Autobahn Therapeutics Starts AMPLIFY Phase 2 Trial for ABX-002 in Major Depression

Autobahn Therapeutics, a biotechnology company focused on developing treatments for neuropsychiatric and neuroimmunologic disorders, has initiated AMPLIFY, a Phase 2 clinical trial. This trial aims to evaluate the effectiveness and safety of ABX-002 as an adjunctive treatment for adults suffering from major depressive disorder (MDD). ABX-002 is an orally administered, highly potent thyroid hormone beta receptor (TRβ) selective agonist, designed to increase the central nervous system (CNS) benefits of thyroid hormone biology with enhanced drug concentrations in the brain, resulting in improved potency, efficacy, and safety.

In a previously completed Phase 1 trial, ABX-002 demonstrated clinical evidence of engaging CNS targets consistent with the effects of brain-activating thyroid hormones. The compound was well-tolerated, and no serious adverse events were observed. This promising data supports ABX-002's potential as a significant treatment option for depression, particularly for patients who do not respond adequately to current antidepressant therapies.

Dr. Dan Iosifescu, a Professor of Psychiatry at NYU Grossman School of Medicine, highlighted the urgent need for more effective treatment options for depression. Over half of the millions of Americans suffering from depression do not experience sufficient relief from existing antidepressant medications. Synthetic thyroid hormone has long been recognized for its benefits as an adjunctive treatment for MDD. A potent and selective TRβ agonist like ABX-002 may offer similar therapeutic benefits with a safety profile suitable for long-term use.

The AMPLIFY trial is a double-blind, placebo-controlled Phase 2 study involving 230 adults with moderate-to-severe depression. The primary objective is to assess the safety, tolerability, efficacy, and pharmacodynamic (PD) effects of ABX-002 when used alongside patients' current selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI) treatments. The primary endpoint is the change from baseline on the Hamilton Depression Rating Scale-17 (HAMD-17) after six weeks of treatment. Secondary endpoints include changes from baseline on the HAMD-29 to evaluate improvements in atypical depression symptoms, the Montgomery-Åsberg Depression Rating Scale (MADRS), and other clinical improvement measures.

Dr. Gudarz Davar, Executive Vice President and Head of Research and Development at Autobahn, expressed enthusiasm for the initiation of the Phase 2 trial. He noted that the clinical data generated with ABX-002 bolster its potential as a brain-penetrating, centrally active thyromimetic with a favorable safety profile. This data gives the company greater confidence in ABX-002's potential as a transformative treatment for depression, particularly for patients underserved by current treatment options. The company remains committed to advancing innovative therapies that can significantly impact patients' lives. This milestone with ABX-002 represents a crucial step toward achieving their mission.

Autobahn Therapeutics expects to report topline data from the AMPLIFY Phase 2 trial in the second half of 2025. Additionally, the company plans to initiate a second Phase 2 trial by the end of 2024 to evaluate ABX-002 in patients with bipolar disorder depression, a challenging and persistent mental health condition.

Autobahn Therapeutics, based in San Diego, is developing a portfolio of neuropsychiatric and neuroimmunologic clinical candidates via its brain-targeting chemistry platform. The company's strategy involves precision tuning of CNS exposure, targeting validated clinical and biological pathways, and guiding development with biomarkers. The pipeline is led by ABX-002, a thyroid hormone receptor beta (TRβ) agonist being developed as a potential adjunctive treatment for major depressive disorder and bipolar disorder depression.