Idera to present data from Phase 2 trial of IMO-3100 in patients with psoriasis at IID 2013

Idera Pharmaceuticals (NASDAQ: IDRA) today announced presentation of data from its randomized, double-blind, placebo-controlled Phase 2 trial that showed improvements from baseline of up to 90% in Psoriasis Area Severity Index (PASI) scores in patients with moderate to severe plaque psoriasis following four weeks of treatment with the Toll-like Receptor (TLR) antagonist IMO-3100. Additionally, analysis of biopsy samples collected from patients during the Phase 2 trial indicated that PASI score improvements were associated with significant improvement of psoriasis disease-associated gene profile, including downregulation of activated genes in the IL-17 pathway, which is central to the pathogenesis of psoriasis. Treatment with IMO-3100 was well tolerated, with no treatment-related discontinuations. The presentation entitled "IMO-3100, an antagonist of Toll-like receptor (TLR) 7 and 9, demonstrates clinical activity in psoriasis patients with 4 weeks of treatment in a Phase 2a trial" was made by Alexa Kimball M.D., M.P.H., Vice Chair, Department of Dermatology at Massachusetts General Hospital, Boston, and an investigator in the trial, at the International Investigative Dermatology meeting in Edinburgh, Scotland May 8^th through 13^th, 2013.

“TLR antagonism provides a novel mechanism of action for the potential treatment of patients with moderate to severe plaque psoriasis. Clinical activity demonstrated in this four-week proof-of-concept trial encourages further development of TLR antagonists over longer treatment periods”

"TLR antagonism provides a novel mechanism of action for the potential treatment of patients with moderate to severe plaque psoriasis. Clinical activity demonstrated in this four-week proof-of-concept trial encourages further development of TLR antagonists over longer treatment periods," said Dr. Kimball.

"We are very pleased that the clinical improvements observed in psoriasis patients treated with IMO-3100 for four weeks correlated with the proposed mechanism of action for TLR antagonism in autoimmune diseases," said Robert Arbeit, MD, VP of Clinical Development at Idera. "Our next step will be a 12-week Phase 2 clinical trial in patients with psoriasis, which we expect will enable us to evaluate the continued trajectory of PASI score improvement over the 12-week treatment period and maximize the clinical benefit of the treatment. We plan to conduct this 12-week Phase 2 trial with IMO-8400, an antagonist of TLRs 7, 8, and 9, and to initiate the trial during the second quarter of 2013."

Data from the Phase 2 Trial

The objectives of the Phase 2 trial of IMO-3100 were to evaluate the safety and tolerability and to evaluate the clinical activity of TLR antagonism in patients with psoriasis after four weeks of treatment. Top-line data from this trial was announced in December 2012. Data presented from this trial include:

Safety:

• Treatment with IMO-3100 was well tolerated at both dose levels studied
• There were no treatment-related discontinuations or changes in laboratory parameters

Clinical Activity:

• On day 57, 48% of patients treated with either dose of IMO-3100 (12 of 25) demonstrated statistically significant improvements of 35% to 90% from baseline PASI scores compared with 0 of 12 in the placebo cohort (p<0.005)
• Rapid improvement in PASI scores was observed in IMO-3100 treated patients compared to placebo-treated patients; Improvement in PASI was sustained through five weeks after the last dose
• The pre-specified clinical endpoint of reduction in PASI score at day 29 was achieved with statistical significance in the 0.16 mg/kg cohort (p<0.02 compared to placebo) but not in the 0.32 mg/kg cohort
• PASI 50 was achieved in 7 of 25 patients treated with IMO-3100 (3 of 12 at 0.16 mg/kg and 4 of 13 at 0.32 mg/kg), compared to 0 of 12 placebo treated patients (p<0.05); PASI 75 was achieved in 1 patient in each IMO-3100 cohort during the trial period
• The pre-specified clinical endpoint of improvement in induration, a measure of plaque thickness, at day 29 was achieved with statistical significance in the 0.16 mg/kg cohort (p<0.02) compared to placebo-treated patients

Mechanism of Action Based on Analysis of Skin Biopsies:

• Median change in epidermal thickness (the histologically defined primary endpoint of the trial) was -6.4% in IMO-3100 treated patients compared to +7.7% in placebo treated patients, representing a favorable, but not statistically significant, trend. A known limitation of skin biopsies after four weeks of treatment is that psoriatic plaques do not resolve in a uniform fashion, and therefore, biopsies may not provide a representative sampling of lesions (ref: Ann Rheum Dis 2005;64:65-68)
• Representative patients treated with IMO-3100 showed K16 staining (marker of keratinocyte proliferation) reverting toward normal and decreasing infiltrates of CD3+ lymphocytes and CD11c+ cells
• DNA microarray analysis of biopsies from the IMO-3100 treated patients compared to placebo treated patients>-6) in psoriasis disease-associated genes (Tian et al, PLoS ONE, Sep 2012) and of genes unique to the IL-17 pathway, which is central to the pathogenesis of psoriasis. Detailed data will be presented at a future scientific meeting.