First-in-class WASp activators targeting autoimmune disorders

The Wiskott-Aldrich syndrome protein (WASp) is essential for healthy immune function, playing a critical role in organizing the cell’s internal skeleton and regulating immune cell activities such as movement, signaling, and response to infection. A dysfunction of WASp activity can cause serious immune system disorders, including autoimmunity, where the body mistakenly attacks its own tissues. Recent research, for example using preclinical models with WASp KO has shown that restoring or boosting WASp activity may help reverse these harmful immune responses. For example, in animal models, enhancing WASp function has been shown to prevent or reduce diseases like colitis and arthritis by rebalancing immune cells.

This project proposes a new therapeutic strategy: the development of small-molecule drugs that activate WASp to treat several autoimmune diseases. Led by an innovative Dutch SME Bimini Biotech and supported by Dr. Marije Koenders and Dr. Arjan van Caam at Radboud University Medical Center, this project will focus on identifying and testing potential drug candidates that selectively activate WASp. Promising compounds will be evaluated through advanced lab and animal studies to assess their ability to correct immune dysfunction.

Bimini has already developed an early lead candidate and validated in a mice model of DSS induced colitis. We now aim to optimize the druggability and build a larger portfolio of WASp modulating leads while delivering a translational package of preclinical efficacy with mechanistic reasonings. The objectives are:

a) Diversifying current asset portfolio while improving druggability (WP1  Deliver new IP)
b) Mechanistic investigation to support the mode of action in context of reducing autoimmunity (WP2)
c) Demonstrate efficacy for leads in a specialized mice model of rheumatoid arthritis (WP2)

By targeting WASp, we aim to open a new treatment avenue for a range of autoimmune disorders with high unmet medical need.