IND-Enabling Pre-clinical Development of Modified P8 for the Treatment of Alzheimer's Disease

摘要 母公司商业化准备计划拨款是为了进行研究 有必要支持与Cenna的临床前开发有关的监管提交 候选多肽药物MP8。MP8正在被开发为一种新的、一流的多肽药物，用于 阿尔茨海默病的治疗。这笔拨款是在取得重大进展的基础上取得的。 在以前资助的SBIR第2阶段和2B阶段赠款下，开展支持未来 首次在人类临床研究中发现了MP8。所要求的研究的必要组成部分 FDA将在#年进行启用IND的药物安全毒性和GLP安全药理学研究 两种动物。对于多肽、小分子和其他药物形式，使用 FDA要求一种啮齿动物和一种非啮齿动物物种支持临床开发和 许可。在提交父母拨款时，我们曾提议使用食蟹猴 作为这些研究的非啮齿动物模型，因为它是临床前研究的公认物种 毒性测试，在系统发育和生理上与人类关系更密切 而不是狗。猴子也比狗小得多，因此需要的多肽要少得多。 这一点很重要，因为到目前为止我们的研究表明，我们的原始肽P8是无毒的 即使在最高剂量的情况下。因此，我们预计在以下情况下必须使用50X-100倍的有效剂量 我们不会产生毒性，如果我们在狗身上测试，就会使这种多肽的成本非常高。 自拨款以来，由于疫情和最近与中国的贸易战， 在猴子来源的地方，非人类灵长类动物严重短缺。因此， 每只猴子的价格翻了一番以上。此行政补充应用程序旨在帮助 抵消在核准奖励范围内的猴子研究增加的费用 但在提交和审查申请时是预料不到的。

Summary The parent Commercialization Readiness Program grant was to conduct studies necessary to support regulatory submissions relating to pre-clinical development of Cenna’s peptide drug candidate mP8. mP8 is being developed as a new, first-in-class peptide drug for the treatment of Alzheimer’s disease. The funded grant builds on the substantial progress made under the previously funded SBIR Phase 2 and 2B grants to carry out activities to support a future first in human clinical study of mP8. A necessary component of the studies that is required by the FDA is to conduct IND-enabling drug safety toxicity and GLP safety pharmacology studies in two species of animals. For peptides, small molecules and other drug modalities, studies using a rodent plus a non-rodent species are required by the FDA to support clinical development and licensing. When the parent grant was submitted, we had proposed to use the cynomolgus monkey as the non-rodent animal model for these studies as it is an accepted species for preclinical toxicity testing and is more closely related, both phylogenetically and physiologically, to humans than dogs. Monkeys are also much smaller than dogs and so would require much less peptide. This is important since our studies to date have indicated that our original peptide P8 is not toxic even at the highest dose. We therefore anticipate having to use 50X-100X the efficacious dose if we cannot produce toxicity, making the cost of the peptide very high if we were to test it in dogs. Since the funding of the grant, because of the pandemic and recent trade-wars with China, where monkeys are sourced, there is a dire shortage of non-human primates. As a result, the price per monkey has more than doubled. This Administrative Supplement application is to help offset the increased cost of the monkey studies that are within the scope of the approved award but were unforeseen when the application was submitted and reviewed.