DARPin

[3][4][5][6] The DARPin platform was discovered and developed in the laboratory of Andreas Plückthun at the University of Zurich, Switzerland while studying engineering and libraries of recombinant antibodies.

[15] Potentially, DARPins can provide clinical benefit by overcoming the limitations of conventional therapeutic approaches, which typically target a single disease pathway and thus may compromise efficacy.

DARPin technology can be leveraged to rapidly generate thousands of different "multi-DARPins" where the binding domains are connected (i.e., by linkers), thereby enabling the targeting of several disease pathways.

The diversity of formats and robustness of multi-DARPins facilitates an empirical approach (such as through outcome-based screening) to efficiently identify DARPins with potential activity in specific disease pathways.

Their small size (14-18 kDa) is thought to enable increased tissue penetration, and their high potency (<5-100 pM) makes DARPins active at low concentrations.

Their pharmacokinetic (PK) properties can be adjusted by fusion to half-life extending molecules, such as polyethylene glycol (PEG), or to DARPins binding to human serum albumin.

[19] In July 2014, Molecular Partners initiated a first-in-human study to investigate the safety, tolerability and blood levels of MP0250, a second DARPin candidate, in patients with cancer.

[21] Molecular Partners AG has several additional DARPins in preclinical development with potential indications in various disease areas, including ophthalmology, oncology, immuno-oncology and immunology.