Autobahn Therapeutics Reports Positive Phase 2 AMPLIFY-BD Results for Elunetirom in Bipolar Depression
Autobahn Therapeutics, Inc., a biotechnology company developing restorative treatments for people living with neuropsychiatric disorders, announced the presentation of complete results from its Phase 2 AMPLIFY-BD clinical trial at Psych Congress 2026, held September 15–19 in New Orleans, Louisiana. The findings provide further support for elunetirom, an investigational oral, once-daily, brain-penetrant central nervous system (CNS) thyroid hormone receptor agonist, as a potential adjunctive treatment for bipolar depression.
In the AMPLIFY-BD study, elunetirom demonstrated statistically significant and clinically meaningful improvements across the primary endpoint and all key secondary depression measures. The trial evaluated the therapy in adults with bipolar I or bipolar II disorder who were experiencing a moderate-to-severe major depressive episode despite treatment with existing mood-stabilizing and/or antipsychotic therapies.
The results build on previously announced topline findings and, according to Autobahn, support the company’s plans to engage with regulatory authorities regarding a potential registration pathway for elunetirom in bipolar depression. The condition is a substantial public health challenge, affecting approximately 7 million adults in the United States.
Elunetirom is designed to selectively engage the thyroid-mood axis in the brain while limiting peripheral thyroid-related effects that have historically constrained the therapeutic use of thyroid hormones in psychiatric disorders. The company believes this mechanism could offer a new approach to treating depressive symptoms and functional impairment associated with bipolar disorder.
“ The thyroid-mood axis has been one of psychiatry’s most compelling mechanisms for decades, but also one of the least accessible,” said Roger S. McIntyre, M.D., FRCPC, Professor of Psychiatry and Pharmacology at the University of Toronto and a global thought leader in depression and bipolar disorder.
According to McIntyre, elunetirom is differentiated by its ability to selectively engage the target without the peripheral effects associated with traditional thyroid hormone approaches. He also highlighted the continued improvement observed through Week 6 across multiple measures, including depressed mood, work and activities, and psychomotor slowing—symptom areas that can be particularly difficult to address in bipolar depression.
The AMPLIFY-BD findings include both clinician-assessed outcomes and patient-reported measures, providing a broader picture of the potential impact of treatment on depressive symptoms, illness severity, daily functioning and productivity.
Phase 2 AMPLIFY-BD Trial Design
AMPLIFY-BD was an open-label Phase 2 study designed to evaluate the efficacy, safety and tolerability of elunetirom as an adjunctive therapy in adults with bipolar I or bipolar II disorder.
The study enrolled 21 adults experiencing a moderate-to-severe major depressive episode. Participants had a mean baseline score of 25.1 on the 17-item Hamilton Rating Scale for Depression (HAMD-17), indicating a substantial level of depressive symptom burden.
Patients received 2.8 micrograms of oral elunetirom once daily for six weeks in addition to their existing treatment regimen. Background therapy consisted of a mood stabilizer and/or atypical antipsychotic, with or without a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).
The primary endpoint was the change from baseline in the HAMD-17 total score at Week 6.
Results presented at Psych Congress demonstrated improvement as early as Week 2, with further gains observed at Week 4 and Week 6.
Significant Improvement in Depression Symptoms
The study met its primary endpoint, with elunetirom producing a statistically significant reduction in HAMD-17 scores.
At Week 6, the mean reduction from baseline was 16.8 points, with a p-value below 0.001. Improvements were already apparent at Week 2, when the mean HAMD-17 reduction was 9.7 points (p<0.001), followed by a 13.7-point reduction at Week 4 (p<0.001).
The progression of improvement across the three assessment points suggests that the antidepressant effect developed rapidly and continued to strengthen during the six-week treatment period.
Response and remission outcomes also increased over time. At Week 2, 38.1% of participants achieved a response and 14.3% achieved remission. By Week 4, those figures had increased to 52.6% and 36.8%, respectively. At Week 6, the response rate reached 75%, while the remission rate reached 50%.
The company also reported statistically significant improvements in the HAMD-6 subscale, which focuses on core depressive symptoms. At Week 6, the mean HAMD-6 score decreased by 9.0 points from baseline (p<0.001).
Improvements were observed across individual HAMD-17 items, including depressed mood, work and activities, feelings of guilt, psychomotor retardation, psychic anxiety and general somatic symptoms. Autobahn reported statistically significant improvement across these measures at every study visit.
The broader HAMD-29 assessment also demonstrated clinically meaningful and statistically significant improvement at all evaluated time points. By Week 6, the mean HAMD-29 score had decreased by 22.9 points from baseline (p<0.001).
Improvements in Overall Bipolar Illness Severity
Elunetirom treatment was also associated with significant improvement on the Clinical Global Impressions-Bipolar Severity (CGI-BP-S) scale at every assessed time point, with p<0.001.
The CGI-BP-S results tracked closely with changes in HAMD-17 scores. Spearman’s Rank Correlation Coefficients between the two measures were 0.82 at Week 2, 0.90 at Week 4 and 0.89 at Week 6.
The findings indicate that the reduction in depressive symptoms measured using the HAMD-17 corresponded with clinicians’ overall assessments of improvement in bipolar illness severity.
McIntyre noted that improvement continued to deepen through Week 6 across the evaluated endpoints. He specifically highlighted domains related to mood, activity and psychomotor function as areas of particular relevance in bipolar depression.
Patient-Reported Outcomes Show Functional Gains
The AMPLIFY-BD results also included patient-reported outcomes intended to assess whether improvements in depressive symptoms translated into changes in everyday functioning.
On the Sheehan Disability Scale (SDS), participants demonstrated a statistically significant 62% mean improvement from baseline in the total score at Week 6 (p<0.001). Significant improvements were reported across all three SDS domains: work and school, social and leisure activities, and family and home life.
The study also found a substantial reduction in the number of days participants reported being unable to function because of their illness.
At baseline, participants reported losing an average of 2.7 days per week due to illness. By Week 6, that figure had fallen to 0.4 days per week, representing an 85% reduction from baseline (p<0.001). A significant decrease in underproductive days was also reported.
These findings suggest that the potential impact of elunetirom extended beyond symptom scores to areas of productivity and daily participation.
On the Symptoms of Depression Questionnaire (SDQ), participants reported a statistically significant 36% improvement from baseline in total score at Week 6 (p<0.001).
Patient perceptions of improvement were also captured using the Patient Global Impression of Improvement (PGI-I). Significant improvement was reported at Weeks 2, 4 and 6, and no participant reported worsening of symptoms at any evaluated time point.
The patient-reported and clinician-rated assessments showed a high degree of alignment. At Week 6, the correlation between percentage change in SDS total score and percentage change in HAMD-17 total score reached a Spearman’s Rank Correlation Coefficient of 0.94.
Safety and Tolerability Profile
Elunetirom was generally well tolerated throughout the study. Autobahn reported no severe or serious treatment-related adverse events.
The company also reported no observations of weight gain, extrapyramidal symptoms or tardive dyskinesia. In addition, there were no clinically meaningful peripheral thyroid effects or concerning ECG findings.
The most frequently reported treatment-related adverse events were dizziness, occurring in 14.3% of participants; diarrhea, reported in 9.5%; and decreased free thyroxine, also reported in 9.5%.
The safety findings are particularly relevant to the development of a CNS-directed thyroid hormone receptor agonist because traditional thyroid hormone approaches can be limited by peripheral effects. Autobahn is developing elunetirom with the goal of selectively targeting CNS pathways associated with mood regulation while avoiding those limitations.
Regulatory Development and Future Plans
Elunetirom has received Fast Track designation from the U.S. Food and Drug Administration for the adjunctive treatment of bipolar depression. The designation provides an opportunity for more frequent interaction with the FDA during development and regulatory review of a therapy intended to address a significant unmet medical need.
Following the complete AMPLIFY-BD results, Autobahn plans to engage with regulatory authorities to discuss a potential path toward registration of elunetirom for bipolar depression.
Gudarz Davar, M.D., Chief Medical Officer and Head of Research and Development at Autobahn, said the full dataset was consistent with the previously reported topline results across the evaluated measures.
“We observed meaningful improvements in both clinician-rated and patient-reported outcomes, at every time point evaluated,” Davar said.
He pointed to the reduction in illness-related lost days, noting that participants moved from losing nearly three days per week to losing less than half a day. Davar also highlighted reports of participants returning to work and re-engaging with family and social activities.
According to Autobahn, these functional outcomes are an important component of the potential clinical value of elunetirom because successful treatment of bipolar depression involves more than reducing symptom scores. Restoration of daily functioning, productivity and social participation can also be important goals for patients and healthcare providers.
Continued Development in Major Depressive Disorder
Autobahn is also investigating elunetirom beyond bipolar depression. The company is currently evaluating the therapy as an adjunctive treatment for major depressive disorder (MDD) in the ongoing Phase 2 AMPLIFY trial, registered under NCT06633016.
Together, the bipolar depression and MDD programs are intended to assess the potential application of elunetirom across major depressive conditions.
The AMPLIFY-BD results presented at Psych Congress 2026 add to the emerging clinical evidence supporting Autobahn’s approach to the thyroid-mood axis. The combination of improvements in clinician-rated depressive symptoms, patient-reported functioning, productivity and overall illness severity provides multiple measures through which the investigational therapy can be evaluated.
While the AMPLIFY-BD study was open-label and involved a relatively small patient population, the reported results provide the basis for further clinical and regulatory discussions. Autobahn now plans to work with regulatory agencies to determine the potential development and registration pathway for elunetirom in bipolar depression.
As the company advances both its bipolar depression and MDD programs, the continued development of elunetirom will provide additional data on whether selective CNS thyroid hormone receptor activation can become a useful therapeutic strategy for patients whose depressive symptoms remain inadequately controlled with existing treatment approaches.
About Bipolar Depression
Bipolar depression, the depressive phase of bipolar disorder, affects approximately 7 million adults in the U.S. and represents one of the most debilitating chronic conditions in psychiatry. Bipolar disorder is characterized by extreme mood swings, including episodes of both mania (or hypomania) and depression. The depressive phase is the predominant and most disabling state for most patients, marked by persistent low mood, loss of interest, fatigue, and impaired functioning.
Patients lose an average of more than one month of work each year and face elevated risks of hospitalization and suicide. More than half of patients do not receive adequate relief from currently available therapies, which are limited by modest efficacy and significant side effects, including weight gain, sexual dysfunction, movement disorders, and metabolic complications.
About Elunetirom
Elunetirom (ABX-002) is an investigational, oral, once daily, brain-penetrant small molecule prodrug that targets CNS thyroid hormone receptors (CNS-TRs). Elunetirom is believed to uniquely boost energy and plasticity in the brain through improving mitochondrial health, increasing cellular energy production, and driving neuroplastic changes in the CNS, offering a potentially fundamentally different mechanism to treat depression and other CNS disorders.
Elunetirom is designed to enhance beneficial neurobiological activity at CNS-TRs while also reducing the liabilities of peripheral thyroid hormone receptor activity from the administration 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.
In nonclinical and clinical studies, elunetirom has demonstrated optimized PK properties, target engagement in brain regions associated with depression, and a favorable safety and tolerability profile. Elunetirom has been granted Fast Track designation by the U.S. Food and Drug Administration for the adjunctive treatment of bipolar depression and is being evaluated in clinical studies as a potential adjunctive treatment for MDD and bipolar depression.
About Autobahn Therapeutics
Autobahn Therapeutics, Inc., is a biotechnology company developing a portfolio of neuropsychiatric clinical candidates leveraging its brain-targeting chemistry platform. Autobahn aims to unlock new therapeutic opportunities through precision tuning of CNS exposure, pursuing validated clinical and biologic targets, and guiding development with biomarkers. The company’s pipeline is led by elunetirom, a CNS thyroid hormone receptor (CNS-TR) agonist being developed as a potential adjunctive treatment for people with major depressive disorder and bipolar disorder depression, including those with atypical depression, a highly prevalent and underserved subpopulation of depression.