Development of a mimetic multimodal peptide for the treatment of macular edema

开发用于治疗黄斑水肿的模拟多模式肽

• 批准号: 8980463
• 负责人: Niranjan B Pandey
• 金额: $ 27.81万
• 依托单位: ASCLEPIX THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8980463
• 关键词: Age; Angiogenic Factor; Animal Model; Antibodies; Aqueous Humor; Blindness; Blood; Blood Vessels; Budgets; Choroidal Neovascularization; Development; Disease; Dose; Drug or chemical Tissue Distribution; Enzyme-Linked Immunosorbent Assay; Extravasation; Eye; Funding; Growth Factor; Hypoxia; Investments; Liquid substance; Lucentis; Medical; Methods; Modeling; Mus; Non-Insulin-Dependent Diabetes Mellitus; Oryctolagus cuniculus; Patients; Peptides; Permeability; Pharmaceutical Preparations; Phase; Pigments; Rest; Retinal Detachment; Retinal Neovascularization; Retinal Vein Occlusion; Secondary to; Serum; Small Business Innovation Research Grant; Testing; Therapeutic; Time; Toxicology; Up-Regulation; Vascular Endothelial Growth Factors; Vision; Visual Acuity; Vitreous humor; Work; analytical method; angiogenesis; aqueous; human disease; improved; intravitreal injection; macular edema; mimetics; neovascular; next generation; public health relevance

 DESCRIPTION (provided by applicant): Macular edema (ME) is a common disease secondary to retinal vein occlusion and both Type I and Type 2 Diabetes. It is the leading cause of blindness in people between the ages of 20-74. Lucentis and Eylea have been approved for the treatment of ME. Although effective, they do not increase the visual acuity for about half the patients suffering from ME. We have developed ACX107, a 20-mer peptide with remarkable activity against a host of pro-angiogenic growth factors, which we believe will improve vision more effectively and in more patients because of its broad anti-angiogenic activity. We have found that ACX107 inhibits choroidal neovascularization, retinal neovascularization, causes neovascular regression, inhibits retinal detachment, and dramatically inhibits VEGF induced vascular leakage in mouse and rabbit models. Remarkably the peptide appears to work even 1 month after a single intravitreal injection. These results suggest that ACX107 could be the next generation drug for the treatment of ME. Here we propose to complete a dose ranging study as well as a duration of activity study, to develop an analytical method to quantify ACX107, and do IND enabling toxicology studies. What we have proposed here is the portion of the full development work that we can accomplish on the budget and time confines of the Phase I SBIR mechanism. The rest of the development work will require significantly more funding which we could accomplish with a Phase II SBIR or other investment like that of a strategic partnership.

 描述（由适用提供）：黄斑水肿（ME）是视网膜静脉闭塞和I型和2型糖尿病继发的常见疾病。这是20-74岁人群失明的主要原因。 Lucentis和Eylea已被批准用于治疗我。尽管有效，但它们不会增加大约一半患者患者的视力。我们已经开发了ACX107，这是一种20-MER肽，具有出色的活性，抗活血管生长因子，我们认为，由于其广泛的抗血管生成活性，我们将在更多的患者中更有效地改善视力。我们发现，ACX107抑制脉络膜新生血管形成，视网膜新血管形成，导致新生血管的消退，抑制视网膜脱离，并大大抑制VEGF诱导的小鼠和兔模型中VEGF诱导的血管泄漏。单次玻璃体内注射后1个月似乎可以工作。这些结果表明，ACX107可能是治疗我的下一代药物。在这里，我们建议完成一项剂量范围研究以及活动研究的持续时间，以开发一种分析方法来量化ACX107并进行IND促进毒理学研究。我们在这里提出的是我们可以在I阶段SBIR机制的预算和时间范围内完成的完整开发工作的一部分。其余的开发工作将需要更多的资金，我们可以通过II期SBIR或其他投资（例如战略合作伙伴关系）来实现的资金。