Idera has two lead candidates in development for the treatment of autoimmune diseases:
- IMO-3100, an antagonist of TLRs 7 and 9, is in clinical development for psoriasis.
- IMO-8400, an antagonist of TLRs 7, 8, and 9, is in development for lupus.
A characteristic of autoimmune and inflammatory diseases such as psoriasis and lupus is the production of aberrant complexes that contain host RNA or DNA and lead to immune to immune system responses. These abnormal complexes activate TLRs 7, 8, and 9 and induce multiple cytokines and signaling cascades that can further exacerbate disease.
Our scientific rationale is to block interaction of the aberrant complexes in autoimmune diseases with TLRs 7, 8, and 9, thereby inhibiting the induction of cytokines and signaling cascades rather than block the activity of any one specific cytokine. In preclinical models of autoimmune diseases, including psoriasis, lupus, and rheumatoid arthritis, our TLR antagonists have been shown to inhibit Th1, Th17 and inflammasome pathways. (Graphic Representation) The TLR antagonists suppressed disease-associated cytokines such as TNF-α, IL-12, IL-6, and IL-17. We believe the key advantage of our approach is the ability to block disease-associated induction of immune responses and thereby inhibit the production of multiple cytokines without affecting the activity of normal levels of cytokines.
About the Phase 2 Trial of IMO-3100 in Patients with Moderate to Severe Plaque Psoriasis
The Phase 2 trial was a randomized, double-blind, placebo-controlled trial of IMO-3100 in patients with moderate-to-severe plaque psoriasis. In the trial, 44 patients were randomized to receive IMO-3100 monotherapy at 0.16 or 0.32 mg/kg or placebo by subcutaneous injection once weekly for four weeks with four weeks of follow-up. Assessments of safety were performed throughout the treatment and follow-up periods. Multiple parameters were monitored to assess the clinical activity of IMO-3100, including Psoriasis Area Severity Index (PASI), mean focal psoriasis severity and Physician Global Assessment (PGA) scores. In addition to the clinical assessments, biopsies of psoriasis plaques were evaluated for treatment-related changes in epidermal thickness and immune cell infiltrates consistent with the intended mechanism of action. Patients were enrolled at eleven sites in the United States.
Idera previously has completed Phase 1 clinical trials of IMO-3100 in healthy subjects. In these studies, IMO-3100 was well-tolerated at the doses studied and showed target engagement of TLR7 and TLR9. (Presentation) (Presentation)
About the Clinical Development of IMO-8400
In the fourth quarter of 2012, Idera initiated a Phase 1 clinical trial in the United States to assess the safety and the pharmacodynamic activity of IMO-8400 in healthy subjects. A total of 42 subjects are scheduled to receive single or multiple ascending doses of IMO-8400 in this trial. The single dose portion of this trial involved three escalating dose levels of 0.1, 0.3, and 0.6 mg/kg of IMO-8400. Six subjects received IMO-8400 by subcutaneous injection at each dose level of 0.1, 0.3, and 0.6 mg/kg, and an additional six subjects received placebo. IMO-8400 treatment was well tolerated, and the intended target engagement of TLR7, TLR8, and TLR9 was observed in IMO-8400-treated subjects compared to the placebo-treated subjects. We have commenced the multiple dose portion of this trial. The multiple-dose portion of this trial involves two dose levels of IMO-8400, 0.3 and 0.6 mg/kg, with six subjects at each dose level receiving four weekly doses of IMO-8400 and a total of six subjects receiving placebo. We expect data from the multiple dose portion of this trial to be available in the second quarter of 2013.
In June 2013, the company announced the initiation of dosing in a randomized, double-blind, placebo-controlled Phase 2 trial of IMO-8400 monotherapy in patients with moderate to severe plaque psoriasis. (Press Release). 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.
Preclinical data from studies of IMO-8400 in models of lupus (Presentation) and other diseases (Presentation) (Presentation) have been presented at various scientific conferences including the American Association of Immunologists (AAI) 2012 meeting, and pharmacodynamic activity of IMO-8400 in non-human primates has been presented at the Federation of Clinical Immunology Societies (FoCIS) 2012 meeting (Presentation).