Betting on bispecifics

CAMBRIDGE, U.K.—In their first collaboration together, AbbVie and F-star, a biopharmaceutical company developing bispecific antibody products in immuno-oncology and inflammation, are looking to develop therapeutics against a pair of immuno-oncology targets. Per the terms of the agreement, F-star and AbbVie will create Fcabs against two immuno-oncology targets and generate several mAb2 drug development candidates from them. AbbVie Biotherapeutics will lead the research activities for AbbVie for this collaboration. Financial details were not released, and additional information on the selected targets was not disclosed.

“We are very excited to be working with AbbVie on these immuno-oncology programs to develop new bispecific antibodies,” Dr. John Haurum, CEO of F-star, commented in a press release. “Bispecific antibodies are expected to be the cornerstone of the next generation of immuno-oncology products, and this collaboration validates our technology as truly novel and differentiated in the space.”

Haurum says the combination is a good match, noting that “We've got a strong focus in immuno-oncology with the work we're doing in building our own pipeline at the moment, and AbbVie is one of the companies that has also a strong focus in that space, so there's a good synergy there. We will be able to work with AbbVie to generate some strong programs together, given our combined capabilities and skills.”

As F-star explains on its website, monoclonal antibodies have two key regions, “one that binds to a specific target protein, called the variable (Fab) region,” and “one responsible for attracting the immune system, called the constant (Fc) region.” The company's Modular Antibody Technology can rapidly and reliably exploit both regions, and its discovery engine can create constant (Fc) regions with desired drug properties against a target of interest, also known as an Fcab. “An Fcab against a target of interest can be combined with the variable region (Fab) of an existing antibody to generate a full-length bispecific antibody or mAb2,” F-star explains, and “These bispecific monoclonal antibodies maintain the full functionality, structural integrity and stability of regular antibodies.”

“We have a platform for making bispecific antibodies where we will in essence create a building block that you can use in conjunction with an existing antibody,” Haurum explains. “If AbbVie has an existing antibody against an existing target, we can replace our building block into their antibody.”

While Haurum says monoclonal antibodies are seeing good responses in patients, some to the extent of complete responses, those reactions are generally limited to small numbers of patients. Combining monoclonal antibodies could potentially improve the response rate and address toxicity issues, and he notes that “We at F-star are of the strong belief that it will be possible for certain and carefully identified combinations to make even further improvements by using bispecifics.” Bispecific antibodies could potentially offer a variety of improvements over combination therapies, such as improved potency, safety profile and cost efficiency.

In other recent news for F-star, the company announced in October that it had published data in Molecular Therapy for FS102, its lead compound, detailing its antitumor effects in preclinical animal models. FS102 was found to bind human epidermal growth factor receptor 2 (HER2) with high affinity and induced complete tumor regression and tumor cell apoptosis in animal models due to internalization and degradation of HER2. The compound was also found to recognize an epitope that does not overlap with those of trastuzumab or pertuzumab.

FS102 is a HER2-specific Fcab currently in Phase 1 clinical testing in HER2-positive breast cancer and gastric cancer patients. Bristol-Myers Squibb is conducting the trial under an agreement with F-star Alpha Ltd. initiated in October 2014 that gives Bristol-Myers Squibb the exclusive option to acquire F-star Alpha and gain worldwide rights to the FS102 program.