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

摘要 系统性红斑狼疮(SLE)是一种自身免疫性疾病，影响着500多万人 全世界的人，包括150万美国人。其中近60%的患者会发展为狼疮性肾炎， 这可能会导致肾衰竭。因此，它给每个患者带来的经济负担可以达到7万美元/年，远远 比许多其他疾病都要高，因为肾移植。狼疮性肾炎虽早期治疗 可以显著延缓甚至阻止疾病进展为肾衰竭、蛋白尿，我们目前 狼疮患者的临床筛查标准不够敏感和准确，不能早期发现狼疮 肾炎。而新的内源性生物标记物或外源性标记物正在进行早期临床试验 狼疮性肾炎的诊断，临床上无一例优于蛋白尿。因此，即使在今天， 蛋白尿仍然是临床的标准，对早期发现和准确的需求仍有很强的未得到满足的需求 狼疮患者肾脏损害的监测。为了解决这一未得到满足的需求，ClearNano Inc.正在开发 一种可作为外源性尿液标志物检测狼疮性肾炎的试剂ClearGold 比蛋白尿更早、更准确。由以前的STTR第一阶段拨款赞助，使用可清除的肾脏 金纳米粒子作为原型测试剂，ClearNano已经成功验证了ClearGold在 狼疮性肾炎小鼠模型的检测和分期比蛋白尿更早和更准确 发现它也优于在临床上评估的其他经典的内源性和外源性标记物 狼疮性肾炎检测试验。在这个STTR第二阶段应用程序中，我们将确定一个主要产品，即开发 在良好实验室规范(GLP)指导下进行大规模合成，并进行内部毒性研究 大鼠模型。这一成功将使我们能够为研究前新药(IND)准备一个强大的一揽子计划 与FDA会面，降低CRO进行全面毒理学研究的风险，并加快 这项新的纳米技术的临床翻译；因此在早期检测中长期未得到满足的需求 狼疮性肾炎最终可以用我们的“ClearGold”检测试剂来解决，这相当于16亿美元 市场机会。

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.