(#27) A Phase 1 Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Ascending Dose Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the Novel Thyromimetic ABX-002 in Healthy Adult Participants

Abstract: Major depressive disorder (MDD) is a leading cause of disability, impacting 280 million people worldwide. The current pharmacological standard of care is selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRIs). However, more than 50% of patients receiving SSRI/SNRIs have an inadequate response, necessitating a switch or augmentation with other agents. Augmentation agents include the thyroid hormones (TH) triiodothyronine (T3) and thyroxine (T4). While THs have demonstrated efficacy as adjunctive treatments for MDD, their use is limited by tolerability and safety concerns. ABX-002 is a novel CNS-targeted prodrug exerting its effects through its active metabolite, LL-340001, a partially preferring thyroid hormone beta receptor (TRβ) agonist. With its preferential CNS distribution, ABX-002 may augment the clinical response for patients with MDD who have had an inadequate response to their antidepressant treatment. ABX-002 and LL-340001 were studied for safety, tolerability, plasma pharmacokinetics (PK) and pharmacodynamics (PD) in a Phase 1, first-in-human (FIH), randomized, double-blind, placebo-controlled study in healthy adult participants. For both single ascending dose (SAD) and multiple ascending dose (MAD) portions of the study, ABX-002 was safe and well-tolerated up to the highest doses tested of 150 and 5.6 μg, respectively. No participants discontinued related to safety or adverse events. ABX-002 is being developed as an adjunctive treatment for mood disorders including MDD and depression in bipolar disorder. With its tolerability profile and CNS targeting, ABX-002 could offer an optimized profile, versus TH and standard of care (e.g., atypical antipsychotics), as an augmentation agent in depression.

Short Description: ABX-002 is a novel CNS-targeted prodrug exerting its effects through its active metabolite, LL-340001, a partially preferring thyroid hormone beta receptor (TRβ) agonist. This poster presents the safety, PK, and PD results from a Phase 1, double-blind, randomized, placebo-controlled, single and multiple ascending dose study which support the clinical advancement of ABX-002 as an adjunctive treatment for mood disorders including MDD and bipolar depression.

Name of Sponsoring Organization(s): Autobahn Therapeutics, Inc.