BioLineRx, a clinical-stage biopharmaceutical company focused on oncology and rare diseases, and Hemispherian AS, a clinical-stage oncology company developing novel small-molecule therapeutics, have announced encouraging preclinical data demonstrating significant synergy between GLIX1 and PARP inhibitors in a Patient-Derived Xenograft (PDX) model of ovarian cancer.

The findings represent a potential breakthrough in addressing the limitations of current PARP inhibitor therapies, particularly in Homologous Recombination (HR)-proficient ovarian cancers, where these treatments have historically shown limited effectiveness. The combination therapy may also offer a promising option for patients with platinum-resistant ovarian cancer, an area with substantial unmet clinical need.

The research is based on the principle of synthetic lethality, where GLIX1 induces single-stranded DNA breaks that enable PARP inhibitors to effectively target HR-proficient cancer cells. Earlier laboratory studies had already demonstrated consistent synergy across multiple PARP inhibitors and HR-proficient ovarian cancer cell lines, and the latest in vivo findings validate this therapeutic approach.

According to the study, the combination of low-dose GLIX1 and olaparib delivered substantially greater tumour reduction than either treatment alone, while achieving efficacy comparable to cisplatin—the current standard chemotherapy for ovarian cancer. Notably, the enhanced response was achieved despite using lower doses in the combination arm, highlighting the potential for improved therapeutic outcomes with reduced toxicity.

Commenting on the results, Philip Serlin, Chief Executive Officer of BioLineRx, said the findings validate the scientific rationale behind combining GLIX1 with PARP inhibitors and support plans to include an ovarian cancer cohort in the expansion phase of the company's ongoing Phase 1/2a clinical trial.

Ovarian cancer remains the deadliest gynaecologic malignancy in the United States, with nearly 21,000 new cases and 12,450 deaths projected in 2026. While PARP inhibitors have transformed treatment for patients with BRCA-mutated or HR-deficient tumours, nearly half of high-grade serous ovarian cancers are HR-proficient, leaving a large patient population with limited therapeutic options and poorer survival outcomes.

GLIX1 is a first-in-class, orally administered, brain-penetrant small molecule that activates the TET2 pathway, overwhelming the DNA repair mechanisms of cancer cells and triggering apoptosis. The therapy is currently being evaluated in an open-label, multicentre Phase 1/2a clinical trial for glioblastoma and other solid tumours, with updates from the dose-escalation phase expected in the second half of 2026.

Building on the latest findings, BioLineRx and Hemispherian plan to expand the Phase 2a portion of the study to include ovarian cancer and other solid tumours, evaluating GLIX1 both as a standalone therapy and in combination with standard treatments, including PARP inhibitors. The companies also intend to present the preclinical data at upcoming international medical conferences.