PROLOR has been developing, under a limited option-to-license agreement from Yeda, a long-acting oxyntomodulin peptide – a drug compound using this technology that is being developed for the treatment of obesity – and PROLOR has now exercised its option to license the technology. The definitive license agreement has an expanded scope and includes all therapeutic indications, with the exception of hemophilia and insulins.

The new licensed technology has the potential to enhance PROLOR’s capabilities in developing long-acting peptide and small molecule drugs, serving as a complementary technology to PROLOR’s core CTP platform for extending the duration of therapeutic proteins and peptides, and potentially enabling PROLOR to develop long-acting therapeutic drugs of many kinds.

“This license from the prestigious Weizmann Institute of Science represents an exciting opportunity for PROLOR,” said Dr. Phillip Frost, Chairman of PROLOR. “It complements our core platform and expands our pipeline of competitive long-acting therapeutic drug candidates to include new, important clinical indications.”

Oxyntomodulin is a naturally occuring peptide hormone released by the digestive system following food ingestion that acts as a natural satiety signal to reduce food intake and increase energy expenditure. Previous third party studies in humans have demonstrated the potential of oxyntomodulin to reduce appetite and food intake, leading to significant weight loss without side effects. However, oxyntomodulin must be administered by subcutaneous injection and its short half-life may require frequent dosing. PROLOR’s long-acting oxyntomodulin, which is expected to have a more favorable dosing profile, is currently in preclinical development.

Yeda Research and Development Company Ltd. is the technology transfer and commercial arm of the Weizmann Institute of Science. The Weizmann Institute of Scienceis a world-renowned center of multidisciplinary research and higher learning based in Rehovot, Israel.

ABOUT PROLOR BIOTECH
PROLOR Biotech, Inc. is a clinical stage biopharmaceutical company applying unique technologies, including its patented CTP technology, primarily to develop longer-acting, proprietary versions of already approved therapeutic proteins that currently generate billions of dollars in annual global sales. The CTP technology is applicable to virtually all proteins, and PROLOR is currently developing long-acting versions of human growth hormone, which is in Phase II clinical development, and factor VII, factor IX, interferon beta and erythropoietin, which are in preclinical development, as well as an anti-obesity peptide and agents for atherosclerosis and rheumatoid arthritis.

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In people with longstanding type 2 diabetes who are at high risk for heart attack and stroke, lowering blood sugar to near-normal levels did not delay the combined risk of diabetic damage to kidneys, eyes, or nerves, but did delay several other signs of diabetic damage, a study has found.  The intensive glucose treatment was compared with standard glucose control.

These findings are from the NIH-funded Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.  Although intensive treatment produced some beneficial changes, this approach was reported in 2008 to increase death rates. 

The new ACCORD findings appear June 29, 2010 in The Lancet’s special online diabetes issue, coinciding with a presentation of the study results at the American Diabetes Association’s 70th annual scientific sessions in Orlando.

Over time, diabetes damages the small blood vessels of the eyes, nerves, kidneys and other organs, leading to pain and disability.  Heart disease due to damaged large blood vessels is a major cause of death in persons with type 2 diabetes. The longer a person has diabetes, the greater the chances of serious complications, including vision loss and blindness, foot ulcers and amputations, kidney disease and kidney failure, and heart disease and stroke.

“In these ACCORD participants with established type 2 diabetes and additional risk factors for cardiovascular disease, intensive lowering of blood glucose reduced some markers of eye, nerve and kidney disease compared with standard glucose control, but the groups did not differ in the rate of progression to kidney failure, nerve disease, and major vision loss,” said lead author Faramarz Ismail-Beigi, M.D., Ph.D., of Case Western Reserve University, Cleveland. 

The ACCORD clinical study compared the effect of intensive control of blood sugar, blood pressure, and blood lipids to standard, less-intensive treatments on the risk of major cardiovascular events in more than 10,000 adults with established type 2 diabetes.  The study’s intensive glycemia arm was halted in February 2008 due to excess deaths in that group.  At that time, participants in the intensively treated group were moved to standard glucose control.

At enrollment, ACCORD participants averaged 62 years of age and were obese.  In addition to having type 2 diabetes for an average of 10 years, about one-third had pre-existing heart disease, and the remainder had at least two additional cardiovascular disease risk factors. They also had high blood sugar, as measured by the hemoglobin A1C test, which shows average blood sugar in the preceding two to three months.  Half of participants had an A1C over 8.1 percent— above the currently recommended target for good control.   A1C values in people without diabetes are less than 6 percent.

Previously reported results showed that over about three-and-a-half years of follow up, participants in the intensive blood sugar group had a 22 percent higher risk of death (5 percent versus 4 percent) and a three times higher risk of seriously low blood sugar (10.5 percent versus 3.5 percent) compared with participants in the standard blood sugar control group.

A secondary goal of the ACCORD blood sugar trial was to determine the effects of near-normal glucose control compared with standard control on microvascular, or small blood vessel, damage to organs and tissues.  Earlier, well conducted clinical trials in patients with newly diagnosed type 1 and type 2 diabetes had proven lowering blood sugar levels reduced eye, nerve and kidney disease.  ACCORD builds on this earlier data by studying benefits of further reduction of glucose to targets near normal, and by studying participants with long-standing rather than newly diagnosed diabetes.

In ACCORD, the A1C target for the intensively treated group was less than 6 percent, a level seen in adults without diabetes and significantly lower than the levels tested in earlier trials.  The goal for standard control was an A1C of 7 to 7.9 percent, an average range achieved by individuals treated for type 2 diabetes in the United States.  Both groups were treated with Food and Drug Administration-approved diabetes medications, as prescribed by their study clinician.

Eye, nerve, and kidney complications in the two groups were compared after 3.7 years, when intensive control was halted, and again at the study’s end after 5 years.  When intensive glucose treatment was halted in the group receiving such treatment, half those participants had an A1C of 6.4 percent or lower, which rose to 7.2 percent at study end.  In the standard treatment group, that A1C measure was 7.5 percent, rising to 7.6 percent by the end of the study.

The treatment groups did not differ in the rate of progression to kidney failure, major vision loss, or advanced peripheral neuropathy, a common nerve problem in diabetes that usually begins as tingling or numbness in the feet.  However, people in intensive control had less deterioration in a vision test, and 20 percent fewer cataract surgeries compared with those in standard control.  They also had a 30 percent lower rate of protein leakage in the urine, a sign of kidney disease and increased risk of heart disease.  Testing for vibratory sensation, an indicator of nerve health, showed no difference between the groups, but the intensively controlled group scored better on other nerve tests. 

ACCORD is continuing follow-up to assess whether the early changes seen in this study will result in differences in blindness, nephropathy and neuropathy. “The study had a relatively short time period – 3.7 years – to see significant differences in serious complications.  Diabetes is a chronic disease, and prevention of complications should be measured over many years,” said Ismail-Beigi.

The effects of intensive blood sugar control on vision are consistent with findings from the ACCORD Eye Study, which explored the effects of intensive treatments on progression of diabetic retinopathy in a subset of about 3,000 ACCORD participants. The most common cause of vision loss in working-age Americans, diabetic retinopathy is a disease in which blood vessels in the eye’s light-sensitive retinal tissue are damaged by diabetes. Intensive blood sugar control was found to be beneficial in retarding the progression of diabetic retinopathy.

“ACCORD provides important data on the risks and benefits of intensive glucose control in people with established type 2 diabetes,” said Susan B. Shurin, M.D., acting director of the NIH’s National Heart, Lung, and Blood Institute (NHLBI).  “Although increasing treatment to try to achieve near-normal blood sugar provides some benefit, clinicians and patients should note that this treatment strategy also potentially increases the risk of adverse effects in patients with additional risk factors for heart disease, such as those studied in ACCORD.” 

“Earlier landmark trials have proven that intensive glucose control early in the course of diabetes provides long-term benefits in reducing microvascular complications.  ACCORD fills an important gap by studying adults with diabetes later in the disease and examining even more stringent glucose control than that previously proven beneficial,” said Judith Fradkin, M.D., director of the Division of Diabetes, Endocrinology, and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).  “This new information will help tailor therapy for individuals with long established diabetes who are at high risk of cardiovascular events or already have cardiovascular disease.” 

About 24 million people in the United States have diabetes. It is the main cause of kidney failure, limb amputations, and new onset blindness in adults and a major cause of heart disease and stroke. Type 2 diabetes, which accounts for up to 95 percent of all diabetes cases, becomes more common with increasing age.  It is strongly associated with obesity, physical inactivity, family history of diabetes, history of gestational diabetes (diabetes that occurs during pregnancy), and impaired glucose metabolism, and it is more common in minority groups.  The prevalence of diagnosed diabetes has more than doubled in the last 30 years, due in large part to the upsurge in obesity and aging of the population.

The NHLBI is the primary sponsor of ACCORD, with additional funding and scientific expertise contributed by the NIDDK. Other components of the NIH — the National Institute on Aging and National Eye Institute — as well as the Centers for Disease Control and Prevention, supported sub-studies. The following companies provided study medications, equipment, or supplies: Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare Inc., GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals, Inc., Novo Nordisk, Inc., Omron Healthcare, Inc., Sanofi-Aventis U.S., and Takeda Pharmaceuticals Inc.

Source: NIH News

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From BioMed Israel Week 2010:

A Novel Therapeutic Method Based on the Ability of Stem Cells to Assist in Treating Juvenile Diabetes Will Replace the Insulin Injection

Ramot, Tel Aviv University’s technology transfer company, will present for the first time a therapeutic approach based on stem cells capability to assist in the treatment of juvenile diabetes, in the Israel BioMed Week 2010, which will be held on the 14^th-16^th of June in Tel Aviv. The main novelty of the treatment is a breakthrough technology which demonstrates how human beta cells, which manufacture insulin, can be grown in a culture. Lab experiments have already proven that the cells can manufacture and keep up normal cells of insulin. This technology thus has the potential to produce insulin-producing cells for transplantation.

The person behind this advancement is Prof. Shimon Efrat from the faculty of Medicine in Tel Aviv University and one of the world-leading researchers in the field of diabetes. “One of the main indicators of juvenile diabetes is a sharp decrease in the number of insulin-producing beta cells in the pancreas,” says Prof. Efrat. “So far they could not have been regenerated, and the patients needed to balance the glucose levels in the blood by constant insulin injection. In extreme cases, a pancreas transplant was required. Transplants, however, are not a simple solution: there are few organ donors, and there is an ever-present danger that the body would reject the implant.”

In the course of the research, Prof. Efrat has developed a method by which beta cells from the human pancreas can be ‘marked’ and tracked. Using this method, Prof. Efrat managed to track their differentiation and proliferation processes, and also succeeded in isolating them from the general population of the cells and obtain a pure culture. In the course of following the cellular life cycle, Prof. Efrat has found conditions in which the beta cells grow in a culture and secrete insulin, and thus could be used to create a vast source of human, insulin secreting cells, for transplantation in diabetes patients.

The commercial potential of the technology is extremely diverse, and includes several possible directions, such as development of the cells themselves as a treatment for diabetes by a specialized company, and using the cells by various companies as a tool for the development of therapeutics against diabetes. This field recently saw light in the prestigious journal Nature, which described a valuable deal of $20 million between Roche and Harvard University for the use of stem cells for the scanning of materials in the drug development process.

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An artificial pancreas system that closely mimics the body’s blood sugar control mechanism was able to maintain near-normal glucose levels without causing hypoglycemia in a small group of patients. The system, combining a blood glucose monitor and insulin pump technology with software that directs administration of insulin and the blood-sugar-raising hormone glucagon, was developed at Boston University (BU). The first clinical trial of the system was conducted at Massachusetts General Hospital (MGH) and confirmed the feasibility of an approach utilizing doses of both hormones. The report appeared in Science Translational Medicine.

I think we can all agree that the system is quite impressive so far. However, there are a few problems to be considered. First and foremost – and also most interesting – is that the researchers also found unexpectedly large differences in insulin absorption rates between study participants. They were able to compensate for the differences by adjustments to the system, but this is another complication that must be taken under consideration even with normal insulin pumps. The second is the fact that the glucose sensor was located in the vein, as opposed to the usual under-the-skin sensor. In other words, this whole experiment took place in a hospital, with the system most probably being quite cumbersome. Hopefully, future versions of this device will be much smaller, and the sensor will not be placed intravenously.

On related note, in the soon-to-come ILSI-BioMed week 2010, there will be at least two seminars concerning potential therapeutics for diabetes, in the first Technology Transfer Session on Tuesday. The first is called ‘Peptides and Cell Therapy – Novel Therapeutics for Diabetes and CNS Related Diseases’, courtesy of Ramot at Tel Aviv University Ltd. The second will be concerned with the ‘Prevention of Human Insulin Resistance and Diabetes’, courtesy of Hadasit Medical Research Services & Development Ltd.  

ILSI-BioMed week 2010

 Source: Massachusetts General Hospital

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Lecture topic:

Edmond Sabo_Legacy Heritage Seminar4 2010 02 24

” פתולוגיה דיגיטלית כמותית – שיטות יישומים”

ד“ר אדמונד סבו, המכון לפתולוגיה, חבר מכון לגסי הריטג’ למחקר רפואי ברמב”ם

ההרצאה תתקיים באולם הקתדרלה בבניין האבן ברמב”ם, בתאריך 24 פברואר 2010 בשעה 13:30.

מרכז המצוינות הראשון ייפתח בשנת 2010  ויהיה המרכז לחקר הסכרת בראשות פרופסור דרק לה-רויט (Derek LeRoith) מארה”ב, אשר ניהל את מרכזי המצוינות לסכרת במכוני הבריאות הלאומיים שבוושינגטון  ובמרכז הרפואי מאונט סיני שבניו יורק, ועתה החליט לעלות ארצה ולהצטרף למכון לגסי הריטג’. מרכז  זה ישוכן  בבניין המרכזי של בית החולים במעבדות  אשר בנייתן הסתיימה בימים אלו. לכשתושלם הקמת “מגדל לגסי הריטג’ לתגליות רפואיות” מעל לחניון התת-קרקעי, ישוכן מכון המחקר בבית הקבע שלו, בצמוד לבית החולים.

בברכה,

פרופ’ מיקי אבירם

מנהל מכון לגסי – הריטג’ למחקר רפואי

קישור למכון לגסי – הריטג’ למחקר רפואי

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