FoRx Therapeutics, a Basel-based clinical-stage biotechnology company developing precision anti-cancer therapies, has announced the dosing of the first patient in a first-in-human Phase 1 clinical study of FORX-428, a proprietary poly (ADP-ribose) glycohydrolase (PARG) inhibitor targeting advanced solid tumors.
The discovery that certain genetic subsets of cancer are highly susceptible to DNA Damage Response (DDR) inhibitors led to the approval of PARP inhibitors over a decade ago, revolutionizing oncology. FoRx aims to build on this success by pursuing PARG inhibition — a next-generation DDR target — to address cancers that are resistant to, or have progressed on, PARP inhibitors.
According to CEO Tarig Bashir, preclinical studies have shown FORX-428 delivers potent anti-tumor efficacy in multiple in vivo models, indicating best-in-class potential. The open-label Phase 1 study, initially underway in the United States, will assess safety, tolerability, pharmacokinetics, and preliminary efficacy in patients with advanced solid tumors who have exhausted standard-of-care options. Initial trial data is expected by mid-2026.
Dr. Manish R. Sharma, Principal Investigator at START Midwest, emphasized the urgent need for new therapeutic options in cancers with DDR deficiencies or high replication stress. He noted that FORX-428’s novel mechanism demonstrated strong preclinical activity even in cancers resistant to chemotherapy and PARP inhibitors.
Following U.S. FDA IND clearance on June 13, the trial’s first patient first visit occurred on July 22, and the first dosing took place on August 6. Dr. Jens Wuerthner, Chief Medical Officer at FoRx, credited the rapid transition from regulatory clearance to patient dosing to the coordinated efforts of clinical, regulatory, and operational teams.
FORX-428 is an orally available small molecule designed to inhibit PARG, a DNA repair enzyme essential for the survival of genetically defined cancers with specific DDR defects or high replication stress. Preclinical research has shown robust activity across multiple tumor types, a favorable safety profile, and potential in both monotherapy and combination regimens.
FoRx Therapeutics’ pipeline includes multiple small molecule programs targeting DNA repair mechanisms, with FORX-428 as its lead candidate now advancing through early clinical evaluation.