#USA #Chicago #oncology #Domain Therapeutics #AACR 2025

Domain Therapeutics Unveils Groundbreaking Oncology Data at AACR 2025 Conference

On April 30, 2025, in Chicago, USA, at the prestigious American Association for Cancer Research (AACR) annual meeting, Domain Therapeutics presented significant advancements in their oncology research. This event underscored the company’s commitment to revolutionizing cancer treatment through innovative therapies targeting G protein-coupled receptors (GPCRs).

Domain Therapeutics, known for its expertise in GPCRs, showcased clinical and preclinical data concerning their lead oncology programs, notably DT-9081, an EP4 receptor antagonist, and DT-7012, an anti-CCR8 antibody designed to enhance anti-tumor immunity. The results demonstrated enduring efficacy and significant advancements in clinical methodologies for battling solid tumors.

Clinical Breakthrough with DT-9081

In a poster presentation labeled #7450, the findings from a Phase I clinical trial focusing on DT-9081 were discussed. The study sought to determine the recommended Phase II dose (RP2D) for patients battling advanced solid tumors. Revealing exciting results, DT-9081 showed promise in promoting tumor suppression while aiding immune responses. Key highlights from the trial include:

• - Target Engagement: Continuous engagement with the EP4 receptor was achieved, illustrated by cytokine release assessments and a favorable pharmacokinetic (PK) profile at a dosage of 600 mg.
• - Safety Profile: The outcomes were encouraging, with no dose-limiting toxicities identified at the maximum dosages (400 mg and 600 mg). Remarkably, one-third of the participants displayed stable disease following just two cycles of treatment.

These results not only confirm the effectiveness of DT-9081 but also map out a pathway for future clinical development targeting patients with advanced solid tumors, particularly focusing on optimizing the dosing strategy.

The Differentiation of DT-7012

Presentation #7080 centered on DT-7012, a Treg-depleting anti-CCR8 monoclonal antibody. Here, preclinical data underscored its distinct advantages compared to other candidates currently in clinical stages. The uniqueness of DT-7012 lies in:

• - Specificity for CCR8: Demonstrated a potent affinity toward CCR8, effectively facilitating the depletion of CCR8+ Tregs without impacting circulating immune cells.
• - Functional Efficacy: This antibody retains its activities even in high concentrations of its ligand, CCL1, enabling it to thwart CCL1-induced receptor internalization.

These revolutionary characteristics position DT-7012 as a frontrunner in combating immune evasion linked to solid tumors, paving the way for its anticipated Phase I/II trials in 2025.

Insights into PAR2 Biased NAM Program

Lastly, presentation #6157 discussed the PAR2 biased negative allosteric modulator (NAM) program. In partnership with Prof. John Stagg, this research illuminates the potential of PAR2 inhibitors in overcoming resistance to immunotherapy—particularly immune checkpoint blockade (ICB)—and revitalizing T-cell effectiveness against cancer.

Initial findings indicate that PAR2 biased NAM can:

• - Synergize with anti-PD1 therapies, transforming macrophage phenotypes and promoting a more inflammatory tumor microenvironment.
• - Enhance T-cell activation, catalyzing powerful antitumor responses through antigen-presenting cells.

The research highlights transformative strategies that could redefine treatment protocols for patients unresponsive to conventional immunotherapy.

Commitment to Innovation

Stephan Schann, the Chief Scientific Officer at Domain Therapeutics, emphasized the significance of the findings presented at AACR 2025, stating that they validate the company's distinct approach to drug discovery and solidify their pivotal role in addressing critical medical needs in oncology. This sentiment was echoed by Prof. John Stagg, endorsing the value of collaborations aiming to tackle intricate cancer targets like PAR2 and enhance treatment efficacy through comprehensive research.

Overall, the data presented at AACR 2025 highlights Domain Therapeutics' innovative strides in oncology, showcasing a bright horizon for cancer treatments as they leverage their unique expertise in GPCR biology to confront some of the most daunting challenges in therapeutic development.