Phase 0/1b Clinical Trial of Novel Therapeutic Agent MT-110 for the Reduction of Methamphetamine Use - Part 2

PROJECT SUMMARY As of 2023, close to 2 million individuals in the United States are identified as having methamphetamine use disorder (MUD), with methamphetamine use rising significantly. Recent estimates suggest that this figure is underreported by about 225%, bringing the 2023 total closer to over 4 million people with MUD, and likely even higher in 2024. MUD is a persistent condition for which there are no FDA-approved medications at present. The current treatments available are behavioral modification therapies, which show limited success, as indicated by high relapse rates (60-90%). This underscores the need for an additional pharmacotherapy that targets relapse triggers to help maintain abstinence. Comprehensive prior studies by our group and others have shown that relapse induced by drug-use reminders (or “triggers”) exerts a strong motivational influence, posing a lifelong relapse risk regardless of the duration of abstinence. Myosin Therapeutics is developing MT-110, a drug marked by the novel therapeutic target of the molecular motor nonmuscle myosin II (NMII). Preclinical research has demonstrated that a single acute inhibition of NMII activity can produce a highly specific, long-lasting effect by restoring the brain’s structural plasticity to a pre-methamphetamine state. Consequently, a single intravenous dose of MT-110 results in a lasting reduction in methamphetamine-seeking behavior in animal models. IND-enabling studies for MT-110 are complete, and Phase 1b clinical trials are set to commence in the first quarter of 2025. MT-110 is being developed as a one-time administration medication to support the reduction of MUD. The primary goal of this Direct to Phase II SBIR application is to support a first-in-human double-blind, placebo-controlled single ascending dose (SAD) Phase Ib dose escalation trial of MT-110 in individuals that consume METH. This proposed 1b trial of MT-110 will recruit up to 44 patients to test 5 dose levels and determine CNS drug concentrations via CSF collection in an additional cohort following administration of an optimal dose. The primary endpoints are focused on determining the safety and tolerability of single ascending doses of MT-110. Secondary endpoints will gather pharmacokinetic parameters, both systemic and CNS. And an exploratory endpoint will assess potential changes from baseline in the craving for METH. In this application (current application – ‘Part 2’), we detail the specific activities that will be performed by the clinical research unit (CRU) to complement the activities that the Sponsor (Myosin Therapeutics) will perform with support from a CRO (detailed in sister application – ‘Part 1’). The Part 2 activities detailed here cover interaction with patients to execute the trial.