Anticalin®-based therapeutics: Expanding new frontiers in drug development.

Abstract

Anticalin proteins are a novel class of clinical-stage biopharmaceuticals with high potential in various disease areas. Anticalin proteins, derived from extracellular human lipocalins are single-chain proteins, with a highly stable structure that can be engineered to bind with high specificity and potency to targets of therapeutic relevance. The small size and stable structure support their development as inhalable biologics in the field of respiratory diseases as already demonstrated for PRS-060/AZD1402, an Anticalin protein currently undergoing clinical development for the treatment of asthma. Anticalin proteins provide formatting flexibility which allows fusion with the same or other Anticalin proteins, or with other biologics to generate multivalent, multiparatopic or multispecific fusion proteins. The fusion of Anticalin proteins to antibodies allows the generation of potent therapeutic proteins with new modes of action, such as antibody-Anticalin bispecific proteins with tumor-localized activity. Cinrebafusp alfa and PRS-344/S095012 antibody-Anticalin bispecific proteins were designed to reduce potential systemic toxicity by localizing the activity to the tumor, and are currently in clinical development in immuno-oncology. Furthermore, the ease in generating bi- and multispecifics as well as the small and stable structure prompted the investigation of Anticalin proteins for the CAR T space, opening additional potential treatment options based on Anticalin protein therapies.