in patients with advanced, recurrent or metastatic solid tumors : the EPRAD study

• EP4R antagonist is Domain Therapeutics ’ first fully -owned  immuno -oncology asset t o enter clinic

• Unique clinical  strategy focused on unlocking new possibilities in the treatment of cancer

Strasbourg, France – Montreal, Canada, January 5, 2023 – Domain Therapeutics  (“Domain” or “the Company”) , a drug discovery and development company fo cused on G Protein -Coupled Receptors (GPCRs) in immuno -oncology (IO), today announce s that the first patient has been dosed  with DT -9081, Domain’s proprietary IO asset,  in a first -in-human Phase I study.
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DT-9081 is an oral small molecule product  which , by blocking the EP4 receptor present on immune cells, is able to reverse the prostaglandin E2 (PGE2) -mediated immunosuppressi on triggered by some tumors to bypass the immune system . In preclinical studies , the asset demonstrated strong anti -tumor effects and synergies with immune checkpoint inhibitors  in multiple models . The Phase I study , named  EPRAD , is a multi - center, open -label study  that will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of DT -9081 in adult patients with advanced, recurrent or metastatic  solid tumors who have failed standard of care therapies.  Domain has developed a p recise biomarker strategy that is being applied in the clinical study to track target engagement  and signs of activity  and to optimize the selection of patients and, ultimately, deliver improved clinical outcomes.

Dr. Pascal Neuville, CEO of Domain Thera peutics, commented: “The successful initiation of this first -in- human study is a significant milestone for Domain. Our differentiated approach to tackling cancer with GPCR - based drug candidates is built on the premise that every cancer  is unique . By treating patients  based on their individual cancer signatures we can deliver targeted, scientifically validated therapies. We look forward to progressing this clinical study as we continue to demonstrate the potential of our optimized pipeline of GPCR assets that we believe will unlock new possibilities in the treatment of cancer .”

Professor Jean -Pascal Machiels , Saint -Luc Hos pital Brussels and  Lead Investigator of the study , commented: “Innate or acquired immunosuppression is a complex and significant challenge in the clinic  and remain s an unmet need in many patient populations.  By blocking the EP4 receptor, I believe th at DT -9081 has the potential to address this challenge  and offer new hope for patients. The findings from the preclinical studies of DT -9081 are clearly encouraging and we are pleased to progress such a promising product with multi - tumor potential through clinical development. ”

The overall objectives of the EPRAD study are to determine the maximum tolerated dose and/or the recommended clinical dose of DT -9081 and to evaluate its safety and preliminary efficacy . The study comprises two parts with the first part focusing on dose -escalation with the ultimate aim of establishing the recommended clinical  dose, and the second part consisting of an expansion phase to validate the dose and schedule of administratio n in addit ion to assessing the preliminary efficacy of the asset. For further details about the study, please refer  to clinicaltrials.gov  NCT0558 2850 .

Four expert clinical investigators  are contributing this clinical study ; in Brussels, Belgium, Prof Jean -Pascal Machiels  from Saint Luc Hospital and Dr Nuria Kotecki from Institut Jules Bordet , in France,  Prof Christophe Le Tourneau from Institut Curie in Paris and Prof Jean -Pierre Delord from Institut Claudius Regaud in Toulouse.

For more information, please contact:

Consilium Strategic Communications Amber Fennell, Namrata Taak , Maya Bennison

Email: DomainTherapeutics@consilium -comms.com

Tel: +44 (0)20 3709 5813

NewCap (for French media)

Annie -Florence Loyer

Email: afloyer@newcap.fr

Tel: +33 (0)1.44. 71.02.12

About Domain Therapeutics

Domain Therapeutics is developing innovative immunotherapies targeting  G Protein -Coupled Receptors (GPCRs ) to unlock new possibilities in cancer. As a leader in GPCRs in immuno -oncology , Domain sees cancer differently, using a precise biomarker strategy to address the specific needs of patients based on unique signatures of individual cancers. Backed by decad es of research and validated by multiple pharma partnerships, the Company’s unriva lled discovery engine enables rigorous GPCR target identification and selection .

Domain has a clinical stage portfolio with its A2aR/A2bR asset in development through a par tnership with Merck KGaA and its fully owned EP4R antagonist, DT -9081, recently en tering Phase I trials. The Company is also progressing an anti -CCR8 asset alongside a rich, optimized pipeline of first -in-class GPCR targets selected through Domain’s drug d iscovery engine. Domain is backed by a syndicate of leading international venture capital funds  from Europe, Asia and North America. For more information, please visit:

www.domaintherapeutics.com