment of B-cell associated diseases. Merck through a subsidiary will acquire full global rights to CN201 for an upfront payment of $700 million in cash. Curon is also eligible to receive up to $600 million in milestone payments associated with the development and regulatory approval of CN201.

CN201 is currently being evaluated in phase 1 and phase 1b/2 clinical trials for the treatment of patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL) and relapsed or refractory B-cell acute lymphocytic leukemia (ALL). Merck plans to evaluate CN201 as a treatment for B-cell malignancies and as potential option to treat autoimmune diseases.

Dean Y. Li, M.D., Ph.D., president

“Early clinical data have provided robust evidence for the potential of CN201 to target and deplete circulating and tissue B cells with the potential to treat a range of malignant and autoimmune diseases,” Dean Y. Li, M.D., Ph.D., president, Merck Research Laboratories, said in a news release.

Bispecific antibodies can bind to multiple targets, and they have been a focus of drug development efforts. The first approved bispecific antibody was Blincyto (blinatumab) in 2014 to treat patients with acute lymphoblastic leukemia. In oncology, bispecific antibody’s act to activate and bring immune cells closer to cancer cells.

There are 14 bispecific antibodies that have been approved, according to a paper in Nature Reviews Drug Discovery. Since this report was published in March 2024, the FDA granted yet another approval —of the first bispecific antibody to treat a solid tumor. In May 2024, the FDA granted accelerated approval to Amgen’s Imdelltra (tarlatamab-dlle) to treat adult patients with extensive-stage small cell lung cancer.

Many more bispecific antibodies are in late-stage development or under FDA review. One is Jazz Pharmaceuticals’ zanidatamab to treat patients with unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC), which as a Prescription Drug User Fee Act (PDUFA) action date of Nov. 29, 2024. Another is Merus’s zenocutuzumab to treat patients with non-small cell lung cancer and pancreatic cancer. The FDA’s target action date is in December 2024.

During the COVID-19 pandemic, antibodies that targeted the SARS-CoV-2 viral spike received emergency authorization by the FDA, although they were not approved for marketing. Research continues of bispecific antibodies that target SARS-CoV-2, including Omicron and other variants.