The genetic mutations that cause epilepsy don’t stop there. Praxis Precision Medicines CEO Marcio Souza says research also links these genes to other neurological conditions. The biotech startup is turning that research into new neuro drugs and it’s coming out of stealth to share details about its science and its pipeline, which already has two programs in mid-stage testing.
Cambridge, MA-based Praxis is developing drugs that address the misfiring circuitry in the central nervous system that is at the heart of many neurological disorders. Some of these pathways are already addressed by other drugs. But Souza (pictured above) says Praxis’s experimental medicines hit them more precisely, which improves the therapeutic benefit and reduces side effects.
Praxis is building on an international research effort that aimed to understand the genetic basis for epilepsy. Epi4K started in 2011 as a project studying the genomes of more than 4,000 patients with various forms of the disorder. That research was intended to support the development of better therapies for epilepsy, which is one of the disease targets for Praxis. But Souza tells Xconomy that further study revealed the potential for much more.
“What became clear pretty quickly is the pathway for epilepsy addresses other diseases,” Souza says.
For the past three years, Praxis has been incubating within Blackstone Life Sciences, a division of New York-based private equity giant Blackstone Group (NYSE: BX). That firm and others have backed the startup with more than $100 million in financing cumulatively since 2016. The most recent fund raise listed in securities filings is a nearly $10 million round last June.
Praxis’s lead program, PRAX-114, is in Phase 2 testing for major depressive disorder and perimenopausal depression. The small molecule targets GABA, a neurotransmitter in the brain. Other drugs target this neurotransmitter, such as benzodiazepines, a class of medicines whose applications include anxiety, seizures, and relaxing muscles. But Souza says those drugs cause side effects including sleepiness, and they aren’t effective in depression.
In tests so far, Souza says PRAX-144 has shown a fast reduction in depression measures without drowsiness. The drug also took effect quickly, a quality that sets it apart from many currently available depression drugs that can take days or weeks before patients notice a change.
Another Praxis drug, PRAX-944, is in Phase 2 testing for essential tremor. This small molecule blocks T-type calcium channels, where mutations lead to the misfiring of neurons that occurs in patients with severe epilepsy. Though essential tremor is a different disease, Souza says research shows patients who have it also have misfiring neurons.
“By looking at the broader biology instead of specific mutations, we are able to engage with that target and we are able to reduce the tremors in animals, and hopefully soon, in patients,” Souza says.
The Praxis depression drug is being prepared for a Phase 3 study later in 2020. In the coming year, the company expects to report Phase 2 data for PRAX-944 in essential tremor. A third program, PRAX-222, is in preclinical development for rare forms of epilepsy. That drug is an antisense oligonucleotide.
Praxis’s science is based on the research of David Goldstein of Columbia University and Steven Petrou of the University of Melbourne in Australia. Goldstein’s research focuses on precision medicine including work that was part of Epi4K. Petrou’s research focuses on ion channels and their role in rare pediatric epilepsies. The third co-founder, Kiran Reddy, is a venture partner and senior advisor at Blackstone Life Sciences. A neurologist, Reddy’s experience includes roles at Biogen (NASDAQ: BIIB) and venture capital firm Third Rock Ventures.
Though Praxis has been developing its pipeline for more than three years, Souza is new to Praxis, having joined late last month from PTC Therapeutics (NASDAQ: PTCT), where he was most recently chief operating officer. Besides Blackstone, Praxis’s financial backers include Novo Holdings, Vida Ventures, and Eventide.
Photo by Praxis Precision Medicines