Domain Therapeutics to Showcase Novel GPCR-Targeting Oncology Programs at AACR 2025
Key Insights
Domain Therapeutics (search) will present Phase I clinical data for DT-9081, an EP4 receptor (search) antagonist showing favorable safety profile and dose-dependent inhibition of EP4R signaling in advanced solid tumors (search).
Preclinical findings for DT-7012, a highly selective anti-CCR8 (search) antibody, demonstrate effective depletion of tumor-resident regulatory T cells, potentially enhancing anti-tumor immunity in solid tumors (search).
The company will also present breakthrough preclinical data on its PAR2 (search) biased negative allosteric modulator program, which shows promise in reducing resistance to immune checkpoint blockade therapy.
Domain Therapeutics (search), a clinical-stage biopharmaceutical company specializing in G protein-coupled receptors (GPCRs (search)), has announced plans to present new data on its lead oncology programs at the upcoming American Association for Cancer Research (search) (AACR) Annual Meeting 2025, scheduled for April 25-30 in Chicago.
The company will showcase both clinical and preclinical findings from three key programs targeting the tumor microenvironment: DT-9081, DT-7012, and a PAR2 (search) biased negative allosteric modulator (NAM) program.
Phase I Results for EP4 Receptor Antagonist DT-9081
Domain will present interim Phase I clinical data for DT-9081, an oral EP4 receptor (search) antagonist designed to block prostaglandin E2 (PGE2)-mediated immune suppression in advanced solid tumors (search). The results demonstrate DT-9081's favorable safety profile, linear pharmacokinetics, and dose-dependent inhibition of EP4R signaling.
The data supports the establishment of a recommended Phase II dose (RP2D), marking a significant milestone in the drug's development pathway. By targeting the EP4 receptor (search), DT-9081 aims to reduce immunosuppression within the tumor microenvironment, potentially enhancing anti-tumor immune responses.
"These promising clinical results for DT-9081 demonstrate our ability to translate deep receptor biology into differentiated oncology treatments," said Stephan Schann, Chief Scientific Officer of Domain Therapeutics (search).
The EP4 receptor (search) has emerged as an important target in oncology due to its role in mediating the immunosuppressive effects of PGE2, which is often overproduced in various cancer (search) types.
DT-7012: A Novel Approach to Treg Depletion
The company will also present comprehensive preclinical characterization of DT-7012, a highly selective, fully humanized monoclonal antibody targeting CCR8 (search). This receptor is predominantly expressed on tumor-resident regulatory T cells (Tregs), which are known to suppress anti-tumor immunity.
The data will highlight DT-7012's binding properties, effector functions, and Treg-depleting activity, providing strong support for its advancement into clinical development. By selectively depleting tumor-resident Tregs while sparing peripheral Tregs, DT-7012 represents a potentially safer approach to enhancing anti-tumor immunity compared to broader immunomodulatory strategies.
Tumor-infiltrating Tregs represent a major barrier to effective anti-tumor immune responses, and selective depletion of these cells has shown promise as a therapeutic strategy in preclinical models.
Breakthrough Findings on PAR2 Inhibition
Perhaps most intriguing are the preclinical findings on Domain's PAR2 (search) biased negative allosteric modulator program, which the company describes as a "transformative breakthrough in immuno-oncology."
The data demonstrates that PAR2 (search) inhibition can reshape the tumor microenvironment by reducing immunosuppressive macrophages and increasing antigen presentation, thereby fostering robust anti-tumor immune responses. Importantly, the findings suggest that PAR2 inhibition may reduce resistance to immune checkpoint blockade (ICB) therapy, potentially improving outcomes for patients who don't respond to existing immunotherapies.
"PAR2 (search) has emerged as a pivotal driver of resistance to immune checkpoint blockade and T cell dysfunction in cancer (search)," explained Schann. "Our biased NAM approach offers a unique mode of action that could significantly improve patient outcomes."
Leveraging GPCR Biology for Cancer Treatment
Domain's presentations highlight the company's strategic focus on GPCRs (search) as targets for cancer (search) therapy. Despite being the most validated drug target family—with 30-35% of all marketed drugs acting on GPCRs—only about 10% of potential GPCR targets have been successfully drugged.
While GPCR-targeted drug development has traditionally focused on central nervous system and cardio-metabolic disorders, Domain is pioneering their application in immuno-oncology and inflammatory diseases.
"These three programs exemplify our unmatched knowledge in leveraging deep receptor biology," Schann noted. "We continue to push the boundaries to ultimately deliver better treatments and transform patients' lives."
About Domain Therapeutics
Domain Therapeutics (search) is developing highly differentiated therapeutic strategies targeting GPCRs (search), with a robust regulatory and clinical pipeline focused on immuno-oncology and inflammation. The company's key programs include a first-in-class biased antagonist of PAR2 (search) and a best-in-class Treg-depleting anti-CCR8 (search) antibody.
The company leverages its proprietary drug discovery and development approach, founded on a unique platform and extensive knowledge of GPCR receptor biology, to unlock challenging GPCR targets. Domain's expertise, developed over two decades, has enabled successful collaborations with major pharmaceutical companies, key opinion leaders, and physicians worldwide.
The AACR Annual Meeting is a leading global event showcasing the latest advances in cancer (search) research, prevention, diagnosis, and treatment. Domain's poster presentations will take place on April 27-29, 2025, providing the scientific community with detailed insights into the company's innovative approaches to cancer treatment.