Idera Pharma (IDRA) Presents IMO-2125 Preclinical Data

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November 3, 2009 9:50 AM EST

Idera Pharmaceuticals, Inc. (NASDAQ: IDRA) today presents preclinical data on the mechanism by which IMO-2125 was shown to induce immune activation through Toll-like Receptor 9 (TLR9). Two presentations are being made today at the 60th Annual Meeting of the American Association for the Study of Liver Diseases being held in Boston, MA.

"Induction of endogenous interferon-alpha and other antiviral proteins by IMO-2125 provides a novel immunotherapy approach to the potential treatment of chronic hepatitis C virus infection," said Sudhir Agrawal, D.Phil., Chief Executive Officer and Chief Scientific Officer. "We currently are evaluating IMO-2125 in two phase 1 clinical trials involving HCV patients non-responsive to standard of care treatment and patients who are treatment-naive. Data from these clinical trials will guide decisions for further development of IMO-2125."

"One of our presentations today provides insights into the mechanism of immune activation by IMO-2125 as mediated through TLR9 and the associated interferon signaling pathways involving MyD88 and IRF7," said Tim Sullivan, Ph.D., Vice President of Development Programs. "We also are presenting data that show endogenous interferon-alpha induced by IMO-2125 exerts potent anti-HCV activity in replicon assays. This activity is augmented by other cytokines induced by IMO-2125."

Abstract 1593: "IMO-2125, a TLR9 agonist, induces Th-1 type cytokines and interferons with potent anti-HCV activity in human peripheral blood mononuclear cells (PBMCs) and plasmacytoid dendritic cells (pDCs)"

In this study, IMO-2125 induction of cytokines was evaluated in human peripheral blood mononuclear cells (hPBMCs) and plasmacytoid dendritic cells (pDCs). The data show that IMO-2125 induced high levels of endogenous interferon-alpha along with interferon-beta, interferon-lambda, and other proteins including IP-10 and 2'-5'-OAS. These IMO-2125-induced cytokines showed potent antiviral activity in the HCV replicon assay. Antiviral activity was decreased by addition of anti-interferon-alpha antibody, but only partially which suggests that other cytokines and chemokines induced by IMO-2125 also contribute to the antiviral activity.

Abstract 1597: "Gene expression profiles induced by IMO-2125, an agonist of Toll-like receptor 9, in human peripheral blood mononuclear cells"

In this study, the mechanism of immune activation by IMO-2125 in hPBMCs was evaluated by gene expression analysis. Gene expression profiles were obtained using TLR signaling pathway microarray, IFN-alpha/beta response microarray, human innate and adaptive immune response microarray, and human Th1-Th2-Th3 response microarray. The results show that IMO-2125 mediated immune responses through TLR9 and associated interferon signaling pathways involving MyD88 and interferon regulatory factor 7 (IRF7). In addition, many type 1 interferon-response genes, interferon-inducible proteins, antiviral proteins, TLR9 signaling molecules and transcription factors were up-regulated.