In the poster presentation entitled, “Translational evidence of reactivated innate and adaptive immunity with intratumoral IMO-2125 in combination with systemic checkpoint inhibitors from a Phase 1/2 study in patients with anti-PD-1 refractory metastatic melanoma,”
The key findings in Dr. Haymaker’s presentation were that intratumoral IMO-2125 monotherapy in the injected lesions results in activation and maturation of dendritic cells, and the induction of type-1 interferon gene signature by 24 hours after first dose. After 8 weeks of therapy with intratumoral IMO-2125 and ipilimumab, increased immune infiltration has been observed in distant lesions of responding patients, suggesting an abscopal effect. Dr. Haymaker concludes that activation of intratumoral dendritic cells and induction of the associated downstream immune cascade enhances T-cell priming. In combination with checkpoint blockade, this mechanism may be an important key in treating patients who have been refractory to prior immune oncology approaches.
“We are excited to be examining the significant amounts of data emerging from this trial, which goes far beyond merely conducting clinical outcome analysis and to our knowledge has not been done to this depth before,” stated
A second poster presentation entitled, “Local treatment with novel TLR9 agonist IMO-2125 demonstrates anti-tumor activity in preclinical models of pancreatic cancer,” presented by
Furthermore, a local treatment of IMO-2125 was evaluated by administering intraperitoneally in a peritoneal metastasis Panc02 model. Mice treated with intraperitoneal IMO-2125 showed increased survival compared to mice treated with placebo, control oligo compound or subcutaneous IMO-2125. Histological analysis showed significant reduction of tumor growth in the peritoneal cavity. This illustrates that while local treatment is necessary, routes of administration other than i.t. may also be effective to generate an antitumor response in pancreatic cancer. Overall, we believe these data demonstrate that treatment with IMO-2125 modulates the tumor microenvironment and increases infiltration by TILs and that these changes are associated with antitumor activity in pancreatic cancer models, and indicate that IMO-2125 may potentiate checkpoint inhibitor therapy for the treatment of pancreatic cancer.
A copy of the poster presentations are currently available on Idera’s corporate website at http://www.iderapharma.com/our-approach/key-publications/.
Toll-like receptors (TLRs) 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 (PD-1) 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 thereby potentiate anti-cancer activity of checkpoint inhibitors in the injected tumor as well as systemically.
Idera’s TLR9 agonist, IMO-2125 has been created using the company's proprietary chemistry-based discovery platform. IMO-2125 has been shown in various scientific presentations and publications 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 and clinical research evaluating the potential of IMO-2125 to enhance the anti-tumor activity of other checkpoint inhibitors in cancer immunotherapy with data being presented at several medical conferences during the past two years. The posters from these presentations can be found at http://www.iderapharma.com/our-approach/key-publications.
About Metastatic Melanoma
Melanoma is a type of skin cancer that begins in a type of skin cell called melanocytes. As is the case in many forms of cancer, melanoma becomes more difficult to treat once the disease has spread beyond the skin to other parts of the body such as by through the lymphatic system (metastatic disease). Melanoma accounts for only one percent of skin cancer cases, but causes a large majority of skin cancer deaths.
About Idera Pharmaceuticals
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