Bispecific biologics rush

Abstract

In late August, Vancouver-based Zymeworks inked a deal worth up to $187 million plus royalties to advance bi-specific antibodies for Merck of Whitehouse Station, New Jersey. A week later Vienna-based f-star announced a collaboration with Merck Serono of Geneva to discover bi-specific IgGs against the pharma’s targets, in a deal worth up to $676 million plus royalties. Such major deals in rapid succession suggest that bi-specific antibody platforms have matured enough to attract investment from big pharma. “Deals tend to come in lumps,” says Carl Gordon, a partner at healthcare investment firm OrbiMed Advisors based in New York. Gordon points to a May publication (J. Clin. Oncol. 29, 2386–2390, 2011) showing strong efficacy for Carlsbad, California–based Micromet’s blinatumomab in a phase 2 trial for acute lymphocytic leukemia. Micromet’s antibody is a bi-specific T-cell engager (BiTE), which binds CD19 on B cells and a CD3 site for T cells. “That is probably a proof of concept for the whole field,” Gordon says. Zymeworks’ platform consists of in silico– designed heterodimeric IgG scaffolds containing two different but complementary heavy chain subunits. f-star’s bi-specific antibodies can be engineered with three antigen binding sites, so that they are heterovalent for one epitope and monovalent for another. The technology has matured enough to solve some inherent problems, and to generate “data that are interesting enough to get those deals,” adds Jean-François Formela, partner at Atlas Venture in Cambridge, Massachusetts, and a member of f-star’s board of directors.