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

 描述（由申请人提供）：黄斑水肿（ME）是继发于视网膜静脉阻塞以及I型和2型糖尿病的常见疾病。它是 20-74 岁人群失明的主要原因。 Lucentis 和 Eylea 已被批准用于治疗 ME。尽管有效，但它们并不能提高大约一半 ME 患者的视力。 我们开发了 ACX107，这是一种 20 聚体肽，对多种促血管生成生长因子具有显着的活性，我们相信，由于其广泛的抗血管生成活性，它将更有效地改善更多患者的视力。我们发现，在小鼠和兔模型中，ACX107 可抑制脉络膜新生血管、视网膜新生血管形成，引起新生血管消退，抑制视网膜脱离，并显着抑制 VEGF 诱导的血管渗漏。值得注意的是，该肽在单次玻璃体内注射后 1 个月似乎仍能发挥作用。 这些结果表明 ACX107 可能成为治疗 ME 的下一代药物。在这里，我们建议完成剂量范围研究以及活性持续时间研究，开发量化 ACX107 的分析方法，并进行 IND 毒理学研究。我们在这里提出的是我们可以在第一阶段 SBIR 机制的预算和时间限制内完成的全部开发工作的一部分。其余的开发工作将需要更多的资金，我们可以通过第二阶段 SBIR 或其他投资（例如战略合作伙伴关系）来完成。

 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.