Pharma Focus Europe

Domain Therapeutics unveils DT-9045, a groundbreaking PAR2 NAM candidate, for potential advancements in cancer treatment

Tuesday, June 06, 2023

Domain Therapeutics, a clinical-stage biopharmaceutical company focused on immuno-oncology drugs that target G Protein-Coupled Receptors (GPCRs), has announced the selection of its latest drug candidate, DT-9045. This candidate is a Negative Allosteric Modulator (NAM) of protease-activated receptor 2 (PAR2) and shows great potential as a first-in-class treatment for fibrotic tumors in immuno-oncology.

The company utilizes a proprietary cross-validation platform, which incorporates preclinical and clinical data, to carefully select and validate GPCR targets associated with immunosuppressive mechanisms. With its extensive expertise in GPCRs accumulated over two decades, Domain has developed a novel series of potent and selective PAR2 NAMs. PAR2 is an innovative therapeutic target in oncology and immuno-oncology, involved in tumor proliferation, immunotherapy resistance, and fibrosis.

DT-9045 has been chosen as the clinical candidate for PAR2 NAM due to its unique properties and superior therapeutic potential compared to biologics targeting PAR2 currently under development by competitors. In syngeneic models, DT-9045 has demonstrated proof-of-concept efficacy by enhancing the anti-tumor activity of an anti-PD1 treatment.

Domain's PAR2 NAM approach offers distinct pharmacological features that differentiate it from competitors:

G-protein biased NAM activity on PAR2, without impacting the b-Arrestin pathway and ligand-induced receptor internalization.

Unsurmountable property that enables efficacy even at high ligand concentrations found in the tumor microenvironment.

Activity maintained at acidic pH levels typically present in inflammatory and tumoral environments.

To guide the clinical positioning of DT-9045, Domain has established a clear biomarker strategy. Pre-IND studies are currently in progress, and the company expects Phase I ascending dose studies to begin by mid-2025, focusing on patients with recurrent or metastatic solid tumors.

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