From Bristol-Myers Squibb:

CheckMate -017, A Phase 3 Study of Opdivo (Nivolumab) Compared to Docetaxel in Patients with Second-Line Squamous Cell Non-small Cell Lung Cancer, Stopped Early

Opdivo demonstrates superior overall survival in this Phase 3 trial

Sunday, January 11, 2015 9:06 pm EST

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) today announced that an open-label, randomized Phase 3 study evaluating Opdivoversus docetaxel in previously treated patients with advanced, squamous cell non-small cell lung cancer (NSCLC) was stopped early because an assessment conducted by the independent Data Monitoring Committee (DMC) concluded that the study met its endpoint, demonstrating superior overall survival in patients receiving Opdivo compared to the control arm. The company will share these data – which for the first time indicate a survival advantage with an anti-PD1 immune checkpoint inhibitor in lung cancer – with health authorities.

CheckMate -017 investigators are being informed of the decision to stop the comparative portion of the trial. Bristol-Myers Squibb is working to ensure that eligible patients will be informed of the opportunity to continue or start treatment with Opdivo in an open-label extension as part of the company’s commitment to providing patient access to Opdivo, and characterizing long-term survival. The company will complete a full evaluation of the final CheckMate -017 data and work with investigators on the future presentation and publication of the results.

About the Study

CheckMate -017 is a Phase 3, open-label, randomized study of Opdivo versus docetaxel in previously treated patients with advanced or metastatic squamous cell NSCLC. The trial randomized 272 patients to receive either nivolumab 3 mg/kg intravenously every two weeks or docetaxel 75 mg/m2 intravenously every three weeks. The primary endpoint is overall survival. Secondary endpoints include objective response rate and progression free survival.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally, resulting in more than 1.5 million deaths each year according the World Health Organization. NSCLC is one of the most common types of the disease and accounts for approximately 85 percent of cases. Survival rates vary depending on the stage and type of the cancer when it is diagnosed. Globally, the five-year survival rate for Stage I NSCLC is between 47 and 50 percent; for Stage IV NSCLC, the five-year survival rate drops to two percent. Historically, the expected one-year survival rate for third-line squamous cell NSCLC patients is approximately 5.5% - 18%.

Immuno-Oncology at Bristol-Myers Squibb

Surgery, radiation, cytotoxic or targeted therapies have represented the mainstay of cancer treatment over the last several decades, but long-term survival and a positive quality of life have remained elusive for many patients with advanced disease.

To address this unmet medical need, Bristol-Myers Squibb is leading research in an innovative field of cancer research and treatment known as immuno-oncology, which involves agents whose primary mechanism is to work directly with the body’s immune system to fight cancer. The company is exploring a variety of compounds and immunotherapeutic approaches for patients with different types of cancer, including researching the potential of combining immuno-oncology agents that target different and complementary pathways in the treatment of cancer.

Bristol-Myers Squibb is committed to advancing the science of immuno-oncology, with the goal of changing survival expectations and the way patients live with cancer.

About Opdivo

Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials – as monotherapy or in combination with other therapies – in which more than 7,000 patients have been enrolled worldwide.

In the U.S., Opdivo is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

IMPORTANT SAFETY INFORMATION

Immune-Mediated Pneumonitis

• Severe pneumonitis or interstitial lung disease, including fatal cases, occurred with OPDIVO treatment. Across the clinical trial experience in 574 patients with solid tumors, fatal immune-mediated pneumonitis occurred in 0.9% (5/574) of patients receiving OPDIVO; no cases occurred in Trial 1. In Trial 1, pneumonitis, including interstitial lung disease, occurred in 3.4% (9/268) of patients receiving OPDIVO and none of the 102 patients receiving chemotherapy. Immune-mediated pneumonitis occurred in 2.2% (6/268) of patients receiving OPDIVO; one with Grade 3 and five with Grade 2. Monitor patients for signs and symptoms of pneumonitis. Administer corticosteroids for Grade 2 or greater pneumonitis. Permanently discontinue OPDIVO for Grade 3 or 4 and withhold OPDIVO until resolution for Grade 2.

Immune-Mediated Colitis

• In Trial 1, diarrhea or colitis occurred in 21% (57/268) of patients receiving OPDIVO and 18% (18/102) of patients receiving chemotherapy. Immune-mediated colitis occurred in 2.2% (6/268) of patients receiving OPDIVO; five with Grade 3 and one with Grade 2. Monitor patients for immune-mediated colitis. Administer corticosteroids for Grade 2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO for Grade 2 or 3. Permanently discontinue OPDIVO for Grade 4 colitis or recurrent colitis upon restarting OPDIVO.

Immune-Mediated Hepatitis

• In Trial 1, there was an increased incidence of liver test abnormalities in the OPDIVO-treated group as compared to the chemotherapy-treated group, with increases in AST (28% vs 12%), alkaline phosphatase (22% vs 13%), ALT (16% vs 5%), and total bilirubin (9% vs 0). Immune-mediated hepatitis occurred in 1.1% (3/268) of patients receiving OPDIVO; two with Grade 3 and one with Grade 2. Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater transaminase elevations. Withhold OPDIVO for Grade 2 and permanently discontinue OPDIVO for Grade 3 or 4 immune-mediated hepatitis.

Immune-Mediated Nephritis and Renal Dysfunction

• In Trial 1, there was an increased incidence of elevated creatinine in the OPDIVO-treated group as compared to the chemotherapy-treated group (13% vs 9%). Grade 2 or 3 immune-mediated nephritis or renal dysfunction occurred in 0.7% (2/268) of patients. Monitor patients for elevated serum creatinine prior to and periodically during treatment. For Grade 2 or 3 serum creatinine elevation, withhold OPDIVO and administer corticosteroids; if worsening or no improvement occurs, permanently discontinue OPDIVO. Administer corticosteroids for Grade 4 serum creatinine elevation and permanently discontinue OPDIVO.

Immune-Mediated Hypothyroidism and Hyperthyroidism

• In Trial 1, Grade 1 or 2 hypothyroidism occurred in 8% (21/268) of patients receiving OPDIVO and none of the 102 patients receiving chemotherapy. Grade 1 or 2 hyperthyroidism occurred in 3% (8/268) of patients receiving OPDIVO and 1% (1/102) of patients receiving chemotherapy. Monitor thyroid function prior to and periodically during treatment. Administer hormone replacement therapy for hypothyroidism. Initiate medical management for control of hyperthyroidism.

Other Immune-Mediated Adverse Reactions

• In Trial 1, the following clinically significant, immune-mediated adverse reactions occurred in less than 1% of OPDIVO-treated patients: pancreatitis, uveitis, demyelination, autoimmune neuropathy, adrenal insufficiency, and facial and abducens nerve paresis. Across clinical trials of OPDIVO administered at doses 3 mg/kg and 10 mg/kg, additional clinically significant, immune-mediated adverse reactions were identified: hypophysitis, diabetic ketoacidosis, hypopituitarism, Guillian-Barré syndrome, and myasthenic syndrome. Based on the severity of adverse reaction, withhold OPDIVO, administer high-dose corticosteroids, and, if appropriate, initiate hormone-replacement therapy.

Embryofetal Toxicity

• Based on its mechanism of action, OPDIVO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and for at least 5 months after the last dose of OPDIVO.

Lactation

• It is not known whether OPDIVO is present in human milk. Because many drugs, including antibodies, are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from OPDIVO, advise women to discontinue breastfeeding during treatment.

Serious Adverse Reactions

• Serious adverse reactions occurred in 41% of patients receiving OPDIVO. Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to <5% of patients receiving OPDIVO were abdominal pain, hyponatremia, increased aspartate aminotransferase, and increased lipase.

Common Adverse Reactions

The most common adverse reaction (≥20%) reported with OPDIVO was rash (21%).

Please see US Full Prescribing Information for OPDIVO.

About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono Pharmaceutical further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan. Ono Pharmaceutical received manufacturing and marketing approval in Japan for Opdivo in July 2014 for the treatment of patients with unresectable melanoma, making Opdivo the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit www.bms.com, or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward-Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that Opdivo will receive regulatory approval for an additional indication in lung cancer or, if approved, that it will become commercially successful. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2013 in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

Sandoz biosimilar filgrastim recommended for approval by FDA Oncologic Drugs Advisory Committee

From Novartis:

January 07, 2015 21:57 CET

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Sandoz biosimilar filgrastim recommended for approval by FDA Oncologic Drugs Advisory Committee

• Oncologic Drugs Advisory Committee (ODAC) votes in favor of recommending biosimilar filgrastim for approval in the US
• Biosimilar filgrastim recommended to be approved for use in all requested indications
• Committee's recommendation based on review of extensive data from analytical, non-clinical, clinical studies and post-marketing pharmacovigilance

Holzkirchen, January 7, 2014 - Sandoz, a Novartis company, announced today that US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) recommended approval of its investigational biosimilar filgrastim in the US. The Committee also recommended approval of the biosimilar for use in all indications included in the reference product's (Amgen's NEUPOGEN®) label.

"We are pleased with the ODAC's recommendation to approve our biosimilar filgrastim and we look forward to continuing to work with FDA as it completes its review of our filing," said Mark McCamish, M.D., Ph.D., Head of Global Biopharmaceutical & Oncology Injectables Development at Sandoz. "We are proud to lead the way in biosimilars globally and believe this positive recommendation brings us one step closer to delivering high-quality biosimilars to patients in the US."

The recommendation was provided after the presentation of a comprehensive package of nonclinical, clinical and post-marketing pharmacovigilance data which confirmed Sandoz' biosimilar filgrastim is highly similar to the reference product (Amgen's NEUPOGEN®). The pivotal clinical package included a pharmacokinetic and pharmacodynamics (PK/PD) study in healthy volunteers, which established bioequivalence, and a clinical efficacy and safety study in breast cancer patients which demonstrated the same clinical performance and safety as the reference product.

The clinical package is also supported by a global program including five randomized, double-blind, single and multiple dose PK/PD studies in healthy volunteers to assess pharmacokinetic and pharmacodynamic equivalence between biosimilar filgrastim and NEUPOGEN® and a European non-comparative clinical safety and efficacy study. Post-marketing pharmacovigilance data from countries outside of the US also contributed to the totality of evidence.

Under the brand name ZARZIO®, the Sandoz biosimilar filgrastim has been marketed in more than 40 countries outside the US, generating nearly 7.5 million patient-exposure days of experience. If approved in the US, Sandoz proposes to market biosimilar filgrastim under the name ZARXIOTM.

FDA frequently seeks the advice of its advisory committees as it reviews and decides whether to approve treatments, although it is not obligated to follow the recommendation.

Sandoz is the global leader with over 50 percent volume share of all biosimilars approved in the highly-regulated markets of Canada, Europe, Japan and Australia. Sandoz currently markets three biosimilars outside the US; each of which occupies the #1 biosimilar position in its respective category. Sandoz biosimilars are sold in over 60 countries and have generated over 200 million patient-exposure days in experience. Sandoz also has an unrivalled biosimilars pipeline with several molecules in various stages of development, including six molecules in Phase III clinical trials/registration - more than any other company in the industry.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "recommended," "votes in favor of recommending," "recommendation," "investigational," "look forward," "believe," "will," or similar terms, or by express or implied discussions regarding potential future product approvals, or regarding potential revenues from biosimilar filgrastim or any potential future products. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that biosimilar filgrastim will be approved for sale in any additional markets, or at any particular time. Neither can there be any guarantee that any other potential future products will be submitted or approved for sale in any market, or at any particular time. Nor can there be any guarantee that biosimilar filgrastim or any other potential future products will be commercially successful in the future. In particular, management's expectations regarding biosimilar filgrastim and such other potential future products could be affected by, among other things, the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; competition in general, including approval of additional versions of biosimilar filgrastim; the company's ability to obtain or maintain proprietary intellectual property protection, including unexpected patent litigation outcomes; government, industry and general public pricing pressures; unexpected manufacturing issues; general economic and industry conditions, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Sandoz
Sandoz, a Novartis company, is a global leader in the generic pharmaceutical sector. Sandoz employs over 26,500 employees across more than 160 countries, offering a broad range of high-quality, affordable products that are no longer protected by patents. With USD 9.2 billion in sales in 2013, Sandoz has a portfolio of approximately 1,100 molecules, and holds the #1 position globally in biosimilars as well as in generic injectables, ophthalmics, dermatology and antibiotics, complemented by leading positions in the cardiovascular, metabolism, central nervous system, pain, gastrointestinal, respiratory, and hormonal therapeutic areas. Sandoz develops, produces, and markets these medicines, as well as active pharmaceutical and biotechnological substances. Nearly half of Sandoz's portfolio is in differentiated products, which are defined as products that are more difficult to scientifically develop and manufacture than standard generics. In addition to strong organic growth since consolidating its generics businesses under the Sandoz brand name in 2003, Sandoz has benefitted from strong growth of its acquisitions, which include Lek (Slovenia), Sabex (Canada), Hexal (Germany), Eon Labs (US), EBEWE Pharma (Austria), Oriel Therapeutics (US), and Fougera Pharmaceuticals (US).

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Novartis collaborates with Intellia Therapeutics and Caribou Biosciences to explore making medicines and drug discovery tools with CRISPR genome editing technology

From Novartis:

January 07, 2015 07:15 CET

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Novartis collaborates with Intellia Therapeutics and Caribou Biosciences to explore making medicines and drug discovery tools with CRISPR genome editing technology

• Collaborations give Novartis access to novel CRISPR technology platforms for the discovery and development of new medicines
• Intellia Therapeutics collaboration to explore therapeutic options for using CRISPR to engineer chimeric antigen receptor T-cells and hematopoietic stem cells
• Caribou Biosciences collaboration focused on using CRISPR as a research tool for drug discovery

Basel, Switzerland, January 7, 2015 - Novartis announced today that it has signed collaboration and licensing agreements with Intellia Therapeutics for the discovery and development of new medicines using CRISPR genome editing technology and Caribou Biosciences for the development of drug discovery tools. Intellia and Caribou are two of the leading biotechnology companies developing this novel technology.

CRISPR, an acronym that stands for clustered regularly interspaced short palindromic repeats, is an approach that allows scientists to easily and precisely edit the genes of targeted cells. In a short period of time it has proven to be a powerful tool for creating very specific models of disease for use in drug discovery and has great potential for use as a therapeutic modality for treating disease at the genetic level by deleting, repairing or replacing the genes that cause disease.

"We have glimpsed the power of CRISPR tools in our scientific programs in NIBR, and it is now time to explore how to safely extend this powerful technology to the clinic," said Mark Fishman, President of the Novartis Institutes for BioMedical Research (NIBR). " CRISPR has the potential to open a new branch of medicine, editing the genome to cure disease. Much remains to be learned, and we are delighted to explore these directions with colleagues from Intellia and Caribou. "

The alliance with Intellia combines the resources, research expertise and cell and gene therapy leadership at the Novartis Institutes for BioMedical Research with Intellia's rapidly growing CRISPR expertise and organization. Research and development activities will focus on using CRISPR ex vivo for engineering chimeric antigen receptor T-cells (CARTs) and hematopoietic stem cells (HSCs). The collaboration and licensing agreement with Caribou is focused on using Caribou's foundational CRISPR platform and intellectual property as a research tool for drug discovery.

Under the terms of the agreement with Intellia, Novartis is receiving exclusive rights to develop all collaboration programs focused on engineered CARTs and the right to develop an undisclosed number of targets for ex vivo editing of HSCs. In addition Novartis receives non-exclusive rights for limited in vivo therapeutic applications of CRISPR systems. Novartis is increasing its equity investment in Intellia, is making an upfront payment and will provide technology access fees and funding for R&D programs during the 5-year term of the collaboration. Intellia is also eligible to receive downstream success-based milestones and royalties. Under the terms of the agreement with Caribou, Novartis is receiving non-exclusive rights to Caribou's CRISPR platform for research conducted during the collaboration and is providing funding for the one-year research program. Novartis is also making an equity investment in the company.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by words such as "commits," "to explore," "focused on," "potential," "may," "remains," "will," "eligible," or similar terms, or by express or implied discussions regarding potential marketing approvals for products developed through the collaborations with Intellia Therapeutics and Caribou Biosciences, or regarding potential future revenues from such products, the application of the CRISPR genome editing technology, or any other technologies developed through these collaborations. You should not place undue reliance on these statements. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that any products or other technologies will arise from the collaborations with Intellia Therapeutics and Caribou Biosciences. Neither can there be any guarantee that any products arising from or developed through these collaborations will be submitted or approved for sale in any market, or at any particular time. Nor can there be any guarantee that any product or other technology arising from or developed through these collaborations will receive regulatory approval or be commercially successful in the future. In particular, management's expectations regarding the CRISPR genome editing technology, potential products and other technologies could be affected by, among other things, the uncertainties inherent in research and development, including unexpected clinical trial results and additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain proprietary intellectual property protection; general economic and industry conditions; global trends toward health care cost containment, including ongoing pricing pressures; unexpected manufacturing issues, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and over-the-counter products. Novartis is the only global company with leading positions in these areas. In 2013, the Group achieved net sales of USD 57.9 billion, while R&D throughout the Group amounted to approximately USD 9.9 billion (USD 9.6 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 130,000 full-time-equivalent associates and sell products in more than 150 countries around the world. For more information, please visit http://www.novartis.com.

Novartis is on Twitter. Sign up to follow @Novartis at http://twitter.com/novartis.

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Merck Partners with Scientists & Biotech Entrepreneurs

Merck Partners with Academic Scientists and Biotechnology Entrepreneurs to Create the California Institute for Biomedical Research (Calibr)

Calibr Presents a New Paradigm for Academic-Industry Cooperation

Whitehouse Station, NJ, and San Diego, March 15, 2012 - Merck, known outside the United States and Canada as MSD, today announced a collaboration to create the California Institute for Biomedical Research (Calibr), an independent, not-for-profit organization (501c3) established to accelerate the translation of basic biomedical research into innovative, new medicines to treat disease. Calibr will be led by Peter G. Schultz, Ph.D., a world-renowned chemist and biotechnology entrepreneur. The Institute will offer academic scientists, around the world, a streamlined, efficient and flexible path for translating their biomedical research into novel medicines. "Calibr represents a new paradigm for early-stage translational research," said Dr. Schultz, director of Calibr and Scripps Professor of Chemistry at The Scripps Research Institute. "By leveraging the drug discovery expertise and resources of Calibr, academic researchers will have the opportunity to maximize the potential therapeutic value of their research." Calibr investigators will work collaboratively with academic scientists to advance new discoveries to preclinical proof of concept at which stage commercial partnerships will be sought for further development. Merck will provide funding to Calibr of up to $90 million over a period of seven years. Merck has an option to obtain an exclusive commercial license to any proteins or small molecule therapeutic candidates derived from work conducted by Calibr. For any projects not licensed by Merck, Calibr will be free to seek alternative sources of funding for further development. In addition, the Institute plans to access funds from government and non-government sources. Revenues derived from licenses will be shared between Calibr and the collaborating institutions. Project proposals from the scientific community will be chosen on the basis of novelty, biomedical impact and technical feasibility and reviewed by a scientific advisory board headed by Christopher T. Walsh, Ph.D., Hamilton Kuhn Professor, Department of Biological Chemistry and Pharmacology, Harvard University. In addition, an independent board of directors headed by John D. Diekman, Ph.D., founder and managing partner of 5AM Ventures will oversee the activities of the Institute. "Effective translation of basic biomedical research is essential to advancing the next generation of novel therapies," said Peter S. Kim, Ph.D., president, Merck Research Laboratories and member of Calibr scientific advisory board. "Calibr will provide an important venue where basic research and drug discovery scientists may leverage each others' strengths in the fight against disease." Calibr will be located in San Diego, Calif., in close proximity to The Scripps Research Institute, Salk Institute, University of California, San Diego and Sanford-Burnham Medical Research Institute. Calibr will be equipped with the latest high through-put screening and imaging, medicinal and protein chemistry and preclinical sciences capabilities.