As the director of the Vanderbilt Center for Neuroscience Drug Discovery, Jeff Conn has specialized in preclinical development work on new drugs biopharma companies can take into the clinic. He’s also seen two of the big companies he’s partnered with — Bristol-Myers Squibb and AstraZeneca — make sudden, unexpected retreats from the field, which has known a steady diet of failures and setbacks in recent years.
So this time, instead of licensing out his drug and taking the risk of another early disappearance, Conn and his colleagues at Vanderbilt are taking their drug directly into an early-stage human study in a rare — perhaps unique — display of academic risk-taking in the clinic.
“This drug candidate is a positive allosteric modulator of an M1 (muscarinic) receptor,” says Conn, referring to a neurotransmitter disrupted in Alzheimer’s and schizophrenia. This is a well plumbed field, with drugs that have been tried in the clinic and failed, says Conn, but no one was able to develop highly selective molecules—at least not until now.
“That’s what we are now advancing,” he tells me, focusing on cognitive impairment in early to moderate Alzheimer’s and also in schizophrenia. And his team is concentrating on some symptoms that haven’t been addressed so far, including: social withdrawal, lack of motivation and a lack of ability to experience reward.
“The model we focused on has been to partner with companies relatively early, certainly before clinical development,” Conn adds. “The shifting landscape in the pharma industry (which included AstraZeneca’s recent decision to quietly scuttle its virtual iMed model for neuroscience) has really caused us to rethink that.”
“For this target, we’re taking it through Phase I, make sure there are none of the adverse effect liability seen in the ‘90s,” he adds. “That would be a major step for de-risking, a good point for partnering with a major company. We can also show we could engage the receptor in the CNS.”
This is no small undertaking for an academic group, emphasizes Craig Lindsley, co-director and chief of medicinal chemistry at the center.
“We all came from industry,” he notes. “Doing an IND on your own is quite an undertaking, including tasks largely unknown in academic circles,” such as meeting rules on manufacturing and product formulation. “It’s an extra day job for everybody. It helped us understand we could do this. And next time it will be easier and faster.”
Next time will come soon enough, he says, with an early stage pipeline in the making. The NIH and nonprofits — including The William K. Warren Foundation — have provided the additional financial firepower needed to push ahead into the clinic. After they get through Phase I, he and Conn believe that they can go back and do higher value deals after nailing down some solid human data on safety and early efficacy signals in healthy volunteers. And if Big Pharma isn’t interested, then perhaps a smaller biotech or spinout can do the job.
The key point, they both say, is that they want their drugs to go as far as possible through the clinic, and all the way to patients if they can. Next time one of their drugs fails to make it, they don’t want it to be because yet another company pulled a sudden and unexpected left turn in their clinical strategy. And for that, they’re willing to assume some of the added risk that has frightened much bigger players out of the Valley of Death.
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