Idera Announces Presentation At AAD Annual Meeting Demonstrating Toll-like Receptor Antagonists Normalize Expression Of Inflammatory Genes In Psoriasis Model

A copy of the presentation is available on the AAD website.

About TLRs and Idera's Autoimmune and Inflammatory Diseases Program

Toll-like receptors (TLRs) play a key role in inflammation and immunity. Of the 10 human TLRs identified to date, Idera is developing compounds targeted to TLRs 3, 7, 8 and 9, which are expressed in different cells and serve unique functions. Using its chemistry-based approach, Idera has created novel drug candidates that modulate immune responses through either activation or inhibition of specific TLRs. Inhibition of specific TLRs may be useful in treating autoimmune disorders, such as systemic lupus erythematosus (SLE), psoriasis and rheumatoid arthritis, by blocking the induction of multiple cytokines and signaling pathways. Idera's clinical candidates for application in autoimmune diseases are IMO-3100, an antagonist of TLR7 and TLR9, and IMO-8400, an antagonist of TLRs 7, 8 and 9.

A characteristic of autoimmune diseases such as SLE and psoriasis is the production of autoantibodies, damage-associated molecular patterns, or DAMPs, and pathogen associated molecular patterns, or PAMPs, that may contain host nucleic acids. These stimuli activate TLRs 7, 8 and 9 and induce multiple cytokines and signaling cascades that cause further damage to the body's own tissues and organs, thereby releasing more self-nucleic acids. Thus, a pathologic amplification cycle is established, promoting disease maintenance and progression. In preclinical models of several autoimmune diseases, IMO-3100 and IMO-8400 inhibited TLR-mediated induction of Th1, Th17 and inflammasome pathways, leading to the suppression of multiple cytokines including tumor necrosis factor-alpha, or TNF-α, and interleukins IL-12, IL-6, IL-17 and IL-1β and improvements in multiple measures of disease. Current treatments for autoimmune and inflammatory diseases include the use of monoclonal antibodies to block the activity of one specific cytokine. TLR antagonists are designed to inhibit induction of immune responses to autoimmune disease stimuli rather than to block the activity of any one specific cytokine.

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