SAN DIEGO, April 18, 2017 /PRNewswire/ — Abide Therapeutics, a developer of innovative pharmaceuticals, announced today initiation of dosing in a Phase 1b study to evaluate the effects of ABX-1431, a first-in-class investigational monoacylglycerol lipase (MGLL) inhibitor in patients with Tourette Syndrome (TS). TS is a neurodevelopmental disorder characterized by sudden, involuntary movements and/or sounds called tics. Additionally, Abide has established a collaboration with the Tourette Association of America (TAA) to gain a better understanding of the unmet needs in the Tourette community.
The ongoing Phase 1b study in adults is a crossover design using ABX-1431, an orally available small molecule that modulates the activity of the endocannabinoid neurotransmitter system. Based on clinical observations with exocannabinoids, there is reason to believe that modulating the endocannabinoid system will improve TS symptoms and certain comorbidities, such as Attention Deficit-Hyperactivity Disorder (ADHD). The ABX-1431 study will provide the opportunity to assess whether a highly specific endocannabinoid modulator tested under controlled conditions will recapitulate the beneficial effects on the movement disorder that were previously observed with exocannabinoids.
“We are excited to begin this trial in adults with Tourette Syndrome, and we hope to subsequently extend our studies to children, since Tourette Syndrome is largely considered to be a disease of childhood,” said Alan Ezekowitz, MBChB, DPhil, CEO and President of Abide Therapeutics. “As we continue to explore the potential utility of ABX-1431 in Tourette Syndrome, we are grateful for the opportunity to partner with the TAA to further understand the challenges faced by those affected by the condition.”
“We are very excited to be partnering with Abide Therapeutics to raise awareness for and better serve the unmet needs of the Tourette Syndrome community,” said John Miller, TAA President and CEO. “With no existing cure for Tourette Syndrome, there is an urgent need for safe, minimally invasive, and effective treatment options. The TAA and Abide Therapeutics have a mutual interest in advancing medical knowledge for Tourette, and we look forward to working together in our shared mission of improving the quality of life of all individuals affected by Tourette Syndrome.”
ABX-1431 has successfully completed dosing in a first-in-human, placebo-controlled, Phase 1a study. The drug was generally well tolerated and there were no serious adverse events. Preliminary data from a PET occupancy study indicate dose-dependent brain penetrance of orally-administered ABX-1431 using [18F]ABX-1488, an Abide proprietary, MGLL-specific PET ligand. Furthermore, an fMRI study aimed at assessing the patterns of neural activity in the brain associated with ABX-1431 administration is scheduled to start dosing in the first quarter of 2017.
“Our previous studies suggest that the endocannabinoid system is involved in the pathophysiology of Tourette Syndrome. We very much hope that this study of ABX-1431 in adults with Tourette Syndrome will substantially improve the available treatment options for these patients,” said Kirsten Müller-Vahl, MD, Professor of Psychiatry at the Department of Psychiatry, Social Psychiatry and Psychotherapy at the Hannover Medical School (MHH), Germany. Dr. Müller-Vahl is the Principal Investigator for this study.
About the Endocannabinoid System
MGLL is an enzyme that catalyzes the breakdown of the endocannabinoid 2-arachidonoylglycerol (2-AG), an endogenous ligand of the cannabinoid receptors CB1 and CB2, which are the molecular targets of the psychoactive component of cannabis, delta-9 tetrahydrocannabinol (THC). MGLL is the major regulator of 2-AG levels available to signal through CB1 and CB2. CB1 is the primary cannabinoid receptor in the nervous system, and its activation accounts for most of the neurobehavioral effects of THC. CB2 is found primarily on immune cells and mediates the immunosuppressive effects of cannabinoids. Direct activation of cannabinoid receptors by medicinal cannabis preparations elicits therapeutically beneficial effects on pain, spasticity, sleep, appetite, and nausea. ABX-1431 is expected to produce similar beneficial therapeutic effects through amplification of endogenous cannabinoid signaling.
About Abide Therapeutics
Abide Therapeutics combines an innovative discovery platform and a library of proprietary small molecules to address biological pathways with therapeutics that enhance the body’s normal physiological response to disease. The platform enables Abide to quickly and efficiently identify, modify and validate small molecule inhibitors that target serine hydrolases, a highly relevant but under-explored class of enzymes. Abide’s initial area of focus is on addressing neurological disorders with limited treatment options through the endocannabinoid pathway.