– First presentations of intratumoral IMO-2125 pre-clinical activity show induction of systemic antitumor immune responses resulting in tumor growth inhibition and changes in checkpoint gene expression –
 – First clinical trial of IMO-2125 and ipilimumab, a commercially available anti-CTLA4 checkpoint inhibitor, planned for initiation in 4Q 2015 –

CAMBRIDGE, MA and EXTON, PA, USA I September 16, 2015 I Idera Pharmaceuticals, Inc. (IDRA), a clinical-stage biopharmaceutical company developing Toll-like receptor (TLR) and RNA therapeutics for patients with cancer and rare diseases, today announced new preclinical data that showed cancer immunotherapy with intratumoral injections of IMO-2125 alone and in combination with ipilimumab demonstrated potent and systemic anti-tumor activity in preclinical cancer models. IMO-2125 is a synthetic oligonucleotide-based agonist of Toll-like receptor 9 discovered and developed by Idera. Ipilimumab is a checkpoint inhibitor targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Additionally, Idera presented preclinical data which demonstrated that IMO-2125 induces a systemic antitumor immune response with the potential to sensitize the tumor microenvironment for combination with various checkpoint inhibitors. These data are being presented at the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference in New York City, beginning today.

“The body of preclinical data that we have assembled further illustrates the potential of intratumoral IMO-2125 to play an important role in the emerging field of cancer immunotherapy,” stated Sudhir Agrawal, D.Phil., President of Research at Idera Pharmaceuticals. “We are looking forward to advancing this approach into clinical development with our first study and exploring additional clinical studies with intratumoral IMO-2125 in other tumor types and with other checkpoint inhibitor combination regimens.”

In the presentation, entitled “Intratumoral administration of IMO-2125, a novel TLR9 agonist, modulates the tumor microenvironment and exerts systemic antitumor activity alone and in combination with an anti-CTLA4 monoclonal antibody (mAb),” Idera scientists presented data suggesting that intratumoral IMO-2125 monotherapy led to dose-dependent decreases in treated and distant tumor volume, an increase in infiltrating CD8+ T cells and specific cytotoxic T cell responses against tumor antigens. Combination of intratumoral IMO-2125 and an anti-CTLA4 mAb showed improved inhibition of tumor growth, regression of systemic lung metastases and infiltration of TILs versus monotherapy with either agent. Collectively, these data demonstrate the potent antitumor activity of IMO-2125, a novel immunostimulatory TLR9 agonist, alone and in combination with a checkpoint inhibitor.

Idera expects to initiate the first clinical study of intratumoral IMO-2125 in combination with ipilimumab in patients with metastatic melanoma in the fourth quarter of this year as part of the previously announced clinical research alliance with MD Anderson Cancer Center.

In the presentation, entitled “Modulation of checkpoint expression in tumor microenvironment by intratumoral administration of a novel TLR9 agonist: Rationale for combination therapy,” Idera scientists presented data suggesting that intratumoral IMO-2125 treatment led to antitumor activity in preclinical tumor models of lymphoma, colon carcinoma and melanoma. Specifically, intratumoral IMO-2125 treatment resulted in changes in the tumor microenvironment in both treated and distant tumors, as demonstrated by modulation of immune checkpoint gene expression. These data showed that intratumoral IMO-2125 has the potential to sensitize the tumor microenvironment for combination with various checkpoint inhibitors.

These presentations are both currently available on Idera’s website at http://www.iderapharma.com/our-science/key-presentations-and-publications.

Additionally, Idera announced that pre-clinical data relating to the combination of intratumoral IMO-2125 and an anti-PD-1 mAb in a murine colon carcinoma model will be presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston from November 5-9th.

About Toll-like Receptors and Idera’s Immuno-Oncology Research Program

Toll-like receptors (TLRs) are believed to play a central role in the innate immune system, the body’s first line of defense against invading pathogens, as well as damaged or dysfunctional cells including cancer cells. The innate immune system is also involved in activating the adaptive immune system, which marshals highly specific immune responses to target pathogens or tissue. Cancer cells may exploit regulatory checkpoint pathways to avoid being recognized by the immune system, thereby shielding the tumor from immune attack. Checkpoint inhibitors such as agents targeting CTLA4 or programmed cell death protein 1 (PD1) are designed to enable the immune system to recognize tumor cells. In this setting, intratumoral TLR9 agonist administration may increase the tumor-infiltrating lymphocytes (TILs); and potentiate anti-cancer activity of checkpoint inhibitors in the injected tumor as well as systemically.

Idera’s TLR9 agonists, IMO-2125 and IMO-2055, have been created using the company’s proprietary chemistry-based discovery platform. IMO-2125 has been shown to activate dendritic cells and induce interferon. Idera selected IMO-2125 to advance into clinical development in combination with checkpoint inhibitors based on this immunological profile. In previously completed clinical trials, subcutaneous administration of IMO-2125 was generally well tolerated in about 80 patients with hepatitis C. Idera has conducted further preclinical research evaluating the potential of IMO-2125 to enhance the anti-tumor activity of other checkpoint inhibitors in cancer immunotherapy with data from these studies to be presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in November in Boston.

About Idera Pharmaceuticals

Idera Pharmaceuticals is a clinical-stage patient focused biopharmaceutical company developing novel therapeutic approaches for the treatment of cancer and rare diseases. Idera’s proprietary technology involves creating novel nucleic acid therapeutics. Idera’s immunotherapy approach is based on the modulation of Toll-like receptors (TLRs). In addition to its TLR modulation programs, Idera is developing third generation antisense technology that it has created to inhibit the production of disease-associated proteins by targeting RNA. To learn more about Idera, visit www.iderapharma.com.

SOURCE: Idera Pharmaceuticals