Promedior Announces Presentation of Preclinical Data at ARVO Demonstrating PRM-151 (rhPTX-2) Reduces Neovascularization in Retinal Diseases
—Novel Pentraxin Therapeutic Platform Offers a New Approach to Suppression of Choroidal and Retinal Neovascularization—
MALVERN, PA, May 4, 2011 —
Promedior, Inc., a clinical stage biotechnology company developing novel therapies to treat fibrotic, inflammatory and neovascular diseases, announced that data from preclinical studies of PRM-151 (recombinant human Pentraxin-2 (PTX-2)) were presented today at the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Ft. Lauderdale, FL. In a poster entitled “PRM-151, recombinant human Pentraxin-2 (PTX-2), Suppresses Choroidal (CNV) and Retinal Neovascularization (RNV)”, Promedior and collaborators from The Johns Hopkins University Wilmer Eye Institute highlight the efficacy and utility of Pentraxin-2 in suppressing neovascularization in independent models of age-related macular degeneration (AMD) and diabetic retinopathy. Pentraxin-2 is a natural human protein that regulates the cell populations that control fibrosis, inflammation and pathologic neovascularization. In AMD, diabetic retinopathy, and macular edema, neovascularization is known to cause retinal damage which can result in visual impairment and progressive loss of vision.
“Together, these results strongly suggest a role for pentraxin-2 therapeutics in the treatment of neovascularization associated with 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 expand the mechanistic evidence that we have underscoring the potential of pentraxin-2 therapeutics to treat and resolve a number of diseases characterized by fibrosis, inflammation, and neovascularization.”
The effects of intraocular injections of rhPTX-2 (PRM-151) on choroidal neovascularization (CNV), retinal neovascularization (RNV) and subretinal neovascularization were investigated. These studies were conducted in three distinct animal models of retinal disease pathologies associated with human AMD, diabetic retinopathy and macular edema, and showed that intraocular injections of PRM-151 suppresses neovascularization and reduced monocyte/macrophage numbers in the retina in all tested model systems. Further, the studies show:
- Intraocular injection of rhPTX-2 at the time of rupture of Bruch’s membrane, and 5 and 9 days after laser resulted in an 80% reduction in CNV area compared to vehicle-injected eyes.
- Single intraocular injection of rhPTX-2 in mice with oxygen-induced ischemic retinopathy resulted in an 80% reduction in RNV area compared to vehicle-injected eyes.
- Single intraocular injection of PRM-151 in rho/VEGF transgenic mice resulted in a 40% reduction in subretinal neovascular area compared to vehicle-injected eyes.
- Immunofluorescent staining for F4/80 in the CNV model and CXCR4 in the RNV model showed that intraocular injection of rhPTX-2 consistently reduced the number of monocytes/macrophages in the retina in both models compared to control.
These results suggest that the positive effect of rhPTX-2 in these neovascular models was mechanistically mediated by regulating similar populations of monocyte-derived cells (macrophages and fibrocytes) as described for PTX-2 in other organ systems, such as the lung and kidney, and provides a novel and complementary mechanism for treatment of debilitating choroidal and retinal neovascular diseases to that currently provided by VEGF antagonists.
PRM-151, Promedior’s lead product, is a recombinant form of a naturally circulating human protein, Pentraxin-2 (PTX-2), that regulates a fundamental mechanism of the innate immune system response to injury and activates the body’s natural ability to resolve tissue damage in disease processes that cause fibrosis, inflammation and neovascularization. PRM-151 has shown broad anti-fibrotic and anti-inflammatory activity in multiple preclinical models of fibrotic disease and inflammation, including pulmonary fibrosis, acute and chronic nephropathy, and glaucoma.
PRM-151 is currently being tested in a Phase 1b clinical study in Idiopathic Pulmonary Fibrosis (IPF) to evaluate the safety, tolerability and dose-responsive changes in validated cellular and soluble biomarkers of disease activity. PRM-151 is also being tested in a Phase 2a clinical study to evaluate the efficacy, safety, and tolerability of PRM-151 in preventing post-surgical scarring in glaucoma patients following glaucoma filtration surgery. Promedior successfully completed a Phase 1 clinical study of PRM-151 in 2010.
About Pentraxin Therapeutics
Promedior’s proprietary platform of pentraxin therapeutics is based upon breakthrough discoveries in how the body’s innate response to injury results in pathologic fibrosis and the loss of tissue and organ function. Promedior’s novel therapeutics are designed to treat and prevent fibrotic pathology by regulating the common cellular mechanisms that control the initiation and progression of fibrosis across a variety of tissues and organ systems. Promedior’s initial drug products are based upon the unique structure of Pentraxin-2, a naturally-occurring protein which has demonstrated a unique role in targeting monocytes at sites of tissue damage. Monocyte-derived cells have been shown to regulate inflammation and fibrosis as well as pathologic neovascularization. Promedior’s approach leverages the natural role of Pentraxin-2 in regulating the response of these important immune and inflammatory processes in the body. Promedior has built a comprehensive patent estate for Pentraxin therapeutics, including recombinant human Pentraxin-2 (rhPTX2 or rhSAP), for a broad range of therapeutic applications in fibrosis and other inflammatory diseases.
Promedior has developed a novel drug discovery platform to regulate the monocyte-derived cell populations that play key roles in fibrotic, inflammatory, autoimmune and neovascular diseases. By specifically targeting these cells at the site of injury, Promedior is able to treat the source of aberrant immune system responses, promote tissue healing and resolution, and greatly reduce the risk of systemic side effects inherent in current therapeutic approaches. Utilizing this novel approach, Promedior is initially developing drugs to address the most severe and difficult-to-treat fibrotic and inflammatory conditions of the eye, lung and kidney such as glaucoma, age-related macular degeneration and diabetic retinopathy (eye); pulmonary fibrosis, scleroderma and COPD (lung); and acute and chronic nephropathy (kidney). For additional information about Promedior, please visit www.promedior.com
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