Praxis Precision Medicines launches with $100M and bold sights on long-evasive neurological disorders
It’s going to be the era of neuroscience, Roche CEO Bill Anderson declared on stage at the JP Morgan Healthcare Conference in January. The field, he said, had “the potential to be in the ‘20s what oncology was for the last decade.”
Five months into that decade, a new biotech is emerging from stealth mode with large investments from Blackstone and two drugs already in Phase II, one of them nearing a pivotal trial. Called Praxis Precision Medicines, since 2016 it’s raised $100 million — with Novo Holdings, Vida Ventures and Eventide also chipping in — to back a bet that, by finding the underlying cause of rare neurological diseases, they could find and treat mechanisms behind more common ones.
For all Anderson’s optimism about the future, though, Praxis emerges at a tough time for neuroscience-focused biotechs. Much of the rest of Big Pharma has all but abandoned the field. The last major piece of neuro-news of the previous decade was the announcement, in December, that Sage Therapeutics’ vaunted drug for major depressive disorder had failed a large trial, a readout that has since cost the company $6 billion in market cap and induced them to cut more than half their staff. Praxis’s lead drug goes after the same indication.
“It’s a challenging field,” Praxis CEO Marcio Souza acknowledged in an interview.
The company began as an effort to find de novo mutations that caused epilepsy — the spontaneous genetic malfunctions that cause the disease in patients who did not inherit it from their parents. The search turned up, among other things, a gene that affects calcium channels in the brain. But instead of trying to fix that mutation, they used that information to figure out how that channel — and how that channel falling out of balance, with neurons firing too much or too little —played a role in other diseases.
“What became quite clear is that when you were looking beyond just the pure mutations … we were all talking about imbalances in a given part of the brain, and normally as it relates to a specific channel,” Souza said. “A lot of people jumped in the past from mutation — correcting that mutation, or correcting the genetic defect. What we’re doing differently is looking into how that manifests and attempting to correct the actual manifestation.”
The result was PRAX-944, a T-type calcium channel blocker that is in the early stages of development for rare forms of genetic epilepsy, but which the company is more aggressively taking forward in essential tremor, one of the more common neurological conditions. They expect to have Phase II proof-of-concept results before the end of the year.
The lead program, though, is PRAX-114, a depression drug. The overlapping indications here are perimenopausal depression, a relatively rare condition compared with major depressive disorder. Despite the vast medical need and market, scientists have struggled for years leading up to Sage’s flop to build better anti-depressants.
Praxis hopes to have an answer on their drug soon, with plans to enter a pivotal trial before the end of the year. The drug works by allosterically targeting GABAa, the neurotransmitter implicated in a long list of disorders and targeted head-on by benzodiazepines. Souza said the new trial will try to track patients as they would use it in their daily lives, hoping to show what he says they saw in Phase II: a safe and quick drug.
“They have the right safety profile,” Souza said. “Most of the issue is not only with the efficacy, but with the safety of these compounds. And we think 114 has that balance.”