MDD is the third most common cause of disability worldwide, and leaves patients to suffer from an exasperated state of helplessness, grief, and increased suicidality. The cause of MDD is not fully understood but has centered around disruption of the monoaminergic system (e.g., serotonin and norepinephrine activity). Approved drugs that enhance monoaminergic signaling in the brain have shown beneficial effects in MDD, but many patients continue to suffer from an inadequate response to treatment that sustains their depressive symptoms and disability.

ABX-002, is a potent and selective, brain-boosting TRβ agonist that is anticipated to enhance serotonin activity in the brain in MDD patients, and may have additional benefits on cellular energy metabolism and neurogenesis and increased brain connectivity. Synthetic thyroid hormone (T3/T4) has been used for over 50 years as an adjunctive treatment for people suffering from MDD and extensive literature suggests that a brain-targeted thyromimetic, such as ABX-002, may, in a more selective fashion, elicit relevant brain pharmacology while also diminishing peripherally-driven side effects of synthetic thyroid hormone. ABX-002 is currently in a Phase 1 clinical study evaluating the safety, tolerability, and pharmacokinetic profile.

We are advancing the development of ABX-003, a next generation TRβ-selective thyromimetic that utilizes combination with a peripheral FAAH inhibitor to further enhance brain distribution of free drug. ABX-003 is currently in IND enabling studies.

Sphingosine-1-Phosphate (S1P) receptor modulators are a well-studied class of drugs that are ideally suited for Autobahn’s FAAH-mediated brain-targeting prodrug platform. Direct anti-inflammatory and neuroprotective actions of S1P in the CNS are known but limited evidence exists to support CNS-specific benefit of other programs, given their inability to achieve meaningful free drug concentrations in the brain. Autobahn is applying a rationale chemistry, PK, and pharmacology approach to demonstrate improved delivery of free drug to the brain and an ability to unlock novel brain pharmacology that would be applicable to both broad neuroimmune/neurodegenerative disorders and rare indications. We are currently conducting drug candidate designation studies.