Domain Therapeutics has presented new clinical and preclinical data from its immuno-oncology pipeline at the American Association for Cancer Research (AACR) Annual Meeting 2025. The company’s presentations focused on three of its GPCR-targeting programs: the EP4 receptor antagonist DT-9081, the anti-CCR8 monoclonal antibody DT-7012, and its PAR2 biased negative allosteric modulator (NAM) program.

DT-9081: Early clinical results in solid tumors

In a Phase I clinical trial, DT-9081 was administered orally to patients with advanced solid tumors. The compound demonstrated dose-proportional pharmacokinetics and sustained engagement of the EP4 receptor, as measured by cytokine release. No dose-limiting toxicities were reported at the highest doses tested (400 mg and 600 mg), and one-third of participants achieved stable disease after two cycles of treatment. Based on these findings, a dose of 600 mg has been selected as the recommended Phase II dose (RP2D).

“These results validate our approach to targeting the EP4 receptor to disrupt immunosuppressive signaling in the tumor microenvironment,” said Dr. Stephan Schann, Chief Scientific Officer at Domain Therapeutics. “The safety profile and biological activity of DT-9081 support its continued development in solid tumors.”

DT-7012: Preclinical validation of a CCR8-targeting antibody

The company also shared data on DT-7012, an anti-CCR8 monoclonal antibody designed to deplete CCR8-expressing regulatory T cells (Tregs) in the tumor microenvironment. The preclinical studies demonstrated strong binding affinity, high selectivity for CCR8, and sustained effector functions under challenging conditions. Importantly, the antibody avoided depletion of non-target immune cells, indicating a favourable safety profile. The program is expected to enter Phase I/II trials later in 2025.

“CCR8 is emerging as a critical target in immuno-oncology, particularly in tumors with high Treg infiltration,” said Dr. Schann. “DT-7012’s profile suggests it could offer a more precise approach to immune modulation compared to current therapies.”

PAR2 biased NAM: Overcoming checkpoint inhibitor resistance

In collaboration with researchers at the Centre Hospitalier de l’Université de Montréal (CHUM), Domain presented findings from its PAR2 biased NAM program. Preclinical data showed that the compound enhanced responses to anti-PD1 treatment, shifted macrophage profiles toward a pro-inflammatory phenotype, and promoted antigen-presenting cell and T cell activity—effects that may help overcome resistance to immune checkpoint blockade.

“This collaboration with Domain Therapeutics highlights the potential of GPCR modulation to address some of the major limitations of current immunotherapies,” said Prof. John Stagg, Principal Investigator at CHUM and a member of Domain’s Scientific Advisory Board. “Targeting PAR2 represents a promising strategy to reinvigorate immune responses in resistant tumors.”

Taken together, the data underscore Domain’s focus on GPCR-targeted strategies to reprogram the tumor microenvironment and support immune-mediated tumor control. The company’s approach is aimed at addressing mechanisms of immune evasion and treatment resistance, key challenges in oncology drug development.