Posted Date: 4/17/2017

Idera Pharmaceuticals Advances Investigational Treatment

Idera Pharmaceuticals, Inc. recently announced successful completion of the Phase I portion of the ongoing Phase I/II clinical trial of intratumoral IMO-2125. Intratumoral IMO-2125 is an agonist of TLR9, in combination with ipilimumab for the treatment of anti-PD-1 refractory metastatic melanoma. Enrollment has begun for the Phase II portion of the trial with the 8-mg dose of intratumoral IMO-2125. The Phase I dose escalation of IMO-2125 in combination with pembrolizumab is ongoing.

“We are very pleased with the progress to date in the Phase I dose escalation trial of IMO-2125 in combination with ipilimumab, and with the outcomes observed,” said Joanna Horobin, MB, ChB, Idera’s Chief Medical Officer. “IMO-2125 in combination with ipilimumab demonstrated preliminary evidence of meaningful clinical activity in this anti-PD-1 refractory metastatic melanoma patient population, which represents a high unmet medical need. All dose levels have been well tolerated and did not exacerbate the safety issues commonly observed with ipilimumab. Furthermore, data from multiple parameters of immune markers from tumor biopsies have been very informative in establishing proof-of-mechanism and supporting the dose selection for the Phase II portion of trial.”

The Phase II portion of the trial utilizes a Simon two-stage design to evaluate the objective response rate of IMO-2125 in combination with ipilimumab, compared to historical data for ipilimumab alone in the anti-PD-1 refractory metastatic melanoma population. The ipilimumab arm of IMO-2125-204 has already met the pre-specified futility assessment to advance immediately into the second stage of the Phase II portion of the trial given that two patients treated at the Phase II dose experienced confirmed responses, including one complete response (CR).

All dose levels of IMO-2125 in the Phase I portion of the trial have been well tolerated; however, the 8-mg dose level has been selected for the Phase II portion of the trial based on its safety, clinical efficacy, and data from multiple translational immune parameters supporting the mechanism. Phase II will evaluate 21 patients dosed at 8 mg, of which 9 are already enrolled. The MD Anderson Cancer Center will continue to lead the trial and will be joined by additional centers. In addition to potential interim updates, the company expects to have overall response rate (ORR) data available in the first quarter of 2018.

Additionally, the company has begun and will continue to engage in discussions with regulatory authorities regarding the path to registration for IMO-2125 in combination with ipilimumab in PD-1 refractory metastatic melanoma patients.
The Phase I clinical trial of intratumoral IMO-2125 in combination with pembrolizumab in PD-1 refractory melanoma patients is enrolling as expected, and patient enrollment in a Phase I trial of intratumoral IMO-2125 monotherapy in multiple tumor types has been activated and the first patient is expected to enroll early this quarter.

“I am very encouraged by the tremendous progress that has been made to date to advance us to this important stage in IMO-2125’s development cycle,” stated Vincent Milano, Idera’s Chief Executive Officer. “There is a very clear unmet medical need for those patients for whom current checkpoint inhibitor therapies are not providing adequate solutions. We are incredibly focused on advancing this program as rapidly as possible for these patients, and we are also looking forward to exploring areas outside of melanoma in which intratumoral IMO-2125 may also serve an important role through its unique mechanism of action within the tumor microenvironment.”

The Phase I/II trial of intratumoral IMO-2125 in combination with ipilimumab is being conducted in patients who are refractory to anti-PD-1 therapy. The Phase I portion of the trial was conducted at MD Anderson Cancer Center, and the Phase II portion of the trial will expand to include additional centers. In the Phase I portion of the trial, four dose levels of IMO-2125 (4, 8, 16, and 32 mg) have been administered intratumorally in one targeted lesion at weeks 1, 2, 3, 5, 8, and 11, in combination with the standard dosing regimen of ipilimumab, beginning on week 2. The Phase II expansion portion of the trial utilizes a Simon two-stage design. If at least two of the first 10 patients treated at the Phase II dose experience confirmed response the futility hurdle has been met and the trial may continue to enroll. Phase II will evaluate 21 patients at the Phase II dose. Tumor biopsies have been collected pre- and post-24 hours of the first dose of IMO-2125, as well as at 8 and 13 weeks to evaluate multiple immune markers. Clinical activity has been evaluated by the RECIST v1.1 criteria. Clinical data from this study has been presented at SITC 2017, ASCO-SITC 2017, and AACR 2017, and can be found also 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 (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 thereby potentiate anti-cancer activity of checkpoint inhibitors in the injected tumor as well as systemically.

IMO-2125, Idera’s TLR9 agonist, 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 very well tolerated in about 114 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 has been presented at several scientific and medical conferences during the past few years. The posters from these presentations can be found at http://www.iderapharma.com/our-approach/key-publications.

Idera Pharmaceuticals is a clinical-stage biopharmaceutical company developing novel nucleic acid-based therapies for the treatment of certain cancers and rare diseases. Idera’s proprietary technology involves designing synthetic oligonucleotide-based drug candidates to modulate the activity of specific TLRs. In addition to its TLR programs, Idera has used its proprietary knowledge to create a third-generation antisense technology platform that inhibits the production of disease-associated proteins by targeting RNA. For more information, visit www.iderapharma.com.

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