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

总结 母公司商业化准备计划赠款是为了进行研究， 支持与Cenna临床前开发相关的监管申报所必需的 肽药物候选物mP8。mP8被开发为一种新的，一流的肽类药物， 阿尔茨海默病的治疗资助的赠款建立在取得的实质性进展的基础上， 根据先前资助的SBIR第2和2B阶段赠款，开展活动，以支持未来的 第一次在人类临床研究的mP8。研究的一个必要组成部分， FDA将在以下国家开展IND药物安全性毒性和GLP安全药理学研究： 两种动物。对于肽、小分子和其他药物形式，使用 FDA要求啮齿动物和非啮齿动物种属支持临床开发， 许可证在提交母公司拨款时，我们曾建议使用食蟹猴 作为这些研究的非啮齿类动物模型，因为它是临床前研究的可接受种属 毒性测试，并且在遗传学和生理学上与人类更密切相关， 而不是狗。猴子也比狗小得多，所以需要的肽少得多。 这是重要的，因为我们迄今为止的研究表明，我们的原始肽P8是无毒的 即使在最高剂量下。因此，我们预计必须使用50 - 100倍的有效剂量，如果 我们不会产生毒性，如果我们在狗身上测试，那么这种肽的成本会非常高。 自赠款提供资金以来，由于大流行和最近与中国的贸易战， 在有猴子的地方，非人类灵长类动物严重短缺。结果导致 每只猴子的价格翻了一倍多。此行政补充申请旨在帮助 抵消已批准的拨款范围内的猴子研究增加的费用 但在提交和审查申请时没有预料到。

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.