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

InterveXion正在开发一种名为IXT-m200的抗甲基苯丙胺（METH）单克隆抗体， METH使用障碍的治疗。IXT-m200单次给药在健康志愿者中耐受良好 以及在IXT-m200给药后给予每周剂量的METH（30 mg，IV）的METH使用者。 重要的是，我们正在进行的2期研究的中期分析表明，IXT-m200改变了METH在小鼠中的分布。 如从非临床数据预测的那样，特别是通过大大降低METH分布容积，即， 在血液中隔离甲基。无严重不良事件或轻度或中度以上不良事件 已在II期研究中报告。 目前提出的长期非临床研究将促进多剂量临床试验，以测试IXT-m200 减少METH使用的有效性。此外，InterveXion将改进IXT的制造工艺- m200，从而符合自IXT-m200开发以来实施的新法规 节目开始了。最后，将探索皮下施用IXT-m200作为潜在的改进 给药方案。皮下注射可以在办公室或咨询环境中进行， 患者更容易接受IXT-m200，并应提高用药依从性。 该提案的主要目标是将IXT-m200推向FDA批准过程的下一个里程碑， 是人体多次给药研究，如关键性2b/3期研究。具体的目标，将允许这一点， 要达到的目标如下。目的1：生产IXT-m200以支持所需的非临床和临床 问题研究将分离单个细胞，并用于生成产量提高的新主细胞库 能力的将生产两批，为目标2和即将进行的临床试验提供材料。目标二： 在大鼠中完成IXT-m200的多次给药研究，以支持在人体中的多次给药。一 6-在大鼠中进行27次每周剂量的IXT-m200的为期一个月的毒理学研究， 完成试点研究。目的3：进行研究以确定皮下给药的可行性 IXT-M200将IXT-m200浓缩至至少140 mg/mL，并通过皮下注射给予大鼠 注射将检测抗体药代动力学、METH结合能力和免疫原性。目标4： 通过与FDA沟通、维护IND和开发，为首次多次给药临床研究做准备 一份完整的临床方案所有监管互动和要求都将在此目标下完成， 多剂量临床试验可在此项工作完成后立即开始。 METH使用障碍的治疗仍然是一个未满足的医疗需求， 美国FDA。InterveXion继续努力满足这一需求，迅速推进 第一个METH结合mAb，IXT-m200。这些研究是满足这一需求的下一步。

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.