GO-4305C is designed to attack cancer cells through multiple independent mechanisms of action to overcome drug resistance.
The therapy combines the investigational new chemical entity (NCE) compound GO-4305 with melphalan, BCNU, and ascorbic acid to produce synergistic antitumor activity.
GO-4305 is a prodrug with a novel, first-in-class mechanism of activation. It is the first drug to activate upon dilution following infusion.
After infusion, GO-4305 distributes throughout the body and converts to its active form, hydroxocobalamin. During this interval, GO-4305 exhibits reduced albumin binding compared with hydroxocobalamin to allow deeper tumor penetration while the accompanying agents are present within tumors.
In the phase 1 SHARON study, patients received two cycles of therapy, after which no further treatments were given.
Prior to January 2026, eligibility was limited to patients with BRCA1, BRCA2, or PALB2 mutations and metastatic pancreatic or breast cancer (N=12).
The study observed:
Beginning in January 2026, a phase 1 expansion cohort was initiated that no longer requires BRCA1/2 or PALB2 mutations. The phase 1 expansion will determine the maximum tolerated dose while further evaluating safety and exploring signals of efficacy in a broader patient population.
GO-4305C was evaluated in vitro using the MIA PaCa-2 human pancreatic cancer cell line. This cell line is BRCA wildtype: it does not have a germline deleterious BRCA mutation, and consequently has an elevated level of drug resistance.
Melphalan alone produced approximately a 3.0-log reduction in clonogenic survival. The combination of hydroxocobalamin, BCNU, and ascorbic acid produced a 1.9-log reduction.
The four-drug combination produced a > 6.8-log reduction in clonogenic survival, eliminating all six million cells seeded in the assay.
GO-4305C is designed to damage cancer cell DNA while suppressing all major DNArepair mechanisms in cancer cells:
Additionally, GO-4305C is designed to:
GO-2301 is a novel drug that induces terminal proliferation arrest. A single molecule of the drug may irreversibly inhibit cell proliferation.
The drug is administered in nanogram concentrations, binds deep within the DNA helix where it cannot be easily removed, and does not cause collateral cellular damage typically associated with alkylating agents. When the cell attempts to proliferate, GO-2301 permanently traps the cell in M phase.
Electroretinography and histopathology were performed through the Day 46 timepoint.
Inhibition of neovascularization was at least as profound as historical data reported for the VEGF inhibitor aflibercept in similar models.
