FoRx Therapeutics, a clinical-stage biotechnology company developing precision anti-cancer therapeutics, today announced the presentation of the molecular structure, discovery, and preclinical data supporting the potential best-in-class profile of its PARG inhibitor, FORX-428, currently in Phase 1 development, at the American Chemical Society (ACS) Spring 2026 meeting in Atlanta.
This disclosure of the novel molecular structure of FORX-428 represents the first description of the discovery and chemical structure of a clinical-stage PARG inhibitor candidate.
Differentiated Preclinical Profile
Data presented at ACS Spring 2026 showed FORX-428’s differentiated preclinical profile relative to a competitor reference compound, including superior selectivity and pharmacokinetics (PK), with potency shown to be at least 10-fold higher across multiple solid tumor cell lines. FORX-428 has demonstrated the potential for a best-in-class profile, supported by favorable preclinical safety and toxicology data and a promising predicted human PK profile.
In preclinical studies, FORX-428 showed robust anti-tumor activity in hard-to-treat models across three distinct target populations: HRD-positive, PARP inhibitor-resistant, and high replication stress tumors. By comparison, the reference compound showed activity primarily in highly sensitive models.
“The robust preclinical data presented at ACS Spring 2026 support FORX-428’s best-in-class potential and why we believe it has the potential to meaningfully improve treatment options for patients. Our ongoing Phase 1 trial is progressing according to plan toward an initial clinical readout in the coming months,” said Tarig Bashir, CEO of FoRx Therapeutics.
Targeting the DNA Damage Response (DDR)
The discovery that distinct genetic subsets of cancer are exceptionally vulnerable to drugs that interfere with the DNA Damage Response (DDR) led to the approval of PARP inhibitors more than 10 years ago, transforming cancer treatment. FoRx is pursuing PARG as a next-generation DDR target with significant potential as a new treatment approach for patients whose cancers are resistant to, or have become resistant to, PARP inhibitors.
Phase 1 Clinical Trial Progress
The Phase 1 trial of FORX-428 is progressing as planned, with initial data readout expected in mid-2026. The open-label study, which began recruitment in August 2025 and is being conducted at leading cancer centers in the United States, is evaluating safety, tolerability, pharmacokinetics, and preliminary efficacy in patients with advanced solid tumors who have exhausted standard-of-care options.
ACS Spring 2026 is taking place in Atlanta, Georgia, USA, from March 22 to 26.
