Amgen has boosted its portfolio of cancer-targeted bispecific antibodies with the purchase of Teneobio for $900 million—plus as much as $1.6 billion more for meeting certain developmental milestones. The acquisition includes a potential treatment for prostate cancer and several other products.

Pharmaceutical giant Amgen has boosted its portfolio of cancer-targeting bispecific antibodies by purchasing Teneobio, a Newark, CA–based biotech for $900 million—and $1.6 billion more for meeting certain milestones. Teneobio has three such products in phase I clinical trials, although two are not part of the sale.

Bispecific antibodies are engineered proteins that feature two coupled antibodies. One binds a T-cell surface protein while the other binds a tumor cell surface protein, tethering the two kinds of cells and stimulating an attack on the cancer. Several companies are developing bispecifics, including Amgen, Regeneron, Affimed, and Teneobio. Amgen's blinatumomab (Blincyto), greenlighted in 2014 for patients with Philadelphia chromosome–negative precursor B-cell acute lymphoblastic leukemia, was the first bispecific approved to treat cancer. One arm of blinatumomab binds CD3 on T cells, while the other binds CD19 on B cells.

Pharmaceutical companies are now developing bispecific antibodies that bind other molecules on cancer cells, including prostate specific membrane antigen (PSMA) for prostate cancer, CD20 for follicular lymphoma, and B-cell maturation antigen for multiple myeloma. More than 200 clinical trials have tested or are testing bispecifics in numerous cancer types.

Bispecific antibodies have several potential advantages over another cellular therapy, chimeric antigen receptor (CAR) T cells, says Shaji Kumar, MD, of the Mayo Clinic in Rochester, MN. For instance, “they can be given at smaller hospitals because they do not require the cellular therapy infrastructure” necessary to produce CAR T cells, says Kumar, who has consulted for Amgen and Teneobio but wasn't involved in the deal. Moreover, oncologists can quickly stop treatment if it isn't working or causes serious side effects, he says, adding that although “the efficacy seems less than [with] CAR T cells, these molecules can be given over a long period of time and lead to deepening responses.”

First-generation bispecific antibodies have some drawbacks. For instance, they rapidly break down—blinatumomab's half-life is about 2 hours—which can make dosing cumbersome. They can also trigger acute side effects, including neurotoxicity and cytokine release syndrome, which may have led to two deaths in a Regeneron trial in 2019. These toxicities and increased infection risk remain the biggest obstacles for the drugs, says Kumar.

Amgen jumped into the bispecific antibody market in 2012 when it purchased Micromet, which pioneered the approach and developed blinatumomab. Amgen is now sponsoring eight clinical trials testing its proprietary bispecific antibodies, known as BiTEs. Twelve more trials are evaluating “half-life extended” BiTEs that carry an Fc domain, the tail of a full-sized antibody, and that may last longer.

By purchasing Teneobio, Amgen gains the promising bispecific antibody TNB-585, which binds PSMA. A phase I trial of TNB-585 is under way in patients with metastatic, castration-resistant prostate cancer. Like Amgen's half-life extended varieties, it carries an Fc domain that may increase its longevity. Amgen has been testing its own half-life extended BiTE, acapatamab, which also binds PSMA. The company hasn't announced whether development of acapatamab will continue, given its similarity to TNB-585.

Industry observers have raised questions about the $900 million price tag because the deal excludes some of Teneobio's closely watched products. For example, AbbVie earlier acquired the bispecific TNB-383B, which was developed by a Teneobio subsidiary and yielded an overall response rate of 80% in a phase I study of patients with relapsed or refractory myeloma. A Teneobio affiliate will retain TNB-486, another bispecific, which is being studied in patients with non-Hodgkin lymphomas. –Mitch Leslie