New Positive Phase 2 Topline Data on Elunetirom for the Treatment of Bipolar Depression

Autobahn Therapeutics today announced positive topline data from its phase 2 AMPLIFY-BD trial evaluating elunetirom as an adjunctive treatment in patients with bipolar I or bipolar II depression. Elunetirom achieved statistical significance across the primary and all key secondary depression endpoints, demonstrating clinically meaningful antidepressant effects with a favorable safety profile.

Elunetirom is a novel, oral, once daily, brain-penetrant CNS thyroid hormone receptor agonist. These data provide the first clinical evidence for CNS-targeted thyroid hormone receptor agonism, which isa differentiated mechanism designed to directly enhance brain energy metabolism and neuroplasticity.

“Bipolar depression poses an enormous burden on the millions of patients affected, many of whom have exhausted existing treatment options that are often either ineffective or have difficult side effects that limit their chronic use,” said Roger S. McIntyre, MD, FRCPC, professor of psychiatry and pharmacology at the University of Toronto and global thought leader in depression and bipolar disorder. “The science has long pointed to thyroid hormone pathways as a promising approach to treating depression, but their use in psychiatry has remained largely anecdotal, limited by peripheral thyroid effects. Multiple lines of scientific evidence have implicated deficits in cellular bioenergetics and neuroplasticity in the disease process of depression and bipolar disorder. The magnitude and clinical meaningfulness of the response, the rapidity of onset, and the tolerability profile seen with elunetirom, a brain-targeted and potent thyroid hormone receptor agonist, provide compelling evidence that a novel treatment option unlocking this promising mechanism may offer benefit to many of the patients we see in clinical practice.”

In the open-label, phase 2 AMPLIFY-BD trial, investigators evaluated the efficacy, safety, and tolerability of elunetirom as an adjunctive treatment in 21 adult participants with bipolar I or bipolar II disorder who were experiencing a moderate-to-severe major depressive episode. Participants received oral, once daily elunetirom for 6 weeks in addition to their existing mood stabilizer and/or atypical antipsychotic regimen. The primary endpoint was the change in Hamilton Depression Rating Scale (HAMD-17) total score from baseline to week 6. Key secondary endpoints included changes in HAMD-17 at weeks 2 and 4, response (defined as a ≥50% reduction from baseline in HAMD-17 total score) and remission (defined as a HAMD-17 total score ≤7) rates, as well as changes in a variety of other scales. These scales included the HAMD-6, HAMD-29, Clinical Global Impressions-Bipolar Severity (CGI-BP-S) scale, Patient Global Impression (PGI), Sheehan Disability Scale (SDS), and Symptoms of Depression Questionnaire (SDQ) at designated timepoints throughout the study. In a subset of patients, investigators conducted neuroimaging, including analysis of functional connectivity using resting-state functional MRI (rs-fMRI), at baseline and week 6.

Elunetirom demonstrated statistically significant and clinically meaningful results across all primary and key secondary depression endpoints.

Elunetirom showed a rapid and robust antidepressant response, with a clinically meaningful 16.8-point mean reduction in HAMD-17 (P <0.001) at week 6, and mean reductions of 9.7 (P<0.001) at Week 2 and 13.7 (P <0.001) at week 4. This indicates not only a rapid onset, but also a continued antidepressant effect. Participants had high response (75%) and remission (50%) rates observed at week 6.

Additionally, participants saw statistically significant and clinically meaningful improvements across all clinical assessments and clinician- and patient-reported measures, including the HAMD-6, HAMD-29, CGI-BP-S, PGI, SDS, and SDQ. This equates to real life improvements in productivity, social functioning, and family relationships.

Notably, elunetirom also demonstrated benefit in an atypical depression subgroup. These patients had distinct symptomatology, with increased appetite, hypersomnia, and low energy. Treating these patients can present unique treatment challenges, so elunetirom’s effectiveness here supports potential applicability in a large, diverse patient population.

Finally, elunetirom led to treatment-associated changes in brain network connectivity. Investigators observed statistically significant changes in functional connectivity between baseline and week 6 in participants treated with elunetirom in regions of the brain highly relevant to depression.

As to safety profile, elunetirom was generally safe and well tolerated. All treatment-related adverse events were mild to moderate, with no severe or serious treatment-related adverse events reported.

“The consistency of effect we observed with elunetirom across multiple measures of depression, including core symptom severity and functional impairment, is very promising,” said Gudarz Davar, MD, the chief medical officer and head of research and development at Autobahn. “Importantly, the rapid onset of activity and tolerability profile support the potential for elunetirom to deliver meaningful and durable benefit for patients without adding treatment burden. We were also highly encouraged to observe changes in functional connectivity in bipolar depression patients treated with elunetirom, giving objective evidence that elunetirom can lead to neuroplastic remodeling in regions and functional networks of the brain affected by depression. The totality of clinical and neurobiological evidence from AMPLIFY-BD points to a strong potential for elunetirom to offer a meaningfully differentiated treatment option for the millions living with bipolar depression and major depressive disorder.”

On May 26, 2026, the US Food and Drug Administration (FDA) granted elunetirom Fast Track designation for the adjunctive treatment of bipolar depression.² Autobahn intends to present full results from the AMPLIFY-BD trial at an upcoming medical conference in the latter half of 2026. Furthermore, Autobahn is evaluating elunetirom as an adjunctive treatment for major depressive disorder in its ongoing phase 2 AMPLIFY trial (NCT06633016), with topline data expected in the third quarter of 2026.

“These initial results position elunetirom to be a differentiated, groundbreaking therapy across the depression landscape, including for those patients with atypical depression, a prominent and highly underserved subpopulation,” concluded Kevin Finney, the president and chief executive officer of Autobahn Therapeutics. “We believe the combination of rapid onset, deep and durable response, and favorable tolerability has the potential to deliver the kind of paradigm-shifting profile clinicians and patients have long needed. These data also further strengthen our confidence in the upcoming readout from our Phase 2 MDD trial later this year and reinforce the opportunity for elunetirom to be a valuable adjunct to existing treatments in both major depressive disorder and bipolar depression. Coupled with the recent FDA Fast Track designation, the strength of these data supports our plans to engage with the FDA to assess the path to registration and bring elunetirom to patients with bipolar depression as quickly as we can.”

References

1. Autobahn Therapeutics reports positive phase 2 topline data for elunetirom in bipolar depression, demonstrating rapid, robust, and durable antidepressant effects. News release. June 4, 2026. Accessed June 4, 2026. https://autobahntx.com/news/autobahn-therapeutics-reports-positive-phase-2-topline-data-for-elunetirom-in-bipolar-depression-demonstrating-rapid-robust-and-durable-antidepressant-effects/

2. Autobahn Therapeutics announces U.S. FDA fast track designation for elunetirom, a CNS-directed thyroid hormone receptor agonist, for the adjunctive treatment of bipolar depression. News release. May 26, 2026. Accessed June 4, 2026. https://www.businesswire.com/news/home/20260526505869/en/Autobahn-Therapeutics-Announces-U.S.-FDA-Fast-Track-Designation-for-Elunetirom-a-CNS-Directed-Thyroid-Hormone-Receptor-Agonist-for-the-Adjunctive-Treatment-of-Bipolar-Depression