STTR Phase II: Advance Early Detection of Lupus Nephritis with ClearGold

STTR II 期：利用 ClearGold 推进狼疮性肾炎的早期检测

• 批准号: 10494086
• 负责人: Mengxiao Yu
• 金额: $ 60.52万
• 依托单位: CLEARNANO, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-19 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10494086
• 关键词: Address; Advanced Development; Affect; American; Area Under Curve; Autoimmune Diseases; Biological Markers; Bladder; Cells; Chemistry; Clinic; Clinical; Clinical Research; Clinical Trials; Creatinine; Cysteine; Detection; Diagnostic tests; Disease; Disease Progression; Dose; Early Diagnosis; Early Intervention; Early treatment; Evaluation; Event; Financial Hardship; Glutathione; Goals; Gold; Grant; Head; Henle' s loop; Hour; Individual; Injections; Injury to Kidney; Intravenous; Investigational Drugs; Iohexol; Kidney; Kidney Failure; Kidney Transplantation; LCN2 gene; Lead; Lupus; Lupus Nephritis; Measures; Medical; Methods; Modeling; Monitor; Mus; Names; Nanotechnology; Outcomes Research; Particle Size; Patients; Performance; Persons; Phase; Practice Guidelines; Production; Proteins; Proteinuria; ROC Curve; Rattus; Reaction; Renal clearance function; Renal dialysis; Risk; Rivers; Small Business Technology Transfer Research; Spottings; Sprague-Dawley Rats; Staging; Surface; Systemic Lupus Erythematosus; Technology; Testing; Toxic effect; Toxicology; Translating; Tumor-infiltrating immune cells; Urine; acute toxicity; base; biomaterial compatibility; clinical translation; disorder prevention; early detection biomarkers; early phase clinical trial; good laboratory practice; immunogenicity; individual patient; innovation; interstitial; meetings; mouse model; nanoGold; nanomedicine; novel; phase 1 study; phase 2 study; prevent; prototype; renal damage; screening; success; urinary; young woman

Abstract Systemic lupus erythematosus (SLE) or lupus is an autoimmune disease that affects more than 5 million people worldwide, including 1.5 million Americans. Nearly 60% of these patients will develop lupus nephritis, which can cause kidney failure. Thus, its financial burden to individual patient can reach $70,000/year, much higher than many other diseases because of kidney transplantation. Although early treatment of lupus nephritis can significantly slow down or even prevent the disease progression to kidney failure, proteinuria, our current clinical standard for screening lupus patients, is not sensitive and accurate enough for early detection of lupus nephritis. While new endogenous biomarkers or exogenous markers are being tested in clinical trials for early diagnosis of lupus nephritis, none of them has outperformed proteinuria in the clinics. As a result, even today, proteinuria remains the clinical standard and there are strong unmet needs for early detection and accurate monitoring of kidney damages in the lupus patients. To address this unmet need, ClearNano Inc. is developing a test agent, named “ClearGold” that can be used as an exogenous urine marker to detect lupus nephritis much earlier and more accurately than proteinuria. Sponsored by previous STTR Phase I grant, using a renal clearable gold nanoparticle as a prototype test agent, ClearNano has successfully validated the feasibility of ClearGold in detection and staging of lupus nephritis in mouse model much earlier and more accurately than proteinuria, and found it also outperformed other classical endogenous and exogenous markers being evaluated in the clinical trials for lupus nephritis detection. In this STTR Phase II application, we will identify a lead product, develop large-scale synthesis under Good Laboratory Practice (GLP) guidelines and conduct in-house toxicity study in rat model. The success will allow us to prepare a strong package for pre-Investigational New Drug (IND) meeting with FDA, reduce the risk for comprehensive toxicology studies carried by CRO, and accelerate the clinical translation of this novel nanotechnology; so that a long-standing unmet need in the early detection of lupus nephritis can be eventually addressed with our “ClearGold” test agent, which represents a $1.6 Billion market opportunity.

摘要 系统性红斑狼疮（SLE）或狼疮是一种自身免疫性疾病，影响超过500万 全世界，包括150万美国人。近60%的患者会发展为狼疮性肾炎， 会导致肾衰竭因此，其对单个患者的经济负担可达到70，000美元/年， 比许多其他疾病高，因为肾移植。狼疮性肾炎的早期治疗 可以显著减缓甚至阻止疾病进展到肾衰竭、蛋白尿，我们目前 筛查狼疮患者的临床标准，对于狼疮的早期检测不够敏感和准确 肾炎虽然新的内源性生物标志物或外源性标志物正在临床试验中进行测试， 诊断狼疮性肾炎，没有一个在临床上优于蛋白尿。因此，即使在今天， 蛋白尿仍然是临床标准，对于早期检测和准确诊断仍存在强烈的未满足的需求 监测狼疮患者的肾脏损害。为了解决这一未满足的需求，ClearNano Inc.正在开发 一种名为“ClearGold”的测试试剂，可用作检测狼疮性肾炎的外源性尿液标记物， 比蛋白尿更早更准确。由之前的STTR I期资助赞助，使用肾可清除 金纳米粒子作为原型测试剂，ClearNano已经成功验证了ClearGold在 在小鼠模型中比蛋白尿更早更准确地检测和分期狼疮性肾炎， 发现它也优于其他经典的内源性和外源性标志物正在评估的临床 狼疮性肾炎的治疗方法在这个STTR第二阶段的应用中，我们将确定一个主导产品，开发 根据药物非临床研究质量管理规范（GLP）指南进行大规模合成，并在 大鼠模型这一成功将使我们能够为临床试验前新药（IND）准备一个强大的包装 与FDA会面，降低CRO进行全面毒理学研究的风险，并加快 这种新型纳米技术的临床转化;因此，在早期检测中长期未满足的需求 狼疮性肾炎最终可以用我们的“ClearGold”测试剂来解决，这代表了16亿美元的投资。 市场机会。