On February 24, 2017 Idera Pharmaceuticals, Inc. (NASDAQ:IDRA), a clinical-stage biopharmaceutical company developing toll-like receptor and RNA therapeutics for patients with cancer and rare diseases, reported additional data from the dose-escalation phase of its ongoing Phase 1/2 clinical trial of intratumoral IMO-2125, an agonist of TLR9 in combination with ipilimumab or pembrolizumab for treatment of patients with metastatic melanoma with disease that is refractory to PD-1 inhibitors (Press release, Idera Pharmaceuticals, FEB 24, 2017, View Source [SID1234517825]).

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In the poster presentation at the 2017 ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium, entitled, "Intratumoral (i.t.) IMO-2125, a TLR9 agonist is active in combination with ipilimumab (ipi) in PD-(L)1 refractory melanoma (RM)," Marc Uemura, M.D. from the University of Texas, MD Anderson Cancer Center, presented an update on the clinical and translational findings from the ongoing trial.

A copy of the poster presentation is currently available on Idera’s corporate website at View Source

"We are very pleased to have achieved successful completion of all our objectives in the Phase 1 portion of this trial which established safety across all doses tested, and demonstrated preliminary evidence of clinical activity, including durable responses of over one year in two of the evaluable patients so far," stated Mark Cornfeld, M.D., Idera’s Medical Lead, Oncology. "Additionally from a scientific standpoint, we’ve established proof of mechanism through our translational effort which has gone well beyond the norm compared to what is typically done in oncology drug development."

Continued Cornfeld, "At this point we have very clear justification to further the development of IMO-2125 and we’ll soon be moving to the phase 2 portion of the trial, which will expand to multiple centers. Additionally we are undertaking a parallel development pathway for IMO-2125 in combination with pembrolizumab and while that is not the focus of this presentation today, we are making good progress with safety and dose evaluation in that arm."

The company is also announcing the acceptance of two abstracts at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2017 Annual Meeting being held April 1-5, in Washington DC. Idera has gained acceptance of two presentations related to IMO-2125.

On Wednesday, April 5, 2017, Dr. Cara Haymaker of MD Anderson Cancer Center will present an update on the translational data outcomes in a 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."

Additionally, on the same day, Daqing Wang, Ph.D., Principal Scientist, Idera Pharmaceuticals will present new IMO-2125 pre-clinical data in a poster entitled, "Local treatment with novel TLR9 agonist IMO-2125 demonstrates anti-tumor activity in preclinical models of pancreatic cancer."

About IMO-2125
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.

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 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 twelve months. The posters from these presentations can be found at View Source

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. The American Cancer Society estimates that in 2016, there will be 76,380 new cases of melanoma in the U.S., and about 10,130 will die of this disease.

On February 24, 2017 Genmab A/S (Nasdaq Copenhagen: GEN)reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending broadening the existing marketing authorization for DARZALEX (daratumumab) in the European Union (Press release, Genmab, FEB 24, 2017, View Source [SID1234517824]). The recommendation is for the use of DARZALEX (daratumumab) in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. The variation to the Marketing Authorization for this indication was submitted to the EMA in August 2016. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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The positive opinion of the CHMP was based on data from two Phase III studies: the CASTOR study of daratumumab in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in patients with relapsed or refractory multiple myeloma, and the POLLUX study of daratumumab in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma. The submission also included supporting data from two early stage studies: the Phase I MMY1001 study (daratumumab in combination with pomalidomide and dexamethasone) and the Phase I/II GEN503 study (daratumumab in combination with lenalidomide and dexamethasone).

"We are very pleased to receive this positive opinion from the CHMP which brings the potential for patients in Europe with relapsed or refractory multiple myeloma to have access to treatment with DARZALEX a key step closer. We very much look forward to a final decision from the European Commission on the application to expand the product label," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

A CHMP opinion is one of the final steps in the regulatory process of the European Medicines Agency. A final decision by the European Commission is anticipated within two months.

About the CASTOR study
The Phase III CASTOR study included 498 patients who had relapsed or refractory multiple myeloma. Patients were randomized to receive either daratumumab combined with subcutaneous bortezomib (a type of chemotherapy, called a proteasome inhibitor) and dexamethasone (a corticosteroid), or bortezomib and dexamethasone alone. The study met the primary endpoint of improving progression free survival (PFS); Hazard Ratio (HR) = 0.39, 95% CI 0.28-0.53, p<0.0001. Patients who received treatment with daratumumab in combination with bortezomib and dexamethasone had a 61% reduction in risk of their disease progressing, compared to those who did not receive daratumumab. The median PFS for patients treated with daratumumab has not been reached, compared to median PFS of 7.2 months for patients who did not receive daratumumab. Daratumumab also significantly increased the overall response rate (ORR) (83% vs. 63%, p<0.0001), including doubling rates of complete response (CR) or better (19% vs. 9%) and rates of very good partial response (VGPR) or better (59% vs. 29%). The proportion of patients that achieved minimal residual disease (MRD) negative status at the 10-4 threshold (one tumor cell in 10,000 white cells) was 13.5% vs 2.8%, p<0.000006 for patients treated with daratumumab versus patients who did not receive daratumumab. The most common grade 3 or 4 adverse events in patients treated with daratumumab in combination with bortezomib and dexamethasone compared to those who only received bortezomib and dexamethasone were thrombocytopenia (45% vs 33%), anemia (14% vs 16%) and neutropenia (13% vs 4%). Daratumumab-associated infusion-related reactions were reported in 45% of patients, were mostly grade 1/2, and occurred predominantly during the first infusion. This is consistent with the reported safety profile of daratumumab monotherapy and combination therapy of bortezomib and dexamethasone.

About the POLLUX study
The Phase III POLLUX study enrolled 569 patients who had relapsed or refractory multiple myeloma. Patients were randomized to receive either daratumumab combined with lenalidomide (an immunomodulatory drug) and dexamethasone, or lenalidomide and dexamethasone alone. The study met the primary endpoint of improving progression-free survival (PFS) (Hazard Ratio (HR) = 0.37; 95% CI 0.27-0.52; p<0.0001) for patients treated with daratumumab versus patients who did not receive daratumumab. Patients who received treatment with daratumumab in combination with lenalidomide and dexamethasone had a 63% reduction in risk of their disease progressing, compared to those who did not receive daratumumab. The median PFS for patients treated with daratumumab in combination with lenalidomide and dexamethasone has not been reached, compared to an estimated median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone.

Additionally, daratumumab significantly increased ORR (93% vs. 76%, p<0.0001), including doubling rates of CR or better (43% vs. 19%), as well as rates of VGPR or better (76% vs. 44%). The proportion of patients that achieved minimal residual disease (MRD) negative status at the 10-4 threshold was 29% vs 7.8%, p<0.000001 for patients treated with daratumumab versus patients who did not receive daratumumab. The most common grade 3 or 4 adverse events in patients treated with daratumumab in combination with lenalidomide and dexamethasone versus those who received only lenalidomide and dexamethasone were neutropenia (52% vs 37%), thrombocytopenia (13% vs 14%), and anemia (12% vs 20%). Daratumumab-associated infusion-related reactions occurred in 48% of patients, were mostly grade 1/2, and occurred predominantly during the first infusion. Overall, the reported safety profile was consistent with known toxicities of daratumumab monotherapy and combination therapy of lenalidomide and dexamethasone.

Data from both the CASTOR study and the POLLUX study were published in The New England Journal of Medicine in August 2016, and October 2016, respectively.

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 30,330 new patients were expected to be diagnosed with multiple myeloma and approximately 12,650 people were expected to die from the disease in the U.S. in 2016.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5 Patients who relapse after treatment with standard therapies, including proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.6

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. For more information, visit www.DARZALEX.com.
Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,7,8,9,10

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline multiple myeloma settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, non-Hodgkin’s lymphoma, NKT-cell lymphoma, amyloidosis, myelodysplastic syndromes and solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.