Idera Pharmaceuticals, Inc. has reported preclinical studies evaluating the mechanism of action of IMO-8400, a selective inhibitor of Toll-like Receptors (TLRs) 7,8 and 9. The data were presented recently during the Federation of Clinical Immunology Societies (FoCIS) meeting in Vancouver, British Columbia, Canada.
In this study, the mechanism of action of IMO-8400 has been studied in non-human primates. The administration of IMO-8400 led to inhibition of immune responses mediated through targeted Toll-like receptors. Multiple cytokines were suppressed, including TNF-a, IL-12, IL-6, IFN-a, IL-1ß. Similar results of IMO-8400 suppression of TLR7, 8 and 9-mediated immune responses were observed in human blood cells. IMO-8400 is a lead candidate in development for the treatment of lupus.
“These studies confirm that in a preclinical primate model and in human blood cells treatment with IMO-8400 specifically blocked cytokine induction mediated through targeted TLRs,” said Tim Sullivan, VP of Development Programmes and Alliance Management. “The selective inhibition of these TLRs is consistent with the preclinical efficacy we have seen in commonly used mouse models of lupus and holds promise for potential use of IMO-8400 in humans with lupus and other autoimmune diseases. The activity demonstrated with IMO-8400 in various models forms the basis for the Investigational New Drug Application we anticipate submitting to the FDA in the fourth quarter of this year.”
Toll-like Receptors (TLRs) represent a class of proteins that play a key role in both inflammation and immunity. Of the 10 human TLRs identified to date, Idera is focusing on compounds targeted to TLRs 3, 7, 8, and 9, which are expressed in different cells and serve unique functions. For example, activation of TLR7 and TLR9 present in certain dendritic cells and lymphocytes may be useful for the treatment of various types of cancer by stimulating immunity. In contrast, inhibition of specific TLRs may be useful in treating autoimmune disorders, such as psoriasis and lupus, by blocking the production of multiple pro-inflammatory mediators. Using its chemistry-based approach, Idera has developed novel drug candidates which modulate immune response through activation or inhibition of specific TLRs to treat a broad range of diseases, including autoimmune diseases and cancer, and to enhance the effectiveness of vaccines.
In autoimmune diseases, Idera is developing inhibitors of TLRs 7, 8, and 9 for the potential treatment of psoriasis, lupus, and other diseases. Idera's lead clinical candidate is IMO-3100, an antagonist of TLR7 and TLR9, which is in phase II development for psoriasis. IMO-8400 is an antagonist of TLRs 7, 8, and 9. Idera expects to submit an IND application for IMO-8400 during the fourth quarter of 2012. Idera has selected lupus as the initial disease indication for clinical development of IMO-8400.
Lupus is a chronic autoimmune disease where the body's immune system becomes hyperactive and attacks normal healthy tissue. This results in symptoms such as inflammation, swelling, and damage to joints and almost every major organ in the body, including the heart, kidneys, skin, lungs and brain. According to The Lupus Foundation of America, an estimated 1.5 million Americans and at least five million people worldwide have a form of lupus.
Idera Pharmaceuticals applies its proprietary Toll-like receptor (TLR) drug discovery platform to create immunomodulatory drug candidates and has clinical development programs in autoimmune diseases and cancer.