Homologous Recombination (HR) gene mutations play a role in genomic stability and plasticity, and sometimes work to repair cellular DNA damage. These mutations cause genetic information to be shared between two double or single-stranded nucleic acids. However, HR mutations and defects can prompt the development of solid tumors and the proliferation of various cancers, in which the cancers are able to repair damage and continue tumor growth. For example, BRCA1, PALB2, and BRCA2 are all potential HR gene mutations which can be deficient in solid tumors (“HR deficiency”). According to a recent news release, the first patient was dosed in a Phase 1b clinical trial evaluating Pidnarulex as a therapy for patients with these tumors and genetic mutations.

Pidnarulex

So what exactly is Pidnarulex? Developed by drug development company Senhwa Biosciences (“Senhwa“), Pidnarulex (CX-5461) is:

a G4-stabilizing compound and able to stabilize the folded conformation and lead to replication fork stalling and unreplicated chromosomal areas, while acting in concert with HR pathway deficiency, such as BRCA1/2 mutations, which stalls replication forks undergo DNA breaks and thus causes cancer cell death.

The treatment is given intravenously. Altogether, Pidnarulex targets HR deficient tumors and prevents the DNA from repairing itself. For example, patients with BRCA-mutated breast cancer may have HR deficient tumors. Pidnarulex then works by stopping DNA repair and prompting cellular death in cancer cells.

In the past, Pidnarulex has shown promise for treatment-averse tumors with BRCA1, BRCA2, or PALB2 gene mutations. This is important, as these mutations increase the risk of pancreatic, ovarian, and breast cancer. Some other treatments include platinum-based chemotherapy, as well as other chemotherapeutic agents. Additionally, PARP inhibitors may be used for BRCA1 or BRCA2 deficient cancer cells, though this treatment is not always efficacious. Thus, Pidnarulex offers the potential to overcome current treatment obstacles and improve patient outcomes. Now, the newer clinical trial seeks to understand the ideal Pidnarulex dose, as well as the treatment’s safety and tolerability.