IMO-3100, an antagonist of TLR7 and TLR9, is a lead drug candidate currently in preclinical development for the potential treatment of autoimmune and inflammatory diseases.  Idera expects to submit an Investigational New Drug application for IMO-3100 to the U.S. Food and Drug Administration by the end of 2009.

IMO-3100 is created through extensive structure-activity relationship studies and is a DNA-based compound. IMO-3100 has been shown in preclinical assays to suppress immune responses mediated through TLR7 and TLR9, including induction of interferon-alpha, TNF-alpha, IP-10, IL-6, and activation of B cells. Studies from independent researchers have suggested that immune complexes involved in certain autoimmune diseases trigger inflammatory immune responses mediated through TLR7 and TLR9. Use of a TLR antagonist to block responses to such immune complexes may provide a novel mechanism of action for potential treatment of autoimmune diseases. IMO-3100 and other TLR antagonists have have shown potent activity in mouse models of autoimmune and inflammatory diseases such as lupus, rheumatoid arthritis, multiple sclerosis, psoriasis, and colitis. Data from these studies have been presented at various scientific meetings:

• Novel Class of DNA-Based Compounds Act as Antagonists for TLR7 and 9: In Vitro and In Vivo Studies in MRL-lpr and NZBW/F1 Mouse Models, Keystone Symposia, February 2007
• A Novel Class of DNA-Based TLR Antagonists Ameliorates Collagen-Induced Arthritis in Mice, FASAB, July 2007
• Studies of Oligonucleotide-Based Antagonists of TLR9 in a Mouse Model of Experimental Autoimmune Encephalomyelitis, American Academy of Neurology, April 2008
• A Toll-like Receptor Antagonist Prevents Development of IL-23-induced Psoriasis-like Dermal Changes in Mice, FOCIS, June 2008
• Synthetic DNA-Based Antagonist of TLR7 and 9 Protects Mice Against TNBS-Induced Colitis, Oligonucleotide Therapeutics Society, October 2008

Idera recently presented preclinical data on IMO-3100 in combination with Enbrel® (etanercept), an inhibitor of TNF-alpha at the 2009 Annual Scientific Meeting of the American College of Rheumatology and Association of Rheumatology Health Professionals. The data showed that the activity of a low Enbrel dosage was markedly enhanced when combined with IMO-3100 in a mouse model of arthritis. [Press Release]

The Company has established an Autoimmune Disease Scientific Advisory Board to advise the Company on development strategies for IMO-3100.