Preclinical development of ONL-101 for photoreceptor protection in retinal detach

描述(申请人提供)：感光细胞的死亡是许多急性和慢性视网膜疾病的结果，这些疾病导致患者严重的视力丧失。如果光感受器能够帮助患者挺过疾病时期，患者的视觉结果将显著改善。视网膜退行性疾病和损伤是美国和发达国家不可逆转的视力丧失和失明的主要原因之一，每年影响数十万人，导致数十亿美元的 增加了医疗成本和生产力损失。限制目前治疗效果的一个问题是，目前还没有专门预防感光的干预措施。 细胞死亡；因此，一种安全、有效的感光细胞保护剂每年将为数十万人提供显著的视觉益处。ONL治疗公司正在开发一种候选产品，一种新型的Fas受体小肽抑制剂(ONL-101)，用于急性视网膜脱离(孤儿适应症)患者的围手术期辅助使用，目的是防止光感受器细胞死亡，直到可以进行明确的手术修复。这一急性适应症提供了一条快速发展的途径，将为ONL-101未来扩大对诸如年龄相关性黄斑变性等慢性适应症的开发奠定基础。治疗急性视网膜脱离的产品将是单次玻璃体内注射(眼科公认的给药途径)的处方药。在完成这项SBIR第二阶段研究后，ONL Treeutics将测试和验证这样一个假设，即可以开发出安全有效的玻璃体内注射ONL-101配方，用于人体临床试验。我们将证明：1)玻璃体内注射ONL-101是安全的，没有明显的眼部或全身毒性，2)可以生产用于临床试验的药用级ONL-101，以及3)可以设计1/2期临床试验来测试ONL-101在人体上的安全性和有效性。第二阶段中介绍的工作是ONL-101商业化所需的下一步，所获得的结果将使最终确定所需的IND包，以开始ONL-101作为视网膜脱离患者的辅助治疗的临床试验。

DESCRIPTION (provided by applicant): Death of photoreceptor cells is a consequence of many acute as well as chronic retinal diseases which lead to severe vision loss in patients. If photoreceptors could be helped to survive the period of disease, the visual outcomes for patients would be significantly better. 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. A problem limiting the efficacy of current treatments is that currently there are no interventions that can specifically prevent photoreceptor cell death; therefore, a safe, potent, photoreceptor protectant would provide a significant visual benefit to hundreds of thousands of people every year. ONL Therapeutics is developing a product candidate, a novel small peptide inhibitor of the FAS- receptor (ONL-101), for peri-operative adjunctive use in patients with acute retinal detachment (an orphan indication), with the goal of preventing photoreceptor cell death until definitive surgical repair can occur. This acute indication provides a rapid development pathway that will lay the groundwork for future expansion of ONL-101 development for chronic indications such as age-related macular degeneration. The product for acute retinal detachment will be a prescription drug for single dose intravitreal injection (an established route of administration in ophthalmology). Upon completion of this SBIR Phase II study, ONL Therapeutics will have tested and validated the hypothesis that a safe and effective formulation for intravitreal injection of ONL-101 can be developed for use in human clinical trials. We will demonstrate that: 1) Intravitreal injection of ONL-101 is safe, and results in no significant ocular or systemic toxicity, 2) Pharmaceutical grade ONL-101 for use in clinical trials can be produced, and 3) A Phase 1/2 clinical trial can be designed to test the safety and efficacy of ONL-101 in humans. The work presented in this Phase II is the next step required for the commercialization of ONL-101, and the results obtained will allow for finalization of the IND package required to begin clinical trials for the ue of ONL-101 as an adjunctive treatment in patients with retinal detachments.