A star is born

Boehringer Ingelheim draws a bead on multiple antibody targets and therapeutic areas in a collaboration with Austria’s f-star

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VIENNA—f-star Biotechnologische Forschungs-und Entwicklungsges mbH recently inked a licensing agreement with Boehringer Ingelheim (BI) for joint discovery of new antibody-derived therapeutic products based on f-star's Modular Antibody Technology, which involves the introduction of antigen binding sites into parts of the antibody molecule that normally do not participate in the antibody-antigen interaction.

The technology is modular in the sense that one Fcab can act as a module for the construction of numerous mAb2s. BI will nominate up to seven targets, which may span multiple therapeutic areas, against which the parties will collaborate to jointly discover Fcabs for further global development and commercialization by BI, either as therapeutic products in their own right, or as modules for the generation of bispecific mAb2 products.

Fcabs are the Fc regions of normal antibodies (IgGs) that have an antigen binding site engineered into the loops found at the very bottom of the CH3 domains; mAb2s are bispecific antibodies in which an existing antibody with specificity for a target of interest is modified by replacing its Fc region with an Fcab that binds to a second target of interest.

Although the two parties aren't divulging details concerning their working relationship, Dr. Kevin FitzGerald, CEO of f-star, did explain the rationale for the collaboration: "Because the discovery technologies associated with conventional antibodies are now old and expiring, it is not easy for developers of conventional antibodies to establish an intellectual property ring-fence around new therapeutic mAbs to a given target," he says. "Companies that have proprietary antibody technology that can claim biological and clinical differentiation from conventional antibodies are therefore of growing interest to pharma."

Under the terms of the agreement, f-star will receive an initial technology access fee, and research-based funding, and is eligible to receive additional license fees, development, regulatory and commercial milestones and undisclosed tiered royalties on product sales. BI can select several therapeutic products from each of seven discovery programs. The total payment to f-star for each of these programs, excluding royalty payments, could reach up to $238 million in case of full commercial success of multiple therapeutic products.

Typical antibody-antigen interaction takes place through contacts with loops in the antibody variable domains called the CDRs or Complementarity Determining Regions. f-star is able to modify any of the other loops in the antibody molecule in order to create antigen binding sites—such loops being polypeptide sequences that join the numerous beta-strands that are contained within the various immunoglobulin domains that form an antibody's overall structure. Non-CDR loops are therefore present in the variable domains, opposite the CDR loops, and in all of the constant domains within the antibody.

f-star's Modular Antibody Technology facilitates the introduction of additional antigen-binding sites into antibodies and antibody fragments by engineering the non-CDR loops of constant or variable domains. This allows the company's scientists to generate antibody fragments with full antibody functionality and long half-life, but with much smaller size (Fcab) and full antibodies with additional functionality or bispecificity (mAb2).

FitzGerald notes that the agreement with BI holds promise of delivering novel therapeutic proteins to patients with poorly treated illnesses.

"f-star's antibody-based products are clearly differentiated from conventional antibodies and other protein-based drugs," he says. "This partnership will enable our company to expand the exploitation of our technology by combining with the impressive global research and development capabilities and resources of Boehringer Ingelheim."



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