858 Therapeutics Receives FDA Fast Track Designation for PARG Inhibitor ETX-19477 in BRCA-Mutated Ovarian Cancer
Key Insights
The FDA has granted Fast Track designation to ETX-19477, a PARG (search) inhibitor developed by 858 Therapeutics (search), for treating adult patients with BRCA (search)-mutated, platinum-resistant, high-grade serous ovarian cancer (search).
The designation enables expedited regulatory review processes and potential eligibility for accelerated approval and priority review based on preclinical data and emerging clinical results showing anti-tumor activity at tolerable doses.
ETX-19477 is currently being evaluated in an ongoing Phase 1/2 multicenter study in patients with advanced solid tumors (search), with enrollment focusing on BRCA (search)-mutated cancers including ovarian cancer (search).
858 Therapeutics (search) announced that the U.S. Food and Drug Administration has granted Fast Track designation to ETX-19477, the company's internally discovered PARG (search) inhibitor, for the treatment of adult patients with BRCA (search)-mutated, platinum-resistant, high-grade serous ovarian cancer (search) (HGSOC). The clinical-stage biotechnology company based in San Diego received this regulatory milestone based on preclinical data and emerging clinical data from their ongoing Phase 1/2 trial.
Addressing Critical Unmet Medical Need
"Patients with platinum-resistant ovarian cancer (search) have a poor prognosis, and treatment options remain extremely limited, highlighting a substantial unmet need for new therapies," said Jeffrey Stafford, Ph.D., CEO of 858 Therapeutics (search). The Fast Track designation was granted based on preclinical data and emerging clinical data from the ongoing Phase 1/2 trial of ETX-19477, including anti-tumor activity at tolerable doses.
Regulatory Advantages and Development Pathway
FDA Fast Track status is designed to facilitate the development and expedite the review of new therapies that are intended to treat serious conditions with unmet medical need. Under the Fast Track designation, the ETX-19477 development program will have access to more frequent interactions with the FDA and may be eligible for accelerated approval and priority review if certain criteria are met.
Current Clinical Development
ETX-19477 is being evaluated in an ongoing Phase 1/2, open-label, multicenter study in patients with advanced solid tumors (search), designed to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity. The trial is currently enrolling patients in Phase 1 backfill cohorts at multiple dose levels and enriching for select solid tumors harboring BRCA (search) mutations, including HGSOC.
Novel Mechanism of Action
Poly(ADP-ribose) glycohydrolase (search) (PARG (search)) is an enzyme that catalyzes the removal of poly-ADP-ribose (PAR) chains from proteins during the DNA damage response. PARG inhibition leads to selective cell death in tumors with underlying replication fork defects, including BRCAm tumors, through a mechanism distinct from PARP inhibition. ETX-19477 is an oral, potent, and selective PARG inhibitor that shows robust preclinical activity in mouse models of ovarian, breast, and gastric cancers.
Company Profile
858 Therapeutics (search) is a biotechnology and drug discovery company developing a portfolio of small molecule therapeutics directed against novel oncology and immunology targets. The company's lead programs focus on important nodes in cancer biology, including DNA damage repair, innate immunity, and RNA epigenetics. 858 is headquartered in the biotech hub of San Diego, California.