Cancer-Associated Fibroblasts (CAF) are responsible for fibrosis-mediated immunoresistance leading to failure of several therapies in the clinic. PAR2 is a GPCR target expressed by both cancer cells & CAF, and modulating the immunosuppression in the tumor microenvironment. Recent studies have shown that PAR2 is associated with lower response to immunotherapy in multiple solid cancers.
Program description
PAR2 antagonist (DT-9045)
- Discovery
- Candidate
- Preclinical
- Phase I
Domain Therapeutics has discovered novel Negative Allosteric Modulators (NAM) of PAR2 with clear advantages over the competitor biologics targeting PAR2 in the clinic. These PAR2 NAM demonstrated PoC efficacy in syngeneic models potentiating the anti-tumor activity of an anti-PD1. Moreover, a clear biomarker strategy guiding clinical positioning has been set-up for this program. Domain has nominated its candidate, DT-9045 and the pre-IND studies are initiated. Current expectations are start of Phase I mid-2025.
PAR2 has also been shown to be involved in inflammation and fibrotic diseases where a PAR2 NAM has great therapeutic potential