Big pharma pursues next generation of antibodies

Seeing monoclonal antibodies rank among the top-selling pharmaceuticals, major drug companies are investing in the next generation of engineered antibodies and antibody-drug conjugates (ADCs).

Leading the way is AbbVie, which had $14 billion in sales last year of the top-selling antibody, Humira, but faces looming patent expirations on the anti-inflammatory drug.

AbbVie will pay $5.8 billion in cash and stock to acquire Stemcentrx, an eight-year-old company that has five oncology agents in clinical trials. The most advanced candidate is Rova-T, a rovalpituzumab tesirine ADC in Phase III trials against small cell lung cancer. AbbVie could pay Stemcentrx shareholders another $4 billion in milestone payments.

At the same time, AbbVie will pay $40 million up front and up to $645 million in milestones to help Argenx develop its preclinical cancer immunotherapy ARGX-115. The Dutch firm engineers the targeting, binding, and other features of antibodies created within the immune system of llamas.

And AbbVie will spend another $30 million up front and up to $470 million more to work with CytomX Therapeutics, which designs ADCs that deliver cytotoxic payloads to tumor cells while avoiding healthy cells. An initial target will be the tumor antigen CD17.

Meanwhile, GlaxoSmithKline is investing $36 million up front and up to $872 million in milestones to get Zymeworks’ technology for generating bispecific antibodies. And Takeda Pharmaceutical and Eli Lilly & Co. have struck agreements with Adimab, a developer of monoclonal and bispecific antibodies.

With only a handful approved, ADCs and engineered or bispecific antibodies are niche products. But 50 or more of each are in development, and annual market growth could reach 40%, according to the market research firm Roots Analysis. ADC sales, for example, are predicted to grow from about $1 billion today to $10 billion by 2025.

“Monoclonals are very useful, but we are seeing more and more cases where we need extra punch or oomph, and that is where bispecifics and ADCs come in,” says David Poon, Zymeworks’ director of R&D alliances. “One of our lead compounds is a bispecific drug conjugate, so we are actually already thinking about combining different aspects of these next-generation platforms.”