Abide begins dosing in Phase Ia trial of endocannabinoid system modulator ABX-1431

Around 60 healthy volunteers will be enrolled in the randomized, double-blinded, placebo-controlled Phase I trial, which is currently underway in Belgium.

The company said that potential indications for ABX-1431 include neuropathic pain, neuroinflammation, neurodegenerative diseases and certain forms of epilepsy.

The trial is designed to evaluate the safety, tolerability, pharmacodynamics, and pharmacokinetics of ABX-1431 in single-ascending and multiple-ascending doses.

ABX-1431 was discovered using the company’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.

It modulates the levels of an endogenous cannabinoid, 2-arachidonoylglycerol (2-AG), through inhibition of monoacylglycerol lipase (MGLL).

In preclinical animal studies, the company showed that increasing the levels of 2-AG mimicked the beneficial analgesic effects of exogenous cannabinoids, without observable side effects on behavior.

Abide Therapeutics co-founder, president and chief executive officer Dr Alan Ezekowitz said in animal models, MGLL regulates a pool of arachidonic acid that contributes to production of pro-inflammatory lipid mediators.

Ezekowitz said: "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."

According to the company, in the ABX-1431 Phase I program, location and activity of the molecule in the brain will be monitored by imaging technologies, including PET scan and fMRI, enabled by radiolabeling with ABX-1488, a proprietary human MGLL-specific PET ligand that has been validated in human studies.

The company intends to assess proof of biology in Phase Ib studies, which are planned to be conducted next year.