De-risking ONL1204 to enable venture capital investment for first-in-human clinical trials

项目总结/摘要 视网膜变性疾病和损伤是不可逆视力丧失的主要原因之一， 失明在美国和发达国家，每年影响数十万人 并导致数十亿美元的医疗成本增加和生产力损失。感光细胞死亡是一种 许多这些急性和慢性视网膜疾病的后果，导致视力丧失，并帮助 在疾病期间存活的光感受器将显着改善视觉结果， 患者限制当前治疗效果的一个问题是缺乏能够特异性地 防止感光细胞死亡;因此，安全有效的感光细胞保护剂将提供 每年为数十万人带来显著的视觉效益。 ONL 1204是一种新型的Fas介导的光感受器细胞死亡的小肽抑制剂 用于急性视网膜脱离患者的围手术期预防性使用（孤儿适应症， ONL 1204已获得孤儿药认定），目的是预防感光细胞死亡， 可以进行明确的手术修复。这种急性适应症提供了一种快速发展途径， 为将来扩展ONL 1204开发用于慢性适应症（如年龄相关性）奠定基础 黄斑变性用于治疗急性视网膜脱离的产品将是一种处方药， 玻璃体内注射 完成这项赠款中的拟议研究将有助于ONL Therapeutics解决最终投资者 问题，并吸引IND提交和临床开发所需的大量财务投资 ONL 1204的。具体而言，在本补助金中，我们将1）确定ONL 1204的最小剂量， 视网膜脱离的大眼睛动物模型中的光感受器保护和功能保存，和2） 在临床上有意义的情况下证明ONL 1204的单次玻璃体内注射的GLP安全性和耐受性。 剂量 本申请中提出的研究对于开发和商业化是必要的。 ONL 1204将降低该计划的风险，并实现重大的财务投资，使ONL Therapeutics能够 评价ONL 1204在视网膜脱离中的临床POC。

PROJECT SUMMARY / ABSTRACT Retinal degenerative disease and injury are among the leading causes of irreversible vision loss and blindness in the United States and the developed world, affecting hundreds of thousands of people every year and resulting in billions of dollars in added healthcare costs and lost productivity. Photoreceptor cell death is a consequence of many of these acute and chronic retinal diseases, leading to vision loss, and helping photoreceptors survive during the period of disease would significantly improve the visual outcomes for patients. A problem that limits the efficacy of current treatments is the lack of interventions that can specifically prevent photoreceptor cell death; therefore, a safe and potent photoreceptor protectant would provide a significant visual benefit to hundreds of thousands of people every year. ONL1204 is a novel, small peptide inhibitor of Fas-mediated photoreceptors cell death in development for peri-operative adjunctive use in patients with acute retinal detachment (an orphan indication for which ONL1204 has received an orphan drug designation) with the goal of preventing photoreceptor cell death until definitive surgical repair can occur. This acute indication provides a rapid development pathway that lays the groundwork for future expansion of ONL1204 development for chronic indications, such as age-related macular degeneration. The product for acute retinal detachment will be a prescription drug administered by intravitreal injection. Completion of the proposed studies in this grant will help ONL Therapeutics address final investor questions and attract the significant financial investment required for IND submission and clinical development of ONL1204. Specifically, in this grant, we will 1) determine the minimal dose of ONL1204 required for photoreceptor protection and preservation of function in large eye animal models of retinal detachment, and 2) demonstrate the GLP safety and tolerability of a single intravitreal injection of ONL1204 at clinically meaningful doses. The studies proposed in this application are necessary for development and commercialization of ONL1204, will de-risk the program, and enable significant financial investment, allowing ONL Therapeutics to evaluate clinical POC for ONL1204 in retinal detachment.