Domain Therapeutics Discloses DT-9046 as a Groundbreaking Oral Drug Candidate for Inflammatory Diseases

• DT-9046 is a highly differentiated first-in-class biased negative allosteric modulator of PAR2 with game changing potential across multiple inflammatory diseases
• Unique mechanism of action with potential to directly impact inflammation, tissue damage, and pain

STRASBOURG, France, MONTREAL, BOSTON, March 20, 2025 /PRNewswire/ -- Domain Therapeutics ("Domain" or "the Company"), the GPCR experts harnessing deep receptor biology to develop breakthrough treatments for patients, today announces it has nominated and is progressing DT-9046, a candidate with game-changing potential in multiple inflammatory disease markets, including atopic dermatitis (AD), inflammatory bowel disease (IBD), arthritis but also neuroinflammation including migraine.

PAR2 has emerged as a pivotal therapeutic in inflammatory diseases due to its unique ability to fine-tune immune and inflammatory responses, barrier integrity, and pain, however it is proven to be a difficult receptor for the pharmaceutical industry to target effectively.

By leveraging Domain's expertise to address challenging GPCRs, DT-9046 represents a groundbreaking advancement in PAR2 modulation employing a differentiated mechanism of action, targeting an allosteric binding site to fine-tune GPCR function and boost efficacy against this complex target. Unlike other PAR2-targeting strategies, primarily biologics and full antagonists, DT-9046 is the first oral PAR2-targeting drug to reach pre-IND studies. Combined with its biased ligand approach, this strategy offers an innovative therapeutic solution, modulating only the pathways critical to therapeutic effects while minimizing the risk of resistance.

Stephan Schann, Chief Scientific Officer of Domain Therapeutics, said: "DT-9046's discovery exemplifies our mission to translate promising science into differentiated therapies that address unmet medical needs. It also illustrates the power of our proprietary platform, which leverages advanced technology and unmatched expertise to fine-tune the activity of GPCRs, unlocking their full therapeutic potential. With its differentiated mechanism of action and oral administration, DT-9046 has the potential to be disease-modifying as a monotherapy and in combination, offering new hope to millions of patients."

DT-9046 is currently progressing through pre-IND studies, supported by a robust data package and strong patent protection. Preclinical studies have demonstrated potent and selective modulation of the immune response, which plays a crucial role in various inflammatory conditions, particularly in AD and IBD.

Inflammation is a key part of the body's immune defense, but when it becomes overactivated it can cause inflammatory conditions or diseases. Domain's innovative approach addresses challenges inherent in PAR2-targeting strategies by leveraging biased signaling, which offers a significant competitive edge compared to other PAR2 biologics with different pharmacological profiles. Beyond creating significant value for Domain's pipeline, it demonstrates the Company's unparalleled expertise in GPCR biology, paving the way for novel treatments for complex diseases.

About Domain Therapeutics

Domain Therapeutics is a clinical-stage biopharmaceutical company developing highly differentiated therapeutic strategies targeting G protein-coupled receptors (GPCRs), a crucial class of drug targets. Its robust regulatory and clinical pipeline aims to address significant unmet medical needs, offering novel solutions for patients, particularly in immuno-oncology and inflammation. Domain's key programs include a first-in-class biased antagonist of PAR2 and a best-in-class Treg-depleting anti-CCR8 antibody. These innovative therapies are driving value creation, positioning the company in a competitive and fast-expanding market.

Domain leverages its proprietary drug discovery and development approach, founded on a unique platform and unmatched knowledge of GPCR receptor biology, to successfully unlock very challenging GPCR targets, including intractable and orphan receptors. The team's expertise, developed over two decades, is reflected in its solid track record of collaboration with major pharma, KOLs and physicians worldwide. By integrating detailed biological understanding of GPCRs at each step of the drug discovery and development process, Domain creates highly effective and differentiated drugs that target specific pathways, thereby improving therapeutic efficacy. For more information, please visit https://www.domaintherapeutics.com/   

About GPCRs

G Protein-Coupled Receptors (GPCRs) are at the top of complex signaling cascades and are responsible for translating extracellular messages into intracellular actions, making them critical for various biological processes and attractive for therapeutic intervention. Despite being the most validated drug target family, with 30-35% of all marketed drugs acting on them, they remain challenging to drug, with existing drugs targeting only 10%  of the total potential GPCR targets. While most efforts in GPCR drug discovery and development have traditionally focused on central nervous system and cardio-metabolic disorders, Domain recognizes the untapped potential of GPCRs in immuno-oncology and inflammatory diseases, areas where GPCRs have not been as extensively explored.