Trihexyphenidyl Hydrochloride

Since Bernard Ravina’s medical training in neurology in the 1990s, there have been few new therapies that treat a movement disorder known as dystonia. “Nothing fundamentally has changed for these patients since then,” the drug development executive said. About two years ago, Ravina joined Atlas Venture as an entrepreneur-in-residence to help fix that. And now the company he helped found — Vima Therapeutics — has raised a $60 million Series A and expects to be in Phase 2 by the end of this year, he exclusively told Endpoints News . A handful of neurotoxins like AbbVie’s Botox are approved for certain forms of dystonia, which impairs muscles and causes them to unexpectedly contract. Other treatments include brain surgery or deep brain stimulation, but “very few people want that,” the Vima CEO said. Using Botox or other neurotoxins requires repeat injections and can only address specific muscles, but dystonia can affect multiple areas of the body. Tremors, voice issues and difficulty chewing are some signs of the chronic neurological disorder. Severe cases can lead to joint dislocations and fractures, Ravina said. Vima aims to deliver an oral treatment with VIM0423, which is currently in Phase 1. The experimental once-a-day drug targets the brain’s muscarinic cholinergic receptors. “You’ve seen the renaissance of muscarinic cholinergic receptor-targeted drugs in psychiatry with Karuna,” Ravina said, referring to the company that Bristol Myers Squibb acquired for its schizophrenia medicine Cobenfy. “There’s a role for those same areas of the brain involved in movement disorders. People have tried to drug this class. In psychiatry, you’re agonizing, enhancing the activity of muscarinic receptors. For movement disorders, it’s antagonizing, inhibiting that activity.” Muscarinic-targeting drugs have been used for movement disorders for decades. In 1949, the FDA approved a muscarinic antagonist known as trihexyphenidyl to treat certain forms of Parkinson’s disease. But most of these drugs have tolerability issues. “What we’ve been able to achieve is a way to selectively target the right muscarinic cholinergic receptors to drive efficacy but to really minimize those safety concerns [and] enhance tolerability,” Ravina said. The upcoming Phase 2 will enroll patients with severe dystonia that affects multiple parts of their bodies. The trial will likely implement three or more months of treatment since it takes about that length of time “for the full benefit to be seen,” according to Ravina. The therapy should work in both adults and children, he said, noting the company is deciding “the right timing” for bringing children into clinical studies of VIM0423. The initial $60 million comes from Atlas Venture, Access Industries and Canaan, which are “committed to making sure that we have capital for completing the Phase 2,” he said. Atlas, one of the main biotech incubation venture firms, just had success in neurology this month. Vigil Neuroscience, one of the companies it founded to work on experimental medicines from Amgen, is being bought by Sanofi for $470 million. Ravina joined Atlas in late 2022 after stints as chief medical officer at neuro biotechs Praxis Precision Medicines and Voyager Therapeutics. “Why hasn’t anybody done this before? And my answer to the team at Atlas was, when was the last time you had a movement disorders doc come and be an entrepreneur-in-residence at a venture capital firm?” Bernard said. “It just doesn’t happen a lot.” Ravina hired Judith Dunn, a former president of R&D at Fulcrum Therapeutics and global head of clinical development at Roche, to lead R&D at Vima. The team may explore dystonia manifestations in other conditions down the road, with Ravina pointing out that about 50% of children with cerebral palsy have a dystonic phenotype. Like other biotechs working through the current funding environment, the 15-employee startup plans to take it one step at a time, just as its Greek name suggests. Vima means “step” or “pursuit” in Greek. It took about six to eight drives between Boston and New York for Ravina and his wife to come up with the biotech’s name. “And a whole lot of scrap paper in the glove compartment,” he said.