Replies to post #1737 on Idera Pharmaceuticals Inc (IDRA)

[Citrati]

Application of TLR Agonists in Immuno-Oncology
We are conducting preclinical studies to characterize potential combination regiments with various checkpoint inhibitors. We intend to initiate clinical development of either IMO-2055 or IMO-2125 in combination with these checkpoint inhibitors by submitting an investigational new drug application, or IND, for, and initiating, the first of two planned Phase 1/2 clinical trials in the second half of 2015.
IMO-8400 Development Program in Rare Diseases
We are planning to initiate clinical development of IMO-8400 for the treatment of rare diseases by the end of 2015. We have selected dermatomyositis and Duchenne muscular dystrophy, or DMD, as the first non-cancer rare diseases for which we plan to develop IMO-8400. We selected these indications for development based on the reported role of TLRs in the pathogenesis of the disease states, clinical feasibility including ease of patient identification, availability of endpoints for regulatory approval and commercial potential. We anticipate commencing clinical development in these two indications by initiating a Phase 2 clinical trial in dermatomyositis by the end of 2015 and a Phase 1/2 clinical trial in DMD in early 2016.
We believe that we demonstrated proof of concept for our approach of using TLRs to inhibit the over-activation of specific TLRs for the treatment of psoriasis in a randomized, double-blind, placebo-controlled Phase 2 clinical trial of IMO-8400 that we conducted in patients with moderate to severe plaque psoriasis, a well-characterized autoimmune disease. In this trial, we evaluated IMO-8400 at four subcutaneous dose levels of 0.075, 0.15, 0.3, and 0.6 mg/kg, versus placebo, administered once weekly for 12 weeks in 46 patients. The trial met its primary objective as IMO-8400 was well tolerated at all dose levels with no treatment-related discontinuations, treatment-related serious adverse events or dose reductions. The trial also met its secondary objective of demonstrating clinical activity in psoriasis patients, as assessed by the Psoriasis Area Severity Index. In March 2015, we presented the complete data from the Phase 2 trial of IMO-8400 in patients with moderate to severe plaque psoriasis at the annual meeting of the American Academy of Dermatology. With our focus on rare diseases, we do not currently plan to conduct further clinical development of IMO-8400 for the treatment of psoriasis.
IMO-8400 Development Program for Dermatomyositis. We are finalizing our clinical trial plan for a Phase 2 clinical trial of IMO-8400 in dermatomyositis and anticipate initiating this trial by the end of 2015. If this clinical trial is successful, we may evaluate the potential of IMO-8400 to treat additional forms of myositis.
IMO-8400 Development Program for Duchenne Muscular Dystrophy. We are conducting additional preclinical studies of TLR antagonist drug candidates in DMD models and are working in collaboration with Parent Project Muscular Dystrophy, a leading U.S. patient advocacy organization, on the design of a clinical development program for IMO-8400 in DMD. We anticipate initiating a Phase 1/2 clinical trial of IMO-8400 in DMD in early 2016.
Program in Autoimmune Diseases
IMO-9200 for Autoimmune Disease. We have developed a second novel synthetic oligonucleotide antagonist of TLR7, TLR8, and TLR9, IMO-9200, as a drug candidate in clinical development for potential use in selected autoimmune disease indications. In October 2014, we initiated subcutaneous dosing in a Phase 1 clinical trial of IMO-9200 in healthy subjects. We have also initiated additional preclinical studies of IMO-9200 for a selected autoimmune disease.
Gene Silencing Oligonucleotide Technology to Target RNA
We are currently undertaking an analysis of oncology and rare disease indications for development of drug candidates generated from our GSO technology. Our key considerations in identifying disease indications in our GSO program include: strong evidence that the disease is caused by a specific protein; clear criteria to identify a target patient population; biomarkers for early assessment of clinical proof of concept; a targeted therapeutic mechanism for action; and unmet medical need to allow for a rapid development path to approval. We are planning to conduct disease model studies and begin IND-enabling development programs in each of the first two disease indications selected for further development in our GSO program in the second half of 2015.

[Citrati]

Idera Pharmaceuticals Reports First Quarter 2015 Financial Results and Provides Corporate Update
7:30 AM ET, 05/11/2015 - GlobeNewswire
CAMBRIDGE, Mass. and EXTON, Pa., May 11, 2015 (GLOBE NEWSWIRE) -- Idera Pharmaceuticals, Inc. (Nasdaq:IDRA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for oncology and rare diseases, today reported its financial and operational results for the first quarter ended March 31, 2015.

"During the first quarter of this year, we continued to build momentum as we executed on our numerous clinical development programs focused on oncology and rare diseases," stated Vincent J. Milano, Chief Executive Officer of Idera. "The focus and efforts of our team are leading to important milestones for our company over the next six to twelve months. We recently completed enrollment into the dose escalation portion of our ongoing clinical trial of IMO-8400 in Waldenström's macroglobulinemia (WM) and we continue to anticipate releasing efficacy and safety data from this trial in the fourth quarter of this year."

"We also are pleased to report that we recently enrolled our first patient harboring the MYD88 L265P oncogenic mutation into our Phase 1/2 clinical trial for diffuse large B-cell lymphoma (DLBCL)," continued Milano. "We are closing in on finalizing clinical arrangements for our intratumoral TLR9 agonist development program and look forward to providing details of the first trial which we plan to initiate in the second half of this year. Our rare disease development programs are on track as we plan to initiate clinical studies in dermatomyositis (DM) and Duchenne muscular dystrophy (DMD) in late 2015 and early 2016, respectively. Finally, our team is continuing the momentum with our gene silencing oligonucleotides (GSO) technology platform as we plan to announce our first disease indications in the second half of this year."

Program Updates

Oncology Programs

Genetically Defined Forms of B-cell Lymphoma

Our program in genetically defined forms of B-cell lymphoma is based on independent research and our pre-clinical studies offering evidence that, in certain B-cell lymphomas, the presence of the MYD88 L265P oncogenic mutation led to over-activation of TLR7 and TLR9 signaling and that blocking these TLRs promoted tumor cell death.

We have enrolled the targeted number of patients at each of the three dose levels to fulfill the requirements for dose escalation, pending successful completion of treatments through the next scheduled data review by the independent safety data monitoring committee, of our Phase 1/2 clinical trial of IMO-8400 in patients with Waldenström's macroglobulinemia, a form of non-Hodgkin lymphoma.

The trial is designed to evaluate IMO-8400's safety, tolerability and potential clinical activity in patients who have a history of relapse or failure to respond to one or more prior therapies. We anticipate efficacy and safety data from this trial will be available in the fourth quarter of 2015.

In April 2015, we announced that the U.S. Food and Drug Administration (FDA) had granted us orphan drug designation for IMO-8400 for the treatment of DLBCL. We continue to activate clinical sites and are now enrolling patients with relapsed or refractory DLBCL, harboring the MYD88 L265P oncogenic mutation in a Phase 1/2 clinical trial of IMO-8400 in DLBCL. We anticipate that efficacy and safety data from this trial will be available in 2016.

Immuno-Oncology Program

We are currently finalizing our first clinical arrangement for our planned clinical trials to determine the safety and efficacy of intratumorally delivered TLR9 agonist in combination with check-point inhibitors. The company intends to initiate the first of multiple clinical trials in the second half of 2015 with anticipated data availability in 2016.

Rare Disease Programs

We are planning to initiate clinical development of IMO-8400 for the treatment of rare diseases. We have selected dermatomyositis and DMD as the first rare diseases for which we plan to develop IMO-8400. We selected these indications for development based on the reported increase in TLR expression in these disease states, expression of cytokines indicative of key TLR-mediated pathways, the identification of prospective biomarkers for evaluation in early clinical trials and with respect to dermatomyositis, the presence of auto-antibodies that can induce TLR-mediated immune responses. We anticipate commencing clinical development in these two indications by initiating a Phase 2 clinical trial in dermatomyositis by the end of 2015 and a Phase 1/2 clinical trial in DMD in early 2016.

Gene Silencing Oligonucleotides

We are currently undertaking an analysis of priority oncology and rare disease indications for development of drug candidates from our GSO technology. Our key considerations in identifying disease indications in our GSO program include: strong evidence that the disease is caused by a specific protein; clear criteria to identify a target patient population; biomarkers for early assessment of clinical proof-of-concept; a targeted therapeutic mechanism for action; and unmet medical need to allow for a rapid development path to approval. We are planning to conduct disease model studies and begin IND-enabling development programs in each of the first two disease indications selected for further development in our GSO program in the second half of 2015.