Our Pipeline

Optimizing Drug Discovery

By leveraging our unique discovery platform, which combines activity-based protein profiling (ABPP) with a tailored chemical library and sophisticated metabolomics capabilities, Abide is defining the roles of serine hydrolases in disease pathways, validating new drug targets, and accelerating the discovery of new therapeutics.

Building a Proprietary First-in-Class Pipeline

Abide’s discovery portfolio includes multiple promising new serine hydrolase targets that may play roles in broad therapeutic areas such as neurology, liver disease, and oncology. We use our deep knowledge of serine hydrolases to develop biomarkers for our chosen targets, facilitating translation to the clinic. Our current pipeline is summarized below.

Our Lead Candidate: ABX-1431

ABX-1431, entering Phase 2, is a first-in-class inhibitor of the serine hydrolase monoacylglycerol lipase (MGLL) that is designed to treat a broad range of CNS diseases by regulating neurotransmitter release. ABX-1431 has shown promising clinical data in a Phase 1b placebo-controlled study in patients with Tourette Syndrome, achieving statistical significance on multiple clinical endpoints.

MGLL inhibitors tune brain signaling networks by increasing levels of the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) and activating the cannabinoid receptor CB1 only in active circuits. This helps to regulate neurotransmission in conditions where synaptic equilibrium is disrupted. Because MGLL inhibitors modulate naturally activated neural circuits, they are clearly differentiated from other therapeutic approaches that target the endocannabinoid system, such as medical cannabis, which causes global, maximal, and sustained activation of CB1 and leads to unwanted psychoactive effects.

We studied ABX-1431 in healthy volunteer trials utilizing translational target engagement biomarkers, thus establishing a generally safe and well-tolerated dose range. Using our ABPP platform, we developed biomarkers that confirm dose-related inhibition of MGLL, and subsequent recovery of MGLL activity following expected metabolism of ABX-1431. We demonstrated occupancy of MGLL in the human brain by orally administered ABX-1431 using PET imaging with a MGLL-specific tracer, developed by Abide Therapeutics. This PET occupancy study confirmed target engagement in the brain by ABX-1431.

Clinical Indications for ABX-1431

ABX-1431 provides a novel mechanism to treat CNS diseases by enhancing the activity of the body’s natural cannabinoid signaling system. This mechanism has broad therapeutic potential for a range of neurological diseases, including movement disorders, behavioral disorders, and pain.

Tourette Syndrome

Tourette Syndrome (TS) is a neuropsychiatric disorder that first appears during childhood. People with TS experience sudden, involuntary, and repetitive tics as well as a substantial buildup in tension when suppressing these tics. Current medical treatments for TS include both approved and off-label antipsychotics.  However, these therapies are associated with significant side effects such as sedation and metabolic effects. The need exists for therapies with improved side effect profiles, as well as those that provide shorter-acting symptomatic treatment. 

An exploratory Phase 1b trial with a single dose of ABX-1431 in adult TS patients demonstrated that ABX-1431 had a positive impact on key measures of TS symptoms, including the Yale Global Tic Severity Scale.  The placebo-controlled response showed a robust drug effect, comparable to observations after 1-2 weeks of continuous therapy with other drugs in clinical trials for TS. The demonstration of statistically significant effects across multiple endpoints after a single dose in this double-blind, crossover study suggests that ABX-1431 has the potential to be a true breakthrough in the treatment of TS, according to Dr. Kirsten Muller-Vahl, MD, the Principal Investigator for the study. These encouraging results strongly support further development of ABX-1431 in children and adults with TS.  

Neuromyelitis Optica

Neuromyelitis optica (NMO) is a rare demyelinating, inflammatory, autoimmune disease of the CNS. In NMO, the immune system cells and antibodies primarily attack the optic nerves and spinal cord. This produces swelling and inflammation that cause pain and vision loss.

No medications are specifically approved to treat NMO, although immunosuppressive therapy, which seeks to prevent relapses, is commonly used. NMO pain, however, is typically refractory to available analgesic agents. In fact, 80% of NMO patients taking analgesic therapy experience daily pain that averages 5 out of 10 or higher in intensity.

Multiple Sclerosis Spasticity

Spasticity in multiple sclerosis (MS) refers to abnormal muscle tone in which muscles become stiff and movement grows difficult. Spasticity occurs across the spectrum of MS and affects approximately 50% of MS patients.

Current treatments have limited efficacy coupled with side effects such as sedation and weakness. Compelling evidence from controlled studies indicates that troublesome spasticity and pain in MS respond to the neurotransmitters modulated by ABX-1431.