Scientific Approach

Realizing the Therapeutic Value of Serine Hydrolases

Abide is focused on one of the largest known enzyme classes, the serine hydrolase superfamily. Comprising approximately 250 enzymes, serine hydrolases represent roughly 1% of the human genome and are involved in a range of physiological processes, including central nervous system signaling, inflammation, and metabolism.

Currently, only three serine hydrolases are targeted by widely prescribed medicines, demonstrating the limited ability to target the serine hydrolase family for drug development – which our platform overcomes.

Prioritizing Target Selection for Impactful Drug Development

At Abide, we combine our scientific expertise with existing knowledge about genetics, biological pathways, and pharmacology to identify the most promising serine hydrolase targets. We have identified multiple attractive targets that may play roles in a variety of disease areas with significant unmet medical need.

Target Pool
Serine Hydrolase Superfamily
Filters for Prioritization

MULTIPLE NEW TARGETS

Unique Discovery Platform for First-in-Class Medicines

Our entire chemical library of covalent inhibitors is designed to react specifically with active-site serines. The library covers approximately 80% of the serine hydrolase family and continually evolves as new targets are characterized and new leads identified.

Abide’s unparalleled platform for drug discovery combines our unique collection of small molecules with a chemical proteomic technology called activity-based protein profiling (ABPP). Pioneered by Dr. Benjamin Cravatt and colleagues at The Scripps Research Institute, ABPP allows small molecules from our library to be simultaneously screened against the entire serine hydrolase family in native biological systems to rapidly and efficiently evaluate inhibitor potency and selectivity.

Complementary to our in vivo ABPP methods, we use metabolomics to provide further biochemical validation of new targets and inhibitors. This in vivo confirmation of activity in target tissues provides a deep understanding of inhibitor potency and target engagement, accelerating preclinical discovery and facilitating biomarker development.

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Through Abide's unique combination of our chemical library, ABPP technology, and metabolomics strategy:

In under three years Abide has produced and advanced a lead clinical candidate to Phase 2 development, with three additional compounds poised to enter the clinic and multiple promising new targets under evaluation.

Scientific Approach

Rapidly Advancing First-in-Class Therapeutics

Abide’s lead product candidate, ABX-1431, is a first-in-class, oral monoacylglycerol lipase (MGLL) inhibitor with potential to treat a broad range of CNS diseases by regulating neurotransmitter release. A placebo-controlled Phase 1b study in patients with Tourette Syndrome has shown the first clinical evidence of a positive therapeutic effect of ABX-1431, with statistical significance on multiple endpoints.  Studies of ABX-1431 in patients with neuromyelitis optica (NMO) are ongoing, while other CNS disorders are being actively explored.

Scientific Publications and Presentations