brain cells in a laboratory dish. The company can expose these neurons to various experimental drugs, and measure what happens through detailed tests on proliferation, migration, and differentiation of neurons. Once that’s done, it seeks to confirm the results in animals. If BrainCells’ science is on the mark, this should increase the abysmally low success rate of neurology drugs in clinical trials, Schoeneck has said.
Barlow walked me through the interesting backstory of how BrainCells discovered what became BCI-952. The company started with buspirone, a generic drug that’s known to be safe, and modestly effective for anxiety, but never shown to be effective for depression. So BrainCells tried buspirone in combination with about 70 different other medications that were available and known to have clean safety profiles—everything from folic acid, to high blood pressure drugs, to melatonin.
“As we’ve seen over many years, it’s very difficult to treat brain disorders with a single drug,” Barlow says. “It’s often better when physicians have multiple opportunities.”
The combination of buspirone and melatonin looked ideal, based on results from the drug discovery platform, Barlow says. Melatonin already was known to affect mood. It is a naturally occurring hormone that is known to interact with the central nervous system, immune system, and to help regulate the sleep-wake cycle in animals. Some people use it as a dietary supplement to help sleep disorders, headaches and other ailments.
But BrainCells still wasn’t ready to go to the clinic. Correct dosing is notoriously tricky in the world of anti-depressants, as one of the pioneers in the field, Eli Lilly’s fluoxetine (Prozac) proved when it passed just four of its first 13 clinical trials, Schoeneck says. Many anti-depressants actually show lower rates of effectiveness when given in higher doses, he adds. For a small biotech on a budget that doesn’t allow for 13 trials, getting the dose correct off the bat was going to be important.
So BrainCells set out to apply its platform to the question of dosing. It tested about 100 different ratios of buspirone and melatonin, and a number of doses, before finding the ideal balance of safety and effectiveness in the lab dish, which was confirmed later in animal studies, Barlow says. The final dose figure was about one-sixth the amount of buspirone that can be safely given for anxiety, and the amount of melatonin was also far lower than the max. “We weren’t worried on the safety side,” Schoeneck says.
BrainCells was so confident in its platform, that it didn’t even run a traditional dose-escalation study in its first clinical trial. “We were able to zoom in on the ratio, and the dose, using the platform,” Schoeneck says. “We did not have to do that in the clinic. I can tell you as we talk to people at other companies, it makes them go ‘Wow’ because in the psychiatric area so many companies have to do dose-ranging studies.”
So the company essentially picked one ideal dose based on its discovery platform, and confirmed it in its first clinical trial of 142 patients. But BrainCells still has more work to do
