San Diego-based 858 Therapeutics announced receipt of US FDA Fast Track Designation for ETX-19477, an oral poly(ADP-ribose) glycohydrolase (PARG) inhibitor, for the treatment of adult patients with BRCA-mutated, hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), unresectable or metastatic breast cancer. The designation is the second granted to ETX-19477, following one awarded in January 2026 for BRCA-mutated, platinum-resistant ovarian cancer.
The company said the designation was supported by preclinical findings and emerging clinical data from the ongoing ERADIC8 trial (NCT06395519), a Phase I/II open-label, multicenter, first-in-human dose-escalation and expansion study in patients with advanced solid tumors. Data presented at the 2026 American Society of Clinical Oncology Annual Meeting in May reported a 57% objective response rate (ORR) in a Phase II-eligible subset of seven patients with BRCA-mutated platinum-resistant ovarian cancer and earlier-line HR+/HER2- breast cancer, with durable RECIST-confirmed responses observed in both tumor types. ETX-19477 was reported as generally well tolerated, with low rates of hematologic toxicity. Per-tumor-type ORR breakdowns and p-values were not disclosed in publicly available materials.
PARG removes poly-ADP-ribose (PAR) chains from proteins during the DNA damage response, a step downstream of PARP. By blocking PAR chain removal rather than synthesis, PARG inhibition causes selective cell death in tumors with replication fork defects — including those harboring BRCA1/2 mutations — through a mechanism distinct from approved PARP inhibitors such as olaparib and niraparib. No PARG inhibitor has received marketing authorization from any major regulatory agency.