The GSK3 inhibitor was developed for CNS diseases, requiring high specificity and the ability to cross the blood-brain barrier. These same pharmaceutical characteristics—potency and lipophilicity—proved highly advantageous for treating cancer, demonstrating an unexpected but effective therapeutic pivot from neuroscience to oncology.
The drug exhibits a multimodal mechanism. It not only reverses chemoresistance and halts tumor growth but also 'turns cold tumors hot' by forcing cancer cells to display markers that make them visible to the immune system. This dual action of direct attack and immune activation creates a powerful synergistic effect.
Despite pancreatic cancer being notoriously difficult, Actuate prioritized it as a lead indication for strategic reasons. Strong preclinical data allowed the company to bypass later-line trials and move directly into a first-line setting, a 'leapfrog' maneuver that significantly accelerates the drug's overall development and regulatory path.
The CEO addresses the old belief that inhibiting its target, GSK3-beta, could be dangerous because it was once considered a tumor suppressor. He explicitly states this theory has 'lost its scientific founding' and 'faded into the myth' as research progressed, demonstrating a command of the target's evolving scientific narrative to stakeholders.
Patients report a temporary, fully reversible blue-gray tint to their vision. This occurs because the drug's target, GSK, is present in eye photoreceptors. Rather than a major concern, this manageable 'nuisance side effect' serves as a real-time biological marker that the drug is successfully engaging its target systemically.
To demonstrate its drug could overcome resistance, Actuate designed a trial where patients who had already failed a specific chemotherapy were given the exact same regimen again, but this time with Actuate's drug added. The resulting increased efficacy across eight different cancers provided powerful, direct proof of the drug's mechanism.