IND Enabling Studies for a Novel Mas Receptor Agonist for Treatment of Cognitive Impairment in Patients at Risk for Alzheimer's Disease Related Dementia

新型 Mas 受体激动剂的 IND 使研究能够治疗有阿尔茨海默病相关痴呆风险的患者的认知障碍

基本信息

批准号：
10437202
负责人：
Meredith Hay
金额：
$ 76.7万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-15 至 2024-03-31
项目状态：
已结题

项目摘要

PROJECT SUMMARY The purpose of this request for an administrative supplement is to cover the increased cost of GMP peptide manufacturing and the increased cost of the in-vivo and in-vitro toxicology studies that will occur in year 2. With regards to manufacturing, since the original submission of this U01 proposal, Polypeptide, our Peptide manufacturing CRO, the cost of a 500gram GMP batch of PNA5 ($970/gram plus stability testing, CMC documentation, and final fill and finish) is now $786,000 vs our original budget of $525,000 for 150 grams ($2500/gram plus stability testing, CMC documentation). This increased batch size is required for our planned extended 21-day repeated dose formal toxicity studies planned in Yr 3 and will also be enough to complete our planned Phase 1a/b studies in humans, thus eliminating the need to produce a second GMP batch for the planned first in human study. The cost difference will be $261,000. This will ultimately save both time and money by not requiring a 2nd GMP batch prior to first-in-human studies batch and a significant $/gram savings. Regarding the 7-day MTD toxicology studies in rat and dog and in vitro assays (hERG, chromosome assay, AMES), we have been able to accelerate the timing of these studies and now plan to have these completed in Year 2. In the original proposal, the original quotes our original vendor (MPI) totaled $452,800. Since then, that vendor was acquired by Charles River and those same studies are now costing $691,456. The cost difference is $238,656. We have included an itemized cost comparison between the original quote and the new quote below. Thus, for Year 2, we are requesting an additional $499,656 in direct costs to cover the increased manufacturing costs and for the increase in-vivo and in-vitro toxicology costs.

项目概要本次行政补充申请的目的是为了弥补 GMP 肽增加的成本制造以及第二年进行的体内和体外毒理学研究的成本增加。关于制造，自从最初提交这个 U01 提案以来，多肽，我们的肽制造 CRO，500 克 GMP 批次 PNA5 的成本（970 美元/克加上稳定性测试、CMC 150 克的成本现在为 786,000 美元，而我们最初的预算为 525,000 美元（2500 美元/克加上稳定性测试、CMC 文件）。我们的计划需要增加批量大小计划在第 3 年进行延长的 21 天重复剂量正式毒性研究，也足以完成我们的研究计划在人体中进行 1a/b 期研究，从而消除了为该药物生产第二批 GMP 的需要首先计划在人类研究中。成本差异将为 261,000 美元。这最终将节省时间和由于在首次人体研究批次之前不需要进行第二批 GMP，因此可以节省大量资金/克。关于大鼠和狗的 7 天 MTD 毒理学研究以及体外测定（hERG、染色体测定、 AMES），我们已经能够加快这些研究的进度，现在计划在第 2 年。在最初的提案中，我们的原始供应商 (MPI) 的原始报价总计为 452,800 美元。从那时起，那供应商被 Charles River 收购，这些相同的研究现在花费 691,456 美元。成本差异是 238,656 美元。我们对原始报价和新报价进行了逐项成本比较以下。因此，对于第 2 年，我们要求额外增加 499,656 美元的直接成本，以弥补增加的费用制造成本以及体内和体外毒理学成本的增加。