Idera Pharmaceuticals Inc (IDRA)

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Clinical and Preclinical Programs

http://ir.iderapharma.com/phoenix.zhtml?c=208904&p=irol-newsArticle&ID=1457240&highlight=

IMO-2125, a TLR9 Agonist, in Chronic Hepatitis C Virus (HCV) Infection

* Phase 1 Clinical Trial of IMO-2125 Monotherapy in Null Responder Patients with Chronic HCV Infection

In April 2010, during the 45th Annual Meeting of the European Association for the Study of the Liver (EASL), the Company presented positive interim data from this trial through the dose level of 0.32-mg/kg/week for four weeks, comprising 33 null responder HCV patients treated with IMO-2125 and 8 null responder HCV patients who received placebo treatment. Based on the data presented at EASL, the clinical trial was extended to a fifth cohort at the dosage of 0.48 mg/kg/week for four weeks and recruitment is continuing at this dose level. We also are recruiting a cohort of eight null responder HCV patients to evaluate the safety and the effect on HCV viral load of twice-weekly IMO-2125 administration for four weeks. The clinical trial of IMO-2125 monotherapy in null responder HCV patients is being conducted at multiple sites in the U.S.

The Company expects data from the Phase 1 clinical trial of IMO-2125 monotherapy in null responder HCV patients to be available in the fourth quarter of 2010.

* Phase 1 Clinical Trial of IMO-2125 in Combination with Ribavirin in Treatment-naïve Patients with Chronic HCV Infection

In this clinical trial, treatment-naïve HCV patients receive IMO-2125 by subcutaneous injection once per week for four weeks at escalating dose levels of 0.08, 0.16, and 0.32 mg/kg in combination with daily oral administration of standard doses of ribavirin. The current plans for this trial are to evaluate IMO-2125 plus ribavirin in a total of 48 patients. In addition, a total of 12 patients are planned to receive pegylated recombinant alfa-2a interferon plus ribavirin as the control arm. The primary objective of the trial is to assess the safety and tolerability of IMO-2125 in combination with standard doses of ribavirin. In addition, this trial is designed to monitor the effect of treatment on HCV viral load and on activation of the immune system. The clinical trial is currently being conducted at sites in France and Russia.

The Company expects preliminary data from the Phase 1 clinical trial of IMO-2125 in combination with ribavirin in treatment-naïve HCV patients to be available in the fourth quarter of 2010.

* Plans for Phase 2 Clinical Evaluation of IMO-2125 in Patients with Chronic HCV Infection

The Company has begun preparations for a 12-week Phase 2 clinical trial of IMO-2125 administered in combination with ribavirin to patients with chronic HCV infection towards intended initiation by the end of the year.

IMO-3100, a Dual Antagonist of TLR7 and TLR9, in Autoimmune and Inflammatory Diseases

IMO-3100 has shown activity in various preclinical models of autoimmune and inflammatory diseases, including lupus, rheumatoid arthritis, psoriasis and hyperlipidemia. As a first step in the clinical development of IMO-3100, we are conducting Phase 1 clinical trials in healthy subjects to evaluate safety and mechanism of action prior to the initiation of clinical trials in patients with autoimmune disease.

* Phase 1 Single-Dose, Dose Escalation Clinical Trial of IMO-3100 in Healthy Subjects: Safety and Mechanism of Action

In January 2010, the Company initiated a single-dose, dose escalation, Phase 1 clinical trial of IMO-3100 in healthy subjects. In this trial, six healthy subjects in each of five dosage cohorts received single doses of IMO-3100 from 0.04 to 0.64 mg/kg. Six additional subjects each received a single dose of placebo. The primary objective was evaluation of safety and tolerability. Secondary objectives were to characterize the blood levels of IMO-3100 and to assess the pharmacodynamic mechanism of action through the response of peripheral blood mononuclear cells to agonists of TLR7 and TLR9. The trial was conducted at a single U.S. site.

In June 2010, the Company announced preliminary results from the Phase 1 single-dose, dose escalation clinical trial of IMO-3100. IMO-3100 was well tolerated at all dose levels. Peripheral blood mononuclear cells from subjects who received IMO-3100 showed suppression of immune responses mediated through TLR7 and TLR9. The immune responses monitored included induction of tumor necrosis factor-alpha (TNF-a), interleukin-1 beta (IL-1B), interleukin-6 (IL-6), interferon-alpha (IFN-a), and other pro-inflammatory cytokines. Peripheral blood mononuclear cells from placebo-treated subjects did not show any consistent suppression of immune responses mediated through TLR7 or TLR9.

The Company is planning to present detailed results of the Phase 1 single-dose, dose escalation clinical trial of IMO-3100 in healthy subjects at a scientific meeting in the fourth quarter of 2010.

* Phase 1 Multiple-Dose Clinical Trial of IMO-3100 in Healthy Subjects: Safety and Mechanism of Action

In July 2010, the Company initiated a four-week multiple-dose clinical trial of IMO-3100 in healthy subjects. The purpose of the multiple-dose clinical trial is to evaluate the safety, blood levels of IMO-3100, and pharmacodynamic mechanism of action of IMO-3100 with multiple-dose subcutaneous administration over four weeks. The trial is designed to include 16 subjects treated with IMO-3100 and eight subjects treated with placebo.

The Company expects preliminary data from the Phase 1 multiple-dose clinical trial of IMO-3100 in healthy subjects to be available in the fourth quarter of 2010.

* Plans for Phase 2 Clinical Evaluation of IMO-3100 in Autoimmune Disease

The Company expects that the safety and pharmacodynamic mechanism of action data from the Phase 1 clinical trials in healthy subjects will help move the clinical evaluation of IMO-3100 rapidly into selected autoimmune disease indications. The Company intends to identify an initial autoimmune disease indication for further clinical development of IMO-3100 and to initiate a Phase 2 clinical trial by the end of 2010.

EMD 1201081 (IMO-2055), a TLR9 Agonist, in Cancer Treatment (Collaboration with Merck KGaA)

In December 2007, the Company entered into an exclusive, worldwide license agreement with Merck KGaA to research, develop and commercialize products containing its TLR9 agonists for the treatment of cancer, excluding cancer vaccines. Merck KGaA currently is conducting the following clinical trials of EMD 1201081:

* Phase 2 Clinical Trial of EMD 1201081 in Combination with Erbitux(R) in Squamous Cell Carcinoma of the Head and Neck (SCCHN)
* Phase 1b Clinical Trial of EMD 1201081 in Combination with Tarceva(R) and Avastin(R) in Non-small Cell Lung Cancer (NSCLC)
* Phase 1b Clinical Trial of EMD 1201081 in Combination with Erbitux(R) and Chemotherapy in Colorectal Cancer (CRC)

IMO-2134, a TLR9 Agonist, for Respiratory Diseases

During our collaboration with Novartis, IMO-2134 was identified as a lead compound for development in asthma and allergy indications and Novartis initiated a Phase 1 clinical trial of IMO-2134, also known as QAX935. Upon the termination of the research collaboration and option agreement in February 2010, the Company regained the rights to IMO-2134. The Company is currently evaluating the next steps in developing IMO-2134 for respiratory diseases.

TLR7, 8 and 9 Agonists as Vaccine Adjuvants (Collaboration with Merck & Co., Inc.)

In December 2006, the Company and Merck & Co., Inc. (now Merck Sharp & Dohme Corp. and referred to herein as Merck) entered into an exclusive license and research collaboration agreement to research, develop and commercialize vaccine products containing the Company's TLR7, 8, and 9 agonists in the fields of oncology, infectious diseases and Alzheimer's disease. As part of the agreement, the two companies engaged in a research collaboration to generate novel agonists targeting TLR7 and TLR8, incorporating both Merck and Idera chemistry, for use in the licensed fields. In November 2009, Merck extended the research collaboration with the Company for a fourth year to December 2010. Under the terms of the agreement, Merck is funding the research and development activities under the collaboration.

Scientists from Merck and Idera have co-authored the following presentation and publication:

* "Novel TLR9 Agonists Combined with Alum for Use as Vaccine Adjuvants" at the Keystone Symposia Molecular and Cellular Biology conference "Innate Immunity: Mechanisms Linking with Adaptive Immunity" held June 7-12, 2010 in Dublin, Ireland.
* A paper entitled "A TLR9 agonist enhances therapeutic effects of telomerase genetic vaccine" in Vaccine, April 2010.

TLR7 and TLR8 Agonists

The Company has created synthetic stabilized immune modulatory RNA (SIMRA) compounds that mimic viral RNA and induce immune responses by functioning as agonists of TLR7 and TLR8. The Company is continuing to study selected dual TLR7 and TLR8 agonists in preclinical models of hematological cancers and has observed antitumor activity of a dual agonist of TLR7 and TLR8 as monotherapy and in combination with selected targeted drugs currently approved for cancer treatment. The Company intends to select a dual TLR7 and TLR8 agonist as a lead drug candidate by the end of the year.

The Company is planning to present preclinical data on its dual agonist of TLR7 and TLR8 in models of hematological cancers at a scientific meeting in the fourth quarter of 2010.

TLR Antisense

The Company has identified antisense compounds targeted to human TLRs 2, 3, 4, 5, 7, 8 and 9 and to the TLR-associated signaling protein MyD88. The Company is studying these compounds for potential applications in autoimmune and inflammatory diseases.

Scientific Highlights

Data Presentations

* An oral presentation, entitled "A Phase 1, Multi-Center, Randomized, Placebo-controlled, Dose-escalation Study of IMO-2125, a TLR9 Agonist, in Hepatitis C Non-responders", was made by John McHutchison, M.D., Associate Director, Duke Clinical Research Institute and Director, Gastroenterology and Hepatology Research, Duke University Medical Center, and Principal Investigator for this trial, at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL) held April 14-18, 2010, in Vienna, Austria.
* A presentation, entitled "IMO-2125, an agonist of TLR9 that induces endogenous IFN-alpha, upregulates broader range of gene expression profiles compared to exogenously added IFN-alpha in human PBMCs" was made by Idera scientists at the 45th Annual Meeting of EASL.
* A presentation, entitled "A novel antagonist of TLR7 and TLR9 exerts anti- atherogenic effects in ApoE-/- mouse model of atherosclerosis" was made by Idera scientists at the American Heart Association conference "Arteriosclerosis, Thrombosis and Vascular Biology 2010 Scientific Sessions" held April 8-10, 2010, in San Francisco, CA.
* A presentation, entitled "Synthetic Agonists and Antagonists of
Toll-like Receptor 7, 8 and 9" was made by Idera scientists at the Keystone Symposia Molecular and Cellular Biology conference "Innate Immunity: Mechanisms Linking with Adaptive Immunity" held June 7-12, 2010 in Dublin, Ireland.

Publications

* A paper entitled "Antitumor Activity and Immune Response Induction of a Dual Agonist of Toll-like Receptors 7 and 8" appeared in Molecular Cancer Therapeutics, June 2010.
* A paper entitled "Impact of nature and length of linker incorporated in agonists on Toll-like receptor 9-mediated immune responses" appeared in Journal of Medicinal Chemistry, May 2010.

Intellectual Property

The Company's intellectual property portfolio contains over 500 patents and patent applications worldwide. In June 2010, the Company was again recognized by the Patent Board(TM) as one of the top 35 companies in the biotechnology field based on its technology and intellectual property advances. The Patent Board is an independent group that tracks and analyzes intellectual property and technology assets across 17 industries globally and publishes its results in the Wall Street Journal.

Immune Modulatory Oligonucleotide (IMO(R)) Technology

This portfolio holds over 290 patents and patent applications worldwide covering the Company's IMO technologies and includes claims covering novel agonists of TLRs 7, 8, and 9, and antagonists of TLR7 and TLR9. These patents and patent applications include claims covering IMO-2055, IMO-2125, IMO-2134, and IMO-3100. The Company was granted the following U.S. patents during the second quarter:

* US 7,700,570, entitled "Oligonucleotide Mediated Specific Cytokine Induction and Prophylaxis and Treatment of Viral Infection in a Mammal."
* US 7,709,617, entitled "Synergistic Stimulation of the Immune System Using Immunostimulatory Oligonucleotides and/or Immunomer Compounds in Conjunction with Cytokines and/or Chemotherapeutic Agents or Radiation Therapy."
* US 7,713,535, entitled "Modulation of Immunostimulatory Properties by Small Oligonucleotide-Based Compounds."

In addition to the recently issued U.S. patents, the Company was granted: AU 20044206820, corresponding to U.S. Patent No. 7,632,822, entitled "Modulation of Immunostimulatory Properties of Oligonucleotide-Based Compounds By Using Modified Immunostimulatory Dinucleotides;" AU 2005222909, corresponding to U.S. Patent Application No. 11/078,654, entitled "Enhanced Activity of HIV Vaccine Using a Second Generation Immunomodulatory Oligonucleotide;" AU 20044304770, corresponding to U.S. Patent No. 7,713,535, entitled "Modulation of Immunostimulatory Properties by Small Oligonucleotide-Based Compounds;" and IN 240192, corresponding to U.S. Patent Application No. 10/865,245, entitled "Stabilized Immunomodulatory Oligonucleotides."

Antisense Technology

The Company's antisense technology portfolio includes 210 patents and patent applications worldwide owned or licensed by Idera covering novel antisense compounds and methods of their use. These patents and patent applications include claims covering second-generation antisense chemistry, oral delivery of second-generation antisense compounds, and certain genes, antisense sequences, and therapeutic targets (including various TLRs and signaling molecules).

About Idera Pharmaceuticals, Inc.

Idera Pharmaceuticals develops drug candidates to treat infectious diseases, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. Our proprietary drug candidates are designed to modulate specific Toll-like Receptors, which are a family of immune system receptors that direct immune system responses. Our pioneering DNA and RNA chemistry expertise enables us to create drug candidates for internal development and generates opportunities for multiple collaborative alliances. For more information, visit http://www.iderapharma.com.