According to the World Health Organization (WHO) global eye disease survey, 14 million people are blind or severely visually impaired due to age-related macular degeneration AMD. This disease affects the central vision of adults over the age 65. Degenerative changes of the Bruch's membrane and the retinal pigment epithelium in the macula (central retina) in addition to the partial / complete vision loss is the hallmark of AMD. It is estimated that greater than 25% of AMD patients will develop severe vision loss due to either geographic atrophy or Choroidal NeoVascularization (CNV), commonly known as wet AMD. CNV development derives from both inflammation and angiogenesis. Thus, both VEGF and inflammatory mediators must be controlled to prevent CNV associated vision loss. Elevated levels of VEGF have been found in pathological neovascularization. The process of angiogenesis is multi-factorial and highly complex with evidence of both neovascularization and inflammation. VEGF is considered important in both physiological and pathological situations. By blocking all VEGF, local wound healing could be impaired, whereas for any ocular surgery treatment the procedure may then be postponed or even stopped altogether. Both neovascularization and inflammation must be controlled in order to achieve the desired benefit in Wet AMD. A strategy to prevent the formation of VEGF &inflammatory mediators, as opposed to just blocking each of them individually, could be important in halting the progression of the disease. To implement this strategy, NovelMed has developed a high affinity highly selective neutralizing antibody of the alternative pathway that prevents complement and cellular activation and production of inflammatory mediators. In a rabbit model of choroidal neovascularization (CNV), the drug prevented the formation of CNV lesions at a concentration of 15 ug per eye over a 28 day period. We would like to develop The Specific Aims of the project are: 1) Production and Purification of Humanized NM9405 for Aims 2 and 3;2) Evaluation of Humanized NM9405 in the Rabbit Model of Choroidal NeoVascularization (CNV) and 3) Efficacy &Safety of the Humanized NM9405 in the Cynomolgus Monkey Model of Choroidal Neovascularization (CNV)- - These studies will address ocular efficacy and toxicity studies required for moving to the next step of Investigational New Drug (IND) filings, pharma-partnering, and investment. The demonstration of efficacy and preliminary ocular safety will move this program to an IND stage application.

Public Health Relevance

Age-related macular degeneration (AMD) affects nearly 14 million people in the U.S as documented by the World Health Organization. Recently, anti-VEGF therapy was approved only for the treatment of Wet AMD. Both neovascularization and inflammation are associated with Wet AMD. The current treatments are effective only in preventing the formation of new blood vessels without inhibiting underlying inflammation. NovelMed neutralizing antibody inhibits both;neovascularization as well as inflammation. The treatment could affect both the Dry and the Wet AMD;however, in this proposal we are addressing only Wet AMD based on the recommendation of the review panel. Choroidal NeoVascularization (CNV) is critical to the onset Wet AMD. This phase II application is to extend our findings of phase I into testing humanized monoclonal antibody for the treatment of Wet AMD in two well established disease models.

National Institute of Health (NIH)
National Eye Institute (NEI)
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
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Special Emphasis Panel (ZRG1-ETTN-E (12))
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Wujek, Jerome R
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Novelmed Therapeutics, Inc.
United States
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