Liothyronine Sodium

AMPLIFY 230-patient trial aims to improve on efficacy and safety established with thyroid hormone as an adjunctive treatment for MDD; topline data expected in the second half of 2025 ABX-002 deemed safe and well-tolerated in Phase 1 and showed clinical evidence of enhanced target engagement consistent with brain-activating thyroid hormone biology Company on-track to expand ABX-002 depression program with Phase 2 trial for bipolar disorder depression to begin late 2024 SAN DIEGO, CA, USA I September 16, 2024 I Autobahn Therapeutics, a biotechnology company developing restorative treatments for people affected by neuropsychiatric and neuroimmunologic disorders, today announced initiation of AMPLIFY, a Phase 2 clinical trial evaluating ABX-002 as an adjunctive treatment for adults with major depressive disorder (MDD). ABX-002 is a highly potent, oral, thyroid hormone beta receptor (TRβ) selective agonist designed to enhance the CNS benefits of thyroid hormone biology and drug concentrations directly in the brain, for greater potency, efficacy and safety. In a completed Phase 1 trial of ABX-002 , ABX-002 demonstrated clinical evidence of CNS target engagement consistent with brain-activating thyroid effects and was well-tolerated, with no serious adverse events observed. “Among the millions of people in the U.S. suffering from the debilitating effects of depression, more than half experience an inadequate response to their current antidepressant, underscoring the urgent need for treatment options that provide relief for patients,” said Dan Iosifescu, M.D., Professor of Psychiatry at NYU Grossman School of Medicine. “Synthetic thyroid hormone has long been known to provide benefit as an adjunctive treatment for MDD, and a highly potent and selective TRβ agonist may offer the therapeutic benefits of synthetic thyroid hormone, with a safety profile that enables chronic use for optimal patient management.” AMPLIFY is a placebo-controlled, double-blind Phase 2 trial in 230 adults with moderate-to-severe depression. The trial will evaluate the safety, tolerability, efficacy and pharmacodynamic (PD) effects of ABX-002 as an adjunctive treatment to patients’ current selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI). The primary endpoint is the change from baseline on the Hamilton Depression Rating Scale-17 (HAMD–17) after six weeks of treatment. Key secondary endpoints include changes from baseline on the HAMD-29 to assess improvements on atypical depression symptoms, the Montgomery–Åsberg Depression Rating Scale (MADRS), and other measures of clinical improvement. “We are thrilled to initiate this Phase 2 trial of ABX-002, marking a substantially evolved profile for Autobahn as a mid-stage development company progressing multiple clinical development candidates,” said Gudarz Davar, M.D., Executive Vice President, Head of Research and Development for Autobahn. “The clinical data we’ve generated with ABX-002 support its promise as a brain-penetrating, centrally active thyromimetic with favorable safety, and give us greater confidence in its potential as a game-changing treatment for depression, especially for patients who remain underserved by today’s treatment options. Our team is dedicated to advancing innovative therapies that have the potential to transform lives, and this milestone with ABX-002 is a significant step toward achieving our vision.” Autobahn anticipates reporting topline data from the AMPLIFY Phase 2 trial of ABX-002 in patients with MDD in the second half of 2025. In addition, by yearend 2024, Autobahn plans to initiate a second Phase 2 trial with ABX-002 in patients with bipolar disorder depression, a chronic and difficult mental health condition. About Autobahn Therapeutics Autobahn Therapeutics is a biotechnology company developing a portfolio of neuropsychiatric and neuroimmunologic 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 ABX-002, a thyroid hormone receptor beta (TRβ) agonist being developed as a potential adjunctive treatment for people with major depressive disorder and bipolar disorder depression. Autobahn Therapeutics is based in San Diego. For more information, visit www.autobahntx.com . About ABX-002 ABX-002 is an orally administered, potent and selective thyroid hormone beta receptor (TRβ) agonist designed to enhance the CNS benefits of thyroid hormone biology while also reducing the peripheral liabilities 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. Thyroid hormone agonism has demonstrated activity on cellular energy metabolism pathways, which play an important role on the regulation of brain bioenergetics and may be uniquely suited to address symptoms of atypical depression, a highly prevalent and underserved sub-population of MDD. In nonclinical and clinical studies, ABX-002 has demonstrated optimized PK properties, target engagement in brain regions associated with depression, and an attractive safety and tolerability profile. SOURCE: Autobahn Therapeutics

Graves’ disease is an autoimmune condition that leads to an overactive thyroid gland. Image credit: Shutterstock / Jo Panuwat D. Immunovant has reported positive results from a trial investigating its monoclonal antibody drug batoclimab in Graves’ disease patients, as its other autoimmune candidate IMVT-1402 inches closer to a pivotal trial later this year. The results for batoclimab include “strong response rates” following an injection with the therapy, according to the US immunology specialist’s CEO Pete Salzmann. Meanwhile, Immunovant has set its sights on a pivotal trial for IMVT-1402 after an investigational new drug application (IND) was cleared by the US Food and Drug Administration. The biopharma expects to initiate the study, which will also involve Graves’ disease patients, by the end of this year. Immunovant has been investigating batoclimab – a monoclonal antibody – in a Phase IIa trial (NCT05907668) with Graves’ disease patients who had hypothyroidism despite antithyroid therapy. Graves’ disease is an autoimmune condition that leads to an overactive thyroid gland, resulting in elevated levels of two main thyroid hormones called triiodothyronine and thyroxine, also known as T3 and T4. Antithyroid drugs (ATDs) are the treatment of choice for most patients with Graves’ hyperthyroidism. See Also: Integrated Nanotherapeutics gains funds for new T1D treatment Moderna’s Laval facility gains Health Canada’s drug establishment licence Immunovant claims that its analysis indicates 25%-30% of Graves’ disease patients per year are uncontrolled on ATDs, adding that this represents an “attractive commercial opportunity with limited competition.” Following a course of a first high-dose 680mg batoclimab once-weekly over 12 weeks, patients had a mean immunoglobulin-G (IgG) reduction of 77%, leading to a response rate, defined as T3 and T4 falling below the upper limit of normal (ULN) without increasing the ATD dose, of 76%. The trial’s primary endpoint is the percentage of participants who achieve normalisation of the two hormone levels or have them below the lower limit of normal (LLN) after 24 weeks. Immunovant did not disclose further details on this measurement. Batoclimab’s efficacy looks promising however, with its higher-dose version achieving a 56% ATD-Free Response, meaning T3 and T4 falling below the ULN and the patient simultaneously tapering completely off their ATD. Salzmann said: “We find the correlation between clinical response and IgG lowering impressive and believe this creates not only a potential first-in-class but also a potential best-in-class opportunity for IMVT-1402. “We are very pleased to have aligned with the FDA on a pivotal trial design that we expect to initiate by the end of the year.” Salzmann previously disclosed that Immunovant would prioritise IMVT-1402 for myasthenia gravis (MG) over batoclimab. The latter’s use is being evaluated in a Phase III trial for the muscle weakness disorder. Immunovant believes that IMVT-1402 may have better efficacy but will wait until topline results from the Phase III trial for confirmation, which are expected in early 2025. Batoclimab is also being evaluated by Immunovant in thyroid eye disease and chronic inflammatory demyelinating polyneuropathy (CIDP).