Autobahn Therapeutics Reports New Nonclinical Data Showing Elunetirom Rapidly Builds Synaptic Connections and Restores Cellular Energy Capacity in Neurons

Elunetirom drove rapid growth in the connections between mature brain cells and simultaneously increased the energy supply that keeps those connections functioning

Brain-cell growth depended on TrkB, a natural growth-signaling pathway, and not on the psychedelic receptor target, supporting a mechanistically distinct route to brain-cell growth

SAN DIEGO, August 25, 2026--Autobahn Therapeutics, Inc., a biotechnology company developing restorative treatments for people affected by neuropsychiatric disorders, today reported new nonclinical data on the antidepressant mechanism of action for elunetirom, its lead investigational therapy in Phase 2 development for adjunctive treatment of bipolar depression and major depressive disorder (MDD). The data show that elunetirom rapidly increased the number of synaptic connections between neurons and enhances the cellular energy machinery that neurons depend on to build and sustain those connections. Together, these findings provide a cellular framework for the rapid onset and robust magnitude of antidepressant effects observed in Autobahn's Phase 2 AMPLIFY-BD clinical trial in bipolar depression.

A manuscript presenting these results, titled "Elunetirom, a brain-targeted TRβ prodrug, promotes neuronal plasticity and mitochondrial biogenesis-related signaling in primary neuronal cultures," is currently under peer review and has been posted to the bioRxiv preprint server. The manuscript is available at https://doi.org/10.64898/2026.07.21.739927.

Thyroid hormone has a long-recognized role in mood regulation, and non-selective thyroid hormone therapies such as liothyronine (T3) and levothyroxine (T4) have shown benefit as augmentation strategies in depression. Their broader adoption, however, has been limited primarily by cardiovascular, skeletal, and metabolic effects and by the associated monitoring burden. As a brain-directed prodrug, elunetirom was designed to address those limitations by preferential distribution to the central nervous system, where it is converted into the receptor-active thyromimetic LL-340001 by fatty acid amide hydrolase (FAAH), an enzyme enriched in the brain.

"There is a substantial body of evidence that depression involves impairments in both synaptic plasticity and cellular bioenergetics, which are usually discussed as separate problems requiring separate solutions," said Stephen M. Stahl, M.D., Ph.D., Professor of Psychiatry at the University of California San Diego and a co-author of the manuscript. "What is notable about these recent results is that a single mechanism appears to engage both. Elunetirom does what a thyroid receptor agonist ought to do developmentally, which is promote neurite growth and synapse formation. Strikingly, it does so in mature neurons, on a timescale of hours rather than weeks, and while increasing the cell's energy-producing capacity rather than drawing it down. It also preserves synapses under amyloid challenge, which suggests the mechanism is not only constructive but protective. What excites me is the prospect of a brain-penetrant thyroid hormone receptor agonist for the treatment of mood disorders that acts where it needs to, without the cardiac and skeletal exposure and associated monitoring burden that have limited the approach historically."