Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) today announced the presentation of data from its multiple-dose Phase 1 clinical trial of IMO-3100 in healthy subjects. The trial was designed to evaluate the safety and mechanism of action of IMO-3100, a Toll-like Receptor (TLR) 7 and TLR9 dual antagonist that is Idera's lead drug candidate in development to treat autoimmune and inflammatory diseases. In the trial, IMO-3100 was well tolerated over the four weeks of treatment. In addition, target engagement of TLR7 and TLR9 was observed, confirming the intended mechanism of action of IMO-3100. The presentation (Abstract #333) entitled "IMO-3100, a novel toll-like receptor antagonist for autoimmune and inflammatory diseases: safety and pharmacodynamics in a multiple-dose Phase 1 clinical trial" is being made today at the Keystone Symposia meeting "Immunoregulatory Networks" being held in Breckenridge, Colorado from April 1-6, 2011.
"We have completed two Phase 1 clinical trials of IMO-3100 involving a total of 60 healthy subjects. The results of this multiple-dose trial are consistent with those from our earlier single-dose study, with demonstration of a good safety profile and evidence of the intended mechanism of action," said Robert Arbeit, M.D., Vice President of Clinical Development of Idera Pharmaceuticals. "The Phase 1 data support our plans to evaluate IMO-3100 in a Phase 2 clinical trial in a selected autoimmune disease indication."
"One of our objectives in the Phase 1 clinical development program was to establish that IMO-3100 engages TLR7 and TLR9, its intended mechanism of action. We are very pleased that in both trials IMO-3100 inhibited TLR7- and TLR9-mediated immune responses, and that in this study suppression of key cytokines such as IL-6 and IFN-α was maintained throughout the four-week treatment period," said Tim Sullivan, Ph.D., Vice President of Development Programs and Alliance Management at Idera. "We are currently conducting nonclinical studies of IMO-3100 which we expect to complete during the first half of 2011 to enable submission of a Phase 2 clinical trial protocol during the third quarter of this year."
"Our scientific rationale for the use of IMO-3100 to treat autoimmune and inflammatory diseases is to suppress immune responses that are mediated through TLR7 or TLR9 and thereby block the induction of multiple cytokines, in contrast to blocking the activity of individual cytokines as do many current treatments of autoimmune diseases," commented Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer of Idera. "IMO-3100, as a dual antagonist of TLR7 and TLR9, has been shown in these Phase 1 clinical trials to block the induction of multiple cytokines and may provide a novel approach for the treatment of autoimmune and inflammatory diseases."
Phase 1 Multiple-Dose Clinical Trial of IMO-3100 in Healthy Subjects
In this trial, 24 healthy subjects were recruited and randomized into three treatment groups each of which received two subcutaneous injections per week for four weeks. The three groups, each comprising eight subjects, were (a) IMO-3100 at 0.64 mg/kg once per week and placebo once per week, (b) IMO-3100 at 0.32 mg/kg twice per week; and (c) placebo twice per week. The primary objective of this study was the evaluation of safety and tolerability. Secondary objectives were to assess IMO-3100 pharmacokinetics and pharmacodynamic mechanism of action. Study visits were performed twice weekly during the four-week treatment period, at Day 29 (End-of-Treatment), at Day 36 (interim follow-up) and at Day 59 (End-of-Study). For pharmacokinetic evaluation, plasma levels of IMO-3100 were measured through 24 hours after the first dose and after the seventh of the twice-weekly doses. For pharmacodynamic evaluation, blood samples were collected pre-dose on Days 1, 4, 8, 15, 22, and 25, and at the visits on Days 29 and 36. To assess the effect of IMO-3100 treatment, peripheral blood mononuclear cells (PBMCs) were isolated from these samples, stimulated with TLR7- and TLR9-agonists and the resulting induced cytokines assayed.
- Safety. IMO-3100 was well tolerated in both treatment regimens. There were no serious adverse events and no treatment discontinuations. Mild injection site reactions were the most common adverse events.
- Pharmacokinetics. The pharmacokinetics of IMO-3100 were found to be dose-proportional and showed no evidence of accumulation after repeated dosing.
- Pharmacodynamics mechanism of action. Suppression of multiple cytokines including IFN- α, IL-6, MIP-1β, and IL-1Ra, mediated through TLR7 and TLR9 was observed in both IMO-3100 groups, when post-dose responses were compared to pre-dose responses in each subject.
Suppression of multiple cytokines was maintained in IMO-3100-treated subjects throughout the four-week treatment period, based on responses measured from the third day after the first dose through four or more days after the last dose.
No consistent suppression of any cytokines was observed in placebo-treated subjects.
These results provide evidence that IMO-3100 suppressed TLR7- and TLR9-mediated immune responses in the trial.
Idera Pharmaceuticals, Inc.