SAN DIEGO, May 17, 2017 /PRNewswire/ — Abide Therapeutics, a developer of innovative pharmaceuticals, announced today that new preclinical and clinical data on ABX-1431, an investigational monoacylglycerol lipase (MGLL) inhibitor, will be presented in a poster session at the European Federation for Exploratory Medicines Development Annual Meeting 2017 (EUFEMED), taking place in London, May 18-19, 2017. ABX-1431 is a first-in-mechanism, orally-available, selective, and potent inhibitor of MGLL in development for the treatment of neurological disorders, pain, and neuroinflammation.
“The Abide Therapeutics team looks forward to sharing these new data on the preclinical and clinical characterization of our first-in-mechanism MGLL inhibitor, ABX-1431,” said Alan Ezekowitz, MBChB, DPhil, CEO and President of Abide Therapeutics. “The ABX-1431 story highlights our unique scientific approach and powerful tools for rapidly and efficiently validating new targets and developing first-in-class drug candidates against those targets.”
In the study presented at EUFEMED, Abide evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABX-1431 in single and multiple ascending doses. The drug was generally well tolerated at doses planned for future studies, with no serious adverse events, and the study data supported further clinical evaluation of this first-in-mechanism MGLL inhibitor in patient populations. A study of ABX-1431 in patients with Tourette Syndrome was initiated in early 2017 and is ongoing.
“Abide’s scientific tools produced an extensively characterized clinical candidate, generated a translatable clinical biomarker, and greatly facilitated this first clinical evaluation of a MGLL inhibitor,” said Iain Fraser, MBChB, DPhil, Head of Early Clinical Development at Abide Therapeutics, and clinical lead for the ABX-1431 first-in-human study. “These clinical data indicate that ABX-1431 modulates CNS activity in a dose-related fashion, and have refined the anticipated ABX-1431 dose range for further clinical evaluation in patient populations.”
Details of the poster presentations are as follows:
Title: Preclinical Characterization and First-in-Human Administration of a Selective Monoacylglycerol Lipase Inhibitor, ABX-1431
Location: Kensington Conference and Events Centre, London
Date & Time: Thursday, May 18, 1:15 – 2:00 PM GMT
About the Endocannabinoid System
Cannabinoid receptor 1 (CB1) is critical to regulating neurotransmission. It is the most highly expressed G-protein coupled receptor in the brain, and its main endogenous ligand is 2-arachidonoylglycerol (2-AG). Monoacylglycerol lipase (MGLL) is an enzyme that catalyzes the breakdown of 2-AG, and as a result regulates the activation of CB1. A second cannabinoid receptor, CB2, which is found primarily on immune cells and is thought to mediate certain immune functions, also has 2-AG as an endogenous ligand. Preclinical studies with MGLL inhibitors demonstrate that raising the level of 2-AG has multiple therapeutic effects, including reduction of pain responses, control of spasticity, anxiolytic effects, and reduction of neurodegenerative pathology.
Direct activation of cannabinoid receptors by medicinal cannabis demonstrates therapeutic benefits on pain, spasticity, sleep, appetite, and nausea. Cannabis indiscriminately activates cannabinoid receptors throughout the body; this non-selective activity is likely responsible for the numerous psychoactive side effects of medical cannabis, and limits clinical use. In contrast, inhibiting MGLL enhances 2-AG concentrations locally, which is expected to rectify neurotransmitter balance through activation of presynaptic CB1 receptors.
Abide Therapeutics is developing ABX-1431, a first-in-class, small-molecule inhibitor of monoacylglycerol lipase (MGLL), to treat neurological disorders, pain, and neuroinflammation. ABX-1431, a potent and selective inhibitor of MGLL, has been shown to modulate 2-arachidonoylglycerol (2-AG) levels in preclinical species and is expected to produce beneficial effects in humans through selective elevation of 2-AG. MGLL inhibition causes an elevation of 2-AG in the brain and propagates signaling through the CB1 endocannabinoid receptor pathway. Additionally, MGLL inhibition by ABX-1431 is believed to deplete the supply of the inflammatory signaling molecule arachidonic acid, thereby providing another potential mechanism for alleviating pain and inflammation.
In September 2016, Celgene exercised its option to obtain ex-US rights to ABX-1431. Celgene will be responsible for development costs for all indications from Phase 2 clinical trials and beyond, while Abide retains US rights and is conducting a number of Phase 1b studies to explore indications where endocannabinoid modulation may affect disease progression.
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.
Abide is located in San Diego, California. To learn more, visit www.abidetx.com