Single Therapy for Wet AMD & Geographic Atrophy

描述(申请人提供)：大约85%的老年性黄斑变性(AMD)患者患有干性黄斑变性。地理性萎缩症(GA)是干性AMD的进展型，由视网膜上皮细胞变性引起。虽然GA没有湿性AMD那么常见，但在美国，它导致了10%-20%的法律失明。目前还没有FDA批准的GA治疗方法。然而，一项评估药物Lampalizumab的最新试验结果提供了令人信服的证据，证明替代补体途径在GA患者视力丧失的发展中发挥关键作用。Lampalizumab是一种针对替代补体途径的抗D因子治疗性抗体。补体介导的RPE、光感受器细胞和Bruch膜的破坏是GA的特征。Lampalizumab对干性AMD患者显示出近44%的益处。NovelMed的主要候选药物NM5072是一种优秀的AP抑制剂，与Lapalizumab相比，预计在较低的剂量下会更有效、持续时间更长。我们预计NM5072在知道患者以后可能发展为这两种病理中的哪一种(如果不治疗)之前，既能抑制CNV，又能抑制GA。NovelMed的主要候选药物是替代补体途径的选择性抑制剂。该分子：a)以高亲和力和选择性结合靶标，b)在有效剂量水平下防止新血管的形成，c)防止炎症，d)具有更长的药代动力学以改善给药计划，鉴于替代补体途径在GA中的作用，我们预计我们的药物将在不影响组织修复的情况下防止CNV和GA的发生和发展。目前还没有一种治疗方法可以同时控制导致视力丧失的湿性和干性AMD。该药物已按FDA规范生产，并已准备好进行GLP毒性研究和人体临床试验。我们打算开发NM5072作为湿性和干性AMD的单一疗法。我们预计NM5072在AMD的早期阶段可以同时抑制CNV和GA，然后才能知道患者后来可能会发展为这两种病理中的哪一种(如果不治疗)。通过在CNV和GA发病前对AMD进行治疗，可以完全预防AMD所致的视力损失。

DESCRIPTION (provided by applicant): Approximately 85% of the total age-related macular degeneration (AMD) patients have the Dry form. Geographic atrophy (GA) is the advanced form of Dry AMD and is caused by the degeneration of the retinal epithelial cells. While GA is less common than Wet AMD, it is responsible for 10-20% of legal blindness in the US. There is currently no FDA approved treatment for GA. However, the latest results from a trial evaluating the drug Lampalizumab, an anti-Factor D therapeutic antibody targeted to the alternative complement pathway, provide convincing evidence that the alternative complement pathway plays a key role in the development of vision loss in patients with GA. Complement-mediated destruction of RPE, photoreceptor cells, and Bruch's membrane are the hallmarks of GA. Lampalizumab demonstrated nearly 44% benefit for patients with Dry AMD. NovelMed's lead drug candidate, NM5072, is a superior AP inhibitor and is expected to be more effective and longer lasting, at lower dosages, when compared to Lapalizumab. We expect NM5072 to inhibit both the CNV and the GA before it can be known which of the two pathologies a patient might develop later on (if not treated). NovelMed's lead drug candidate is a selective inhibitor of the alternative complement pathway. The molecule; a) binds the target with high affinity and selectivity, b) prevents formation of new blood vessels at potent dose levels, c) prevents inflammation, and d) has longer pharmacokinetics for improved dosing schedule, Given the role of the alternative complement pathway in GA, we expect our drug to prevent the onset and progression of CNV and GA without affecting tissue repair. There is no therapy available today that could control both the Wet and the Dry form of AMD that leads to vision loss. The drug has been manufactured to FDA specifications and ready for GLP toxicity studies and for human clinical trial. We intend to develop NM5072 as a single therapy for both Wet and Dry AMD. We expect NM5072 to inhibit both CNV and GA at an early stage of AMD, before it can be known which of the two pathologies a patient might develop later on (if left untreated). By treating AMD prior to onset of CNV and GA, AMD driven vision loss could be prevented entirely.