FDA Grants ETX-19477 Fast Track Designation in BRCA-Mutated Breast Cancer

The FDA has granted fast track designation to ETX-19477, 858 Therapeutics' internally discovered PARG (poly[ADP-ribose] glycohydrolase) inhibitor, for the treatment of adult patients with BRCA-mutated, hormone receptor–positive (HR+), HER2-negative (–), unresectable or metastatic breast cancer.¹

The designation gives the ETX-19477 program access to more frequent interactions with the FDA and may make it eligible for accelerated approval and/or priority review if the relevant criteria are met.

Trial Design and Supporting Data

ETX-19477 is being evaluated in ERADIC8 (NCT06395519), an ongoing, 2-part, open-label, multicenter phase 1/2 trial assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the agent in patients with advanced solid tumors.^1,2 The study is currently enrolling patients in phase 2 monotherapy expansion cohorts in BRCA-mutated ovarian cancer and BRCA-mutated HR+/HER2– breast cancer.¹ The designation was supported by preclinical findings and emerging clinical data from the trial, including evidence of antitumor activity.

"For patients with advanced HR+/HER2– breast cancer, there is an urgent need for new treatment options that can delay disease progression. We are pleased that the FDA has granted fast track designation to ETX-19477 and are committed to working closely with the agency to accelerate its development,” said Jeffrey Stafford, PhD, CEO of 858 Therapeutics, in a news release.

About ETX-19477

PARG is an enzyme that removes poly-ADP-ribose chains from proteins during the DNA damage response. PARG inhibition leads to selective cell death in tumors with underlying replication fork defects, including BRCA-mutated tumors, through a mechanism distinct from PARP inhibition.¹ ETX-19477 is an oral, potent, and selective PARG inhibitor that has shown activity in preclinical mouse models of ovarian, breast, and gastric cancers.

Prior Regulatory Designation

This is the second fast track designation the FDA has granted to ETX-19477. In January 2026, the agency granted fast track designation to the agent for BRCA-mutated, platinum-resistant high-grade serous ovarian cancer, also based on preclinical and early clinical data from ERADIC8.³

REFERENCES

1. 858 Therapeutics Announces FDA Fast Track Designation for PARG Inhibitor ETX-19477 for the Treatment of Patients with BRCA-Mutated, HR+/HER2- Unresectable or Metastatic Breast Cancer. News release. 858 Therapeutics. August 18, 2026. Accessed August 19, 2026. https://tinyurl.com/57tws89b

2. A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies (ERADIC8). ClinicalTrials.gov. Updated August 5, 2025. Accessed August 19, 2026. https://clinicaltrials.gov/study/NCT06395519

4. 858 Therapeutics announces FDA fast track designation for PARG inhibitor ETX-19477 for the treatment of patients with BRCA-mutated, platinum-resistant ovarian cancer. News release. 858 Therapeutics. January 8, 2026. Accessed August 19, 2026. https://tinyurl.com/tj5f5psd