F-star antibodies reaching for the sky

The Austrian company only came into being a year ago, yet has raised €10m so far, including €6m from the newly finished Series A financing. The rest of the cash has come from €1.5m in seed financing and loads and grants from Austrian government agencies. With some traditional monoclonal antibodies (mAbs) now reaching 'blockbuster' status, billions of pharma dollars have been spent this year alone on next-stage synthetically enhanced antibodies or antibody-like drugs​. With productivity within the industry at a low, big pharma firms are spending more and more on license deals in an attempt to fill pipelines. F-star's technology is based on the concept that since only a small proportion of an antibody actually binds to an antigen, it should be possible to use some of this extra molecular space to add in new binding sites. Specifically, the 'Modular Antibody Technology' introduces new binding sites to the non- CDR (complementarity-determining region) loops of constant or variable domains i.e. those loops which do not normally bind to antigens. The company has generated full-sized antibodies that have two extra binding sites engineered into the CH3 domains. It likens these 'mAb²​' molecules to normal antibodies with a "second pair of arms capable of performing therapeutically useful tasks"​. However, this is not the limit of the technology. F-star claims the same technique can be applied to antibody fragments to yield molecules that it claims retain antibody functionality and long half-life but are much smaller. The idea of antibody-like drugs that are much smaller then mAbs - 'mini-antibodies' - is also being exploited at other companies such as Ablynx​ and GlaxoSmithKline, the latter through its acquisition of Domantis​. Fragments that could be used include immunoglobulin constant regions (Fc), antigen binding fragments (Fab) and single chain antibodies (scFv) as well as diabodies, unibodies and single domain antibodies, according to F-star. Of those, it is concentrating on antigen binding Fc fragments (Fcab), which consist of the CH2 and CH3 domains of an antibody, naturally folded as a homodimer with a size of approximately 50kDa - around a third of the size of a full antibody. The molecule has two identical antigen binding sites engineered into the CH3 domains. The non-CDR loops are created using standard techniques such as phage display to generate randomised libraries of antibody fragments. Then, molecules with desired binding properties are selected from these libraries. Gottfried Himmler, CEO and co-founder of F-star said: "This Series A financing...provides a solid financial basis for further development and full exploitation of our unique Modular Antibody Technology. At the same time, it strengthens our international profile and will help us to recruit top talent on an international basis."​ The company currently only employs 15 people at its research site in Vienna. As well as developing the technology, the firm plans to generate lead candidates, both for its own pipeline and for potential partners. One of the venture capitalist firms now investing in F-star is Aescap Venture. That decision was down to Kreske Nickelsen, a partner at the firm. He said: "It's very hard nowadays to find an antibody technology that is both broadly applicable and has strong IP protection. F-star's Modular Antibody Technology is one of these rare cases."​ Atlas Venture has supported the company since its inception, providing both the seed financing and some of this latest cash. Regina Hodits at the company said: "The company now truly has the chance to take antibody-based therapeutics to the next level."​ F-star will hope that in the future, its technology will prove successful in the clinic and that it too can cash in on some of those billions burning a hole in big pharma pockets.