On June 28, 2016 Xencor, Inc. (Xencor) (NASDAQ:XNCR) reported that it has entered into a collaboration and license agreement with Novartis to develop and commercialize novel therapeutics, including XmAb14045 expected to begin clinical development for acute myeloid leukemia in 2016; and XmAb13676 also expected to begin clinical development for B-cell malignancies in 2016 (Press release, Xencor, JUN 28, 2016, View Source [SID:1234513582]). Schedule your 30 min Free 1stOncology Demo! "We are excited to move forward in collaboration with Novartis on the development of XmAb14045 and XmAb13676, while maintaining our rights in the U.S.," said Bassil Dahiyat, Ph.D., president and chief executive officer of Xencor. "This opportunity to work with and learn from a world leader in the late-stage development and commercialization of immune-oncology drugs gives us the opportunity to take our lead drugs through clinical development and into commercialization in the U.S. and, with the other molecules to be developed, continues to expand the reach of our technology."
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Under the terms of the agreement, the parties will collaborate and share development costs for the worldwide development of XmAb14045 and XmAb13676, with Xencor maintaining U.S. commercialization rights and Novartis having commercialization rights in the rest of the world. Novartis will receive worldwide rights to Xencor’s bispecific technology to develop and commercialize four additional targets selected by Novartis, one of which Xencor may elect to co-detail in the U.S. The bispecific collaboration will include molecular engineering by Xencor. Additionally, Novartis will receive a worldwide non-exclusive license to use Xencor’s XmAb Fc technologies in up to ten molecules.
Xencor will receive a $150 million upfront payment and is eligible to receive clinical, regulatory and sales milestone payments for successful programs. Xencor is also eligible to receive tiered, low double-digit royalties for sales of XmAb14045 and XmAb13676 outside of the U.S., mid single-digit tiered royalties for worldwide sales of the four proprietary Novartis bi-specific molecules, unless Xencor exercises its right to co-detail one of these molecules and share in the costs and U.S. profit, and low single-digit royalties on Novartis molecules incorporating Xencor’s XmAb Fc technology.
Xencor will discuss this collaboration and licensing agreement among additional items today, Tuesday, June 28, 2016, at the Company’s Analyst Day from 8:30 a.m. – 11:30 a.m. ET in New York City. A live audio webcast of the presentation will be available under the "Events & Presentations" section in the Investors section of the Xencor’s website located at View Source
About Xencor’s XmAb Bispecific Technology
As opposed to traditional monoclonal antibodies that target and bind to a single antigen, bispecific antibodies are designed to elicit multiple biological effects that require simultaneous binding to two different antigen targets. Xencor’s XmAb bispecific Fc domain technology is designed to maintain full-length antibody properties in a bispecific antibody, potentially enabling favorable in vivo half-life and simplified manufacturing.
Efforts at bispecific antibody design are typically frustrated by poor molecular stability, difficulties in production and short in vivo half-life. Xencor has engineered a series of Fc domain variants that spontaneously form stable, heterodimeric bispecific antibodies and that can be made and purified with standard antibody production methods. These bispecific Fc domains are used to generate a broad array of novel drug candidates in a range of molecule formats.
Xencor’s initial bispecific programs are tumor-targeted antibodies that contain both a tumor antigen binding domain and a cytotoxic T-cell binding domain (CD3 binding domain). These bispecific antibodies activate T cells at the site of the tumor for highly potent killing of malignant cells. The XmAb Fc domain format allows Xencor to tune the potency of the T-cell killing, potentially improving the tolerability of tumor immunotherapy.
About Xencor’s XmAb Fc Technologies
Xencor’s proprietary XmAb antibody engineering platform creates subtle, precise alterations to the antibody’s Fc domain — the stem of the structure that is responsible for antibodies’ natural immune functions and highly stable structure. These subtle changes elicit dramatically enhanced performance. XmAb Fc domains are plug-and-play and can be substituted into nearly any antibody. The resulting engineered antibodies retain the beneficial stability, pharmacokinetics and ease of development of natural antibodies, and are produced with standard methods for antibody manufacturing. We have created four lead XmAb Fc domains, each enhancing a key property for antibody therapeutics: our Bispecific, Immune Inhibitor, Cytotoxic and Xtend Fc domains.
Month: June 2016
BioLineRx Announces Regulatory Submissions for Phase 2a Trial of BL-8040 in Combination with KEYTRUDA® (pembrolizumab) for Treatment of Pancreatic Cancer
On June 28, 2016 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported the filing of regulatory submissions required to commence a Phase 2a trial for BL-8040 in combination with KEYTRUDA (pembrolizumab) for the treatment of patients with pancreatic cancer (Press release, BioLineRx, JUN 28, 2016, View Source [SID:1234513580]). The study is expected to commence shortly after receipt of regulatory approval, anticipated in the third quarter of 2016.
The Phase 2a study, named the COMBAT study, is an open-label, multicenter, single-arm trial designed to evaluate the safety and efficacy of the combination of BL-8040 and KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 therapy, in up to 30 subjects with metastatic pancreatic adenocarcinoma. The study is designed to evaluate the clinical response, safety and tolerability of the combination of these therapies as well as multiple pharmacodynamic parameters, including the ability to improve infiltration of T cells into the tumor and their reactivity. It is expected to take place in the US, Israel and additional territories.
In January 2016, BioLineRx entered into a collaboration with MSD, known as Merck in the US and Canada, to support a Phase 2 study investigating BioLineRx’s BL-8040 in combination with KEYTRUDA in patients with metastatic pancreatic cancer. BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in several clinical trials to be a robust mobilizer of immune cells and to be effective at inducing direct tumor cell death. Additional findings in the field of immuno-oncology suggest that CXCR4 antagonists may be effective in inducing the infiltration of anti-tumor T cells into the tumor. Therefore, when combined with KEYTRUDA, which blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells, BL-8040 has the potential to enable activated T cells to better reach tumor cells in the fight against pancreatic cancer.
“We are looking forward to commencing this combination study of our lead oncology product and Merck’s immune checkpoint inhibitor, which marks the entrance of BL-8040 into the exciting and promising field of cancer immunotherapy,” stated Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx. “Over the past few months, we have worked closely with Merck’s clinical team on the design and finalization of the study protocol. We believe that the combination of BL-8040 with KEYTRUDA has the potential to expand the benefit of immunotherapy to cancer types currently resistant to immuno-oncology treatments, such as pancreatic cancer, which represent a significant unmet medical need. Furthermore, we view BL-8040’s inhibition of CXCR4, which effects a change in the protective tumor micro-environment, as potentially synergistic with immune checkpoint inhibitors in additional oncological indications.”
About Pancreatic Cancer
Pancreatic cancers of all types are the seventh most common cause of cancer deaths. According to the American Cancer Society, in 2015, nearly 50,000 were diagnosed with pancreatic cancer and an estimated 40,000 will die from the disease. The most common type of pancreatic cancer is pancreatic adenocarcinoma, which accounts for about 85 percent of cases. These adenocarcinomas start within the part of the pancreas that makes digestive enzymes. There are usually no symptoms in the early stages of the disease and symptoms that are specific enough to suggest the onset of pancreatic cancer typically do not develop until the disease has reached an advanced stage. The five-year survival rate of pancreatic adenocarcinoma is around 7 percent.
About BL-8040
BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and certain hematological indications. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing apoptosis. In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, and T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.
BioLineRx Announces Regulatory Submissions for Phase 2a Trial of BL-8040 in Combination with KEYTRUDA® (pembrolizumab) for Treatment of Pancreatic Cancer
On June 28, 2016 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported the filing of regulatory submissions required to commence a Phase 2a trial for BL-8040 in combination with KEYTRUDA (pembrolizumab) for the treatment of patients with pancreatic cancer (Press release, BioLineRx, JUN 28, 2016, View Source [SID:1234513580]).The study is expected to commence shortly after receipt of regulatory approval, anticipated in the third quarter of 2016. Schedule your 30 min Free 1stOncology Demo! The Phase 2a study, named the COMBAT study, is an open-label, multicenter, single-arm trial designed to evaluate the safety and efficacy of the combination of BL-8040 and KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 therapy, in up to 30 subjects with metastatic pancreatic adenocarcinoma. The study is designed to evaluate the clinical response, safety and tolerability of the combination of these therapies as well as multiple pharmacodynamic parameters, including the ability to improve infiltration of T cells into the tumor and their reactivity. It is expected to take place in the US, Israel and additional territories.
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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
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In January 2016, BioLineRx entered into a collaboration with MSD, known as Merck in the US and Canada, to support a Phase 2 study investigating BioLineRx’s BL-8040 in combination with KEYTRUDA in patients with metastatic pancreatic cancer. BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in several clinical trials to be a robust mobilizer of immune cells and to be effective at inducing direct tumor cell death. Additional findings in the field of immuno-oncology suggest that CXCR4 antagonists may be effective in inducing the infiltration of anti-tumor T cells into the tumor. Therefore, when combined with KEYTRUDA, which blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells, BL-8040 has the potential to enable activated T cells to better reach tumor cells in the fight against pancreatic cancer.
"We are looking forward to commencing this combination study of our lead oncology product and Merck’s immune checkpoint inhibitor, which marks the entrance of BL-8040 into the exciting and promising field of cancer immunotherapy," stated Dr. Kinneret Savitsky, Chief Executive Officer of BioLineRx. "Over the past few months, we have worked closely with Merck’s clinical team on the design and finalization of the study protocol. We believe that the combination of BL-8040 with KEYTRUDA has the potential to expand the benefit of immunotherapy to cancer types currently resistant to immuno-oncology treatments, such as pancreatic cancer, which represent a significant unmet medical need. Furthermore, we view BL-8040’s inhibition of CXCR4, which effects a change in the protective tumor micro-environment, as potentially synergistic with immune checkpoint inhibitors in additional oncological indications."
About Pancreatic Cancer
Pancreatic cancers of all types are the seventh most common cause of cancer deaths. According to the American Cancer Society, in 2015, nearly 50,000 were diagnosed with pancreatic cancer and an estimated 40,000 will die from the disease. The most common type of pancreatic cancer is pancreatic adenocarcinoma, which accounts for about 85 percent of cases. These adenocarcinomas start within the part of the pancreas that makes digestive enzymes. There are usually no symptoms in the early stages of the disease and symptoms that are specific enough to suggest the onset of pancreatic cancer typically do not develop until the disease has reached an advanced stage. The five-year survival rate of pancreatic adenocarcinoma is around 7 percent.
About BL-8040
BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and certain hematological indications. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing apoptosis. In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, and T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.
Medtronic to Expand Heart Failure Portfolio with Acquisition of HeartWare International
On June 27, 2016 Medtronic plc (NYSE: MDT), the global leader in medical technology, and HeartWare International, Inc. (NASDAQ: HTWR), a leading innovator of less-invasive, miniaturized circulatory support technologies for the treatment of advanced heart failure, reported that the companies have entered into a definitive merger agreement under which Medtronic will acquire HeartWare in a transaction valued at approximately $1.1 billion (Press release, HeartWare International, JUN 27, 2016, View Source;p=irol-newsArticle&ID=2180056 [SID:1234514705]). Under the terms of the agreement, Medtronic will commence a tender offer for all outstanding shares of HeartWare common stock for $58.00 per share, in cash. The boards of directors of both Medtronic and HeartWare have unanimously approved the transaction. The acquisition is expected to close during Medtronic’s second fiscal quarter ending Oct. 28, 2016, subject to the satisfaction of customary closing conditions.
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Medtronic’s acquisition of HeartWare will expand Medtronic’s portfolio of diagnostic tools, therapies and services for patients suffering from heart failure, aligning with Medtronic’s Mission of alleviating pain, restoring health and extending life, and is in line with the Company’s strategy to surround the physician with innovative products while focusing on patients and disease states.
HeartWare’s flagship product, the HVAD System, features the world’s smallest full-support ventricular assist device (VAD) and is designed to reduce surgical invasiveness, improve patient recovery times and enhance patient outcomes. In addition, HeartWare has multiple technologies in development designed to offer progressively less-invasive mechanical circulatory support options for patients with end-stage heart failure. Medtronic estimates that the global VAD market is approximately $800 million currently and worldwide is expected to grow in the mid-to-high single digits for CY16-17, and accelerate to high-single/low-double digits beyond CY17.
"The addition of HeartWare’s innovative portfolio adds to our expanding portfolio of diagnostics, therapeutics and services that address heart failure patients," said Mike Coyle, executive vice president and president of the Cardiac and Vascular Group at Medtronic. "The team at HeartWare has established excellent relationships with its hospital customers and built a strong position and reputation in the marketplace. This transaction, once closed, will be a further, important step toward Medtronic offering a complete suite of solutions to address patient needs across the heart failure care continuum."
"Medtronic is the worldwide leader in cardiovascular device technologies. Its expansive expertise in the development of implantable systems and battery technologies, patient monitoring, manufacturing, global regulatory policy and commercialization should help accelerate the development and introduction of our innovative pipeline products, and will expand access to our therapies and offerings to the sizeable heart failure population," said Doug Godshall, president and chief executive officer, HeartWare. "Combining the unique capabilities of the HeartWare team, which has been entirely focused on mechanical support technologies, with the broad strength of the Medtronic organization provides a unique opportunity to enhance growth in the mechanical circulatory support market. All of our stakeholders, including customers, employees, shareholders, and most importantly, patients, will benefit meaningfully from this complementary combination."
Heart failure, also known as congestive heart failure, is a condition or a collection of symptoms in which the heart isn’t pumping enough blood to meet the body’s needs. Heart failure usually develops slowly after an injury to the heart. Some injuries may include a heart attack, too much strain on the heart due to years of untreated high blood pressure, or a diseased heart valve, among others. Heart failure remains a leading cause of hospitalization and death in the United States, and its prevalence continues to increase, affecting more than five million people in the U.S. alone. The cost of heart failure is high. Healthcare expenditures in the U.S. on heart failure are estimated to be approximately $39 billion per year, making it one of the largest expenses to the healthcare system. With the aging of the population, Medtronic estimates that the number of patients with heart failure could exceed eight million by 2030.
"HeartWare’s HVAD System enhances the portfolio of our Cardiac & Vascular Group, a team with a proven track record of executing and a demonstrated ability to scale early stage concepts into large, sustainable end markets," said Omar Ishrak, chairman and chief executive officer of Medtronic. "In addition, from a financial perspective, we are pleased to reach an agreement that meets our acquisition criteria of adding minimal to no net EPS dilution in the near-term, while at the same time creating strong, long-term expected returns for our shareholders."
This acquisition supports Medtronic’s therapy innovation strategic priority. In collaboration with leading clinicians, researchers and scientists worldwide, Medtronic offers the broadest range of innovative medical technology for the interventional and surgical treatment of cardiovascular disease and cardiac arrhythmias. The company strives to offer products and services that deliver clinical and economic value to healthcare consumers and providers around the world.
This transaction is expected to meet Medtronic’s long-term financial metrics for acquisitions. Medtronic does not intend to modify its fiscal year 2017 revenue outlook or earnings per share (EPS) guidance as a result of this transaction, although it is expected to provide increased confidence in the company’s ability to deliver on its FY17 revenue growth outlook. In addition, Medtronic expects minimal to no net EPS dilution from this transaction for the first two years as the company intends to offset the expected dilutive impact. The acquisition is expected to be earnings accretive in year three. Medtronic intends to report results from the acquired HeartWare business as part of its Cardiac Rhythm & Heart Failure division within the Cardiac & Vascular Group.
Medtronic’s financial advisor for the transaction is J.P. Morgan Securities LLC, with Ropes & Gray LLP acting as legal advisor. HeartWare’s financial advisor is Perella Weinberg Partners LP, with Shearman & Sterling LLP acting as legal advisor.
Advanced Accelerator Applications Announces FDA Priority Review for Lutathera
On June 27, 2016 Advanced Accelerator Applications S.A. (NASDAQ:AAAP) ("AAA" or "the Company"), an international specialist in Molecular Nuclear Medicine (MNM), reported that the U.S. Food and Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) and granted Priority Review for Lutathera, a Lu-177-labeled somatostatin analogue peptide currently under development for the treatment of gastro entero pancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults (Press release, Advanced Accelerator Applications, JUN 27, 2016, View Source [SID:1234513596]). The Prescription Drug User Fee Act (PDUFA) target action date is December 28, 2016.
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Priority review is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions.
The Lutathera NDA is based on the results of a randomized pivotal Phase 3 study, NETTER-1 that compared treatment using Lutathera with a double dose of Octreotide LAR in patients with inoperable midgut NETs progressive under Octreotide LAR treatment and overexpressing somatostatin receptors. The NETTER-1 study met its primary endpoint by demonstrating that treatment with Lutathera was associated with a statistically significant and clinically meaningful risk reduction of 79% in disease progression or death versus a treatment with a double dose of Octreotide LAR. Efficacy and safety data from a large Phase I-II trial conducted in more than 1,200 patients in NET indications is also part of the NDA.
"We are encouraged that the FDA has granted Priority Review for Lutathera as a potential treatment for GEP-NETs," said Stefano Buono, Chief Executive Officer of AAA. "We believe this action emphasizes the need to improve the lives of these patients."
About Neuro Endocrine Tumors (NETs)
Neuro Endocrine Tumors, also known as NETs, are a group of tumors originating in the neuroendocrine cells of many different organs. NETs can remain clinically silent for years delaying the diagnosis in a large number of patients. These cancers are rare but they are the second most common type of gastrointestinal malignancy and their incidence is increasing. The estimated incidence of NETs for the combined populations of the United States and the European Union is approximately 47,300.
NETs are classified as orphan diseases by U.S. and European regulatory authorities, meaning that they affect a relatively small population of individuals in the relevant jurisdiction. In the United States, orphan drugs are defined as drugs that treat diseases or conditions that affect 200,000 or fewer individuals in the country. In the European Union, orphan drugs are defined as drugs that treat diseases or conditions that affect fewer than five out of 10,000 individuals in the European Union.
About Lutathera
Lutathera (or lutetium Lu 177 dotatate) is a Lu-177-labeled somatostatin analogue peptide currently in development for the treatment of gastro entero pancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults. Lutathera belongs to an emerging form of treatments called Peptide Receptor Radionuclide Therapy ("PRRT"), which involves targeting carcinoid tumors with radiolabeled somatostatin analogue peptides. This novel compound has received orphan drug designation from the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Lutathera was also granted fast-track designation by the FDA in April 2015 for the treatment of inoperable progressive midgut NETs. Lutathera is also currently administered on a compassionate use and named patient basis for the treatment of NETs and other tumors over-expressing somatostatin receptors in ten European countries and in the US under an Expanded Access Program (EAP) for midgut NETs. In an analysis of the Phase 3 trial’s primary endpoint of PFS assessment, completed by the Company in September 2015, the Lutathera arm of the trial demonstrated a significant improvement in PFS compared to the PFS for Octreotide LAR 60 mg arm, suggesting a significant therapeutic effect for patients with midgut NETs. NDA and MAA submissions to the FDA and EMA are currently under review.