Idera advances its second TLR therapeutic

Company initiates clinical development of proprietary Toll-like receptor antagonist candidate IMO-9200

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CAMBRIDGE, Mass.—Idera Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing nucleic acid therapeutics for patients with cancer and rare diseases, today announced it has advanced IMO-9200 into Phase 1 clinical development following acceptance of an Investigational New Drug application by the U.S. Food and Drug Administration. In addition, the company announced the presentation of new data that showed IMO-9200 inhibited Toll-like receptor (TLR)-mediated immune responses in multiple preclinical models at the 10th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) in San Diego. These data support the development of IMO-9200, a synthetic oligonucleotide-based antagonist of TLRs 7, 8 and 9, as a potential treatment for autoimmune diseases in which TLRs are over-activated. Idera’s pipeline of clinical-stage TLR antagonists also includes IMO-8400, the company’s lead product candidate currently in development for genetically defined forms of B-cell lymphoma and rare autoimmune diseases.
In two presentations at the OTS meeting, Idera scientists summarized the results of several preclinical studies of IMO-9200. Collectively, the data showed that IMO-9200 dose-dependently inhibited the induction of multiple inflammatory cytokines, including IL-12, IP-10, IFN-α, IL-6, IL-1β and MCP-1, in cell-based assays, mice and non-human primates. In addition, data from a well-characterized preclinical model of lupus showed that IMO-9200 improved disease-associated parameters in MRL/lpr mice, with decreases in blood urea nitrogen levels, proteinuria, autoantibodies and kidney interstitial inflammation. Idera has evaluated IMO-9200 in additional autoimmune disease models, and plans to present data from these studies in the future.
“The findings announced today provide further support for our proprietary TLR antagonism technology by demonstrating the specific and potent inhibitory activity of IMO-9200 against TLRs that have been implicated in multiple autoimmune diseases,” said Sudhir Agrawal, Ph.D., Idera CEO. “While we continue to advance our lead TLR antagonist candidate IMO-8400 in ongoing and planned clinical trials in genetically defined forms of B-cell lymphoma and rare autoimmune diseases, we believe that the expansion of our clinical-stage pipeline with IMO-9200 may allow us to address an even broader range of autoimmune and inflammatory disorders in which TLRs have been shown to be over-activated.”
Idera plans to begin dosing of IMO-9200 in a Phase 1 clinical trial in healthy volunteers in the fourth quarter. In addition, the company plans to finalize a strategic assessment of potential indications for further clinical development of IMO-9200 by year end.
The two OST presentations, "IMO-9200, a Novel Clinical-stage TLR Antagonist for the Treatment of Autoimmune Diseases, Inhibits TLR-mediated Immune Responses and Shows Activity in Animal Models" and "IMO-9200, a Novel Clinical-stage TLR Antagonist for the Treatment of Autoimmune Diseases, Suppresses TLR-mediated Immune Responses in Non-human Primates following Systemic Administration,” are available on Idera’s website.
Toll-like receptors (TLRs) play a central role in the innate immune system and in regulating inflammation, and published data have implicated TLR dysfunction across a broad range of autoimmune diseases and genetically defined forms of B-cell lymphoma.
In autoimmune diseases, endogenous nucleic acids released from damaged or dying cells initiate signaling cascades through TLRs, inducing multiple cytokines. Subsequent inflammation causes further damage to the body’s own tissues and organs and the release of more self-nucleic acids. Thus, a pathological amplification cycle is established, promoting disease progression.
In B-cell lymphomas characterized by the MYD88 L265P genetic mutation, an oncoprotein is produced that over-activates TLR-initiated signaling, thereby activating transcription factors that promote the survival and proliferation of tumor cells.
Based on the company’s proprietary chemistry-based discovery platform, Idera designed and developed two synthetic oligonucleotide-based TLR antagonists, IMO-8400 and IMO-9200. These clinical-stage candidates have demonstrated activity in multiple preclinical models of autoimmune disease and cancer, including psoriasis, lupus, arthritis, and MYD88 L265P-positive B-cell lymphoma.
Idera Pharmaceuticals is a clinical-stage biopharmaceutical company developing a novel therapeutic approach for the treatment of genetically defined forms of B-cell lymphoma and rare autoimmune diseases. Idera’s proprietary technology involves creating novel nucleic acid therapeutics designed to inhibit over-activation of Toll-like receptors. In addition to its TLR programs, Idera is developing gene silencing oligonucleotides that it has created using its proprietary technology to inhibit the production of disease-associated proteins by targeting RNA.
Source: Idera Pharmaceuticals, Inc.

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