Promedior Announces Presentation of Preclinical Data at ARVO Demonstrating that Pentraxin-2 Suppressed Fibrosis, Neovascularization, and Vascular Leakage
—Novel Pentraxin Therapeutics Offer a Promising New Approach for Treating
Fibroproliferative Retinal Diseases—
MALVERN, PA, May 7, 2012 —Promedior, Inc.
, a clinical stage biotechnology company developing novel biologic therapeutics for the treatment of fibroproliferative diseases, today announced that data from preclinical studies of Pentraxin-2 (PTX-2) were presented yesterday at the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Ft. Lauderdale, FL. In a poster entitled “Recombinant Pentraxin-2 (rPTX-2) Shifts Macrophage Phenotype, Suppresses Subretinal NV, and Reduces Associated Vascular Leakage and Collagen Deposition”, Promedior and collaborators from The Johns Hopkins University Wilmer Eye Institute highlighted the efficacy and utility of Pentraxin-2 in suppressing fibrosis, neovascularization and vascular leak in independent models of age-related macular degeneration (AMD) and diabetic retinopathy.
Promedior is developing PRM-167 (rPTX-2 variant for intravitreal injection) for the treatment of fibroproliferative retinal diseases like AMD, diabetic retinopathy and proliferative vitreoretinopathy (PVR, retinal detachment). Pentraxin-2 is a natural human protein that regulates the cell populations, such as monocytes and macrophages, that control fibrosis, inflammation and pathologic neovascularization. In AMD and diabetic retinopathy, neovascularization and fibrosis are known to cause retinal damage which can result in visual impairment and progressive loss of vision.
“These results underscore the significant potential of Pentraxin-2 therapeutics in the treatment of fibroproliferative human retinal diseases such as AMD, diabetic retinopathy and macular edema.” said Mark L. Lupher, Jr., Ph.D., Chief Scientific Officer. “Additionally, we are excited that these compelling results further confirm the novel mechanism of Pentraxin-2 therapeutics to both treat and resolve serious diseases characterized by fibrosis and neovascularization.”
In the studies presented at ARVO, the effects of intraocular injections of rPTX-2 on subretinal neovascularization, vascular leakage and collagen deposition were investigated. These studies were conducted in animal models of retinal disease pathologies associated with human AMD, diabetic retinopathy and macular edema, and showed that intraocular injections of rPTX-2 suppressed neovascularization, vascular leak and collagen deposition which correlated with reduced monocyte/macrophage numbers in the retina in all tested model systems. Further, the studies showed:
There was a significant and dose dependent reduction in the mean area of neovascularization after injection of 2μg (40%), 5μg (43%) or 20μg (50%) of rPTX-2, but not 0.2μg.
Compared to eyes injected with vehicle, those injected with rPTX-2 had a significant increase in mRNA of IL-10, which is an anti-inflammatory cytokine produced by regulatory macrophages.
Mice with ischemia-induced retinal neovascularization treated with rPTX-2 had significantly fewer CXCR4+, CCR2+ and F4/80+ cells in the retina compared to controls, but no difference in CX3CR1+ cells in ischemic retina. This resulted in a substantial increase in the ratio of regulatory (CX3CR1+) to inflammatory (CCR2+) macrophages remaining in the retina, thereby promoting healing.
These results confirm that rhPTX-2 mediated suppression of neovascularization and fibrosis in these neovascular retinal models is mediated through similar inductions in IL-10 associated regulatory macrophage activity and selective inhibition of inflammatory macrophages and fibrocytes observed with rhPTX-2 therapy in models of pulmonary and renal fibrosis. Thus, PTX-2 provides a novel and complementary mechanism for the treatment of debilitating choroidal and retinal neovascular diseases to that currently provided by VEGF antagonists.
PRM-167 (rPTX-2 variant for intravitreal injection) is a variant of a recombinant form of human Pentraxin-2 that is in development for the treatment of fibrovascular retinal diseases. Intravitreally administered rhPTX-2 has demonstrated robust preclinical efficacy in validated models of choroidal neovascularization, retinal neovascularization and proliferative vitreoretinopathy (PVR, retinal detachment). With a novel mechanism of action that is highly differentiated from other approaches to treat fibrovascular diseases, recombinant Pentraxin-2 therapeutics offer the potential to effectively reverse fibrotic and neovascular disease processes and promote normal healing.
is a clinical-stage biotechnology company developing a pipeline of novel Pentraxin-2 therapeutics for the treatment of fibrovascular diseases. Pentraxin-2 therapeutics treat fibrovascular diseases by naturally regulating monocyte-derived cells (macrophages and fibrocytes) that control the fibrotic process and drive pathologic neovascularization. Based on a unique mechanism of action
, Pentraxin-2 localizes to sites of tissue damage and stimulates monocytes to differentiate into regulatory macrophages rather than pro-fibrotic macrophages and fibrocytes, thereby reversing inflammatory, fibrotic and neovascular processes and promoting normal healing. By acting upstream of these pathologic processes using a natural regulatory pathway, Pentraxin-2 therapeutics provide a superior therapeutic approach and an inherently safer profile. For additional information about Promedior, please visit www.promedior.com
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