Boehringer Ingelheim (BI) is teaming up with f-star for a collaboration focused on developing antibody-derived therapeutics based on the latter’s Modular Antibody Technology. Under terms of the deal BI can designate up to seven targets in multiple therapeutic areas, against which the firms will develop Fcab™ antibody fragment candidates. BI will have the opportunity to license these fragments for development and commercialization either as therapeutic products, or for use in the development of bispecific mAb2 products.
F-star will receive an initial technology access fee and research funding, and could receive additional license fees and milestones of up to €180 million if multiple products reach the market.
Based in Austria and the U.K., f-star’s Modular Antibody Technology allows the introduction of additional binding sites into antibodies and antibody fragments, by engineering the non-CDR loops of constant or variable domains. The firm claims the technology enables the design of both small-sized antibody fragments that retain full antibody functionality (its Fcab™ antigen binding fc molecules), or full-length antibodies that have additional functionality built in (known as mAb² products).
The Modular Antibody Technology can be used to build extra functionality into therapeutic antibodies or antibody fragments of any size without changing the basic molecular structure of the respective starting molecule, f-star claims. The platform can be applied to full antibodies, immunoglobulin constant regions (Fc), antigen-binding fragments (Fab), and single-chain antibodies (scFv) as well as diabodies, unibodies, and single-domain antibodies. Binding sites can be engineered against a broad range of therapeutically useful targets, the firm adds.
The resulting Fcab platform is a protein-engineering scaffold comprising the CH2 and CH3 domains of an antibody, naturally folded as a homodimer of about 50 kDa but with two identical antigen-binding sites engineered into the CH3 domains. F-star says that because the essential functional antibody sites are localized in the CH2 and CH3 domains, the Fcab molecule has the potential to offer full antibody functionality but in a much smaller sized molecule.
In contrast, mAb² antibodies are full IgG antibodies with two additional binding sites engineered into the CH3 domains. This type of engineering essentially results in the generation of a normal antibody molecule with a second "pair of arms" capable of performing an additional therapeutic task, f-star maintains. The added binding sites can be designed to impart different forms of new functionality into the final molecule, such as oligovalence (additional binding sites to the same disease antigen), dual targeting (additional binding sites to a second disease antigen), or tissue targeting (additional binding site to tissue-specific markers).
F-star aims to exploit the Modular Antibody Technology both for the in-house development of therapeutic product candidates, and through partnerships with biotech and pharma companies.