Anti-properdin antibody demonstrates efficacy in a primate model of wet-AMD and dry-AMD

Figure 1 - Fluoresceine angiogram data from three animals treated with NM3086 (bottom) and three that received placebo control. The picture shows reduced hemorrhage and neovascularization (Left) and Fibrosis (Right) in the drug-treated animals. (Image courtesy of NovelMed Therapeutics)

NovelMed Therapeutics announced today that NM3086, the lead clinical asset in its properdin-associated alternative pathway (AP) program, demonstrated favorable efficacy in an animal model of neovascular age-related macular degeneration (AMD) in rhesus monkeys.

According to the news release, this animal model is characterized not only by the abnormal growth of new blood vessels behind the retina, as shown in Figure 1, but also by retinal fibrosis and vascular hemorrhage, which are the critical characteristics of wet-AMD, dry-AMD, and geographic atrophy (GA). While it is difficult to extrapolate the visual acuity score in animals, the damage prevented by NM3086 in this model suggests the drug's efficacy in treating the disease.

The company noted that researchers at Charles River Laboratories established a preclinical choroidal neovascularization (CNV) efficacy model in rhesus monkeys. This study administered NM3086 (1.2 mg/eye ) intravitreally to monkeys before creating nine laser-induced retinal lesions. Following a two-week observation period, choroidal neovascularization (formation of new blood vessels), retinal fibrosis (scar tissue), and hemorrhage (vascular leakage) were quantified against a placebo control. NM3086 resulted in a significant decrease in the extent of all three damage markers.

"This all-in-one approach in ophthalmic space is a significant achievement for treating multiple ocular chronic ailments with a single therapy," Rekha Bansal, PhD, founder and CEO of NovelMed Therapeutics, said in the news release.

About NM3086

NM3086 selectively binds Properdin and blocks the AP activation. As a result, the formation of C3 and C5 convertases is blocked. In general, the C3 convertase converts C3 to C3a and C3b, while the C5 convertase converts C5 to C5a and C5b. C3a and C5a are potent inflammation-causing agents which activate a variety of cells.

Activated cells release pro-inflammatory molecules such as tumor necrosis factor alfa (TNFα), vascular endothelial growth factor (VEGF) and other cytokines. The C5b molecule converts into a membrane attack complex (MAC) which damages cells and tissues. This cycle repeats itself until the entire tissue is damaged and gone. This vicious cycle produces excessive levels of pro-inflammatory cytokines such as TNF and VEGF, typically elevated in ocular diseases.

The VEGF is known to promote the growth of new blood vessels and makes the blood vessels leaky in Wet-AMD. Anti-VEGF drugs (Lucentis and Eyelea) stop the development of these new blood vessels. These drugs prevent the loss of central vision in Wet AMD, diabetic macular edema (DME), and diabetic retinopathy (DR).

As an investigational drug, NM3086 has been extensively studied in various in vitro and in vivo disease models, which prove that the drug: a) blocks AP-driven cellular lysis, TNF production, and VEGF production, and b) prevents neovascularization, scar formation, hemorrhage, and inflammation in animal models. Treatment with NM3086 is specific to the AP while preserving the regular activity of the classical Pathway (CP). Collectively, selective blockade of the AP without impacting the CP will allow patients to maintain host defense mechanisms responsible for preventing infections.

"NM3086 is expected to be therapeutically effective across a broad range of rare and common complement-mediated disorders including ocular (Wet AMD, Dry AMD, and GA), inflammatory, renal, and hematological," Bansal concluded