Idera Pharmaceuticals has initiated dosing in a randomized, double-blind, placebo-controlled phase II trial of IMO-8400 in patients with moderate to severe plaque psoriasis. IMO-8400, an antagonist of the Toll-like receptors (TLRs) 7, 8, and 9, is a lead clinical candidate in Idera’s autoimmune disease programme. In a phase I trial involving single escalating doses and multiple doses, IMO-8400 was well tolerated and inhibited TLRs 7, 8, and 9-mediated immune responses. Data from the phase I study will be presented at a scientific meeting in June 2013.

"This phase II trial of IMO-8400 will enable us to evaluate over a 12-week treatment period the continued trajectory of Psoriasis Area Severity Index (PASI) score improvement that we observed in the previous four-week study of our TLR 7 and 9 antagonist, IMO-3100,” said Robert Arbeit, MD, vice president of Clinical Development at Idera. “We anticipate top-line data from the phase II trial of IMO-8400 to be available by the end of 2013.”

“In our proof-of-concept study with IMO-3100 in patients with psoriasis, we observed PASI score improvement, which correlated with significant improvement in psoriasis disease-associated gene profile, including downregulation of the IL-17 pathway. We believe the inclusion of TLR8 activity with IMO-8400 would further enhance the clinical activity observed with IMO-3100 in patients with psoriasis,” said Sudhir Agrawal, D.Phil., chairman and chief executive officer of Idera. “We expect that data from the present phase II trial will help inform our decision on further development of IMO-8400 in patients with psoriasis. In addition, during the fourth quarter of 2013, we expect to be in a position to initiate phase II clinical trials in additional autoimmune disease indications, including lupus.”

The phase II trial is a randomized, double-blind, placebo-controlled trial of IMO-8400 monotherapy in patients with moderate to severe plaque psoriasis. In this trial, 32 patients with PASI scores of 12.5 or greater will be randomized 1:1:1:1 to receive weekly subcutaneous doses of IMO-8400 at 0.075, 0.15, or 0.3 mg/kg/week or placebo for 12 weeks. Safety and improvements in PASI score will be monitored throughout the trial. The trial is being conducted in the Netherlands.

Toll-like Receptors (TLRs) play a key role in immunity and inflammation. Using a chemistry-based approach, Idera has created compounds targeted to endosomal TLRs 3, 7, 8, and 9. In autoimmune diseases, immune complexes containing host DNA/RNA activate TLRs 7, 8, and 9, which induces multiple cytokines that further exacerbate the disease. Inhibition of these TLRs is a novel approach for the potential treatment of autoimmune diseases. IMO-8400 is an antagonist of TLRs 7, 8, and 9, and has shown therapeutic activity in preclinical models of psoriasis, lupus, and arthritis. In a phase I trial involving single escalating doses and multiple doses, IMO-8400 was well tolerated and inhibited TLRs 7, 8, and 9-mediated immune responses. A proof-of-concept phase II study of TLR antagonism in patients with psoriasis using Idera’s antagonist of TLRs 7 and 9, IMO-3100, showed PASI score improvements which correlated with significant improvement in psoriasis disease associated gene profile, including downregulation of the IL-17 pathway.

Idera Pharmaceuticals applies its proprietary Toll-like receptor (TLR) drug discovery platform to create immunomodulatory drug candidates and is conducting clinical development in autoimmune and inflammatory diseases.