MDD is the third most common cause of disability worldwide, and leaves patients suffering from an exasperated state of helplessness, grief, and increased suicidality. Further, depression remains a prominent, underserved, and chronic feature of bipolar disorder, where patients experience intense emotional states of both highs (mania or hypomania) and lows (depression). The cause of depression 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 and bipolar depression, but many patients inadequately respond to current treatments, presenting the need for new treatments and novel mechanisms of actions.

ABX-002 is a potent and selective, brain-boosting TRβ agonist that is anticipated to enhance serotonin activity and elicit a brain bioenergetic effect in the brains of people suffering from MDD. Synthetic thyroid hormone (e.g., T3 or T4) has been used off-label for over 50 years as an adjunctive treatment for MDD, with an extensive literature set and clinical use supporting its potential effectiveness as a treatment for depression. Evidence suggests that a brain-targeted thyromimetic such as ABX-002 may, in a more selective fashion, evoke favorable thyroid hormone pharmacology in the CNS, while simultaneously eliminating the peripherally-mediated side effects of synthetic thyroid hormone (i.e., cardiac effects and effects on the thyroid hormone axis).

We have completed IND-enabling activities for 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 offers a lifecycle management and franchise opportunity to maximize the value of selective and potent, CNS-active thyromimetics.

We have completed IND-enabling activities for 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 offers lifecycle management and franchise opportunity to maximize the value of selective and potent, CNS-active thyromimetics.

Sphingosine-1-Phosphate (S1P) receptor modulators are a well-studied and clinically validated class of drugs that are ideally suited for Autobahn’s FAAH-mediated brain-targeting prodrug platform. Direct neuroinflammatory and neuroprotective actions of S1P receptor modulation 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 rational chemistry, PK, and pharmacology approach to demonstrate improved delivery of free drug to the brain and an ability to unlock novel central pharmacology that would be applicable to both broad neuroinflammatory/neurodegenerative disorders and rare indications. Autobahn has demonstrated robust neuroinflammatory and neuroprotective benefits with ABX-101 in multiple disease-relevant nonclinical models. We are currently conducting IND-enabling studies and plan to enter the clinic in the first half of 2025.