On June 2, 2016 Mylan N.V. (NASDAQ, TASE: MYL) reported the U.S. launch of Azacitidine for Injection, 100 mg/vial, which is a generic version of Celgene’s Vidaza Injection, 100 mg/vial. Mylan received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for this product (Press release, Mylan, JUN 2, 2016, View Source [SID:1234512966]). Azacitidine for Injection is a nucleoside metabolic inhibitor indicated for the treatment of the five French-American-British (FAB) subtypes of myelodysplastic syndrome, a blood cell disorder that can occur as a result of cancer treatments or can progress to leukemia.

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Mylan
Azacitidine for Injection, 100 mg/vial, had U.S. sales of approximately $236.3 million for the 12 months ending March 31, 2016, according to IMS Health.
Mylan’s launch of this product adds to the company’s portfolio of more than 150 injectable products available to patients in the U.S. across a broad array of therapeutic categories. Azacitidine for Injection is also a part of a growing U.S. portfolio of more than 20 oncology medications that includes treatments for breast, lung, colorectal, ovarian and hematologic cancers.
Currently, Mylan has 254 ANDAs pending FDA approval representing $108.3 billion in annual brand sales, according to IMS Health. Forty-three of these pending ANDAs are potential first-to-file opportunities, representing $37.2 billion in annual brand sales, for the 12 months ending December 31, 2015, according to IMS Health.

On June 2, 2016 MiNA Therapeutics, the pioneer in RNA activation therapeutics, reported the initiation and first patient treated in the OUTREACH Phase I clinical study of their lead program, MTL-CEBPA, in severe liver cancer (Press release, MiNA Therapeutics, JUN 2, 2016, View Source [SID:1234512962]).

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The study is the first-in-human trial of a small activating RNA (saRNA) and is designed to assess the safety and tolerability of MTL-CEBPA, an saRNA restoring the expression of CCAAT/enhancer binding protein alpha (C/EBP-a). C/EBP-a plays an important role in normal liver function and the benefits of increasing its expression have been demonstrated in multiple pre-clinical models of disease.

"Initiation of the Phase I study is an important achievement in our mission to improve patients’ lives with our groundbreaking class of medicines known as small activating RNAs," said Robert Habib, CEO of MiNA Therapeutics. "There is increasing excitement about the possibility of using RNA to induce therapeutic protein production. We believe our unique approach, here applied to the upregulation of C/EBP-a protein, may provide to patients significant benefits over conventional medicines."

"MTL-CEBPA has shown great promise in pre-clinical studies in liver disease models," commented Dr. Debashis Sarker, Principal Investigator of the National Institute for Health Research Biomedical Research Centre at Guy’s and St. Thomas’ and King’s College London, and chief investigator of the study. "We are looking forward to evaluating this highly innovative therapy in the upcoming Phase I trial. We hope MTL-CEBPA could represent an important new treatment option for patients with advanced liver cancer."

About the OUTREACH Study

OUTREACH is a first-in-human Phase I clinical study in patients with severe liver cancer. The multi-centre Phase I study will assess the safety and tolerability of MTL-CEBPA in patients with advanced primary or metastatic liver cancer who are ineligible or resistant to standard therapies. The study consists of a dose-escalation followed by a dose expansion. MTL-CEBPA will initially be administered as an intravenous infusion once weekly for three weeks followed by one week of rest. To learn more about the OUTREACH clinical study, please visit our listing at clinicaltrials.gov.

About MTL-CEBPA

MTL-CEBPA consists of a double stranded RNA formulated into a SMARTICLES liposomal nanoparticle and is designed to activate the CEBPA gene. The CEBPA gene encodes for the CCAAT/enhancer binding protein alpha (C/EBP-a), a transcription factor that acts as a master regulator of cell lineage determination and differentiation in several tissues including liver, myeloid cells and adipose tissue. In the liver, C/EBP-a plays an important role in normal hepatocyte function and response to injury. By restoring C/EBP-a expression to normal levels, MTL-CEBPA has been demonstrated to attenuate or reverse liver disease in a range of pre-clinical studies including models of liver cancer, liver cirrhosis, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In the future MiNA Therapeutics expects to initiate clinical trials of MTL-CEBPA in a number of diseases beyond liver cancer.

On June 2, 2016 Oxford BioMedica plc ("Oxford BioMedica" or "the Group") (LSE: OXB), a leading gene and cell therapy group, today announces that it has entered into a Research & Development Collaboration with Green Cross LabCell ("GCLC"), a subsidiary of Green Cross Holdings, a leading South Korean biopharmaceutical company that delivers life-saving and life-sustaining protein therapeutics and vaccines (Press release, Oxford BioMedica, JUN 2, 2016, View Source [SID:1234512959]). The collaboration will focus on identifying and developing gene modified natural killer (NK) cell-based therapeutics for treatment of life-threatening diseases such as cancer.

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This collaboration brings together two clinically validated platform technologies with the aim of generating a pipeline of novel and differentiated cell-based products in areas of serious unmet medical need. Oxford BioMedica is contributing its clinically tested LentiVector gene delivery platform for the efficient modification of immune cells, as well as its expertise in GMP bioprocessing, clinical development and regulatory affairs in ex vivo cell & gene therapy. GCLC is contributing its clinically tested platform for production of highly potent and activated NK cells.

During the initial Research Collaboration, Oxford BioMedica and GCLC (the "Parties") will collaborate to identify potential NK cell-based product candidates, modified using lentiviral vectors. The collaboration will focus on allogeneic CAR-NK cell-based products. Under the terms of the agreement, Oxford BioMedica and GCLC will share the costs associated with the Research Collaboration equally. Oxford BioMedica’s contribution to the Research Collaboration will be funded from its existing Discovery resources and budget. The Parties will agree which product candidates from the Research Collaboration will be taken forward into the Development Collaboration stage of the programme on a product-by-product basis.

After nearly a decade of research on NK cells, GCLC has gathered a substantial body of evidence that their proprietary manufacturing platform for activated NK cells derived from peripheral blood mononuclear cells (PBMCs), such as MG4101, has potential to act as the basis for a pipeline of CAR-NK and other gene-modified NK cell products. By forming a partnership with GCLC, Oxford BioMedica gains access to one of the leading, clinically validated NK cell platforms in the industry and access to a highly skilled and experienced R&D partner in Korea, one of the most dynamic biotechnology markets in Asia.

Commenting on the new partnership, John Dawson, CEO of Oxford BioMedica, said: "We are very excited to form a key partnership with Green Cross LabCell, who have the industry-leading production platform for NK cell therapeutics for cancer. Over the years Green Cross LabCell has built a significant depth of scientific, technical and industrial expertise in NK cells that is difficult to find elsewhere.

"We are therefore delighted to be collaborating with Green Cross LabCell in a new partnership which brings our LentiVector delivery platform and expertise to the relationship and which builds on our existing partnerships with other companies including Novartis, Sanofi, GSK and Immune Design. We believe that our collaboration will lead to the generation of a rich pipeline of novel gene-modified NK cell therapeutics for both companies."

Bok-Soo Park, Chief Executive Officer of Green Cross LabCell, commented "To work with Oxford BioMedica as our partner for the development and future commercialization of gene-modified NK cell products is exciting, given their world-leading expertise in the clinical development and bioprocessing of lentiviral vector based products. This agreement underscores our commitment to maximise the value of our technologies and accelerate their progress to the market through partnering with industry leaders. We chose to work with Oxford BioMedica as we believe they are best positioned to accelerate development of these programs and are fully committed to their success. We look forward to working with the team at Oxford BioMedica to bring desperately needed new treatment options to cancer to patients all around the world."

On June 2, 2016 Kite Pharma, Inc. (NASDAQ: KITE) ("Kite") and Cell Design Labs, Inc. reported a research collaboration and license agreement to develop next generation, precision-controlled chimeric antigen receptor (CAR) product candidates that incorporate Cell Design Labs’ molecular "on/off switch" technology (Press release, Kite Pharma, JUN 2, 2016, View Source [SID:1234512956]).

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The use of CARs to redirect T-cells against B-cell malignancies has shown promise as a powerful tool to eradicate cancers. The switch technology employs small molecule-mediated protein dimerization domains to functionally activate the CAR and, similarly, to turn "off" the CAR in the absence of the small molecule. By incorporating "on/off switches" into next generation CAR products, physicians will have the potential to rapidly control and reversibly titrate the activity of CAR T-cells.

Under the agreement, Cell Design Labs will develop "on/off switches" for Kite’s CAR T-cell pipeline. Kite will receive exclusive worldwide rights to develop and commercialize CAR T-cell therapies containing Cell Design Labs’ "on/off switches" directed to certain targets for the treatment of acute myeloid leukemia (AML). Kite also has the exclusive option to develop and commercialize CAR T-cell products containing "on/off switches" directed to certain targets for the treatment of B-cell malignancies.

"Cell Design Labs was established to deploy exciting advances in synthetic biology to build and control cell signaling networks through our "on/off switch" technology," said Brian Atwood, Co-founder, President, and Chief Executive Officer of Cell Design Labs. "Our platform takes advantage of the modular design of CARs that we believe will create a next generation of CARs whose activation can be titrated or switched on and off by using small molecules that are clinically available. We look forward to working with Kite, a company whose deep understanding of CAR T-cell biology and manufacturing has already generated advanced clinical programs for cancer patients."

"Kite remains highly focused on accessing important technologies that could augment the activity and/or improve the safety of our engineered T-cell therapy candidates," said Arie Belldegrun, M.D., FACS, Chairman, President, and Chief Executive Officer of Kite. "Cell Design Labs has developed an elegant approach to designing CARs. Our collaboration with Cell Design Labs exemplifies Kite’s commitment to bringing the next generation CAR T-cell immunotherapies to patients."

Under the terms of the agreement, Kite will pay Cell Design Labs an upfront payment and additional payments to support Cell Design Labs’ research. Cell Design Labs will be eligible to receive milestone payments based upon the successful achievement of pre-specified research, clinical, regulatory and commercial milestones, as well as tiered royalties on product sales. Kite has increased its equity investment in Cell Design Labs as part of Cell Design Labs’ recent private financings. Arie Belldegrun will join the Board of Directors of Cell Design Labs and David Chang, M.D., Ph.D., Executive Vice President, Research & Development, and Chief Medical Officer of Kite, will join as a Board Observer.

On June 2, 2016 Novartis reported that the European Commission has approved Afinitor (everolimus) tablets for the treatment of unresectable or metastatic, well-differentiated (Grade 1 or Grade 2) nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin in adults with progressive disease (Press release, Novartis, JUN 2, 2016, View Source [SID:1234512955]). Afinitor is the first approved therapy in all 28 member states of the European Union (EU), plus Iceland and Norway, for this type of lung NET, and one of very few treatment options available for this type of GI NET.

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"With this decision, Afinitor is now approved in the EU to treat the three most common types of advanced NET," said Bruno Strigini, President, Novartis Oncology. "As a company that has long been dedicated to advancing care for NET patients, we are pleased that this latest milestone makes Afinitor available to patients in the EU who previously had few or no approved treatment options."

Neuroendocrine tumors are a type of cancer that originate in neuroendocrine cells throughout the body, and most commonly arise in the GI tract, lungs or pancreas[1],[4]. NET can be defined as functional or nonfunctional[5]. The majority of patients with NET (72%) have nonfunctional NET, which are characterized by symptoms caused by tumor growth, such as intestinal obstruction, pain and bleeding for GI NET, and asthma, chronic obstructive pulmonary disease and pneumonia for lung NET[5],[6],[7],[8],[9]. In contrast, functional NET are characterized by symptoms caused by the oversecretion of hormones and other substances[5]. Five to 44% (depending on site of tumor origin) of those with GI NET and 28% of those with lung NET have advanced disease at time of diagnosis, meaning the cancer has spread to other areas of the body, and patients face limited treatment options[1],[4]. Progression, or the continued growth or spread of the tumor, is typically associated with poor prognoses[10].

The EU approval of Afinitor was based on efficacy and safety data from a pivotal Phase III study (RADIANT-4) evaluating Afinitor versus placebo in patients with advanced, progressive, well-differentiated nonfunctional NET of GI or lung origin. Results showed that Afinitor reduced the risk of disease progression by 52% (hazard ratio = 0.48; 95% confidence interval [CI], 0.35-0.67; p<0.00001) compared to placebo. The data also showed Afinitor increased median progression-free survival (PFS) by 7.1 months: median PFS by central review was 11.0 months (95% CI, 9.2-13.3) in the Afinitor arm and 3.9 months (95% CI, 3.6-7.4) in the placebo arm[3].

In the pivotal trial, the most common treatment-related, all-grade adverse events (AEs) (incidence >=20%) for Afinitor and placebo, respectively, were stomatitis (63% vs 19%), diarrhea (31% vs 16%), fatigue (31% vs 24%), infections (29% vs 4%), rash (27% vs 8%) and peripheral edema (26% vs 4%). The most common treatment-related grade 3/4 AEs (incidence >=5%) for Afinitor versus placebo were stomatitis (9.0% vs 0.0%), diarrhea (7.0% vs 2.0%) and infections (7.0% vs 0.0%)[3].

In February 2016, the US Food and Drug Administration approved Afinitor for the treatment of adult patients with progressive, well-differentiated nonfunctional NET of GI or lung origin that are unresectable, locally advanced or metastatic. In April 2016, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Afinitor tablets for the treatment of unresectable or metastatic, well-differentiated (Grade 1 or Grade 2) nonfunctional NET of GI or lung origin in adults with progressive disease. Afinitor received approval for this indication in Canada in May 2016, and additional worldwide regulatory filings are underway.

About RADIANT-4 Study: Part of the largest clinical trial program in advanced NET
RADIANT-4 (RAD001 In Advanced Neuroendocrine Tumors) is a Phase III prospective, double-blind, randomized, parallel group, placebo-controlled, multicenter study. It examined the efficacy and safety of Afinitor plus best supportive care (BSC) vs placebo plus BSC in 302 patients with unresectable, progressive, well-differentiated nonfunctional, locally advanced or metastatic NET of GI (excluding pancreatic) or lung origin. The primary endpoint of RADIANT-4 was PFS based on independent radiological assessment evaluated by Response Evaluation Criteria in Solid Tumors. Secondary endpoints included overall survival and best overall response rate (defined as complete response plus partial response)[3].

Patients were randomized 2:1 to receive a daily dose of Afinitor 10 mg or placebo (supplied as tablets). During treatment, all patients received BSC, which excluded somatostatin analogues (SSAs). Patients had low or intermediate grade histology, no history or active symptoms of carcinoid syndrome, and documented disease progression within the previous 6 months, and were required to have stopped treatment with SSAs for 4 weeks before study entry[3],[11].

The safety profile of Afinitor was consistent with what has been observed in previous studies of this drug[3].

About Afinitor (everolimus) tablets
Afinitor (everolimus) tablets is approved in in more than 110 countries, including the US and in the European Union, for locally advanced, metastatic or unresectable progressive NET of pancreatic origin. Afinitor is not indicated for the treatment of patients with functional carcinoid tumors in the US. Afinitor is now also approved in the US and EU for the treatment of adult patients with progressive, well-differentiated (Grade 1 or Grade 2), nonfunctional neuroendocrine tumors of gastrointestinal or lung origin that are unresectable, locally advanced or metastatic.

It is also approved in more than 120 countries including the US and European Union for advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy (in the US, specifically following sunitinib and sorafenib).

Additionally, Afinitor is approved in more than 110 countries including the United States and European Union for advanced HR+/HER2- breast cancer in combination with
exemestane, after prior endocrine therapy.

Everolimus is also available from Novartis for use in certain non-oncology patient populations under the brand names Afinitor or Votubia, Certican and Zortress and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Indications vary by country and not all indications are available in every country. The safety and efficacy profile of everolimus has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for additional indications anywhere else in the world.

Important Safety Information about Afinitor (everolimus) tablets
Afinitor/Votubia can cause serious side effects including lung or breathing problems, infections (including sepsis), and kidney failure, which can lead to death. Patients taking concomitant angiotensin-converting enzyme (ACE) inhibitors may be at an increased risk for angioedema. Mouth ulcers and mouth sores are common side effects. Afinitor/Votubia can affect blood cell counts, kidney and liver function, and blood sugar, cholesterol, and triglyceride levels. Afinitor/Votubia may cause fetal harm in pregnant women. Highly effective contraception is recommended for women of child-bearing potential while receiving Afinitor/Votubia and for up to eight weeks after ending treatment. Women taking Afinitor/Votubia should not breast feed. Fertility in women and men may be affected by treatment with Afinitor/Votubia.