Abide Therapeutics, a developer of innovative pharmaceuticals, announced today initiation of enrollment and dosing of the first subject in a Phase 1a clinical study of ABX-1431, a first-in-class, investigational endocannabinoid system modulator. ABX-1431 was discovered with Abide's proprietary technology platform, which finds new small molecule drug candidates that target serine hydrolases, a large class of enzymes with important regulatory roles in human physiology and disease.
"This is a significant milestone for the company and shows the power of Abide's unique approach to target the validated but largely underexplored class of serine hydrolases," said Alan Ezekowitz, MBChB, D.Phil., co-founder, president and chief executive officer of Abide Therapeutics.
The randomized, double-blinded, placebo-controlled Phase 1 study is currently underway in Belgium. Approximately 60 healthy volunteers will participate in the study, which is designed to assess the safety, tolerability, pharmacodynamics, and pharmacokinetics of ABX-1431 in single-ascending and multiple-ascending doses.
ABX-1431 is a novel small molecule that modulates the levels of an endogenous cannabinoid, 2-arachidonoylglycerol (2-AG), through inhibition of monoacylglycerol lipase (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.
"Additionally, in animal models, MGLL regulates a pool of arachidonic acid that contributes to production of pro-inflammatory lipid mediators. Therefore, we expect that MGLL inhibition by ABX-1431 will play a dual role – selectively activating the cannabinoid receptor system while independently exerting an anti-inflammatory effect," explained Dr. Ezekowitz.
In the ABX-1431 Phase 1 program, the location and activity of the molecule in the brain will be monitored by imaging technologies, including PET scan and fMRI, enabled by radiolabeling with [18F]ABX-1488, a proprietary human MGLL-specific PET ligand that has been validated in human studies.
According to Dr. Ezekowitz, "The imaging component of our 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 the dosing."
"Clinical indications for ABX-1431 were selected based on well-established human pharmacology and approved uses of medicinal cannabinoids. There is currently a large unmet medical need for effective alternatives to current pain management, especially for treatments with non-opioid, non-addictive mechanisms," said Dr. Ezekowitz.
Potential indications for ABX-1431 include neuropathic pain, neuroinflammation, neurodegenerative diseases, and certain forms of epilepsy. The company intends to assess proof of biology in Phase 1b studies planned for 2016.