STTR Phase II: Developing a novel drug delivery system to enable an oral peptide-based drug for kidney stones

STTR II 期：开发一种新型药物输送系统，使基于口服肽的药物能够治疗肾结石

• 批准号: 2200058
• 负责人: Jessica Rodriguez Arias
• 金额: $ 100万
• 依托单位: OXALO THERAPEUTICS, INC.
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2200058&HistoricalAwards=false
• 关键词: STTR; Phase; II; Developing; novel

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase II project is a novel drug delivery system composed of peptide-loaded nanoparticles (NPs) for targeted and sustained release of therapeutic peptides to the intestine. The drug resulting from this project will be first-in-class comprehensive treatment for hyperoxaluria (high urine oxalate), hyperoxalemia (high blood oxalate), and related calcium oxalate kidney stones (COKS). Millions of patients suffering from COKS will finally be able to prevent this painful and damaging disease and preserve their long-term kidney health. Since a single kidney stone increases the risk of kidney failure, payers will not only appreciate the annual savings on treatment, but also the economic benefits of preventing chronic kidney disease (CKD) and kidney failure requiring permanent dialysis, affecting ~45 M and ~500 K patients in the US, respectively. Importantly, it will also impact the outcome of other disorders potentially affected by oxalate, including CKD and its progression, progression of cyst growth in autosomal dominant polycystic kidney disease, kidney disease-associated cardiovascular diseases, and poor renal transplant survival. This STTR Phase II project aims to develop the oral route component of an innovative drug delivery system using peptide-loaded NPs for localized and sustained delivery of novel therapeutic peptides to the intestinal mucosa to address oxalate-related disorders. This project will: (1) Develop and characterize multiple NPs formulations. (2) Ensure that the peptide-loaded NPs are largely delivered to the small and large intestines, but not to the stomach. (3) Confirm that the NPs have no cellular toxicity in vitro. (4) Confirm that NPs significantly reduce plasma and urinary oxalate levels in hyperoxalemia and hyperoxaluric mice without causing significant in vivo toxicity, and achieving no or minimal systemic absorption. (5) Obtain initial safety data for the peptide-loaded NP via an exploratory preclinical toxicology study. At least one of the developed NP formulations should deliver the peptides to the small and large intestines, present no significant cellular toxicity in vitro, and reduce plasma and urinary oxalate levels without causing significant in vivo toxicity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个小企业技术转让（STTR）第二阶段项目的更广泛的影响/商业潜力是一种新型的药物递送系统，由负载肽的纳米颗粒（NP）组成，用于向肠道靶向和持续释放治疗肽。该项目产生的药物将成为高尿酸（高尿草酸盐）、高尿酸血症（高血草酸盐）和相关草酸钙肾结石（COKS）的一流综合治疗药物。数百万患有COKS的患者最终将能够预防这种痛苦和破坏性的疾病，并保持长期的肾脏健康。由于单个肾结石会增加肾衰竭的风险，因此付款人不仅会欣赏每年的治疗费用节省，而且还会欣赏预防慢性肾脏疾病（CKD）和需要永久透析的肾衰竭的经济效益，在美国，这两种疾病分别影响约45 M和约500 K患者。重要的是，它还将影响可能受草酸盐影响的其他疾病的结局，包括CKD及其进展、常染色体显性遗传性多囊肾病中囊肿生长的进展、肾脏疾病相关的心血管疾病和肾移植存活率低。该STTR II期项目旨在开发一种创新药物递送系统的口服途径组分，该系统使用负载肽的NP将新型治疗性肽局部和持续递送至肠粘膜，以解决腹泻相关疾病。该项目将：（1）开发和表征多种NP制剂。(2)确保负载肽的NP大部分被递送到小肠和大肠，但不递送到胃。(3)确认纳米粒在体外没有细胞毒性。(4)确认NP显著降低高胆固醇血症和高胆固醇尿小鼠的血浆和尿液草酸盐水平，而不会引起显著的体内毒性，并且没有或实现最小的全身吸收。(5)通过探索性临床前毒理学研究获得负载肽的NP的初始安全性数据。至少有一个开发的NP配方应提供的肽到小肠和大肠，目前没有显着的细胞毒性在体外，并降低血浆和尿液中的草酸水平，而不会造成显着的体内toxicity.This奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。