Actuate’s drug was designed to be highly lipophilic (fat-soluble) to cross the blood-brain barrier for CNS treatment. This same property proved crucial for its success in oncology, as it allows the drug to easily penetrate cancer cell membranes and reach the nucleus.
Dan Schmitt used his role as an Entrepreneur in Residence at Northwestern University to gain priority access to new technologies. This strategic position allowed him to secure the foundational asset for Actuate Therapeutics, directly bridging academic innovation with commercial enterprise.
Actuate Therapeutics maintains high capital efficiency by keeping its full-time headcount low. The company is built around a trusted core team and supplemented by an extensive stable of "best of breed" consultants who are engaged on an as-needed basis, minimizing overhead costs.
Instead of hoarding early capital, Actuate's CEO synthesized a kilogram of their molecule and sent it to labs worldwide. The goal was to fail fast by seeing if promising results could be replicated, a crucial de-risking step before committing larger funds.
The company's lead molecule was initially invented to treat CNS diseases like Alzheimer's. A pivot occurred when a postdoc with an interest in oncology tested the compounds against refractory tumors, uncovering their true potential and leading to the company's formation around a new indication.
For years, Actuate's CEO has shared progress with large pharma companies, not just for early deal-making, but to get critical feedback on their development plan. This helps them understand what data potential acquirers need to see to make a compelling offer later.
Actuate employed a master protocol that tested their drug alongside eight different standard-of-care chemotherapies in patients who had already failed them. This design efficiently demonstrated the drug's ability to reverse chemo-resistance across multiple histologies, informing their Phase 2 strategy.
For final drug product manufacturing, Actuate engaged two separate US-based partners. This parallel track strategy provided crucial redundancy during the COVID pandemic, ensuring that a shutdown or material shortage (e.g., glass vials) at one plant wouldn't derail their clinical programs.
Actuate's CEO advises against out-licensing different indications of a single molecule to separate partners, calling it "splitting the baby." Because all programs rely on a single, shared safety database, one partner's negative safety event would impact all other programs, making the model unworkable.