On May 3, 2024 FoRx Therapeutics AG, a company committed to discovering and developing innovative drugs targeting cancer-relevant DNA Damage Response (DDR) pathways, reported the nomination of its first preclinical development candidate, FORX-428, an inhibitor of Poly(ADP-ribose) glycohydrolase (PARG) (Press release, FoRx Therapeutics, MAY 3, 2024, View Source [SID1234644973]). FORX-428 has strong best-in-class potential and is being developed for the treatment of solid tumors. IND-enabling activities have already been initiated.
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FORX-428 is an oral, highly potent and selective inhibitor of PARG that shows excellent single-agent activity in multiple relevant preclinical tumor models. The compound is well tolerated and demonstrates a favorable pharmacological and safety profile. In addition to single-agent activity resulting in tumor regressions, FORX-428 exhibits synergistic tumor cell killing in combination with various targeted agents, underscoring the compound’s outstanding potential in both monotherapy and combination settings to address genetically defined cancers. FoRx Therapeutics has identified novel predictive biomarkers which allow for the selection of patient populations most likely to benefit from treatment. FORX-428 has the potential to achieve transformative outcomes in patients with cancers of high medical need or affected by therapy resistance.
FoRx Therapeutics holds all development and commercial rights to FORX-428.
Dr Tarig Bashir, CEO of FoRx Therapeutics, commented: "We are proud to announce the nomination of our first development candidate FORX-428. The achievement of this important milestone is a testimony to FoRx Therapeutics’ ability to tackle and successfully deliver on challenging targets in the DNA Damage Response field. We look forward to advancing FORX-428 with its best-in-class profile into the clinic and to bring a novel treatment option with transformative potential to cancer patients who have at this point only limited therapy options or suffer from therapy resistance."
Dr Frank Zenke, CSO of FoRx Therapeutics, added: Our dedicated research team has achieved a remarkable milestone, conducting an extensive investigation of various chemical series aimed at identifying a development candidate with best-in-class potential. FORX-428 exhibits compelling anti-tumor efficacy and exceptional tolerability in numerous cancer models, and we are excited to advance this promising compound into clinical trials for cancer patients."
About PARG
Poly(ADP-ribose) glycohydrolase (PARG) is a key protein that plays a pivotal role in repairing damaged DNA. PARG breaks down poly(ADP-ribose) (PAR) chains, which serve to attract DNA repair factors to sites of DNA damage. Cancers are by default genomically instable and cannot tolerate excessive DNA damage as opposed to normal cells. By inhibiting PARG, the degradation of PAR chains is halted, leading to a block of DNA repair and the accumulation of persistent and lethal DNA damage. Cancers with intrinsic deficiencies in particular DNA repair pathways exhibit exceptional sensitivity to pharmacological PARG inhibition, which presents a prime opportunity for therapeutic intervention.