Autobahn Therapeutics has announced the initiation of a Phase 2 clinical trial evaluating ABX-002 as an adjunctive treatment for adults with bipolar depression. This trial aims to establish biological and clinical proof-of-concept for ABX-002, a highly potent, oral, thyroid hormone beta receptor (TRβ) selective agonist, and will inform Autobahn’s further clinical development strategy. Topline data is expected in the second half of 2025.
The Phase 2 open-label trial will study ABX-002 as an adjunctive treatment in 30 adult patients with depressive episodes associated with bipolar I and bipolar II disorder. The trial will utilize neuroimaging assessments and validated clinical scales to evaluate changes in metabolites associated with brain energy metabolism and improvements in depressive symptoms.
Study Design and Endpoints
The primary endpoints will assess the correlation of change from baseline of nucleoside triphosphate (NTP) and phosphocreatine (PCr) in the brain, as determined by phosphorus magnetic resonance spectroscopy imaging (31P-MRS), with percent change in the Hamilton Depression Rating Scale-17 (HAMD-17) over six weeks of dosing, respectively. Key secondary and exploratory endpoints will evaluate changes from baseline in the HAMD-17, HAMD-29, as well as other neuroimaging assessments, including brain activity as measured by resting state functional magnetic resonance imaging (rs-fMRI).
Clinical Need and ABX-002 Potential
"Bipolar depression is one of the most prevalent and difficult-to-treat psychiatric conditions due to a host of burdensome symptoms," said Roger McIntyre, MD, Professor of Psychiatry and Pharmacology at University of Toronto. "People living with bipolar disorder often experience prolonged periods of depression, many of whom are not adequately benefiting from, or have had difficulties tolerating, existing treatments. For decades, preclinical and clinical evidence has supported the effectiveness of thyroid hormone as an adjunctive treatment in adults living with bipolar depression, providing the basis for rigorously evaluating an optimized, brain-targeted, potent and selective TRβ agonist which could serve as a highly promising therapeutic option in the future."
Broader Development Program
ABX-002 is also being evaluated in the company’s ongoing AMPLIFY Phase 2 trial as an adjunctive treatment for patients with major depressive disorder (MDD), with topline data expected in the second half of 2025. According to Autobahn Therapeutics, clinical evidence generated to date for ABX-002 supports its promise as a centrally-active, differentiated thyromimetic, with a potentially favorable safety profile.
About ABX-002
ABX-002 is an orally administered, potent and selective thyroid hormone beta receptor (TRβ) agonist designed to enhance the CNS benefits of thyroid hormone biology while also reducing the peripheral liabilities of synthetic thyroid hormone (e.g., triiodothyronine, T3), a treatment which has shown efficacy in numerous placebo-controlled human studies across MDD and bipolar disorder depression. Thyroid hormone agonism has demonstrated activity on cellular energy metabolism pathways, which play an important role on the regulation of brain bioenergetics and may be uniquely suited to address symptoms of atypical depression, a highly prevalent and underserved sub-population of MDD. In nonclinical and clinical studies, ABX-002 has demonstrated optimized PK properties, target engagement in brain regions associated with depression, and an attractive safety and tolerability profile.
