Liothyronine Sodium

Elunetirom, an oral small molecule given once daily, eased depression severity by an average of 16.8 points after six weeks, as measured by the Hamilton Depression Rating Scale.\n A stimulator of thyroid hormone receptors in the brain has successfully reduced depression severity in patients with bipolar disorder, positioning its maker Autobahn Therapeutics to speed along to late-stage testing with its ultimate goal of approval resting further ahead at the finish line.Autobahn reported this morning that elunetirom, an oral small-molecule given once daily, eased depression severity by an average of 16.8 points after six weeks, as measured by the Hamilton Depression Rating Scale.This result met the primary endpoint of the open-label phase 2 Amplify-BD trial, which enrolled 21 patients with bipolar disorder who were experiencing a depressive episode. Patients took elunetirom in addition to their typical treatment regimen of mood stabilizers and/or antipsychotics. After six weeks of a daily pill, 75% of patients had responded to treatment and half were in remission, Autobahn said in the release. All adverse events related to elunetirom were mild or moderate, the company added. The biotech also reported that treatment led to significant changes in brain connectivity. Autobahn plans to share full data from the study at a medical conference later this year. As an open-label psychiatry study, Autobahn is well aware that the placebo effect—benefits driven by a patient\'s belief that they\'ve received an effective medicine—could muck up results, CEO Kevin Finney told Fierce Biotech.“A few things give us real confidence that what we’re seeing is a genuine treatment effect,” Finney said. First is the fact that patients were already receiving other treatments but still saw a boost from elunetirom, he said. “Historical data on those background agents simply don’t produce results of that magnitude.”The second line of evidence comes from all the trial’s secondary measures, namely assessments of daily life function.“Patients went from missing roughly three days of work per week at baseline to about half a day by week six,” Finney explained. “As our investigators have framed it, a change of that magnitude in patients already on therapy is difficult to attribute to placebo [effect].” Autobahn nabbed a fast track designation from the FDA for elunetirom in these patients back in May. The San Diego biotech is also testing the molecule in a placebo-controlled phase 2 study for major depressive disorder.Autobahn is already prepping for a pivotal phase 3 trial in bipolar depression, Finney told Fierce, with the goal “to bring elunetirom to patients as quickly as we responsibly can.”“We are already preparing for our next study and plan to hold an end-of-phase 2 meeting with the agency to align on the path forward,” Finney said. “We anticipate our next trial would be registration-enabling and would begin in the first half of 2027.”Bipolar disorder is characterized by extreme shifts in mood, with patients swinging from peaks of mania to troughs of depression. Thyroid hormones and their mimics, like Pfizer’s synthetic compound Cytomel (liothyronine), are often prescribed off-label for depression that doesn’t respond to other therapies. But because they also activate thyroid receptors outside of the brain, these drugs can be plagued by side effects like those of hyperthyroidism, including weight loss, hand tremors and a quickened or irregular heartbeat.“Synthetic thyroid hormone has been used off-label by psychiatrists for more than 50 years as an adjunctive treatment in depression,” Finney told Fierce. “The historical limitation has never been efficacy. It’s been the peripheral side effects: cardiac effects and disruption of the thyroid hormone axis that come with dosing systemic thyroid hormone.”By specifically targeting receptors in the brain, elunetirom is designed to avoid the side effects that have limited thyroid hormone therapy’s availability for patients struggling with depression.“On the measures that matter most for this mechanism, it has looked cardiac-safe and weight-neutral,” Finney said. “It’s built to deliver the part of the biology that helps the brain without the part that historically caused problems in the body.”

Clinically meaningful, statistically significant 16.8-point HAMD-17 improvement (p < 0.001), 75% response rate and 50% remission rate at Week 6, with rapid onset of action by Week 2 Favorable safety and tolerability profile, with no serious treatment-related adverse events reported Elunetirom recently granted U.S. FDA Fast Track designation for the adjunctive treatment of bipolar depression Anticipated positive read-through to ongoing Phase 2 trial in major depressive disorder (MDD), the most prevalent and disabling form of depression SAN DIEGO--(BUSINESS WIRE)--Autobahn Therapeutics, Inc., a biotechnology company developing restorative treatments for people affected by neuropsychiatric disorders, 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, a disorder affecting approximately 7 million adults in the U.S. Elunetirom, a novel, oral, once daily, brain-penetrant CNS thyroid hormone receptor agonist, achieved statistical significance across the primary and all key secondary depression endpoints in AMPLIFY-BD, demonstrating clinically meaningful antidepressant effects with a favorable safety profile. These data provide the first clinical evidence for CNS-targeted thyroid hormone receptor agonism, a 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, M.D., 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 pro 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.” “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,” said Kevin Finney, 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 pro 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.” Topline Efficacy and Safety Data AMPLIFY-BD was an open-label Phase 2 trial designed to evaluate the efficacy, safety, and tolerability of elunetirom as an adjunctive treatment in 21 adults with bipolar I or bipolar II disorder who were experiencing a moderate-to-severe major depressive episode. Patients received oral elunetirom once daily for six 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, and changes in 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. Neuroimaging, including analysis of functional connectivity using resting-state functional MRI (rs-fMRI), was conducted at baseline and Week 6 in a subset of patients. Elunetirom demonstrated statistically significant and clinically meaningful results across all primary and key secondary depression endpoints: Rapid and robust antidepressant response: Clinically meaningful 16.8-point mean reduction in HAMD-17 (p<0.001) at Week 6, with mean reductions of 9.7 (p<0.001) at Week 2 and 13.7 (p<0.001) at Week 4, indicating rapid onset and a continued antidepressant effect. High response and remission rates: 75% response rate and 50% remission rate observed at Week 6, consistent with a broad and durable treatment benefit. Broad symptomatic and functional benefit: 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, reflecting improvements in key depression domains, such as productivity, social functioning, and family relationships. Atypical depression subgroup: Significant improvements observed in patients with features of atypical depression, a subtype characterized by distinct symptomatology (increased appetite, hypersomnia, and low energy) and by particular treatment challenges, supporting potential applicability in this large patient segment. Treatment-associated changes in brain network connectivity: Statistically significant changes in functional connectivity were observed between baseline and Week 6 in patients treated with elunetirom in regions of the brain highly relevant to depression, providing objective evidence of enhanced brain network connectivity convergent with the reported clinical improvements. 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, M.D., Chief Medical Officer and Head of Research and Development at Autobahn. “Importantly, the rapid onset of activity and tolerability pro 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.” Elunetirom recently received Fast Track designation from the U.S. Food and Drug Administration (FDA) for the adjunctive treatment of bipolar depression, underscoring the significant unmet need in this serious condition and supporting continued close engagement with the FDA as the program advances. Autobahn plans to present full results from the AMPLIFY-BD trial at an upcoming medical conference in the second half of 2026. In addition, Autobahn is evaluating elunetirom as an adjunctive treatment for MDD in its ongoing Phase 2 AMPLIFY trial ( NCT06633016 ). Topline data from AMPLIFY are expected in the third quarter of 2026. 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. For more information, visit . Contacts Investors Monique Allaire, THRUST monique@thrustsc.com Media Carly Scaduto, THRUST carly@thrustsc.com