Domain Therapeutics to Present Data on its GPCR Lead Programs at AACR Annual Meeting 2025

• Presentation of Phase I clinical results from DT-9081, an EP4 receptor antagonist, and preclinical data on DT-7012, a Treg depleting anti-CCR8 antibody
• Preclinical findings highlight immuno-oncology breakthrough properties for its PAR2 biased negative allosteric modulator program
• Posters present the potential of GPCRs to modulate the tumor microenvironment and enhance anti-tumor immunity

STRASBOURG, France, MONTREAL and BOSTON, April 1, 2025 /PRNewswire/ -- Domain Therapeutics ("Domain" or "the Company"), the GPCR experts harnessing deep receptor biology to develop breakthrough treatments for patients, today announces that it will be presenting new preclinical and clinical data on its key oncology programs – DT-7012, and DT-9081, alongside preclinical findings on its PAR2 biased negative allosteric modulator (NAM) program – at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2025, taking place in Chicago, US from 25-30 April 2025.

The poster presentations will highlight Domain's progress in leveraging GPCR-targeting therapies to modulate the tumor microenvironment and enhance anti-cancer immune responses.

Details of the poster presentations are as follows:

Poster Title: Comprehensive Characterization of DT-7012, a Differentiated CCR8-Depleting Antibody for the Treatment of Solid Tumors
Session Category: Experimental and Molecular Therapeutics
Session Title: Antireceptors and Other Biological Therapeutic Agents
Date and Time: Sunday 27^th April 2025, 14:00 – 17:00 CDT
Location: Poster Section 15
Poster Board Number: 4
Abstract Number: 7080

DT-7012 – A Differentiated CCR8-Depleting Antibody for Solid Tumors
DT-7012 is a highly selective, fully humanized monoclonal antibody targeting CCR8, a receptor predominantly expressed on tumor-resident regulatory T cells (Tregs), which suppress anti-tumor immunity. The study characterizes DT-7012's binding properties, effector functions, and Treg-depleting activity, supporting its transition into clinical development.

Poster Title: Clinical PK, PD and safety analysis of a phase I clinical trial of DT-9081, an EP4R-antagonist, for RP2D determination in patients with advanced solid tumors
Session Category: Clinical Research
Session Title: Modifiers of the Tumor Microenvironment
Date and Time: Monday 28^th April 2025, 14:00 – 17:00 CDT
Location: Poster Section 30
Poster Board Number: 8
Abstract Number: 7450

DT-9081 – Phase I Clinical Data of an EP4R Antagonist for Advanced Solid Tumors
DT-9081 is an oral EP4 receptor (EP4R) antagonist designed to inhibit growth by blocking prostaglandin E2 (PGE2)-mediated immune suppression. Interim Phase I results demonstrate DT-9081's favorable safety profile, linear pharmacokinetics, and dose-dependent inhibition of EP4R signaling, with data supporting the recommended Phase II dose (RP2D).

Poster Title: PAR2 inhibitors reduce resistance to immunotherapy against cancer
Session Category: Immunology
Session Title: Interplay between Immune System and Radio-, Chemo- and Targeted Therapies 2
Date and Time: Tuesday 29^th April, 14:00 – 17:00 CDT
Location: Poster Section 40
Poster Board Number: 9
Abstract Number: 6606

PAR2 - Pivotal driver of resistance to immune checkpoint blockade (ICB) and T cell dysfunction in cancer
PAR2 biased NAM represents a transformative breakthrough in immuno-oncology, targeting tumor resistance to ICB. Preclinical findings demonstrate the unique mode of action of PAR2 inhibition. By reshaping the tumor microenvironment, it reduces immunosuppressive macrophages and increases antigen presentation, fostering robust anti-tumor immune responses and thereby improving patient outcomes.

Stephan Schann, Chief Scientific Officer of Domain Therapeutics, said: "These promising preclinical and clinical results for DT-7012 and DT-9081, alongside the preclinical findings on our PAR2 biased NAM demonstrate Domain's unmatched knowledge in leveraging deep receptor biology to develop differentiated oncology treatments. We look forward to sharing these promising insights with the scientific community as we continue to push the boundaries to ultimately deliver better treatments and transform patients' lives."

Abstracts are available in an online itinerary planner found here and will be available in an online only supplement to the AACR journal Cancer Research one month after the conference.

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.

About American Association for Cancer Research (AACR) Annual Meeting
The American Association for Cancer Research (AACR) Annual Meeting is a leading global event showcasing the latest advances in cancer research, prevention, diagnosis, and treatment. It brings together researchers, clinicians, industry leaders, and patient advocates to drive progress against cancer.