**BIOTECH AND PHARMA NEWS**

[Preciouslife1]

Clinic Roundup.

BIOWORLD Today - Jul. 21, 2007

Affiris, of Vienna, Austria, initiated a Phase I clinical trial of Alzheimer's vaccine Affitope AD01. In the trial, up to 24 Alzheimer's patients will receive four vaccinations over a three-month period, with results monitored for six months. The trial initiation triggers a venture capital payment from Munich, Germany-based MIG-Fonds.

Cougar Biotechnology Inc., of Los Angeles, said the FDA has allowed its investigational new drug application for CB3304 in the treatment of relapsed or refractory multiple myeloma. The company expects to begin a Phase I trial soon. CB3304 is an orally active, opium-derived alkaloid that inhibits microtubule dynamics, blocks cell division and induces apoptosis.

MedImmune Inc., a Gaithersburg, Md., unit of AstraZeneca plc, began dosing patients in a Phase Ib trial of MEDI-545, a fully human monoclonal antibody targeting interferon-alpha. The study is designed to evaluate the safety and tolerability of multiple doses in patients with systemic lupus erythematosus. The antibody separately is being evaluated in a single-dose Phase I trial in lupus patients and a Phase I study in patients with psoriasis. It plans to begin a trial in idiopathic inflammatory myopathies later this year. The antibody was generated with technology from Princeton, N.J.-based Medarex Inc.

Me.tabolex Inc., of Hayward, Calif., completed enrollment in the 400-patient Phase II/III trial of MBX-102/JNJ 39659100 in Type II diabetes, triggering a milestone payment from worldwide development and commercialization partner Ortho-McNeil Inc., of Titusville, N.J. Data are expected early next year from the randomized, double-blind trial, which will compare the drug to Actos (pioglitazone, Takeda Pharmaceutical Co. Ltd. and Eli Lilly and Co.) and insulin. MBX-102/JNJ 39659100 is an insulin sensitizer but does not appear to affect genes associated with weight gain and edema. (See BioWorld Today, June 27, 2006.)

Peplin Ltd., of Brisbane, Australia, said results from a Phase IIb trial of PEP005 topical in actinic keratosis indicate the drug was well-tolerated, with no drug-related serious adverse events, and resulted in statistically significant lesion clearance at all doses tested. When administered at a concentration of 0.025 percent for three consecutive days, PEP005 resulted in 56 percent of patients clearing three quarters or more of their lesions (p=0.0002). When administered at a concentration of 0.05 percent for three consecutive days, PEP005 resulted in 75 percent of patients clearing three quarters or more of their lesions (p<0.0001). Peplin intends to begin a Phase III trial in the first quarter of next year.

UCB SA, of Brussels, Belgium, published previously released results of its two Phase III trials of Cimzia (certolizumab pegol, CDP 870) in Crohn's disease in the New England Journal of Medicine. In the Precise 1 trial, 23 percent of Cimzia patients and 16 percent of placebo patients responded to the drug at week 26 (p= 0.02). In the Precise 2 trial, 48 percent of Cimzia patients and 29 percent of placebo patients achieved disease remission at week 26 (p<0.001). Cimzia, a PEGylated anti-TNF alpha antibody, is under regulatory review in the U.S. and Europe.

[Preciouslife1]

Roche pleases investors with 15% hike in first-half sales and strong guidance

Marketletter - Jul. 30, 2007


Switzerland's number two drugmaker, Roche, released a strong set of first-half 2007 financial results, with revenues boosted by a good performance from most of its cancer drugs and confirmed its guidance for the full year of double-digit growth for the group and its pharmaceutical division. The news, which beat consensus analysts' forecasts, sent the firm's stock 3% higher to 249.30 Swiss francs, unlike local rival Novartis, which saw its shares dip after posting an 18% hike in profits a few days earlier.

However, taking the markets by surpise, the company also announced that Franz Humer, its chairman and chief executive of 10 years standing, was to relinquish the CEO post (remaining chairman) next March in favor of Severin Schwan, now head of the group's diagnostics business, indicating a possible change of emphasis for Roche.

Group sales for the six months rose 15% to 22.83 billion francs ($18.98 billion), with 3.0 billion francs coming from organic growth. The operating profit margin increased 3.6 percentage points to 32.8% and net income leapt 29% to 5.9 billion francs, resulting in core earnings per share of 5.95 francs, up 21% on the like 2006 period, boosted by higher-than-expected financial income and a lower tax rate, noted analysts at Lehman Brothers.

Pharma growth three times global market rate

Pharmaceutical sales, which make up around 80% of group turnover, increased 18% to 18.27 billion francs, a rate of growth at almost three times the global market, said Roche. Contributing to this was Japanese subsidiary Chugai, with 1.67 billion revenues, and US majority-owned Genentech, whose contribution was 5.23 billion francs. The division's operating profit grew 31% to 6.64 billion francs.

Leading the drug sector growth, were Roche's oncology products, which delivered a robust 22% increase. Global sales of MabThera/Rituxan (rituximab) for non-Hodgkin's lymphoma continued to rise strongly, reaching 2.70 million francs. The increase continues to be driven primarily by widespread use of the product in the first-line treatment of both indolent and aggressive NHL in Europe and the USA.

Herceptin (trastuzumab), for early and advanced HER2-positive breast cancer, again recorded a strong global sales increase, driven primarily by data demonstrating the product's survival benefit in early-stage disease. The drug's turnover was 2.38 billion, which fell short of Lehman's estimates of2.46 billion francs, and was the one small disappointment, the analysts said.

Avastin (bevacizumab), the first anti-angiogenic therapy to demonstrate survival benefits in advanced colorectal, breast, lung and kidney cancer, continues to record very strong sales growth in all regions, with turnover reaching 1.91 billion francs. The drug should get a further boost, with the EU approval of its use in advanced lung cancer (see page 19).

In Roche's virology sector, continued growth in sales of the influenza medicine Tamiflu (oseltamivir) in the first half-year was driven by stockpiling orders, with revenue reaching 1.32 billion francs, as governments and corporations prepare for a potential flu pandemic. The mild 2006/2007 flu season resulted in lower sales of the product for seasonal use. It has now received government orders for a total of some 215 million treatment courses from more than 80 countries worldwide.

Turnover of Pegasys (peginterferon alfa-2a), for hepatitis B and C, was 807.0 million francs, boosted by continuing uptake in emerging markets, particularly Brazil and China. Following approval by the Japanese authorities of combined Pegasys and Copegus (ribavirin) for chronic hepatitis C in January, Chugai started the market rollout in March.

The HIV drug Fuzeon (enfuvirtide) posted a sales increase of 8% to 155.0 million francs, with growth in all regions where the product is sold. Valcyte (valganciclovir) and Cymevene (ganciclovir), for the prevention and treatment of cytomegalovirus disease in transplant patients and people with HIV/AIDS, recorded combined revenues rising 17% to 261.0 million francs, with all markets contributing, the company noted.

Among me.tabolic disease drugs, Bonviva/Boniva (ibandronic acid), available as a once-monthly tablet and three-monthly injection for the treatment of postmenopausal osteoporosis, increased 127% to 374.0 million francs. Successful launches in France and Spain earlier this year helped further strengthen European sales. In the USA, Boniva has widened its share of the oral bisphosphonate market to over 13%. Turnover of Roche's prescription weight-loss agent Xenical (orlistat), however, decreased 8% to 339.0 million francs.

Diagnostics advance 5%

Roche's diagnositcs business, which it has expanded with acquisitions, generated revenues of 4.56 billion francs, up 5% on first-half 2006, with professional diagnostics contributing 2.11 billion francs, diabetes care 1.54 billion francs, both up 6%, molecular diagnostics 574.0 million francs, down 2%, and applied science products rising 9% to 331.0 million francs.

[Preciouslife1]

Main Genetic Variants Involved In Response To HIV Identified

An international collaboration between European, Australian and American researchers has unveiled some of the genetic mysteries explaining why some people naturally keep HIV levels almost undetectable, whereas others quickly lose control of the infection. Foundation irsiCaixa from the Hospital Germans Trias i Pujol, and Hospital Clínic are the two Catalan centres in this study, published in Science.

This international collaboration has been the largest ever to have taken place in a large scale study on genetic differences between patients infected by HIV, and is the first study of this kind in the field of infectious disease. Catalan participants have been coordinated by Javier Martínez-Picado, ICREA research professor in the Foundation irsiCaixa of Hospital Germans Trias i Pujol, and Josep M. Miró, consultant of the Unit of Infectious Diseases and AIDS of Hospital Clínic-IDIBAPS of Barcelona, and had the collaboration of Hospital de la Santa Creu i Sant Pau, and Hospital Mútua de Terrassa.
Research has been conducted with the latest genomics and bioinformatics technologies, analysing 550,000 variations of the complete human genome in 486 patients, mostly European, preselected from 30,000 potential candidates.
These variations, known as simple nucleotide polymorphisms (SNPs), are single variations affecting only one nucleotide or base of the genomic sequence. Despite humans sharing 99.9% of the genome sequence, there are still 3 million genetic variations –which make us different from one another– 90% of which are due to SNPs. Hence, a good knowledge of these variations is highly valuable for the determination of the progression of AIDS.
During the present study, obtained genetic data was compared to blood virus load in patients during the first two years after the infection, and also to the rhythm of immune degradation as a result of the infection. This type of comparison, known as association study, permitted to deduct main genetic variations playing a central role in the control of viral infection.
Results point to two gene variants related to the immune system. More precisely, these variations are in a genetic region responsible for the determination of immune response capacity against a number of infectious diseases, including AIDS. These variations are located in the short arm of chromosome 6 in genes controlling HLA-B and HLA-C molecular systems, responsible for the activation of the immune system so that it is able to locate and destroys cells infected by HIV. This study has also identified a third genetic variation involved in immune damage of patients, particularly in a gene encoding a protein which seemingly participates in viral replication, and is also located in chromosome 6.
Genetic variants associated to genes encoding HLA-B and HLA-C molecular systems would explain up to 15% of viral load variation among patients, whereas the third genetic variation would explain 5.8% of these differences. Further study of other genetic regions involved in this process is needed. Nevertheless, HLA-B variation presents the highest correlation with the immune response described until now.
Obtained information will be very useful in the long road to a more rational vaccine development. This and similar studies should push us toward more personalised medicine, where the most suitable drugs for each individual would be determined on the basis of their gene characteristics.
Researchers participating in this study have been coordinated by Amalio Telenti, co-director of the Institute of Macrobiology of the University of Lausanne, Switzerland, and by David Goldstein, director of the Center for Population Genomics and Pharmacogenetics of the Duke Institute for Genome Sciences and Policy, US.
The article concerning this project will be published in Science (paper edition) in August 2007.

[Preciouslife1]

TINY BOMBS NEW HOPE IN CANCER

Mercury (Hobart, Australia) - Jul. 21, 2007

TINY ``nanobombs'' that penetrate deep into a tumour and release powerful drugs could help fight cancer.

Scientists have developed a way of sneaking toxic anti-tumour medicine inside cancerous growths by hiding it inside particles so small they are invisible to the naked eye. Once inside the tumour, the bombs ``explode'', releasing the potent drug to attack cancer cells.

They are expected to work on any solid tumour, such as those in the breast, prostate or ovaries. These solid tumours make up an estimated 85 per cent of all cancer cases.

The new technology, developed at the Chinese Academy of Sciences in Beijing, is at an early stage and it could be three to four years before it is available.

************************************************** **************

RASPBERRIES could help to combat some of the harmful effects of sunburn.

Research shows that as well as easing inflammation associated with overexposure to the sun, black raspberries, a variety of the common raspberry, may significantly slow the growth of skin cancers that have been linked to ultraviolet B (UVB) radiation, the light most dangerous to health. UVB radiation inflames the skin, resulting in sunburn, and is thought to cause most non-melanoma skin cancers.

In laboratory research at Ohio State University, doctors used an extract of black raspberries made into a rub-on jelly applied to the skin to test its effect. The fruit contains anthacyanins, powerful antioxidants that give black raspberries their rich, dark colour.

Results of the research on animals exposed to UVB show that levels of compounds associated with skin damage rose 500 per cent on untreated skin, but only 37 per cent on skin treated with the gel. The gel also significantly reduced the size and number of tumours.

************************************************** *************

BOTOX injections are being used to treat knee pain.

Doctors believe the toxin could help to ease patellofemoral pain syndrome, a leading cause of knee problems in people under 45, and especially common in women. It is thought to be the most common complaint seen by knee specialists, though the exact cause is not known.

Botox blocks messages from nerves to muscles so they relax and don't contract. In the trial at Virginia Commonwealth University in the US, patients are being injected with Botox in a thigh muscle.

************************************************** *************

MICROSCOPIC particles based on a material commonly found in cleaning products are the basis of a new treatment for glaucoma.

Researchers have discovered that particles of the compound cerium oxide are exactly the right shape to penetrate the cornea and can be used to deliver drugs to treat the eye disease that causes blindness and affects millions of people worldwide. The disease involves abnormally high pressure of the fluid inside the eye which, if left untreated, can result in damage to the optic nerve and vision loss.

The researchers created a nanoparticle made of cerium oxide combined with a compound that can block an enzyme central to causing glaucoma.

************************************************** **************

HIGH levels of urate in the blood may be associated with a reduced risk of Parkinson's disease.

Urate is a normal component of blood, and though high levels can lead to gout, it is a potent antioxidant. Harvard University researchers monitored 18,000 men and found that those with the highest blood urate levels had a 55 per cent lower risk of developing Parkinson's than men with the lowest levels.

[Preciouslife1]

Posted by: Preciouslife1
In reply to: NoneDate:7/22/2007 7:27:29 AM
Post #of 50027
Quack~quack...'DUD' CLINIC SLAMMED

Sunday Mirror - Jul. 22, 2007
http://www.therapeuticsdaily.com/news/article.cfm?***********************************typ e=sentryarticle&********************************** *value=1437023....

DESPERATE Irish patients are being exploited by a cruel clinic selling stem-cell treatments that do NOT work, a top doctor claimed last night.

The Embryonic Tissues Centre (EmCell), based in Ukraine, claims to be able to cure cancer, Aids and diabetes.

The dud treatment, which is illegal in the European Union and the US, costs more than EUR15,000.

Yesterday, a leading Irish neurologist blasted the clinic for ripping off sick and vulnerable people.

Dr Orla Hardiman, who works in Beaumont Hospital in Dublin, said the clinic's stem-cell therapy was "useless".

She said: "I've had patients who have raised money to go to places such as the Ukraine in the vain hope that stem-cell therapy is going to cure their incurable disease. I think it's very important to be clear about what stem cells can do.

"There are just a lot of technical and logistical problems in figuring out how to manipulate them to turn into the cells you want them to turn into."

The clinic owner, Professor Alexander Smikodub, claims he can cure life-threatening illnesses.

The treatment involves injecting cells taken from embryos into patients. Yesterday, an EmCell spokesman claimed the centre could treat Irish patients only in its clinic in the Ukrainian capital Kiev.

He said: "We will analyse your case and will give you a complete and forthright answer. The answers will be available only to you personally.

Confidentiality of correspondence between patient and doctor will be maintained absolutely.

"If you have a problem that we can really help you, upon an evaluation of your personal medical situation, we'll invite you to our cell therapy clinic."

EmCell says the stem cells are used to repair damaged tissue.

But experts have slammed the treatment as dangerous and reckless.

Professor Huseyin Mehmet, a stem-cell researcher at Imperial College in London, called the treatment "nonsense".

He said: "Animal experiments have shown that very, very small numbers of stem cells actually make it in terms of reaching the site of damage because most of these cells are dying.

"We haven't found the correct way to persuade them to carry on differentiating and proliferating once we've put them into the body."

Last year, US scientists slammed EmCell for not publishing details of the supposed cures.

In response, EmCell boss Prof Smikodub said: "So does this mean that I have to write an article which will be published in a journal and that only after that will I be respected?

"No, I do not think that my mission lies there. My mission is to cure, to help as many patients as possible, and then I can be respected."

.....as he drives off in his new Mercedes S 65 AMG 12 Cylinder Biturbo, with 22 inch custom wheels, to his Chalet....Altruistic
intentions......ya think?

[Preciouslife1]

Clinic Roundup.

BIOWORLD Today - Jul. 25, 2007

Akela Pharma Inc., of Montreal, completed enrolling patients in its Fentanyl Taifun Phase IIb trial. The product is a fast-acting fentanyl formulation delivered using the company's Taifun dry-powder inhaler platform. The multinational trial is being run in cancer patients on maintenance opioid therapy who have severe persistent pain. The first part of the trial is an open-label study to evaluate dosing. The second part includes 28 responders from the open-label arm randomized to receive the titrated doses or placebo. Safety and efficacy data from the double-blind, placebo-controlled extension arm are expected to be available by early September.

EpiCept Corp., of Tarrytown, N.Y., said it will study EpiCept NP-1, its topical cream formulation of two FDA-approved drugs, amitriptyline (4 percent) and ketamine (2 percent), in a Phase III study in chemotherapy-induced peripheral neuropathy. The ATTRACT-CPN (Assessment of Topical Treatment Response with Amitriptyline and Ketamine: Combination Trial in Chemotherapy Peripheral Neuropathy) trial is expected to start before the end of this quarter and will enroll about 400 patients suffering from CPN for at least 28 days following the conclusion of chemotherapy. The primary endpoint for the 12-week trial is defined as the change in average daily pain intensity scores from baseline to the end point. Secondary endpoints include the percentage of patients whose pain intensity decreases are greater or equal to 30 percent from baseline and other measures. EpiCept also has initiated two additional Phase IIb trial of EpiCept NP-1, enrolling a total of 700 patients. The first of those studies will test the drug in diabetic neuropathy, with preliminary results expected in the fourth quarter, and the second study involves patients with peripheral herpetic neuropathy, with preliminary results expected in the first quarter of 2008.

Gilead Sciences Inc., of Foster City, Calif., presented 144-week data from an ongoing Phase III trial, Study 934, comparing a once-daily regimen of Truvada (emtricitabine and tenofovir disoproxil fumarate) and Sustiva (efavirenz) to a twice-daily regimen of Combivir (lamivudine/zidovudine) and Sustiva in treatment-naive adults with HIV. Data from 456 patients after 144 weeks of treatment showed 71 percent of Truvada/Sustiva patients compared to 58 percent of Combivir/Sustiva patients achieved and maintained viral load less than 400 copies/mL (p=0.004). Sixty-four percent of patients in the Truvada/Sustiva arm compared to 56 percent of patients in the Combivir/Sustiva arm achieved and maintained viral load less than 50 copies/mL (p=0.08). The mean increase from baseline in CD4 cell counts at week 144 was 312 and 271 cells/mm3 in the Truvada/Sustiva and Combivir/Sustiva arms, respectively (p=0.09). Also, a significantly greater percentage of patients in the Combivir/Sustiva group experienced adverse events that resulted in discontinuation of study medications compared to the Truvada/Sustiva arm (11 percent vs. 5 percent, respectively; p=0.01).

Hoffmann-La Roche Inc., a subsidiary of Basel, Switzerland-based F. Hoffmann-La Roche Ltd., and Trimeris Inc., of Morrisville, N.C., disclosed interim results from BLQ (Below the Level of Quantification), an ongoing study evaluating the use of the fusion inhibitor Fuzeon (enfuvirtide) with the most recently approved boosted protease inhibitor, darunavir/ritonavir, in combination with other anti-HIV drugs. Data showed that 64 percent of the treatment-experienced patients at 24 weeks achieved undetectable HIV of less than 50 copies per mL of blood, and that baseline sensitivity to darunavir did not appear to influence patient response to the regimen. Also, 78 percent of patients achieved HIV levels of less than 400 copies per mL, and 86 percent achieved a viral load reduction of at least 1 log10. The prospective, open-label, single-arm, multicenter study is being conducted in the U.S. and Australia. Data came from the first 58 patients in the study.

Isotechnika Inc., of Edmonton, Alberta, completed recruitment for the pivotal Phase III European/Canadian ESSENCE trial of ISA247 in psoriasis. Recruitment was closed at 638 patients. A second pivotal Phase III European psoriasis trial in 360 patients is expected to begin in the first quarter of 2008. That trial, along with the ESSENCE study, is designed to provide sufficient patient numbers to support regulatory approvals in Europe and Canada. The product is a calcineurin inhibitor.

MedImmune Inc., a U.S. unit of London-based AstraZeneca plc, presented interim clinical data suggesting that its monoclonal antibody targeting the interleukin-5 receptor was well tolerated and showed evidence of biological activity in a Phase I study of adults with mild asthma. Results suggested that the antibody-dependent cellular cytotoxicity-enhanced molecule successfully depleted eosinophils, a class of white blood cells implicated in asthma and other inflammatory diseases. In addition to direct depletion of eosinophils, the antibody also aims to neutralize the activity of IL-5, which is believed to play a key role in the growth and development of eosinophils, the company said.

Nventa Biopharmaceuticals Corp., of San Diego, published final results, including new immunological data, from a Phase II trial testing HspE7, a therapeutic vaccine for human papillomavirus-related diseases. Data from the study in women with high-grade cervical intraepithelial neoplasia were published in Gynecologic Oncology. Results showed 95 percent of patients had disease regression or their disease remained stable. Seven of 20 women (35 percent) had complete regression of their CIN II/III, one had regression to low-grade CIN, 11 had stable disease and one had progression due to enlargement of her lesion. Immune responses were seen in nine of the 17 women tested.

Oncolytics Biotech Inc., of Calgary, Alberta, started enrolling patients in its UK trial of Reolysin in combination with docetaxel (Taxotere, Sanofi-Aventis Group) in patients with advanced cancers, including bladder, prostate, lung and upper gastrointestinal. The study has two components. The first is an open-label, dose-escalating, nonrandomized trial of Reolysin given intravenously with docetaxel every three weeks, and the second component will follow immediately and will involve the enrollment of a further 12 patients at the maximum dosage of Reolysin in combination with docetaxel. The primary objectives are to determine the maximum tolerated dose, dose-limiting toxicity, recommended dose and dosing schedule and safety profile of the combination therapy. Secondary objectives include the evaluation of immune response to the drug combination, the body's response to the drug combination compared to chemotherapy alone and any evidence of antitumor activity.
Sygnis Pharma AG, of Heidelberg, Germany, said safety and tolerability were demonstrated in a 44-patient Phase IIa study of AX200 in stroke. The trial in Germany also provided hints of efficacy, Sygnis said. The company said results clear it for further study of AX200, which is designed to stop neuronal cell death in the acute phase of stroke, and to stimulate the regeneration of the already-damaged nerve tissue through the induction of new nerve cells and blood vessels and the reorganization of neuronal networks.

Targacept Inc., of Winston-Salem, N.C., said partner AstraZeneca plc, of London, initiated a Phase IIb trial of AZD3480 (TC-1734) in Alzheimer's disease. The double-blind, placebo-controlled study is being conducted in about 500 patients in Western Europe, Eastern Europe and Canada. The trial is expected to be completed by the end of 2008. AstraZeneca also is scheduled to begin dosing in a Phase IIb trial of AZD3480 in cognitive deficits in schizophrenia in August. AZD3480, Targacept's lead product candidate, is designed to act selectively on neuronal nicotinic receptors.

[Preciouslife1]

BIOWORLD Today - Jul. 25, 2007


Adventrx Pharmaceuticals Inc., of San Diego, presented results demonstrating synergistic HIV inhibitory activity of its broad spectrum antiviral drug candidate, ANX-201, when combined with approved nucleoside and nucleotide reverse transcriptase inhibitors (N(t)RTI) in preclinical tests. The results were presented at the 4th Annual International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Sydney, Australia. The preclinical results suggested that ANX-201 and commonly prescribed N(t)RTIs represent a promising combination in multidrug antiretroviral therapy, the company said.

Affymetrix Inc., of Santa Clara, Calif., and Partners HealthCare, of Boston, have extended their translational research collaboration with a new contract array manufacturing supply agreement, enabling Partners researchers to transform recent microarray discoveries into fully validated, laboratory-developed molecular diagnostic tests. Affymetrix will create custom microarrays based on the recent discovery data from Partners researchers. The arrays will be used to produce molecular diagnostic tests, which will be validated and implemented by Partners HealthCare. Partners will begin focusing on array-based tests for hypertrophic cardiomyopathy and will explore many indications in a large number of diseases. Terms were not disclosed.


Alfacell Corp., of Somerset, N.J., said a paper published in Cancer Biology & Therapy confirmed previous in vitro research that the cytotoxic effects of Onconase results from its catalytic activity. The paper is the result of preclinical research conducted by Alfacell and collaborators at Martin-Luther University in Halle-Wittenberg, Germany, that investigated the relationship between the stability and ribonucleolytic activity of Onconase and several genetically engineered variants of it, and their cytostatic and cytotoxic properties in several tumor cell lines.


Amorfix Life Sciences Ltd., of Toronto, received notice from Cambridge, Mass.-based Biogen Idec Inc. that it will be exercising the first milestone investment under the companies' August 2006 research and investment agreement. That investment allows Biogen to retain its exclusive worldwide option to license Amorfix's drug candidates for amyotrophic lateral sclerosis. Under the terms, Biogen will subscribe for 91,445 shares of Amorfix priced at C$1.76 (US$1.69) per share for gross proceeds of $150,000. The research collaboration is focused on the role of monoclonal antibodies targeted to misfolded superoxide dismutase 1 (SOD1) in ALS, and to date, Amorfix has demonstrated that a targeted immunotherapy approach can diminish the motor neuron effects of ALS in animals. If Biogen chooses to exercise its option for the program, Amorfix will receive an up-front payment, potential milestones in excess of $25 million, plus royalties on any product sales.


Arius Research Inc., of Toronto, has initiated the first study, a dose-finding toxicology study, in the formal preclinical toxicology program for its lead anti-CD44 drug candidate, which is under development for the treatment of breast, prostate and liver cancers. Arius expects to file an investigational new drug application and begin human clinical trials in 2008. ARIUS is developing its novel CD44-targeting antibody for the treatment of solid tumors such as breast, prostate and liver cancers.


BioLineRx Ltd., of Jerusalem, and the University of Illinois at Champaign-Urbana have entered into an exclusive worldwide licensing agreement to research, develop and commercialize BL-4030, a small molecule for treating cancer. Financial terms were not disclosed. BL-4030 is designed to induce apoptosis by activating a specific protein called procaspase 3. The compound takes advantage of the fact that procaspase 3 levels are highly elevated in certain cancers, and activation of procaspase 3 may kill only malignant cells and spare normal cells that have low levels of the apoptotic protein. Cancers with elevated levels of procaspase 3 include lung and breast cancer, certain lymphomas, melanoma and certain liver and nervous system cancers.


Depomed Inc., of Menlo Park, Calif., and Watson Pharmaceuticals Inc., of Corona, Calif, have entered into a co-promotion agreement for ProQuin XR, Depomed's extended-release formulation of ciprofloxacin hydrochloride for the treatment of uncomplicated urinary tract infections. Under the agreement, Depomed granted Watson a co-exclusive right to promote ProQuin XR for the urology and long-term care specialties in the U.S. and its possessions, including Puerto Rico. Depomed will book top-line revenue and Watson will receive a portion of the profits. Watson and Depomed plan to re-launch ProQuin XR in the U.S. urology market by the end of this year. Depomed retains manufacturing and distribution rights, and Watson will be responsible for promotion to physicians in urology and long-term care.


Genzyme Corp., of Cambridge, Mass., and the Oswaldo Cruz Foundation (Fiocruz), of Brazil, have formed a research collaboration on neglected diseases, focusing initially on Chagas disease, a life-threatening infectious disease affecting millions of people in Latin America. One research program will focus on identifying novel biological targets within the parasite that causes Chagas disease and will include screening for potential compounds that affect those targets, which could be developed into drugs. A second program will test the effectiveness of using monoclonal antibodies to neutralize a protein that contributes to heart damage in Chagas disease, known as transforming growth factor-beta. Scientists from each institution will work in each other's laboratories from time to time. The collaboration includes providing Fiocruz rights to commercial uses within the field of neglected disease on a royalty-free basis. Specific terms were not disclosed.


Grifols SA, of Barcelona, Spain, and Cerus Corp., of Concord, Calif., have entered into an agreement to commercialize Cerus' Intercept Blood System in Spain and Portugal. The system is designed to provide increased protection from a broad range of transfusion-transmitted pathogens. Under terms of the agreement, Grifols and Cerus will sell, deploy and support the system in Spanish and Portuguese blood centers. In addition, Grifols will be responsible for servicing the Intercept system illuminators and will manage the supply chain through its distribution sites in Spain and Portugal. Financial details were not disclosed.

IDM Pharma Inc., of Irvine, Calif., said it recently informed the FDA that it intends to take immediate action to supplement the data in its current new drug application for mifamurtide (L-MTP-PE), formerly known as Junovan, which is being reviewed for the treatment of children and adolescents with non-me.tastatic osteosarcoma. The company plans to submit additional data on whether subjects in the Phase III trial remain alive or have died, which was not available at the time of filing of the NDA in October 2006. After the data are analyzed, the company expects to submit an amendment to the NDA by the first quarter of 2008. In May the FDA's Oncologic Drugs Advisory Committee voted 12 to 2 that the data in the NDA do not provide substantial evidence of effectiveness of L-MTP-PE in the treatment of patients with non-me.tastatic, resectable osteosarcoma receiving combination chemotherapy. The company anticipates an FDA decision in late August.

Illumina Inc., of San Diego, has entered into a collaboration with the Institute of Translational Medicine and Therapeutics at the University of Pennsylvania; the Broad Institute; and the National Heart, Lung, and Blood Institute's Candidate-gene Association REsource Consortium to develop a customized chip for vascular disease. Called the IBC chip, the array will be developed to analyze more than 55,000 single-nucleotide polymorphisms in candidate genes selected for cardiovascular and other associated phenotypes. Researchers, using Illumina's iSelect Custom Genotyping BeadChip, will assess the genetic diversity within pathways of approximately 2,100 genes believed to underpin primary and secondary vascular disease processes, such as blood pressure, myocardial infarction, heart failure, stroke, insulin resistance, me.tabolic disorders, dyslipidemia and inflammation. More than 120,000 samples from large population studies and clinical trials will be analyzed for genetic links to vascular disease.

InterMune Inc., of Brisbane, Calif., saw its shares fall nearly $2 Monday after an analyst reported possible delays in an expected Phase Ib trial of ITMN-191 in hepatitis C. Analyst Howard Liang, of Leerink, Swann & Co. wrote in a research note that there has been "at least a slight delay relative to our expectations," though he maintained an "outperform" rating on the stock and said the overall program remains on track. ITMN-191, a NS3/4 protease inhibitor, is partnered with Basel, Switzerland-based F. Hoffmann-La Roche Ltd. Shares of InterMune (NASDAQ:ITMN) lost $1.95, or 7.8 percent, to close at $22.99.

end part #1

[Preciouslife1]

Nabi Biopharmaceuticals, of Boca Raton, Fla., has created the second of its two planned strategic business units, called Nabi Pharmaceuticals, and has eliminated 33 positions in its Rockville, Md., research and development facility. That reduction - approximately 5 percent of the company's total current work force - is expected to yield approximately $3.3 million in savings on an annualized basis. The new unit will be responsible for the NicVAX (Nicotine Conjugate Vaccine) and StaphVAX (Staphylococcus aureus Polysaccharide Conjugate Vaccine) development programs, as well as for the continuing milestone-related development obligations following the sale of PhosLo (calcium acetate). The company previously had announced it created the Nabi Biologics unit, as well as a corporate shared services group, to support those business units.

Nuon Therapeutics Inc., of San Francisco, completed its licensing, supply and collaboration agreement with Kissei Pharmaceutical Co. Ltd., of Matsumoto City, Japan, for tranilast, a product marketed in Japan and Korea for bronchial asthma. Financial terms of the deal were not disclosed, but the agreement gives Nuon worldwide rights to develop tranilast in autoimmune and inflammatory diseases, such as multiple sclerosis, rheumatoid arthritis, pain and other indications. Kissei retains the exclusive option right for research, development and marketing of the drug in Japan and Korea in the field of autoimmune diseases, and the agreement establishes a collaborative relationship between the companies for the development of additional portfolio products.

Peregrine Pharmaceuticals Inc., of Tustin, Calif., said its proposal to investigate bavituximab and other anti-phosphotidylserine antibodies as potential therapies for hemorrhagic fever virus (HFV) infections was selected for a contract award by the Defense Threat Reduction Agency (DTRA), pending negotiation of a final contract, expected to be awarded within the next few months. In its proposal, Peregrine outlined a five-year program to assess the use of bavituximab, a monoclonal antibody that has shown promising antiviral activity in preclinical studies, and other anti-PS antibodies, and called for funding to support preclinical studies to confirm activity against HFV infections, manufacturing and product scale-up and initiation of clinical trials. Peregrine has sought funding of about $44.5 million over the course of the program, and DTRA accepted Peregrine's full proposal as the basis of contract negotiations.

Pluristem Life Systems Inc., of New York, said favorable results have been obtained in preclinical testing using the its proprietary PLX cells to treat limb ischemia, a potential market of more than $1 billion. Scientists administered Pluristem's PLX cells in vivo to one set of ischemic mice. Post-treatment evaluation using Doppler technology indicated revascularization of the limb treated with PLX cells but not in those that were not treated with PLX. The hind legs of mice were rendered ischemic using standard industry methodologies.

Pro-Pharmaceuticals Inc., of Newton, Mass., has entered into a research agreement with an unnamed bio-pharmaceutical company to enhance the efficacy and safety of its chemotherapeutic drug utilizing, Davanat, its proprietary target delivery compound. The goal of the research agreement is to investigate the application of Davanat to the partner's chemotherapy to improve its pharmacokinetic and pharmacodynamic profile to enhance treatment against cancer. In addition, the company said it has submitted data to the FDA seeking marketing approval for Davanat to be used as a functional excipient with 5-FU and Irinotecan, for cancer applications. A new drug application is planned when clinical trials for first-line treatment of advanced biliary and colorectal cancers are completed. While the partner was not named, the company described it as "one of the world's largest biopharmaceutical companies." Financial details were not disclosed.

Qiagen NV, of Venlo, the Netherlands, said its offer to exchange cash and stock for all outstanding shares of Digene Corp., of Gaithersburg, Md., expired as scheduled Friday. All conditions of the exchange offer have either been satisfied or waived, and Qiagen intends to accept all tendered shares. Preliminary tabulations indicated that the number of shares tendered constituted well in excess of 90 percent of the outstanding stock. Accordingly, Qiagen intends to complete its acquisition of Digene by merger without the approval of the Digene stockholders, promptly after its acceptance of the shares. Pro-ration calculations will be announced when completed, and payment for the Digene shares will be made as soon as practicable.

QLT Inc., of Vancouver, British Columbia, said the FDA has accepted for filing and review its labeling supplement for Aczone, requesting the removal of the glucose-6-phosphate dehydrogenase (G6PD) screening and blood monitoring requirements from its current label. A decision by the FDA on the label revision is expected by the end of March 2008. The sNDA is primarily based on the Phase IV clinical trial completed in 56 safety-evaluable G6PD-deficient patients, which demonstrated no clinical evidence of hemolytic anemia in that patient population.

Xencor Inc., of Monrovia, Calif., said a first-in-class protein therapeutic drug candidate has been shown to selectively inhibit its therapeutic target, according its research, which is being published in the Aug. 1, 2007 issue of the Journal of Immunology. The data indicated that this new class of therapeutics may offer an alternative to nonselective therapeutics, which currently are used to treat inflammatory diseases such as rheumatoid arthritis. Target selectivity has the potential to significantly enhance efficacy of therapeutics while limiting their toxicity and side effects. In the published research, clinical candidate XPro 1595 DN-TNF, was shown to selectively inhibit the soluble form of Tumor Necrosis Factor in both human and animal cell lines and blocked inflammation in animal models.

[Preciouslife1]

Tasigna approved in Switzerland based on impressive efficacy in patients with a form of leukemia no longer responding to Glivec

Hugin - Jul. 25, 2007

First worldwide approval for new anti-cancer therapy designed to more potently and preferentially target the cause of chronic myeloid leukemia.

Data shows Tasigna to be generally well-tolerated with high response rates and manageable safety profile in patients who are resistant or intolerant to Glivec
US and EU regulatory decisions expected in 2007 with filing in Japan completed during the second quarter
Rapid development of Tasigna demonstrates commitment to speeding innovative medicines to patients with unmet medical need.

Basel, July 25, 2007 - Switzerland has granted the first worldwide approval for Tasigna (nilotinib), a potent and novel targeted cancer therapy for patients with a form of the life-threatening blood cancer chronic myeloid leukemia (CML) who are resistant or intolerant to treatment with Gliveca (imatinib)[1] - the leading therapy for CML patients also developed by Novartis.

The approval of Tasigna came after an accelerated review by the Swiss health authority Swissmedic based on positive findings from a pivotal Phase II trial, Trial results showed high response rates in these patients with a generally well-tolerated, manageable safety profile.

Taken twice-daily, Tasigna inhibits production of cancer cells containing an abnormal chromosome by targeting the Bcr-Abl protein.

This protein, which is produced by cells containing the abnormal Philadelphia chromosome, is recognized as the key driver of the overproduction of cancer-causing white blood cells in patients with CML.

In clinical trials, Tasigna reduced or eliminated this abnormal chromosome in 42% of Glivec-resistant patients with Philadelphia chromosome-positive (Ph+) CML in the chronic phase of the disease, as well as in 31% of patients in the accelerated phase of the disease.

"While over 90% of patients on Glivec survive after five years, we focused on helping the small percentage of patients who developed resistance or intolerance to Glivec, which led to the discovery of Tasigna," said Dr. Daniel Vasella, Chairman and CEO of Novartis. "I am pleased that we set a record of less than five years from synthesis to market, rapidly bringing Tasigna - our second-generation, more selective and more potent Bcr-Abl tyrosine kinase inhibitor - to those patients who need it."

Additional regulatory decisions on Tasigna are expected in the US and Europe later this year, while a regulatory submission was completed in Japan during the second quarter of 2007. In the US, the Food and Drug Administration requested on July 16 a three-month extension in the regulatory review period.

Also planned for 2007 are Phase III studies involving Tasigna in CML patients responding sub-optimally to other therapies as well as newly-diagnosed CML patients. A registration study is already underway in patients with gastrointestinal stromal tumors (GIST), which can also be treated with Glivec in certain countries.

Recent landmark clinical trial results for Glivec showed that nearly 90% of newly-diagnosed chronic phase Ph+ CML adults patients treated with Glivec were alive after five years[2], but some develop resistance or cannot tolerate this therapy.

Applying key learnings from Glivec, a team of Novartis scientists created Tasigna in August 2002, just a year after the launch of Glivec. Tasigna was specifically designed to target Bcr-Abl more potently and preferentially without adding new mechanisms of action that might cause additional side effects. Tasigna moved from synthesis to its first regulatory approval in less than five years.

"The speed of developing Tasigna reflects our passion to help cancer patients," said David Epstein, President and CEO of Novartis Oncology. "A designer cancer treatment, Tasigna also highlights our leadership in targeted therapies."

Chronic myeloid leukemia is one of the four most common types of leukemia, responsible for about 15% of all leukemia cases worldwide[3], and caused by an overproduction of immature white blood cells. Approximately 95% of CML patients have the Philadelphia chromosome.

Approval based on impressive Phase II results Tasigna has been approved for use in the treatment of chronic or accelerated phase of Ph+ CML patients resistant to, or experiencing significant toxicity during treatment with Glivec. The Swiss filing was based on an open-label Phase II study designed to evaluate the safety and efficacy of Tasigna in Glivec-resistant or -intolerant patients with Ph+ CML in chronic and accelerated phase. Efficacy was measured by cytogenetic response, i.e. reduction or elimination of the Ph+ chromosome, and hematologic response, i.e. normalization of white blood cell counts..

Among 132 patients with chronic phase disease, major cytogenetic response was observed in 55 patients (42%) after a median of 7.7 months' treatment. Among 64 patients with accelerated phase disease, major cytogenetic response was observed after a median of five month' follow-up in 20 (31%).

Longer-term data from this pivotal Phase II trial presented last month at the American Society of Clinical Oncology annual meeting showed even further positive results.

Tasigna safety information The safety of Tasigna was studied in 438 patients. The most frequent Grade 3 or 4 adverse events for Tasigna were primarily hematological in nature and included neutropenia and thrombocytopenia. Elevations were seen in bilirubin, liver function tests, lipase enzymes and blood sugar, which were mostly transient and resolved over time.

These cases were easily managed and rarely led to discontinuation.

Pancreatitis was reported in less than 1% of cases. The most frequent non-hematologic drug-related adverse events were rash, pruritus, nausea, fatigue, headache, constipation, and diarrhea. Most of these adverse events were mild to moderate in severity.

Tasigna should be used with caution in patients who have or may develop prolongation of QTc. These include patients with abnormally low potassium or magnesium levels, patients with congenital long QT syndrome, patients taking anti-arrhythmic medicines or other drugs that may lead to QT prolongation, and cumulative high-dose anthracycline therapy. Low levels of potassium or magnesium must be corrected prior to Tasigna administration.

The bioavailability of Tasigna is increased by food. Tasigna should not be taken in conjunction with food and should be taken two hours after a meal. No food should be consumed for at least one hour after the dose is taken.

About Glivec Glivec is approved in more than 90 countries including the US, EU and Japan for the treatment of all phases of Ph+ CML. Glivec is also approved in the EU, US and other countries for the treatment of patients with Kit (CD117)-positive gastrointestinal tumors (GIST), which cannot be surgically removed and/or have already spread to other parts of the body (********************stasized). Glivec has also been approved in various countries for use in treating patients with certain rare types of cancer.

The majority of patients treated with Glivec in clinical trials experienced adverse events at some time. Most events were of mild to moderate grade and treatment discontinuation was not necessary in the majority of cases.

Rare/serious adverse reactions include: sepsis, pneumonia, depression, convulsions, cardiac failure, thrombosis/embolism, ileus, pancreatitis, hepatic failure, exfoliative dermatitis, angioedema, Stevens-Johnson syndrome, renal failure, fluid retention, edema (including brain, eye, pericardium, abdomen and lung), hemorrhage (including brain, eye, kidney and gastrointestinal tract), diverticulitis, gastrointestinal perforation, tumor hemorrhage/ necrosis, hip osteonecrosis/avascular necrosis.

Patients with cardiac disease or risk factors for cardiac failure should be monitored carefully and any patient with signs or symptoms consistent with cardiac failure should be evaluated and treated.

Cardiac screening should be considered in patients with HES/CEL, and patients with MDS/MPD with high level of eosinophils (echocardiogram, serum troponin level).

[Preciouslife1]

AVII - Animal Studies Show Promising Therapeutic Dosing Results Using an Antisense Agent to Treat Heart Disease

Last update: 7/25/2007

Upcoming human studies could create potentially revolutionary new treatment for nation's top killer

BROOMFIELD, Colo., Jul 25, 2007 (BUSINESS WIRE) -- Animal studies of a potentially breakthrough medical technology that uses a novel antisense agent to arrest the process of coronary arteries becoming reblocked after treatment with angioplasty and stenting have shown highly promising results, a spokesman for Global Therapeutics, a Cook Medical company, announced today. Global Therapeutics reports that preclinical studies have shown successful delivery of the agent to the specific site of stenting. Delivery of a therapeutic dose of the antisense agent was achieved safely without any adverse systemic effects. Furthermore, it was shown that the target RNA, from the c-myc gene, one of the main causes of restenosis, was effectively inhibited by the antisense compound AVI-5126 developed by Cook Medical's partner AVI BioPharma, Inc. (AVII). "Our main goal, following the achieved silencing of the target RNA, was to develop a system that is user-friendly and would not add time to the overall procedure for the physician," said Joseph B. Horn, president of Global Therapeutics. "The animal studies just completed have shown conclusively that the c-myc inhibitor (AVI-5126) we have been exploring produces a therapeutic effect at the dosages used. With the success of this phase of our preclinical investigation, our plans are to initiate a human clinical trial in the near future, pending regulatory consent." Global Therapeutics plans to pursue this technology beyond the preclinical setting and into a clinical trial in Europe later this year. The study design will incorporate up to 20 investigational centers throughout Europe with the intent to support a CE-mark filing. "We view this kit as a unique system needed by the industry given all the negative press surrounding the current generation of pharmaceutical-eluting coronary stents. It was developed in conjunction with Cook Medical's product development team and includes a bare eq.uivalent cobalt chromium stent, a sub-selective drug delivery catheter and the AVI-5126 antisense drug component," Horn said. "This technology will allow cardiologists to treat lesions with a drug designed to prevent restenosis without the use of any non-therapeutic additives such as a polymer." Sebastian Phillip, M.D., head of the Cardiovascular Research Center at the Westgerman Heart Center in Essen and a key investigator in the APPRAISAL Trial, remarked. "Antisense therapy to prevent in-stent stenosis is an exciting breakthrough in the treatment of coronary artery disease. Sub-selective delivery of AVI-5126 will open a new approach combining the safety of a bare eq.uivalent stent with reducing restenosis comparable to DES. We are excited to begin this trial at the end of the year." Global Therapeutics licenses the AVI-5126 c-myc antisense agent from AVI BioPharma, which has ongoing manufacturing responsibilities. The technology is an investigational device not available in the United States or other markets at this time. About Cook Medical Cook Medical was the first company to introduce interventional devices in the United States. Today, the company integrates device design, biopharma, gene and cell therapy and biotech to enhance patient safety and improve clinical outcomes in the fields of aortic intervention; cardiology; critical care medicine; gastroenterology; radiology, peripheral vascular, bone access and oncology; surgery and soft tissue repair; urology; and assisted reproductive technology, gynecology and high-risk obstetrics. Cook won the prestigious Medical Device Manufacturer of the Year Award for 2006 from Medical Device & Diagnostic Industry magazine. For more information, visit . About AVI BioPharma AVI BioPharma develops therapeutic products for the treatment of life-threatening diseases using third-generation NeuGene(R) antisense drugs and ESPRIT exon skipping technology. AVI's lead NeuGene antisense compound is designed to target cell proliferation disorders, including cardiovascular restenosis. In addition to targeting specific genes in the body, AVI's antiviral program uses NeuGene antisense compounds to combat disease by targeting single-stranded RNA viruses, including West Nile virus, hepatitis C virus, dengue virus, Ebola virus, and H5N1 avian influenza virus. AVI's NeuGene-based ESPRIT technology is initially being applied to potential treatments for Duchenne muscular dystrophy. More information about AVI is available on the company's Web site.

[Preciouslife1]

T-cell responses: Howdy, partner!

Sharon Ahmad

A recent study published in Immunity has shown that the T-cell co-stimulatory molecules B7.1 (also known as CD80) and programmed cell death 1 ligand 1 (PDL1) are binding partners, thereby revealing a new means of regulating T-cell responses.
The interaction of co-stimulatory molecules B7.1 and B7.2 (also known as CD86) on the surface of antigen-presenting cells with receptors CD28 and cytotoxic T-lymphocyte antigen 4 (CTLA4) on the surface of T cells is essential for the generation and regulation of robust adaptive immune responses. This pathway of the B7–CD28 family of co-stimulatory molecules is well characterized but complex, as B7.1 and B7.2 have dual specificity for the stimulatory CD28 receptor and the inhibitory CTLA4 receptor. One of the newer identified pathways of this family comprises the PD1 receptor and its two ligands PDL1 and PDL2. The roles of PDL1 and PDL2 in T-cell activation have not yet been fully elucidated.
Previous studies have shown evidence for B7-dependent responses in T cells that lack both CD28 and CTLA4, and these findings, together with conflicting reports of both stimulatory and inhibitory functions for PDL1 and PDL2, prompted the authors to consider that there may be an additional functional receptor for B7.1 or B7.2 on T cells. Using a cDNA library made from Cd28-/-Ctla4-/- CD4+ T cells, the authors identified PDL1 as a ligand for B7.1. Surface plasmon resonance characterized the affinity of the B7.1–PDL1 interaction and indicated that B7.1 interacts more strongly with PDL1 than with CD28 but less strongly than with CTLA4, and that PDL1 interacts less strongly with B7.1 than with PD1. To identify the B7.1–PDL1 interaction site, Butte et al. used protein crosslinking and mass spectrometry and found that there was partial overlap of the B7.1–PDL1 interface with those of B7.1–CTLA4 and PD1–PDL1. This suggests that CTLA4, CD28 and PDL1 could compete for binding to B7.1, and that B7.1 and PD1 could compete for binding to PDL1.
Next, the authors investigated the functional significance of the interaction between B7.1 and PDL1 in vitro. B7.1-coated beads delivered an inhibitory signal to Cd28-/-Ctla4-/- T cells, resulting in a decrease in proliferation, cytokine production and activation-marker expression. In vitro proliferation of PD1-deficient T cells was inhibited by PDL1-coated beads. Finally, to confirm the specificity of the B7.1–PDL1 interaction, responses of Pd1-/- T cells versus Pd1-/-Cd80-/- T cells to PDL1, and of Cd28-/-Ctla4-/- T cells versus Cd28-/-Ctla4-/-Pdl1-/- T cells to B7.1 were measured. The results showed that B7.1 acts specifically through PDL1 to inhibit T-cell proliferation in the absence of CD28 and CTLA4, and that PDL1 can exert an inhibitory effect on T cells either through B7.1 or PD1. Therefore, there is a specific and significant bidirectional interaction between B7.1 and PDL1 that inhibits T-cell responses.
This previously unsuspected interaction indicates increased functional significance of B7.1 and PDL1 on T cells, and means that the roles of B7.1 and PDL1 in regulating the activation and inhibition of immune responses need to be reassessed. These findings also have implications for the use of these molecules as therapeutic agents.

References and links

ORIGINAL RESEARCH PAPER

1. Butte, M. J. et al. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 12 July 2007 (doi: 10.1016/j.immuni.2007.05.016)

[Preciouslife1]

Myriad Genetics Launches New Molecular Diagnostic Test

Market Wire - Jul. 26, 2007 SALT LAKE CITY, UT, July 26 / MARKET WIRE/ --
Myriad Genetics, Inc. (NASDAQ: MYGN) (www.myriad.com) announced today that it has introduced a new product, TheraGuide 5-FU(TM), to help predict which cancer patients are likely to suffer serious toxic reactions to the drug 5-Fluorouracil (5-FU) or the oral form of the drug, capecitabine. More than 500,000 Americans with breast cancer, colon cancer, skin cancer or head and neck cancer are treated with 5-FU each year. Approximately 30% of those patients experience severe toxicity.
TheraGuide 5-FU is a comprehensive analysis of the genetic variations in two genes, DPYD and TYMS, which increase a patient's risk for toxicity to 5-FU chemotherapy. With the TheraGuide 5-FU test results, oncologists and their patients can take steps to reduce the risk of avoidable toxicity, including using alternative therapies, reducing the size of the dose and increasing patient monitoring for side effects. TheraGuide 5-FU provides the critical guidance oncologists need to personalize chemotherapy for their cancer patients who are being considered for chemotherapy regimens.
"TheraGuide 5-FU is a new personalized medicine test that has the potential to save many cancer patients from serious toxic reactions to the medicine that is supposed to help them," said Greg Critchfield, M.D., President of Myriad Genetic Laboratories, Inc. "TheraGuide 5-FU points the way to the future promise of personalized medicine, where tests can guide the therapeutic choice for improved patient care, while limiting the side effects of otherwise efficacious drugs."
Approximately one third of all patients given 5-FU will experience dose-limiting toxicity that can be severe to life-threatening. The majority of these toxic reactions are due to genetic variations in the DPYD and TYMS genes. The DPYD gene makes the enzyme that is primarily responsible for ********************bolizing or breaking down 5-FU and clearing it from the body quickly. If the DPYD enzyme activity is compromised, 5-FU will be cleared more slowly from the system resulting in a longer period of exposure to 5-FU and a subsequent increased risk for toxicity. An estimated 9 million individuals in the U.S. have low DPYD enzyme activity due to mutations in the DPYD gene.
Thymidylate synthase (TYMS) is an essential enzyme for DNA synthesis. The chemotherapy drug, 5-FU, binds to the TYMS enzyme, inhibiting its function. When the TYMS enzyme is inhibited, DNA synthesis does not go forward and the cell dies. Since cancer cells multiply rapidly, requiring a high level of DNA synthesis, they are much more sensitive to thymidine depletion than normal cells. The human TYMS gene has genetic variations that cause differential production of the TYMS enzyme. If a variation causes underproduction of TYMS, only a portion of the 5-FU dose is used to bind to, and inhibit, the TYMS enzyme, and the rest remains unbound in the body resulting in increased toxicity. Variations causing overproduction of TYMS enzyme lead to excess TYMS and insufficient 5-FU to completely inhibit the enzyme and a resulting loss of efficacy with the 5-FU chemotherapeutic.
Toxicity reactions due to reduced enzyme activity may include hand-foot syndrome, fever, mucositis, stomatitis and severe diarrhea. Nausea, vomiting, rectal bleeding and skin changes may also occur. Neurologic abnormalities include cerebellar ataxia (uncoordinated muscle movement) and changes in cognitive ability. Elimination of 5-FU from the treatment regimen is usually sufficient to prevent additional unexpected toxicities.
TheraGuide 5-FU is Myriad's fifth molecular diagnostic product. The Company is now accepting samples for testing with TheraGuide 5-FU. The test cost is $1,100 and includes a comprehensive DNA sequence analysis of the DPYD gene and the important variations in the TYMS gene. The result is returned to the requesting physician within seven days of receipt at Myriad.
Myriad Genetics, Inc. is a biotechnology company focused on the development and marketing of novel therapeutic and molecular diagnostic products. Myriad's news and other information are available on the Company's Web site at www.myriad.com.
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include statements relating to TheraGuide 5-FU's ability to save many cancer patients from serious toxic reactions to the medicine that is supposed to help them and the Company's ability to return the result to the requesting physician within seven days of receipt at Myriad. These risks and uncertainties include, but are not limited to, our inability to further identify, develop and achieve commercial success for new products and technologies; our ability to discover drugs that are safer and more efficacious than our competitors; our ability to develop molecular diagnostic products that help assess which patients are subject to greater risk of developing diseases and who would therefore benefit from new preventive therapies; the possibility of delays in the research and development necessary to select drug development candidates and delays in clinical trials; the risk that clinical trials may not result in marketable products; the risk that we may be unable to successfully finance and secure regulatory approval of and market our drug candidates, or that clinical trials will be completed on the timelines we have estimated; uncertainties about our ability to obtain new corporate collaborations and acquire new technologies on satisfactory terms, if at all; the development of competing products and services; our ability to protect our proprietary technologies; patent-infringement claims; risks of new, changing and competitive technologies and regulations in the United States and internationally; and other factors discussed under the heading "Risk Factors" contained in Item 1A in our Annual Report on Form 10-K for the year ended June 30, 2006, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

[Preciouslife1]

Glaxo Signs Up To $1.5 Billion Drug Deal With Targacept!

Fri Jul 27, 2007 8:11AM EDT
LONDON, July 27 (Reuters) - GlaxoSmithKline Plc ( GSK ) took a further step to boost its new drug pipeline on Friday by clinching a drug development deal potentially worth more than $1.5 billion with U.S. biotech firm Targacept Inc. ( TRGT ).
The alliance gives Europe's biggest drugmaker access to Targacept's neuronal nicotinic receptor compounds, including an experimental drug in mid-stage Phase II clinical trials for acute post-operative pain.
Under terms of the deal, Glaxo will pay $35 million to Targacept, which includes an investment of $15 million for the purchase of 1.3 million Targacept common shares, the companies said in a statement. Targacept is also eligible to receive up to $1.5 billion in payments from London-based Glaxo, depending upon the achievement of certain milestones.
In addition to pain, the tie-up also gives Glaxo to other Targacept drug discovery programmes in smoking cessation, obesity, addiction and Parkinson's disease.

******Glaxo Heads Down Tobacco Road ******
Kerry A. Dolan
07.27.07, 7:30 AM ET

SAN FRANCISCO - Even tobacco companies can make the world a healthier place — or at least former units of them. Targacept, which was spun out of the research division of R.J. Reynolds Tobacco in 2000, announced Friday that it has struck a drug development deal with GlaxoSmithKline worth up to $1.5 billion if all milestones are met.
Targacept is developing drugs that target neuronal nicotinic receptors in the brain to treat Alzheimer’s disease, pain, obesity and other indications. GlaxoSmithKline agreed to pay Targacept $35 million up front and gets the exclusive option, after completion of a phase two “proof of concept” trial, to license Targacept compounds in five areas: pain, smoking cessation, obesity, Parkinson’s disease and addiction. Targacept has a drug candidate called TC-2696 currently in a phase two clinical trial for acute post-operative pain, which is included in the GlaxoSmithKline alliance.
Two-thirds of the $1.5 billion in milestone payments — what many in the industry call bio-bucks — are scheduled to be paid before any of Targacept’s compounds go on the market, should they be approved.
“Normally you have to take all the risk [of developing a drug] and then go find a partner, which takes a year,” said J. Donald deBethizy, chief executive of Targacept. “With this model, we have the cash to fund early discovery. These are all areas we have wanted to develop for a long time, but when you’re a young company, you have to focus.”
Thus far, Targacept’s main focus has been on Alzheimer’s, schizophrenia, depression and pain.
This is Targacept’s second ongoing partnership with a large pharmaceutical company. In December 2005, Targacept licensed rights to develop a drug for Alzheimer’s disease and schizophrenia to AstraZeneca for up to $300 million in payments and double-digit royalties if the drug was approved for sale. That drug, called AZD3480, has just entered phase two clinical trials.
Neuronal nicotinic receptors are found on nerve cells throughout the nervous system. Though the receptors got their name through their association with nicotine, which is why the former R.J. Reynolds unit developed an expertise in them, their primary function in the brain is to regulate the release of a variety of neurotransmitters, including acetylcholine, which aids learning and memory.
Drugs targeting neuronal nicotinic receptors are in the early stage of development. The only approved nicotinic receptor drug is Chantix, a smoking-cessation drug from Pfizer, which has performed above expectations since its approval in May 2006. Some analysts expect Chantix to reach sales of $1 billion next year.
Through a GlaxoSmithKline unit called the Center for Excellence in External Drug Development, Glaxo has entered into deals similar to the Targacept agreement with nine other drug companies, including Exelixis, Theravance and ChemoCentryx, a privately held company in Mountain View, Calif. DeBethizy said negotiations with Glaxo had been going on for nearly nine months, beginning with a dinner he had with Glaxo’s research and development executives during the JP Morgan Chase Healthcare Conference in San Francisco in January.
Glaxo’s $35 million upfront payment to Targacept is comprised of $20 million in cash and $15 million to purchase Targacept stock at $11.76 a share, a 31% premium to Thursday’s close of $9 a share.

~~~~~ <*(((<< ~~~~~ ((PL1))

[Preciouslife1]

Zelnorm to be Made Available to US Patients Under Restricted Access Program

From the PharmaLive.com News Archive - Jul. 27, 2007 -- FDA approves limited treatment IND program for Zelnorm
EAST HANOVER, N.J., July 27, 2007 /PRNewswire/ -- In cooperation with the US Food and Drug Administration (FDA), Novartis has established a restricted access program for Zelnorm(R) (tegaserod maleate) so that patients in need of this medicine can be considered for treatment.
The program, called a treatment IND, is designed to help women in the US under 55 years of age who suffer from irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC), and for whom no other treatment has provided satisfactory relief and/or patients who had satisfactory improvement of their symptoms with prior Zelnorm treatment for IBS-C or CIC. Novartis and the FDA are moving forward with this program because of requests from physicians and patients following the marketing suspension of Zelnorm in March 2007.
Treatment INDs are generally used to allow restricted access to medications for patients in need if no comparable alternative drug or therapy is available to treat the disease. Patients given access through a treatment IND must meet specific FDA-approved criteria for enrollment.
Through the program, appropriate female patients with IBS-C or CIC who are assessed by their physicians as being in critical need can have access to Zelnorm for relief of the often painful and disruptive symptoms associated with these conditions. The program protocol and consent materials are designed to ensure that patients and physicians are fully informed of the potential risks and benefits of Zelnorm.
To be considered for access to Zelnorm through the treatment IND, patients must have IBS-C or CIC and meet the specific criteria in the treatment IND protocol. To become part of the treatment IND, patients should contact their physicians to inquire about the protocol and evaluate if they meet the criteria. For further details of the program's protocol, physicians can call 866-248-1348 or 888-669-6682 or go to www.zelnorm.com.
For patients who do not meet the criteria of the treatment IND but have an urgent need for Zelnorm based on a life-threatening or severely debilitating condition, there may be an alternative option available through the FDA. Physicians may inquire about this potential access option by contacting Novartis at (888-NOW-NOVA) or the FDA CDER Division of Drug Information at 301-827-4570 or www.fda.gov/cder.
Novartis suspended US marketing and sales of Zelnorm as a result of an FDA request in order to permit further discussion of its benefit/risk profile. This decision was based on a review of a new retrospective analysis of pooled clinical trial data which showed that the incidence of cardiovascular ischemic events was higher in patients taking Zelnorm than in those taking placebo. However, no causal relationship between Zelnorm and cardiovascular ischemic events has been demonstrated.
Novartis has extensively studied Zelnorm and believes that this medicine provides important benefits for appropriate patients. Novartis is in discussions with the FDA to better understand the findings and to determine appropriate next steps. IBS is a disorder characterized by abdominal pain or discomfort, bloating, and altered bowel function. An estimated 12 million Americans suffer from IBS with constipation. Many have symptoms for five to 10 years, which trigger missed work days and often prevent them from participating in everyday activities with their family and friends. Chronic constipation accounts for more than 5.7 million constipation-related outpatient visits each year, with more than 990,000 visits to emergency rooms and more than 580,000 to hospital outpatient facilities. It leads to more than 282,000 in-patient hospitalizations with constipation as the primary diagnosis.

[Preciouslife1]

FYI:Study findings on ovarian cancer are outlined in reports from P.M. Machado and colleagues

Women's Health Weekly - Aug. 02, 2007

According to recent research from Lisbon, Portugal, "BRCA2 rearrangements are rare genetic events. A large BRCA2 genomic insertion was recurrently observed in our participants, and we sought to characterize it at the molecular and phenotypic level. We studied 210 high-risk breast/ovarian cancer families."

"Fifty-three probands were fully screened for BRCA1/2 mutations, and three of 53 had a large insertion in exon 3 of BRCA2. This finding was analyzed by polymerase chain reaction (PCR), reverse transcriptase PCR (RT-PCR), and sequencing. An additional 157 consecutive families were screened for this mutation by a three-step PCR method. Phenotype and haplotype analysis was also performed. Results Sixteen BRCA mutations were observed in 19 of 53 patients (36% detection rate).

A recurrent Alu motif insertion in position c.156_157 was observed after sequencing of an abnormal fragment obtained after the amplification of BRCA2 exon 3. RT-PCR revealed exon 3 skipping. Screening of this rearrangement identified 14 additional families (out of 157). In total, 17 (8%) of 210 high-risk families ascertained in our clinic were positive for this mutation. Segregation of a common haplotype (from D13S260 to D13S1695) confirmed a common origin, estimated to have occurred 2,400 to 2,600 years ago. The following four cancer phenotypes were observed in the 17 positive families: female breast (n = 9), male breast (n = 4), breast/ovarian In = 2), and heterogeneous (n = 2). Male breast cancer was more frequently observed in c. 1 56-157insAlu-positive families compared with negative families (23% v 12%, respectively), and 33% of all male breast cancer families with an identified BRCA mutation were c. 156_157insAlu positive," wrote P.M. Machado and colleagues.

The researchers concluded: "C.156_157insAlu is a founder mutation of Portuguese origin and is the most frequent BRCA2 rearrangement described to date."

Machado and colleagues published their study in the Journal of Clinical Oncology (Study findings on ovarian cancer are outlined in reports from P.M. Machado and colleagues. Journal of Clinical Oncology, 2007;25(15):2027-2034).