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NMDA-modulating drugs that could be given at a high enough concentration without causing side effects was challenging. Sage’s platform, he says, “will provide a quicker way to optimize compounds that can be made into drugs.”
Paul hopes Sage’s drugs will be able to address more of the symptoms of schizophrenia than current treatments can. Most schizophrenia products treat “positive” symptoms, which include hallucinations and delusions. But they don’t relieve “negative” symptoms, such as the inability to experience pleasure or to carry on normal social interactions. “Negative symptoms are still left basically untreated,” Paul says. “We believe we might be able to address them.”
Sage will face some competition from other companies that are making headway in schizophrenia. Roche has been reporting positive trial results of a drug that targets NMDA receptor functioning by blocking a protein called glycine transporter one (GlyT1). And in September, PureTech Ventures startup Karuna Pharmaceuticals, based in Boston, licensed a group of compounds from Vanderbilt University that also inhibit GlyT1.
Paul says Sage is also looking at finding new ways to modulate GABA—a neurotransmitter that can run low in patients suffering from depression. Many popular antidepressants are benzodiazepines, which enhance GABA but can cause side effects such as drowsiness and decreased libido. What’s more, says Paul, “two-thirds of patients don’t have an optimum response to them.”
Starr says Sage represents “a classic Third Rock approach” to starting companies. The idea came out of conversations with Paul, he says. The firm then went about pulling together some key intellectual property and assets, including, he says, “a series of interesting compounds” developed by co-founder Covey. Third Rock also assembled a large group of advisors for Sage, including Stephen Moss, professor of neuroscience at Tufts University, and David Farb, professor and chair of pharmacology at Boston University School of Medicine.
If all goes well in preclinical trials, Starr expects Sage will have one or two molecules in human testing within two years. All in all, he says, the company has the expertise to go after as many as five major conditions of the central nervous system, including pain and traumatic brain injury. “We believed this would be a great area of science where we could make a difference for patients,” he says of the original concept for the company. “A year and a half later, we’re even more excited.”
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