Monday, November 7, 2011

AASLD-Pentraxin-2 Suppresses Liver Fibrosis and Has a Clear Hepatoprotective Effect

Promedior Presents Preclinical Data at AASLD Demonstrating That Pentraxin-2 Suppresses Liver Fibrosis and Has a Clear Hepatoprotective Effect


Promedior, Inc., a clinical stage biotechnology company developing novel therapies to treat fibrotic, inflammatory and neovascular diseases, today announced that data from preclinical studies of Serum Amyloid P (Pentraxin-2) were presented at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2011) on Sunday, November 6, 2011, in San Francisco, CA. In a poster entitled “Serum amyloid P attenuates hepatic fibrosis in mice by inhibiting the activation of fibrocytes and hepatic stellate cells,” Promedior and collaborators from the University of California, San Diego School of Medicine presented data which highlight the efficacy and utility of Pentraxin-2 in suppressing fibrosis and providing a strong hepatoprotective effect in two independent models of liver fibrosis. Promedior's lead product, PRM-151, is a recombinant form of the naturally circulating human protein, Pentraxin-2, which has been shown to regulate the cell populations that control fibrosis, inflammation and pathologic neovascularization. In liver fibrosis, Pentraxin-2 is seen to inhibit the activation of monocytes, fibrocytes and hepatic stellate cells.

“These studies clearly highlight the significant potential for Pentraxin-2 therapeutics in the treatment of liver fibrosis, a disease which is characterized by massive accumulation of extracellular matrix along with the undesirable activation of quiescent hepatic stellate cells and fibrocytes in the liver. By acting upstream of these pathologic liver fibrosis processes using a natural regulatory pathway, Pentraxin-2 therapeutics offer a compelling new approach,” said Mark L. Lupher, Jr., Ph.D., Chief Scientific Officer of Pulmatrix. “These strong preclinical results further expand the comprehensive 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.”

To study the potential of Pentraxin-2 for the treatment of liver fibrosis, wild type mice were subjected to Carbon Tetrachloride-induced liver injury or Bile Duct Ligation. Liver injured mice were treated with human Pentraxin-2 (hPTX-2) or vehicle (control mice). Livers were analyzed by Sirius Red, H&E staining, immunostaining and RT-PCR. In addition, the effect of hPTX-2 on activation of hepatic stellate cells and fibrocytes into collagen producing cells was tested in vitro. Significant results of the studies include:

  • Administration of hPTX-2 significantly reduced the development of liver fibrosis in both BDL and CCl4-injured mice.
  • Collagen deposition was inhibited by 47±5% in hPTX-2-treated BDL-operated mice as compared to vehicle-treated BDL mice, and was accompanied by inhibition of hepatocyte necrosis, proliferation of the bile ducts, infiltration with inflammatory cells, and activation of Collagen-α1(I)-GFP+ α-SMA+ fibrogenic myofibroblasts (approx.. 45-50% reduction). Strong downregulation of pro-fibrogenic genes (Collagen-α1(I), α-SMA, TIMP-1, and TGF- β1) and inflammatory cytokines (IL-1β, IL-6 and TNF-α) was also observed in hPTX-2-treated mice.
  • Similar results were obtained in response to CCl4-injured hPTX-2-treated mice, which demonstrated 52±4% reduction of collagen deposition (versus vehicle-treated CCl4-injured mice), and similar downregulation of the same gene products.

These findings suggest that hPTX-2 may mediate its anti-fibrogenic effects through inhibition of inflammatory cells (monocytes and fibrocytes) and collagen producing myofibroblasts. Consistent with this mechanism, the population of activated CD68+ macrophages was strongly reduced (55±7%) in hPTX-2-treated mice. Additionally, pre-treatment with hPTX-2 attenuated in vitro activation of fibrocytes and hepatic stellate cells into collagen Type I expressing myofibroblasts.

About PRM-151

Promedior is developing PRM-151 (rhPTX-2 for injection) for the treatment of Idiopathic Pulmonary Fibrosis (IPF) and other chronic systemic fibrosis indications. In a Phase 1 study in healthy volunteers and IPF patients, PRM-151 was safe and well-tolerated, and showed activity against efficacy biomarkers by reducing IPF-related peripheral blood fibrocyte and IL-6 levels. PRM-151 currently is being tested in a Phase 1b clinical study in IPF patients to evaluate the safety, tolerability and dose-responsive changes in validated cellular and soluble biomarkers of disease. 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.

About Promedior

Promedior is a clinical-stage biotechnology company developing a novel biology platform for the treatment of fibrosis, inflammation and neovascular retinal diseases. Promedior's platform of protein therapeutics is based upon Pentraxin-2, an endogenous human serum protein that regulates the body's response to injury. Pentraxin-2 therapeutics treat fibrosis and neovascular diseases by naturally regulating monocyte-derived cells (macrophages and fibrocytes) that control the fibrotic process and drive pathologic neovascularization. Based upon 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 utilizing a natural regulatory pathway, Pentraxin-2 therapeutics provide a superior therapeutic approach and an inherently safer profile.

Using its novel approach, Promedior is initially developing a pipeline of 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

The Yates Network
Kathryn Morris, 845-635-9828

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