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Bayer HealthCare announced that data from more than 30 clinical trials evaluating three products in the company’s oncology portfolio – Nexavar(R) (sorafenib) tablets, regorafenib (BAY 73-4506) and Alpharadin(TM) – will be presented at the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress, September 20-24, 2009 in Berlin, Germany.

“Bayer is committed to discovering and developing innovative cancer-fighting therapies, and as a global organization with widespread reach and impact, we are able to apply our experience, knowledge and passion to offer treatments that may make life better for cancer patients across the globe,” said Rob Rosen, Head of the Therapeutic Area Oncology at Bayer HealthCare. “While much progress has been made in the treatment of cancer, there is still an unmet medical need for improved therapies that may help patients manage their disease, ultimately treating cancer as a chronic illness, rather than a devastating disease.”

Nexavar Data Highlights

Nexavar is currently approved in more than 80 countries for the treatment of patients with hepatocellular carcinoma (HCC), or liver cancer, and in more than 90 countries for the treatment of patients with advanced renal cell carcinoma (RCC), or kidney cancer. Even though these indications are well established, the utility of Nexavar continues to be evaluated in these tumor types, with ongoing studies examining special patient populations and long-term use. Data on these indications being presented at ECCO-ESMO include results from two Phase III studies evaluating Nexavar in HCC and six studies examining Nexavar in RCC.

In addition to its current indications, Nexavar continues to be evaluated as a single agent or combination treatment in a wide range of cancers, including breast cancer, thyroid cancer, and as an adjuvant therapy for kidney cancer and liver cancer. Data from a recently unblinded Phase II trial evaluating the safety and efficacy of Nexavar as a potential treatment for breast cancer will be presented during an oral session at ECCO-ESMO. This trial examined Nexavar compared to placebo in combination with the oral chemotherapeutic agent, capecitabine, in patients with locally advanced or metastatic breast cancer. (Late-breaking presentation 3LBA, Presidential Session III, Wednesday, September 23, 1:30 p.m. CET, Hall 1)

Additionally, data from a completed Phase II study of single-agent Nexavar in patients with thyroid cancer will be presented at the congress. (Late-breaking poster 51LBA, Poster 276, Tuesday, September 22, 9:00 a.m.-5:00 p.m. CET, Hall 14.1)

Nexavar is being co-developed by Bayer HealthCare Pharmaceuticals Inc. and Onyx Pharmaceuticals, Inc.

Regorafenib Data Highlights

A promising development compound in the oncology portfolio pipeline is regorafenib (BAY 73-4506), a potent oral multi-kinase inhibitor with a kinase inhibition profile targeting angiogenic, stromal and oncogenic receptor tyrosine kinases (TK). The anti-angiogenic activity found with regorafenib is due to its distinct dual targeted VEGFR2-TIE2 TK inhibition. Regorafenib is currently being studied as a potential treatment option in multiple tumor types. Updated results from a Phase II trial of regorafenib in patients with RCC will be presented at ECCO-ESMO during an oral session. (Abstract 7105, Tuesday, September 22, 10:15 a.m. CET, Hall 15.1)

Alpharadin Data Highlights

Bayer Schering Pharma AG, Germany, recently entered into a global agreement with Algeta ASA, Oslo, Norway for the development and commercialization of Alpharadin, a novel alpha-emitting radiopharmaceutical, based on radium-223. Alpharadin is currently being evaluated in a global Phase III trial for the treatment of bone metastases in symptomatic hormone-refractory prostate cancer (HRPC) patients. Three Phase II trials evaluating the safety and efficacy of Alpharadin will be presented at ECCO-ESMO, including an oral presentation on the results from a 122-patient efficacy and safety study designed to compare the prostate cancer specific antigen (PSA) response rate of three different repeat doses of Alpharadin. (Abstract 7003, Monday, September 21, 11:45 a.m. CET, Hall 3)

Nexavar’s Differentiated Mechanism

Nexavar targets both the tumor cell and tumor vasculature. In preclinical studies, Nexavar has been shown to target members of two classes of kinases known to be involved in both cell proliferation (growth) and angiogenesis (blood supply) – two important processes that enable cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET.

Nexavar is currently approved in more than 80 countries for the treatment of patients with liver cancer and in more than 90 countries for the treatment of patients with advanced kidney cancer. Nexavar is also being evaluated by the companies, international study groups, government agencies and individual investigators as a single agent or combination treatment in a wide range of cancers, including breast cancer, colorectal cancer, lung cancer, ovarian cancer, and as an adjuvant therapy for kidney cancer and liver cancer.

Important Safety Considerations For Patients Taking Nexavar

Based on the currently approved U.S. package insert for the treatment of patients with unresectable hepatocellular carcinoma and advanced kidney cancer, hypertension may occur early in the course of therapy and blood pressure should be monitored weekly during the first six weeks of therapy and treated as needed. In HCC patients, bleeding with a fatal outcome from any site was reported in 2.4% for Nexavar and 4% in placebo. The incidence of treatment-emergent cardiac ischemia/infarction was 2.7% for Nexavar vs. 1.3% for placebo. In RCC patients, incidence of bleeding regardless of causality was 15% for Nexavar vs. 8% for placebo and the incidence of treatment-emergent cardiac ischemia/infarction was 2.9% for Nexavar vs. 0.4% for placebo. Most common adverse events 20% related to Nexavar for both HCC and RCC were fatigue, weight loss, rash/desquamation, hand-foot skin reaction, alopecia, diarrhea, nausea, and abdominal pain. Grade 3/4 adverse events in HCC and RCC patients, respectively, were 45% for Nexavar vs. 32% for placebo and 38% for Nexavar and 28% for placebo. Women of child-bearing potential should be advised to avoid becoming pregnant and advised against breast-feeding. In cases of any severe or persistent side effects, temporary treatment interruption, dose modification or permanent discontinuation should be considered.

About Regorafenib (BAY 73-4506)

Regorafenib (BAY 73-4506) is a potent oral multi-kinase inhibitor with a kinase inhibition profile targeting angiogenic, stromal and oncogenic receptor tyrosine kinases (TK). The anti-angiogenic activity found with regorafenib is due to its distinct dual targeted VEGFR2-TIE2 TK inhibition. Regorafenib has also been shown in preclinical studies to prevent the proliferation of tumor cell lines while promoting apoptosis (cell death) by directly targeting several oncogenic TK receptors. The clinical significance of these studies is not known and warrant further investigation in a broad spectrum of tumors.

About Alpharadin

Alpharadin (radium-223 chloride) represents a first in class opportunity of cancer therapy based on alpha-radiation, offering highly targeted treatment of bone metastases by delivering radiation directly to the tumor cells with low exposure to the surrounding tissue. Alpharadin is being co-developed between Bayer Schering Pharma and Algeta ASA. While Alpharadin is currently being evaluated in a global Phase III trial in patients with HRPC and skeletal metastases, the companies see potential in investigating Alpharadin for the treatment of bone metastases from other tumor types.

About Bayer HealthCare Pharmaceuticals Inc.

Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals unit of Bayer HealthCare LLC, a division of Bayer AG. One of the world’s leading, innovative companies in the healthcare and medical products industry, Bayer HealthCare combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. In the U.S., Bayer HealthCare Pharmaceuticals comprises the following business units: Women’s Healthcare, Diagnostic Imaging, Specialized Therapeutics, Hematology/Cardiology and Oncology. The company’s aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

About Onyx Pharmaceuticals, Inc.

Onyx Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of people with cancer. The company, in collaboration with Bayer HealthCare Pharmaceuticals, Inc., is developing and marketing Nexavar((R)) (sorafenib) tablets, a small molecule drug.

Forward Looking Statements

This news release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here.

Nexavar((R)) (sorafenib) tablets is a registered trademark of Bayer HealthCare Pharmaceuticals Inc.

Source: Bayer HealthCare

View drug information on Nexavar.

Intarcia Therapeutics, Inc. announced the start of enrollment for a phase 2 study comparing its proprietary drug candidate ITCA 650 (DUROS continuous delivery of exenatide) with Byetta, an FDA-approved twice-daily injection form of exenatide. Building upon the successful completion of a 28-day phase 1b study of ITCA 650 in May of this year, the phase 2 study is intended to evaluate the doses achieving the best results in the phase 1b in a larger study population and for a longer duration of treatment. In addition, an extension phase of the phase 2 study will evaluate dose response of ITCA 650. Patients receiving Byetta for the first 12 weeks will be switched from Byetta to one of two doses of ITCA 650 to evaluate the potential for improving treatment effect.

“We are very pleased with the rapid progress and positive results achieved thus far in the ITCA 650 program” said Ken Luskey, MD, VP, Clinical Research for Intarcia. “In 2009, we expect to move the ITCA 650 program from IND-filing through completion of phase 2 enrollment.”

The ITCA 650 phase 2 study will involve 150 patients with sub-optimally controlled type 2 diabetes treated with metformin. Patients will be recruited at 50 clinical trial sites in the US and will be randomized equally to receive one of two doses of ITCA 650 or twice-daily injections of Byetta. Upon completion of the 12-week course of treatment, patients on all three arms will be further randomized to receive higher doses of ITCA 650 for an additional 12 weeks. The extension phase will evaluate efficacy and tolerability of higher doses of ITCA 650, as well as the effects of switching patients from twice-daily injections of Byetta to ITCA 650. The study will provide important information to support dose selection for ITCA 650 phase 3 evaluation, anticipated to begin in the second half of 2010. Additionally, this phase 2 study will provide important insights into future clinical use of ITCA 650 with respect to switching patients from injectable Byetta therapy to ITCA 650.

“We have received strong interest in the ITCA 650 program since the late-breaker presentation of preliminary phase 1b study results at the American Diabetes Association Conference in June” said K. Alice Leung, President and CEO of Intarcia. “We intend to select a commercial partner for ITCA 650 prior to the start of phase 3 in the second half of 2010.”

About ITCA 650

ITCA 650 therapy for type 2 diabetes consists of DUROS continuous delivery of exenatide. The DUROS delivery technology comprises the proprietary DUROS device, a matchstick-size miniature osmotic pump that is inserted subcutaneously to provide continuous and consistent drug therapy, and proprietary formulation technology that maintains stability of therapeutic proteins and peptides at human body temperature for extended periods of time. The DUROS technology can deliver up to a full year of therapy from a single ITCA 650 insertion. Unlike other extended delivery technologies, such as polymers or albumin fusions, DUROS delivery allows for steady state drug delivery upon insertion and near immediate withdrawal of therapy to manage side effects, if required. Exenatide, the active agent in ITCA 650, has been approved in the US, Europe and many other markets and is currently marketed as a twice-daily self-injection therapy for type 2 diabetes.

About Intarcia

Intarcia Therapeutics, Inc. is a biopharmaceutical company developing therapies to ensure enhanced treatment outcome by optimizing patient adherence and improving the convenience and tolerability of drug therapies. Intarcia’s drug development expertise and competitive edge are demonstrated by its abilities to stabilize proteins and peptides at human body temperature and to deliver them in a constant and consistent manner via the proprietary DUROS drug delivery platform. Intarcia is pursuing clinical stage development programs for type 2 diabetes and hepatitis C.

Intarcia and its logo are registered trademarks of Intarcia Therapeutics, Inc. DUROS is a registered trademark of ALZA Corporation licensed to Intarcia Therapeutics, Inc. in certain fields. Byetta is a registered trademark of Amylin Pharmaceuticals, Inc.

Source: Intarcia Therapeutics, Inc

View drug information on Byetta.

The US Food and Drug Administration (FDA) has approved Valturna((R)) (aliskiren and valsartan) tablets, the first and only medicine to target two key points within the renin system, also known as the renin angiotensin aldosterone system (RAAS), an important regulator of blood pressure. This is the first approval for Valturna, which is indicated for the treatment of high blood pressure in patients not adequately controlled on aliskiren or angiotensin receptor blocker (ARB) monotherapy and as initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals.

“This unique combination brings together the powerful blood pressure lowering effects of valsartan and aliskiren,” said Joe Jimenez, CEO of the Novartis Pharmaceuticals Division. “It offers an important additional treatment option for physicians and hypertension patients, many of whom are not at their blood pressure goal. Valturna builds upon our strong cardiovascular franchise and is consistent with our long-term commitment to developing effective and innovative therapies. It further strengthens our growing portfolio of single-pill combinations to treat high blood pressure.”

Valturna combines in a single pill valsartan, the active ingredient in Diovan((R)), the number one selling branded high blood pressure medicine worldwide, and aliskiren, the active ingredient in Tekturna((R)), the only approved direct renin inhibitor (DRI). Valturna offers significantly greater blood pressure reduction than either valsartan or aliskiren alone.

“When it comes to diagnosing and treating high blood pressure, there is a real need for innovative therapies that help patients get to a healthier blood pressure range,” said John Flack, M.D., Valturna investigator, and Chairman of the Department of Internal Medicine, Wayne State University, Detroit. “Now for the first time, we have a treatment option in one pill that targets two key points of the RAAS, which may be overactive in many hypertensive patients.”

This approval was primarily based on a pivotal eight-week randomized, double-blind, placebo-controlled clinical trial in approximately 1,800 patients, which studied aliskiren 150 mg and 300 mg and valsartan 160 mg and 320 mg alone and in combination. The initial doses of aliskiren and valsartan were 150 mg and 160 mg, respectively, and were increased at four weeks to 300 mg and 320 mg, respectively. Blood pressure reductions with the aliskiren/valsartan combination were significantly greater than with the monotherapies or placebo at the eight-week primary endpoint. Mean systolic and diastolic blood pressure reductions from baseline were 17.2/12.2 mmHg for aliskiren 300 mg/valsartan 320 mg, compared with 12.8/9.7 mmHg for valsartan 320 mg, 13.0/9.0 mmHg for aliskiren 300 mg, and 4.6/4.1 mmHg for placebo (p

The single-pill combination Valturna targets the RAAS in two ways. The valsartan component blocks, at the receptor level, the action of angiotensin II, an important end product of the RAAS that causes blood vessels to tighten and narrow. The aliskiren component reduces angiotensin II levels by directly inhibiting renin, an enzyme produced by the kidneys that starts a process which leads to formation of angiotensin II. An overactive RAAS is an important contributor to high blood pressure in many patients. By targeting two key points within the RAAS, Valturna helps blood vessels relax and widen so blood pressure is lowered.

Research suggests that up to 85% of hypertensive patients may need multiple medications to help control their blood pressure, underscoring the need for effective combination treatments.

High blood pressure affects approximately 74 million, or nearly one in three, US adults. Although high blood pressure can be easily diagnosed and often successfully managed, approximately 36% of US adults treated with antihypertensive medication do not have their blood pressure controlled. If left untreated, high blood pressure can lead to stroke, heart attack, heart failure, kidney failure and vision problems.

Valturna, Tekturna and Diovan are not approved to treat or prevent stroke, heart attack, heart failure, kidney failure or eye problems resulting from high blood pressure.

History of Diovan((R)) (valsartan) tablets and Tekturna((R)) (aliskiren) tablets

Diovan, which marked its 10th anniversary in 2007, is the number one selling branded high blood pressure medicine worldwide. Diovan’s extensive clinical trials program demonstrates the longstanding commitment of Novartis to research.

Tekturna is a direct renin inhibitor in the first new approved class of high blood pressure medicine in more than a decade. Tekturna was approved by the FDA in March 2007 for the treatment of high blood pressure as monotherapy or in combination with other high blood pressure medications. The use of Tekturna in combination with maximal doses of angiotensin-converting enzyme (ACE) inhibitors has not been adequately studied.

The long-term potential of the direct renin inhibitor Tekturna is being evaluated in an extensive clinical program known as ASPIRE HIGHER.

Novartis and Hypertension Management

For decades Novartis has been a leader and innovator in hypertension management, offering a range of innovative therapies designed to help patients with different needs achieve their blood pressure goals. Novartis is dedicated to helping physicians and patients improve cardiovascular and metabolic health through effective medicines, programs and an ongoing commitment to research.

Valturna is available in two strengths as tablets containing aliskiren and valsartan: 150 mg/160 mg and 300 mg/320 mg.

Valturna is a prescription medication for adults containing two medicines in one tablet that work together to lower blood pressure when one is not enough. Valturna may also be used as the first medicine if your doctor decides you are likely to need more than one. Tekturna and Diovan may be used to treat high blood pressure. Tekturna may be used alone or in combination with other high blood pressure medicines. Tekturna has not been adequately studied in combination with the maximum doses of a class of medicines called ACE inhibitors.

Important Safety Information

IMPORTANT WARNING: Valturna, Tekturna, or Diovan may harm an unborn baby, causing injury and death. If you get pregnant, stop taking Valturna, Tekturna, or Diovan and call your doctor right away. If you plan to become pregnant, talk to your doctor about other medicines to treat your high blood pressure before taking Valturna, Tekturna, or Diovan.

Tell your doctor about all of your medical conditions, including kidney or liver problems. Also, tell your doctor about all medicines you take, including those to treat fungal infections, atorvastatin, cyclosporine, and potassium-containing medicines, supplements, or salt substitutes containing potassium.

If you develop an allergic reaction involving swelling of the face, lips, throat and/or tongue that may cause difficulty in breathing or swallowing, stop taking Valturna or Tekturna and contact your doctor immediately.

Your blood pressure may get too low if you also take water pills, are on a low-salt diet, get dialysis treatments, have heart problems, or get sick with vomiting or diarrhea. Lie down if you feel faint or dizzy. Call your doctor right away.

The most serious side effects with Diovan are low blood pressure (hypotension) and kidney problems. Other side effects with Diovan have generally been mild. The most common side effects with Diovan are viral infection, fatigue, and abdominal pain. In clinical studies, the most common side effects experienced by more patients taking Valturna than patients taking a sugar pill was tiredness, sore throat, runny nose, diarrhea, upper respiratory tract infection, urinary tract infection, flu or flu-like symptoms, and dizziness, and for Tekturna, it was diarrhea. Other less common reactions to Tekturna include skin rash, and cough.

Disclaimer

The foregoing release contains forward-looking statements that can be identified by terminology such as “commitment,” “may,” “can,” “risk,” “potential,” “dedicated,” or similar expressions, or by express or implied discussions regarding potential additional marketing approvals for Valturna, potential new indications or labeling for Tekturna, or regarding potential future revenues from Valturna, Tekturna or Diovan. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Valturna will be approved for sale in any additional markets. Nor can there be any guarantee that Tekturna will be approved for any additional indications or labeling in any market. Neither can there be any guarantee that Valturna, Tekturna or Diovan will achieve any particular levels of revenue in the future. In particular, management’s expectations regarding these products could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; the impact that the foregoing factors could have on the values attributed to the Novartis Group’s assets and liabilities as recorded in the Group’s consolidated balance sheet, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. 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 Pharmaceuticals Corporation

Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including those in the cardiovascular, metabolic, cancer, organ transplantation, central nervous system, dermatological, GI and respiratory areas. The company’s mission is to improve people’s lives by pioneering novel healthcare solutions.

Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG, which provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, preventive vaccines, diagnostic tools, cost-saving generic pharmaceuticals, and consumer health products. Novartis is the only company with leading positions in these areas. In 2008, the Group’s continuing operations achieved net sales of USD 41.5 billion and net income of USD 8.2 billion. Approximately USD 7.2 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 98,000 full-time-equivalent associates and operate in more than 140 countries around the world.

Source: Novartis

View drug information on Diovan; Tekturna.

Bolder BioTechnology, Inc. announced that it has been awarded two Phase I Small Business Innovation Research (SBIR) grants totaling $1.2 million from the National Institute of Allergy and Infectious Diseases (NIAID) of The National Institutes of Health (NIH). The grants will be used to perform additional preclinical toxicology and pharmacology studies of the company’s proprietary long-acting G-CSF and GM-CSF analogs. Receipt of the entire grant award is contingent upon the achievement of certain research milestones.

George (Joe) Cox, Ph.D., Company President and Principal Investigator for the grants, said, “We are delighted to receive these grant awards from NIAID to conduct research in Acute Radiation Syndrome (ARS). Through prior research grants from the National Cancer Institute (NCI) we were able to demonstrate that our modified G-CSF and GM-CSF analogs were very effective at accelerating white blood cell recovery in chemotherapy-treated rats. We hope to show similar beneficial effects of our proteins for treating ARS.”

Development of radiological/nuclear countermeasures to treat ARS is a high priority research area for NIAID. Bone marrow is one of the most sensitive tissues to radiation damage and impaired production of blood cells is one of the first clinical signs of excessive radiation exposure, often resulting in death. Drugs such as G-CSF and GM-CSF that stimulate production of white blood cells may potentially improve survival in patients with ARS. Current G-CSF and GM-CSF products require daily administration, typically for 10-15 days, to restore normal white blood cell production. Long-acting G-CSF and GM-CSF analogs that do not require frequent dosing could provide significant treatment advantages in a nuclear emergency setting.

The NIH SBIR program is a peer-reviewed grant program that provides research support to small businesses to discover and develop innovative biomedical products for the treatment of serious unmet medical needs.

Bolder BioTechnology, Inc. uses advanced protein engineering technologies to create proprietary human protein pharmaceuticals with enhanced therapeutic properties for the treatment of hematopoietic and endocrine disorders, cancer and infectious diseases.

Statements contained herein that are not historical facts are forward-looking statements that are subject to a variety of risks and uncertainties. There are a number of important factors that could cause actual results to differ materially from those expressed in any forward-looking statements made by the Company. These factors include, but are not limited to: (1) the Company’s ability to successfully complete product research and development, including pre-clinical and clinical studies, and commercialization; (2) the Company’s ability to obtain required government approvals; (3) the Company’s ability to attract and/or maintain manufacturing, sales, distribution and marketing partners; and (4) the Company’s ability to develop and commercialize its products before its competitors.

Source: Bolder BioTechnology, Inc

Cancer and cell biology experts at the University of Cincinnati (UC) have developed a new mass spectrometry-based tool they say provides more precise, cost-effective data collection for drug discovery efforts.

Preliminary studies have shown that the new mass spectrometry tool – known as MALDI-QqQMS (matrix-assisted laser desorption ionization-triple quadruple mass spectrometer) – provides a superior means of measuring the enzyme reactions critical to drug discovery at speeds comparable to currently available high-throughput screening systems at significantly lower costs.

“If introduced broadly, the new generation mass spectrometry-based method we are proposing could significantly reduce the cost of running drug compound screening assays while also saving drug development teams substantial time by improving the accuracy of data collected,” explains Ken Greis, PhD, associate professor and director of proteomics for the UC College of Medicine’s cancer and cell biology department.

Greis and his colleague Rakesh Rathore, PhD, report their findings online ahead of print Sept. 17, 2009, in the scientific journal Rapid Communications in Mass Spectrometry.

In the drug discovery field, scientists use what is known as a “high-throughput screening system” to rapidly run thousands to millions of tests to screen for inhibitors of molecular targets that could be useful in pharmaceutical drug development and in furthering of understanding of the overall biological mechanisms behind a particular disease.

Typical assays for enzyme screening are fluorescence and chemiluminescence-based systems. To make those assays universal, vendors have developed standard kits using specialized – and costly – reagents to identify changes in the fluorescent or chemiluminescent signals.

“There are a couple of problems with the current approach: For starters, it’s an imperfect method that generates many false-positive “hits” and for due diligence, you have to follow up on all inhibitors identified, which results in a lot of time and money wasted on false leads,” says Greis.

“Reagents are very costly often ranging between 50 cents to $1 per sample. That adds up very quickly when you’re screening against a million-compound library,” adds Rathore, a postdoctoral fellow in Greis’ laboratory.

Greis and Rathore have developed a custom high-throughput screening method using a generalized platform. Unlike the commercially available systems that analyze byproducts and coupled reactions, their system directly measures and quantifies the substrate and the end product of the reaction.

They say using mass spectrometry to measure the mass and quantity of the product gives researchers a direct measure of the assay and more reliable compounds to explore, eliminating the chances for molecular interference common with chemiluminescence and fluorescence-based systems.

“Analytically, our mass spectrometry-based application provides superior data and also eliminates the issue of producing high numbers of false results, saving a tremendous amount of time chasing down bad leads on drug targets. And because we are using these non-tagged reagents, it only costs us 3 to 5 cents per sample to run these assays, which is a huge cost savings,” adds Greis. “That can mean the difference between $50,000 and $1 million in reagent costs for a single screening project.”

The approach developed by the UC group also holds appeal in that it has multiplexing capabilities – making it possible to, measure inhibitors for two or more enzymes with one pass through the compound repository. Typical assays start with one target enzyme and that is tested against an entire compound repository to look for inhibitors. Once inhibitors are identified, researchers must then follow up on each one to see if it has any validity as a drug target.

“Now instead of doing a million-dollar campaign that takes a month to run and then another million-dollar campaign that takes another month to run, we can do both at the same time while still avoiding the false-positives and false-negatives common with currently available methods,” says Greis. “This is one of those disruptive technologies that could completely change the way people do this type of screening work.”

The UC team is working on identifying funding to transition this mass spectrometry-based technology into a fully automated system for commercial use.

In addition to Greis and Rathore, coauthors of the study include William Siebel, PhD, of UC’s Drug Discovery Center and Jay Corr, PhD and Daniel Lebre, PhD, of MDS Analytical Technologies. Rathore’s fellowship is funded by MDS Analytical Technologies.

Source:
Amanda Harper

University of Cincinnati Academic Health Center

Anemia and other conditions related to chronic kidney disease are independently associated with the risk of cardiovascular disease; conversely, heart disease is associated with a decline in kidney function and the development of kidney disease, according to two reports in Archives of Internal Medicine, one of the JAMA/Archives journals.

Chronic kidney disease is becoming increasingly prevalent in the United States and worldwide, according to background information in the articles. Chronic kidney disease is associated with a wide variety of complications, including anemia (low red blood cell count, or red blood cells that are deficient in oxygen-transporting hemoglobin), nerve pain, bone disease, death and cardiovascular disease. Most patients with chronic kidney disease die of complications from heart disease rather than of kidney failure.

In one study, Peter A. McCullough, M.D., M.P.H., of William Beaumont Hospital, Royal Oak, Mich., and colleagues assessed a group of 37,153 individuals who were screened for kidney disease through a community-based program between 2000 and 2003. The participants (average age of 52.9 years) all reported a personal or family history of diabetes, hypertension or kidney disease on a screening survey. Patients had their blood pressure measured and provided blood and urine samples, which were processed to assess three markers of chronic kidney disease:

* estimated glomerular filtration rates (eGFR), or the rate at which kidneys filter blood, calculated based on levels of the waste product creatinine in the blood

* anemia, determined by blood hemoglobin levels

* and microalbuminuria, or slightly high levels (20 milligrams per liter or more) of the protein albumin in the urine

Of the participants who were followed for a maximum of 47.5 months, 5,504 (14.8 percent) had eGFR values of less than 60 milliliters per minute per 1.73 square meters, which were considered abnormal and signs of declining kidney function. In addition, 4,588 (13.1 percent) had anemia; and 15,959 (49.5 percent) had microalbuminuria. A total of 1,835 (4.9 percent) had a history of heart attack, 1,336 (3.6 percent) had a history of stroke and 2,897 (7.8 percent) had a self-reported history of heart attack or stroke.

Each of the three variables – anemia, microalbuminuria and low eGFR – was associated with cardiovascular disease. More than one-fourth of the patients who had all three kidney disease measures had cardiovascular disease, and their survival rates over the course of the study were lower by approximately 93 percent than those of any other group.

“These data suggest that screening for cardiovascular disease would be of high yield among patients with these risk markers but who do not report any history of cardiovascular disease symptoms,” the authors conclude.

In a related study, Essam F. Elsayed, M.D., of Tufts – New England Medical Center, Boston, and colleagues evaluated a total of 13,826 individuals (average age 57.6) who had participated in one of two large cardiovascular health studies. Participants were recruited to the studies between 1987 and 1990 and followed up at approximately three-year intervals for an average of 9.3 years. At the beginning of the study and at each subsequent visit, blood creatinine levels were measured and used to track the decline in kidney function and the development of kidney disease both directly and by calculating eGFR. History of cardiovascular disease, as well as medication use, lifestyle characteristics, and other variables also were collected at the initial assessment.

At the beginning of the studies, 1,787 (12.9 percent) of the participants had cardiovascular disease. As measured by creatinine levels, 520 individuals (3.8 percent) experienced a decline in kidney function – including 128 (7.2 percent) of those with cardiovascular disease and 392 (3.3 percent) of those without cardiovascular disease – and 314 (2.3 percent) developed kidney disease. The presence of cardiovascular disease at the beginning of the study was associated with a decline in kidney function and the development of kidney disease as measured by both creatinine levels and eGFR.

“Our study demonstrates that cardiovascular disease is associated with subsequent kidney function decline and development of kidney disease,” the authors conclude. “This study identifies a population that may benefit from (1) increased cardiovascular disease risk factor surveillance and intervention, (2) heightened awareness of the risk factors associated with kidney disease, and (3) greater attention to and treatment for sequelae of kidney disease.”

“Because these patients are mainly under the care of primary care physicians and cardiologists, it is important to draw attention to the increased risk of kidney disease in this population, with goals of preventing further progression, managing sequelae of kidney disease as they arise and adequately preparing individuals for kidney failure with timely nephrology referrals. Only with recognition of risk factors for kidney disease can this happen.”

(Arch Intern Med. 2007;167:1122-1129, 1130-1136)

Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Focused Approach Will Reduce Heart and Kidney Disease Rates

The presence of cardiovascular disease should now be recognized as a risk factor for the development of kidney disease, and patients with both should be screened and treated accordingly, write Barry I. Freedman, M.D., and Thomas D. DuBose Jr., M.D., of the Wake Forest University School of Medicine, Winston-Salem, N.C., in an accompanying editorial.

These two reports “address the interactive effects of kidney disease and cardiovascular disease risk in more than 50,000 subjects,” they write. “These studies provide novel insights into the relationship between kidney disease and the vasculature.”

“The chances for reducing the current high rates of chronic kidney disease and cardiovascular disease will be maximized when primary care physicians, nephrologists and cardiologists work in partnership to reduce and treat modifiable vascular disease risk factors, including those that are a consequence of kidney disease,” Drs. Freedman and DuBose conclude. “In addition, the potential for achieving current treatment goals in individuals at risk for nephropathy and cardiovascular disease using a more focused approach promises greater reductions in future cardiovascular disease and end-stage renal disease events.”

(Arch Intern Med. 2007;167:1113-1115)

Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

###

Contact: Ilene Wolff
JAMA and Archives Journals

In response to the high demand for key information and best practices for working with clinical oversight groups, ExL proudly presents the Clinical Oversight Groups conference to take place on October 14-15, 2009 in Loews, Philadelphia, Pennsylvania. Sponsors now have the opportunity to learn from industry professionals on how to improve trial managements and decision making through successful interactions with oversight groups.

This groundbreaking event provides clinical trial sponsors with practical information about the purpose, role and responsibilities of each of these types of oversight groups. The overall objectives of the conference are to:
Establish parameters for the use of oversight groups, so that sponsors have a clear understanding of when each type of oversight group is needed for a clinical study.

Provide practical guidance on how to develop appropriate guidelines for oversight group implementation, so that sponsors are familiar with best practice for oversight group compilation, workflow, dataflow, data capture and data analysis.

Present effective models for use of multiple oversight groups on a single trial, so that sponsors gain insight into the relationships between their CECs, DMCs and Steering Committees. This aspect of the conference will address the areas in which oversight group communications and data exchanges most often intersect. It will also cover the areas in which appropriate boundaries and firewalls must be established between oversight groups.

Address best practices to support effective interactions between sponsors and their oversight groups, so that appropriate communications and data exchanges transpire, yet the independent nature of the oversight groups is preserved.
Background:

Clinical oversight groups are an important part of a sponsor’s management strategy for multiple aspects of a wide number of clinical studies. Implementation of expert oversight groups, whose members are independent of the trial sponsor, ensures an objective review of trial data for a number of purposes. Clinical Endpoint Committees (CECs) review and adjudicate study endpoints and provide standardized results which are utilized for statistical analyses of efficacy and safety outcomes. Data Monitoring Committees (DMCs) conduct periodic review of accumulating trial data to monitor patient safety and continually evaluate the emerging Benefit-Risk balance data that is produced as a result of protocol implementation. Steering Committees collaborate with the sponsor across the continuum of trial management, from protocol development to oversight of trial conduct to interpretation of study results. Clinical oversight groups bring value by helping sponsors design and conduct trials that are ethical and that produce valid and credible results.

Having full knowledge and understanding of CEC, DMC and Steering Committee processes enables sponsors to successfully implement oversight groups in appropriate settings, resulting in sound and effective decision making for on-going clinical projects.

Conference Sponsors:

The event is sponsored by Axio and Quintiles, and supported by the Society for Clinical Data Management (SCDM) and the Association of Clinical Research Professionals (ACRP).

Additional Information:

The Clinical Oversight Groups’ complete program is available for review here.

For registration information, visit the conference website or email: registerexlpharma. Please reference priority code P434PR when registering or inquiring about the event.

Take advantage of the special group discounts. Register three people and receive 15% off of each registration. Register four people and receive 25% off of each registration. Please note that all three must register at the same time.

About ExL Pharma:

ExL Pharma is a leader in developing innovative, educational events that serve the healthcare community and allied professionals. Behind a diverse conference portfolio, an experienced team conducts extensive market research and targeted outreach. The results translate into innovative, high-quality conference events designed to exceed the dynamic informational needs of the healthcare community.

Source:
Jasmaine John
Marketing Director 
ExL Pharma 

555 8th Avenue, Suite.310

New York, NY 10018

Abbott today reported further progress in meeting its goal of a 5 percent reduction in the amount of packaging used in its key products by 2013, part of a multi-faceted effort to minimize its impact on the environment. To achieve this goal, the company has launched, or is in the process of launching, more than 40 sustainable packaging initiatives across its nutrition, pharmaceutical and medical products businesses. The initiatives are driven by new standards and guidelines developed by Abbott that encourage increased use of lighter and sustainable materials in package design.

“Abbott’s sustainable packaging initiatives will reduce our environmental footprint through less waste in landfills, more responsible forest management and fewer emissions. At the same time, it lowers cost, and, in some cases, reduces shelf space for our customers,” said John Landgraf, senior vice president, Pharmaceuticals, Manufacturing and Supply, Abbott. “Throughout the world, consumers increasingly expect the companies they do business with to be environmentally responsible citizens and Abbott is rising to that challenge.”

Abbott partners with a number of industry and independent groups in the area of sustainable packaging, such as the Sustainable Packaging Coalition. Abbott also is working with suppliers who have achieved or are pursuing certification, with respected sustainability organizations, such as the Program for the Endorsement of Forest Certification, the Forest Stewardship Council and the Sustainable Forestry Initiative. In addition, Abbott recently announced sponsorship of the newly created Michigan State University’s Center for Packaging Innovation and Sustainability, which provides a forum to bridge academic research with Abbott’s real-world application expertise.

“Abbott has been actively working to benchmark and measure progress in making its packaging more sustainable,” said Anne Johnson, director, Sustainable Packaging Coalition, a project of GreenBlue, a nonprofit sustainability institute that works with the private sector to enable the positive redesign of industrial systems. “Given the material challenges of packaging for health care products, it is impressive to see that they have put systems in place in recent years that have resulted in tangible results. We look forward to continuing our collaboration with them and other industry leaders to develop packaging systems that promote economic and environmental health.”

In addition, Abbott works with major retail customers, sharing information on packaging reductions the company has achieved in its consumer products. The company also screens its suppliers, holding them to stringent packaging requirements. In 2008, the company created an internal packaging design guideline document to facilitate improved sustainable packaging decisions throughout the design and development phase of packaging.

“Our sustainable packaging commitment is the latest example of Abbott’s legacy of doing its part to safeguard the environment,” explained Donald Patton, Jr., senior vice president, U.S. Nutrition, Abbott. “Across the company, Abbott is transitioning to packaging that performs its essential functions while using less material and more environmentally-friendly components.”

Abbott is working toward delivery on this commitment through a variety of strategies, including embracing the four R’s (reduce, recycle, renew and re-use). Since 2007, Abbott has eliminated an estimated 2.88 million pounds of packaging on an annualized basis through reduction initiatives on a few select products, the equivalent of preventing 15,000 pounds of polystyrene foam from going into landfills. In addition, Abbott reduced the amount of plastic used in infant formula containers by 15 percent in 2008. Some of Abbott’s major sustainable packaging initiatives include:

- Abbott Nutrition reduced the amount of plastic in its eight ounce re-closable bottles by 8.3 percent. Through better design, the company cut polypropylene plastic usage by 2.7 million pounds annually. The reduced-weight bottles also will help save 436,000 gallons of gasoline used for transportation per year.

- Abbott recently implemented a pilot program for shipments of some physician samples that require refrigeration. During the pilot, Abbott is exploring ways to make this environmentally-friendly alternative comparable in cost to current packaging. The reusable box – which replaces a larger, single-use box – is smaller, made of reusable, recyclable and 100 percent organic-based materials, and can be used more than 100 times.

These are just a couple of examples of the more than 40 sustainable packaging projects already introduced or in the process of being launched across Abbott’s health care businesses. The company’s sustainable packaging team continues to find new ways to reduce Abbott’s environmental footprint through innovative design and the application of the latest packaging technology.

Safeguarding the environment is an important part of Abbott’s mission to improve people’s health and the company’s efforts to be a leader in global citizenship. In addition to expanded use of sustainable packaging, Abbott has identified reductions in greenhouse gas emissions, water conservation and increased use of cleaner and renewable energy as environmental priorities. The company has set measurable goals in each of these areas to track its progress. All of Abbott’s various health care businesses are examining their manufacturing processes and needs, as well as their product packaging, to develop environmentally friendly and sustainable approaches to help the company meet or exceed these goals.

Abbott was recently named to the Dow Jones Sustainability World Index and Sustainability North America Index for the fifth consecutive year, and was one of just two U.S.-based pharmaceutical companies listed on both indices. The Dow Jones Sustainability World Index ranks Abbott among the top 300 of the world’s largest 2,500 companies, based on an assessment of economic, social and environmental performance.

Source
Abbott Laboratories

Abbott announced it has been named the overall Gold winner of the 2009 Wall Street Journal Technology Innovation Awards for its Ibis T5000 Biosensor system, which is designed to detect and characterize a broad range of infectious agents in a given sample, including viruses, bacteria and fungi.

“Abbott is dedicated to pursuing innovation to find meaningful solutions that improve lives,” said Stafford O’Kelly, head of Abbott’s molecular diagnostics business. “This technology represents scientific innovation at its very best, and Abbott is honored to receive this important award.”

Abbott’s Ibis system (now marketed under the PLEX-ID trade name) was singled out for the top honor, in part, because it promises to alert health officials to new disease strains, and may also guard against bioterrorism and enable hospitals to identify antibiotic-resistant bacteria in its environment.

The Wall Street Journal reports that since the first system was completed in 2005, the technology has “been deployed in 20 sites around the U.S., including the Centers for Disease Control. This spring, the device helped the Naval Health Research Center in San Diego to identify the first two cases of the H1N1 swine flu in the U.S.”

The PLEX-ID is a high-throughput technology based on a combination of molecular technologies, including polymerase chain reaction (PCR) and mass spectrometry analysis. The system is designed to address a significant unmet need by providing test results in six to seven hours instead of three or more days as required with current culturing methods.

PLEX-ID is currently intended for research use only and not for use in diagnostic procedures. It is capable of identifying virtually all bacteria, viruses and fungi, and can provide information about drug resistance, virulence and strain type of these agents. Commercial applications for the system include epidemiologic surveillance, monitoring of pandemic diseases, identification of emerging or previously unknown agents, forensic characterization of human samples, identification of sources of hospital-associated infections. Abbott is currently developing the system for human infectious disease diagnostics.

Source
Abbott Laboratories

The 2009 Enzyme Engineering Award, presented in the name of Engineering Conferences International and the Genencor division of Danisco A/S, will be awarded to Professor Sakayu Shimizu of Kyoto University. Dr. Shimizu has made extraordinary contributions to both fundamental and applied sciences. He has contributed greatly to our understanding and utilization of microbial functions, reactions and enzymes as biotechnological tools for practical large-scale production of vitamins, co-enzymes, lipids, fatty acids, etc.

His work is characterized by discoveries of novel or unique microbial reactions and enzymes, and the ingenious application of microbial or enzymatic methods to achieve hitherto impossible or difficult biochemical or biosynthetic transformations. Many of the strategies and methods he has developed are breakthrough achievements that laid the framework for much of the current use of microorganisms or enzymes as catalysts in large-scale practical production of useful products. His own discoveries have led directly to the commercialization of many biotechnological processes, some at the 1,000 ton/year scale. Thus, Dr. Shimizu is considered one of the world leaders in “Green or White Chemistry”.

Dr. Shimizu is an internationally recognized leader in the field of enzyme engineering, and has won many awards, including the Lifetime Achievement Award of the Biotechnology Division of the American Oil Chemists Society. He has published more than 300 peer reviewed research articles, 91 review articles, and has been awarded more than 2 dozen international patents and almost 200 Japanese patents.

The Enzyme Engineering Award has been presented at the biennial International Enzyme Engineering Conference since 1983. The 2009 Award will be presented at the 20th Enzyme Engineering Conference in Groningen, The Netherlands, September 20-24, 2009. The award recognizes outstanding achievement in the field of enzyme engineering, through basic or applied research in academia or industry. The award is sponsored by Genencor and includes an engraved piece of Steuben glass.

Source:
Barbara Hickernell

Engineering Conferences International