GO-4

GO-4 Addresses BRCA Deficient and Proficient Cells

GO-4 is our patented, repurposed combination of four drugs:

The combination is designed to overcome multiple mechanisms of drug resistance.

GO-4 has the following primary mechanism of action:

Melphalan cross-links cancer cell DNA, which kills the cancer cell if the cross-link is not repaired.
Hydroxocobalamin increases the rate at which ascorbic acid is converted into dehydroascorbic acid (DHA). In the process, hydrogen peroxide is generated. DHA and hydrogen peroxide are preferentially taken up by tumor cells.
Inside tumor cells, the DHA and hydrogen peroxide convert glutathione (GSH) to glutathione disulfide (GSSG). BCNU inactivates an enzyme that converts GSSG back to GSH.
Changing the ratio of GSSG to GSH inhibits DNA repair in tumor cells, hypersensitizing them to melphalan.

Inhibition of DNA Repair Increases Melphalan Efficacy

DHA: dehydroascorbic acid, H2O2: hydrogen peroxide, GSH: glutathione, GSSG: glutathione disulfide

General Oncology sponsored the nearly complete phase 1 SHARON trial, which is evaluating the safety of GO-4 in patients with BRCA-mutated Stage IV pancreatic cancer and stage IV breast cancer. We are currently preparing for a phase 2 follow-on study SHARON-2.