SAN DIEGO, May 10, 2016 /PRNewswire/ -- Abide Therapeutics, a developer of innovative pharmaceuticals, announced today initiation of enrollment and dosing in a Phase 1 PET occupancy study with ABX-1431, a first-in-class investigational monoacylglycerol lipase (MGLL) inhibitor, and [18F]ABX-1488, a human MGLL-specific PET ligand. ABX-1431, which was discovered with Abide's proprietary technology platform targeting serine hydrolases, has successfully completed dosing in a first-in-human study assessing the safety, tolerability, pharmacodynamics, and pharmacokinetics of the molecule in single-ascending and multiple-ascending doses in healthy volunteers. [18F]ABX-1488 has also successfully completed dosing in a first-in-human study that evaluated safety, tolerability, test-retest reproducibility, and radiation dosimetry in healthy volunteers.
"The Abide technology platform by design yields translational target engagement biomarkers," said Alan Ezekowitz, MBChB, D.Phil., co-founder, president and chief executive officer of Abide Therapeutics. "The development of this highly selective MGLL-specific PET ligand will enable a direct comparison between MGLL target engagement in peripheral blood, plasma pharmacokinetics, and MGLL target engagement in the brain."
In the Phase 1 PET occupancy study in healthy volunteers that is now underway, the location and MGLL enzyme occupancy of orally administered ABX-1431 in the brain will be monitored by PET scan, using radiolabeled ABX-1488. ABX-1431 is an orally available small molecule that modulates the levels of an endogenous cannabinoid, 2-arachidonoylglycerol (2-AG), through inhibition of MGLL. In preclinical animal studies, Abide Therapeutics showed that increasing the levels of 2-AG mimicked the beneficial analgesic effects of exogenous cannabinoids, without observable side effects on behavior.
"The PET study, together with a planned fMRI study, adds an extra level of precision that will allow us to learn more about the mechanism of action of ABX-1431 and to calibrate dosing in subsequent studies," explained Dr. Ezekowitz.
Potential indications for ABX-1431 include neurodegenerative diseases (such as multiple sclerosis and Alzheimer's disease), central pain in neuromyelitis optica, neuroinflammation, and certain forms of epilepsy. Abide Therapeutics intends to assess proof of biology in multiple indications in a series of ABX-1431 Phase 1b studies planned for 2016 and 2017.
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 is focused on developing innovative medicines that target serine hydrolases, one of the largest enzyme classes in nature with validated but mostly untapped therapeutic potential. Serine hydrolases play important regulatory roles in human physiology and disease. Abide has created a proprietary platform, based on technology developed at The Scripps Research Institute by Professors Ben Cravatt and Dale Boger, that specifically targets serine hydrolases with selective small molecules. The ability to target and modulate serine hydrolases has potential to develop new medicines in many therapeutic areas. Abide is located in San Diego. To learn more, visit www.abidetx.com.
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SOURCE Abide Therapeutics