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

ONL-101用于视网膜脱离光感受器保护的临床前开发

基本信息

批准号：
8776582
负责人：
Linda Lea Johnson
金额：
$ 137.24万
依托单位：
ONL THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8776582
关键词：
Acute Affect Age related macular degeneration Agreement Anatomy Animals Apoptosis Applications Grants Automobile Driving Back Biotechnology Blindness Brain Cell Death Cessation of life Chronic Clinical Clinical Research Clinical Trials Clinical trial protocol document Data Development Disease Dose Drug Formulations Drug Kinetics Drug Packaging Drug Prescriptions Environment Eye Funding Future Goals Grant Health Care Costs Homeostasis Human Injury Intervention Investigational Drugs Investigational New Drug Application Lead Macular degeneration Medical Metabolic Michigan Neuroprotective Agents New Drug Approvals Operative Surgical Procedures Ophthalmology Orphan Orphan Drugs Outcome Pathway interactions Patients Peptides Persons Pharmaceutical Preparations Pharmacologic Substance Phase Photoreceptors Physicians Process Production Productivity Protective Agents Receptor Inhibition Retina Retinal Retinal Degeneration Retinal Detachment Retinal Diseases Route Safety Signal Transduction Small Business Innovation Research Grant Social Impacts Societies Staging Sterility Structure of retinal pigment epithelium Testing Therapeutic Therapeutic Agents Tissues Toxic effect United States United States Food and Drug Administration Universities Vision Visual Visual Acuity Work commercial application commercialization cost design economic impact improved inhibitor/antagonist intravitreal injection macula manufacturing process meetings novel novel therapeutics phase 2 study pre-clinical prevent public health relevance receptor relating to nervous system repaired response safety testing success

项目摘要

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.

描述（由申请人提供）：光感受器细胞的死亡是许多急性和慢性视网膜疾病的结果，导致患者严重视力丧失。如果可以帮助光感受器在疾病时期生存，那么患者的视觉结果将会好得多。视网膜退行性疾病和伤害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，每年影响成千上万的人，并导致数十亿美元增加了医疗保健成本并失去生产力。限制当前治疗功效的问题是，目前没有干预措施可以特别防止感光器细胞死亡；因此，安全，有效的感光器保护剂每年将为成千上万的人提供可观的视觉益处。 ONL Therapeutics正在开发一种候选产品，即FAS受体的新型小肽抑制剂（ONL-101），用于急性视网膜脱离患者的围手术期辅助用途（孤儿指示），目的是防止光感受器细胞死亡直到发生明确的手术修复。这种急性指示提供了一种快速的开发途径，该途径将为ONL-101开发的未来扩展奠定基础，以造成与年龄相关的黄斑变性等慢性指示。急性视网膜脱离的产物将是单剂量玻璃体内注射的处方药（眼科既定的给药途径）。这项SBIR II期研究完成后，ONL Therapeutics将测试并验证了以下假设：玻璃体内注射ONL-101的安全有效配方可以用于人类临床试验。我们将证明：1）玻璃体内注射ONL-101是安全的，导致没有明显的眼或全身毒性，2）可以生产用于临床试验的药物级ONL-101，3）3）可以设计1/2阶段的临床试验来测试Onl-101 Inlansmans的安全性和效率。 II阶段中提出的工作是ONL-101商业化所需的下一步，获得的结果将允许在视网膜脱离患者中开始对ONL-101 UE开始临床试验所需的IND套件作为辅助治疗。