On December 14, 2015 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 that the company has commenced enrollment in a Phase 1/2 clinical trial evaluating intra-tumoral IMO-2125, a TLR9 agonist in combination with ipilimumab (an anti-CTLA4 antibody) in patients with previously treated metastatic melanoma (Press release, Idera Pharmaceuticals, DEC 14, 2015, View Source [SID:1234508567]). Schedule your 30 min Free 1stOncology Demo! The study is being conducted at The University of Texas MD Anderson Cancer Center and is being led by Adi Diab, MD, Assistant Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, MD Anderson.
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In this clinical trial, escalating doses of IMO-2125 ranging from 4 mg/kg through 32 mg/kg will be administered intra-tumorally into one of two selected tumor lesions, with a standard dosing regimen of ipilimumab. The primary objectives of the phase 1 portion of the trial will be to determine the maximum tolerated dose (MTD) and characterize the dose-limiting toxicities (DLTs) of IMO-2125 when administered intra-tumorally in combination with ipilimumab. The primary objective of the phase 2 portion will be to determine the efficacy of the combination utilizing the immune-related response criteria (irRC) in additional to traditional RECIST criteria. Serial biopsies will be taken of selected injected and non-injected tumor lesions to assess immune changes and response assessments. The trial will enroll approximately 45 patients. The company expects initial data from the ongoing trial to be available in 2016.
Preclinical evidence shows that IMO-2125 delivered intra-tumorally in combination with anti-CTLA-4 mAb demonstrates improved inhibition of tumor growth, regression of metastases and infiltration of the number and nature of tumor specific immune cells in injected and non-injected tumor lesions versus monotherapy with either agent. Additional pre-clinical evidence suggests that intra-tumoral IMO-2125 modulates checkpoint gene expression, including IDO1, PDL1, TIM3, LAG3 and CTLA4, in both treated and distant tumor nodules. The company is currently considering additional clinical studies to evaluate IMO-2125 in combination with other select checkpoint inhibitors.
"We are eager to demonstrate translation of the compelling preclinical data into the clinical setting with this novel approach to cancer immunotherapy with intra-tumoral IMO-2125," stated Joanna Horobin, M.B., Ch.B, Idera’s Chief Medical Officer. "The momentum and enthusiasm among our team along with our research alliance partner, MD Anderson is very strong. This is a beginning step in a broad strategy to demonstrate a major advancement in efficacy and safety over existing treatment regimens."
"We are anxious to understand whether the local immune changes observed in the injected tumor will be transferred to non-injected tumor lesions and that both will correlate with improved clinical efficacy for our patients," stated Dr. Diab.
About Toll-like Receptors and Idera’s Immuno-Oncology Research Program
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 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 being presented at several medical conferences during the past twelve months. The posters from these presentations can be found at View Source
Author: [email protected]
Bristol-Myers Squibb and UCLA Enter into a Collaboration Agreement as Part of U.S. Immuno-Oncology Rare Population Malignancy Research Program
On December 14, 2015 Bristol-Myers Squibb Company (NYSE:BMY) reported that they have entered into a collaboration agreement with UCLA as part of Bristol-Myers Squibb’s Immuno-Oncology Rare Population Malignancy (I-O RPM) research program in the U.S (Press release, Bristol-Myers Squibb, DEC 14, 2015, View Source [SID:1234508563]). Schedule your 30 min Free 1stOncology Demo! The I-O RPM research program is a multi-institutional initiative with academic-based cancer centers focused on the clinical investigation of immuno-oncology therapeutics as potential treatment options for patients with high risk, poor prognostic cancers, defined as a rare population malignancy.
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Bristol-Myers Squibb and the David Geffen School of Medicine at UCLA will conduct a range of early phase clinical studies as part of the I-O RPM research program, and Bristol-Myers Squibb will fund positions within UCLA’s fellowship program in the UCLA Division of Hematology/Oncology.
"The I-O RPM research program is an important complement to Bristol-Myers Squibb’s broad research and development program for immuno-oncology," said Laura Bessen, M.D., head of U.S. Medical, Bristol-Myers Squibb. "We look forward to working with UCLA in an effort to continue advancing the science in this innovative field of research and cancer treatment."
About I-O RPM
Immuno-oncology is an innovative approach to cancer research and treatment that is designed to harness the body’s own immune system to fight cancer. The I-O RPM research program focuses on significant areas of high unmet need marked by poor outcomes among patients with rare population malignancies. A rare population malignancy is a subpopulation within a higher incident disease population. These patients have aggressive disease with an increased potential for early metastasis to multiple sites and/or are initially refractory or subject to early recurrences with conventional cancer therapies. Existing clinical research provide a strong rationale for further research into the potential of immunotherapies for these cancers.
The I-O RPM research program is a multi-institutional initiative with Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Northwestern Medicine Developmental Therapeutics Institute, Moffitt Cancer Center, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and now UCLA. I-O RPM builds on Bristol-Myers Squibb’s formation in 2012 of the International Immuno-Oncology Network (II-ON), which is a global collaboration between Bristol-Myers Squibb and academia focused on facilitating the translation of scientific research findings into clinical trials and, eventually, clinical practice.
Advaxis Receives Orphan Drug Designation in the European Union for Axalimogene Filolisbac for the Treatment of Anal Cancer
On December 14, 2015 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported that the European Medicines Agency (EMA) has granted Orphan Drug Designation to axalimogene filolisbac for the treatment of anal cancer (Press release, Advaxis, DEC 14, 2015, View Source [SID:1234508560]). Schedule your 30 min Free 1stOncology Demo! "We’re pleased to announce Advaxis’ second EMA Orphan Drug Designation within four weeks, which strengthens our pipeline and confirms the potential that Lm Technology immunotherapies may offer to patients with high unmet medical needs," said Daniel J. O’Connor, CEO of Advaxis. "Our clinical program in anal cancer is building momentum as a result of this designation, the encouraging preliminary data in patients with anal cancer, as well as the honor of receiving the Farrah Fawcett Foundation’s ‘Medical Visionary Angel Award’ for our commitment to innovative research in anal cancer and HPV-related cancers. Receiving Orphan Drug Designation moves us one step closer to our goal of bringing a valuable new treatment to patients as quickly as possible."
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Orphan Drug Designation in the European Union (EU) is granted to drugs or biologics that treat a life-threatening or chronically debilitating rare disease affecting fewer than five in 10,000 individuals in the EU. Products receiving orphan drug designation are eligible to receive market exclusivity for a period of up to ten years, as well as development incentives such as regulatory and protocol assistance and scientific advice.
About Anal Cancer
Anal cancer is a fairly rare form of cancer in the United States, but the number of new anal cancer cases has been rising for years. The risk of being diagnosed with anal cancer in one’s lifetime is about 1 in 500. According to the American Cancer Society, approximately 7,270 new cases of anal cancer were diagnosed and about 1,010 people died of the disease in 2014.
About Axalimogene Filolisbac
Axalimogene filolisbac (ADXS-HPV) is Advaxis’s lead Lm Technology immunotherapy candidate for the treatment of HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. In a completed randomized Phase 2 study in recurrent/refractory cervical cancer, axalimogene filolisbac showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the company’s Lm Technology. Axalimogene filolisbac has Orphan Drug Designation in the U.S. for the treatment of anal cancer.
Aduro Biotech Receives Orphan Drug Designation in the European Union for CRS-207 and GVAX Pancreas for the Treatment of Pancreatic Cancer
On December 14, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that the European Medicines Agency (EMA) granted Orphan Drug Designation to CRS-207 and GVAX for the treatment of pancreatic cancer (Press release, Aduro BioTech, DEC 14, 2015, View Source [SID:1234508559]). Schedule your 30 min Free 1stOncology Demo! "We are extremely pleased to receive Orphan Drug Designation in the EU for CRS-207 and GVAX pancreas, which, taken together with our Breakthrough Designation granted by the U.S. Food and Drug Administration in the U.S., represent important regulatory milestones in our global strategy to develop new immunotherapies for this underserved population," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "As an integral step in our pursuit to bring this combination to patients with pancreatic cancer, we expect to report topline results from the ongoing Phase 2b ECLIPSE study evaluating this combination in the first half of 2016."
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To receive Orphan Drug Designation from the EMA, a therapy must be intended for the treatment of a life-threatening or chronically debilitating rare condition with a prevalence of less than five in 10,000 in the European Union. Orphan Drug Designation provides incentives designed to facilitate development, including protocol assistance and scientific advice and importantly, may provide up to ten years of market exclusivity in the EU following product approval.
Aduro has completed enrollment in the Phase 2b ECLIPSE trial of its novel LADD and GVAX immunotherapies being developed for the treatment of metastatic pancreatic cancer. The randomized, controlled three-arm trial enrolled 303 patients in the United States and Canada. Top line results are expected in the first half of 2016.
ECLIPSE was designed to evaluate the safety, immune response and efficacy of the combination immunotherapy of CRS-207 and GVAX Pancreas compared to chemotherapy. The trial also included a treatment arm to evaluate CRS-207 as a monotherapy. The primary endpoint of the trial is overall survival in the primary cohort of patients who have received two or more prior therapies for metastatic disease. A second cohort of patients who received one prior therapy for metastatic disease is also being evaluated.
About CRS-207
CRS-207 is one of a family of product candidates based on Aduro’s live-attenuated, double-deleted (LADD) Listeria monocytogenes immuno-oncology platform that are designed to induce potent innate and adaptive immune responses. CRS-207 has been engineered to express the tumor-associated antigen mesothelin, which is over-expressed in many cancers including mesothelioma and pancreatic, non-small cell lung, ovarian and gastric cancers.
About GVAX Pancreas
GVAX Pancreas is one of a family of GVAX immunotherapies derived from human cancer cell lines that are genetically modified to express granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune system-stimulating cytokine. GVAX Pancreas is derived from human pancreatic cancer cell lines and is designed to activate specific T cell immunity to pancreatic cancer antigens, including mesothelin.
X4 Pharmaceuticals Unveils Development Strategy for CXCR4 Inhibitor Pipeline in Cancer Supported by $37.5 million Series A Financing
On December 14, 2015 X4 Pharmaceuticals reported the launch of the company’s development strategy for its pipeline of C-X-C receptor type 4 (CXCR4 inhibitors), including two clinical studies initiating in 2016 in refractory cancers with its lead drug candidate, X4P-001 (Press release, X4 Pharmaceuticals, DEC 14, 2015, View Source [SID:1234508555]). The formation of X4 is based on drug compounds that originate from a portfolio of oral CXCR4 inhibitors exclusively licensed from Sanofi.
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Development of X4’s CXCR4 inhibitors will be funded initially through a $37.5 million Series A financing, which the Company recently closed. Maxim Merchant Capital, a wholly owned division of Maxim Group LLC, served as the sole placement agent for the financing, with Cormorant Asset Management serving as lead investor.
Henri Termeer, the former Chairman, president and CEO of Genzyme, and a founding advisor and investor in X4, stated, "X4 has assembled the expertise, drug assets and strategies to build extraordinary value for its constituents, including the potential to have a significant impact on the treatment of cancer."
X4 will launch multiple clinical studies with X4P-001 in 2016 in advanced cancers, including refractory clear cell renal cell carcinoma (ccRCC) and a second solid tumor indication. A second drug program, X4P-002, which is currently in pre-clinical development, is being optimized for the treatment of brain cancers, and is expected to enter the clinic in 2017. Inhibition of CXCR4, a receptor over-expressed in many cancers, is designed to block non-cancerous immuno-suppressive and pro-angiogenic cells from populating the tumor, thereby disrupting the cancer microenvironment and restoring normal immune surveillance functions. The novel mechanism of CXCR4 inhibition increases the ability of T-Cells to track and destroy cancer.
"CXCR4 inhibition is a novel approach to immunotherapy whose potential we are only beginning to explore for the treatment of cancer," said Keith Flaherty, MD, the director of the Henri and Belinda Termeer Center for Targeted Therapies at the Massachusetts General Hospital and co-founder of X4. "Immune system surveillance is the front line of keeping cancer in check and CXCR4 plays a key role in the trafficking of immunosuppressive cells. Inhibition of this receptor may be beneficial in addressing a broad range of cancers, offering the potential to improve both the magnitude and durability of treatment responses."
The development of X4’s clinical candidates will be led by the company’s seasoned management team and founders, who bring unique experience in the study the CXCR4 pathway. The team is led by Chief Executive Officer Paula Ragan, PhD, who brings more than 15 years of experience in senior leadership roles at biotechnology companies, including Genzyme. Other members of the team include:
Robert Arbeit, MD, Senior Vice President of Clinical Development and Translational Research, who served in leadership roles at Idera Pharmaceuticals, Paratek Pharmaceuticals and Cubist Pharmaceuticals;
Alison Lawton, consulting Chief Operating Officer, who has 30 years of global biopharmaceutical experience, including 21 years at Genzyme where she led the regulatory team for the approval of plerixafor, a CXCR4 inhibitor, in 2008.
Alan Walts, PhD, co-founder of X4 and Interim Chairman, spent over 25 years with Genzyme, where his roles included President of Genzyme Pharmaceuticals, Senior Vice President of Corporate Development, and Managing Director of Genzyme Ventures
"With a strong financial foundation and leadership team in place, X4 is well positioned to bring forward CXCR4 inhibitors as an innovative new immunotherapy treatment approach for a broad spectrum of cancers," said Dr. Ragan. "We look forward to executing on our plans for advancing our CXCR4 pipeline programs, and to seeing the early promise of this approach translate in the clinic."
X4’s scientific founder is Renato Skerlj, PhD, whose work in immune-mediated drug discovery led him to become an inventor of both plerixafor, a stem cell mobilizer approved in 2008, and ertapenem, an anti-bacterial approved in 2001. Dr. Skerlj has over 20 years of pharmaceutical experience in the discovery and development of novel therapies. Most recently, he was the Head of Small Molecule Discovery at Genzyme and prior to joining Genzyme, was part of the executive team at AnorMED, a publicly-traded company acquired by Genzyme for $580 million in 2006.
About X4 Pharmaceuticals
X4 Pharmaceuticals is developing novel therapeutics designed to improve immune cell trafficking and increase the ability for T-Cells to track and destroy cancer cells. The company’s oral small molecule drug candidates inhibit the CXCR4 receptor, a pathway which plays a central role in promoting the immunosuppressive and pro-angiogenic microenvironment of many cancers. X4P-001, the company’s lead program, is expected to enter Phase 1/2 testing in refractory clear cell renal cell carcinoma (ccRCC) and other solid tumor indications, and its second program, X4P-002, is in pre-clinical development for oncology applications. X4 was founded and is led by a team with deep product development and commercialization expertise, including several former members of the Genzyme leadership team, and is located in Cambridge, MA.