Optimization and testing of anti-methamphetamine antibody therapy to support pivotal clinical trials and commercialization

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InterveXion is developing an anti-methamphetamine (METH) monoclonal antibody called IXT-m200 for the treatment of METH use disorders. Single doses of IXT-m200 have been well-tolerated in healthy volunteers and also METH users who are given weekly doses of METH (30 mg, IV) following IXT-m200 administration. Importantly, an interim analysis of our ongoing Phase 2 study shows that IXT-m200 alters METH distribution in humans as predicted from nonclinical data, specifically by greatly reducing METH volume of distribution, i.e., sequestering METH in the blood. No serious adverse events or adverse event greater than mild or moderate have been reported in the Phase 2 study. The currently proposed long-term nonclinical studies will facilitate multiple dose clinical trials to test IXT-m200 for efficacy in reducing METH use. In addition, InterveXion will improve the manufacturing process for IXT- m200 and thereby comply with new regulations that have been imposed since the IXT-m200 development program began. Finally, subcutaneous administration of IXT-m200 will be explored as a potential improvement to the dosing regimen. Subcutaneous injections may be given in an office or counseling setting, would allow patients to more easily receive IXT-m200, and should improve medication compliance. The major goal of this proposal is to move IXT-m200 to the next milestone in the FDA approval process, which is multiple dose studies in humans, such as pivotal Phase 2b/3 studies. The specific aims that will allow this goal to be met are as follows. Aim 1: Manufacture IXT-m200 to support required nonclinical and clinical studies. A single cell will be isolated and used to generate a new Master Cell Bank with improved production capabilities. Two batches will be made to provide material for Aim 2 and upcoming clinical trials. Aim 2: Complete multiple dose studies of IXT-m200 in rats to support multiple dose administration in humans. A 6-month toxicology study with 27 weekly doses of IXT-m200 in rats will be done following the successful completion of a pilot study. Aim 3: Conduct studies to determine the feasibility of subcutaneous administration of IXT-m200. IXT-m200 will be concentrated to at least 140 mg/mL and given to rats by subcutaneous injection. Antibody pharmacokinetics, METH binding capability and immunogenicity will be tested. Aim 4: Prepare for first multiple dose clinical study by communicating with FDA, maintaining the IND, and developing a full clinical protocol. All regulatory interactions and requirements will be completed under this aim so that a multiple dose clinical trial may begin as soon as this work is completed. The treatment of METH use disorder remains an unmet medical need with no medications yet approved by the US FDA. InterveXion continues to strive to meet this need by pushing forward quickly with the development of the first METH-binding mAb, IXT-m200. These studies are the next steps toward meeting that need.