Pipeline Series Oct 2, 2006 till Oct 9, 2006

Final data from Antisoma's AS1404 lung cancer trial show clear survival benefit
Cancer drug developer Antisoma plc announces final data from its phase II trial of AS1404 in non-small cell lung cancer. These show a very substantial survival benefit. Patients who received AS1404 on top of standard chemotherapy had a median survival of 14.0 months, compared with 8.8 months in patients treated with chemotherapy alone. This 5.2-month difference is one of the largest ever seen in a randomised controlled trial combining a novel agent with first-line chemotherapy for lung cancer. Across the duration of the trial, patients treated with AS1404 had a 27% lower risk of dying than those receiving chemotherapy alone. Safety data from the trial were also encouraging. The addition of AS1404 to chemotherapy was well tolerated. These findings extend thoseannounced in June and strongly support Antisoma's plans for a phase III trial in lung cancer. The lung cancer study is one of three phase II trials of AS1404. Positive PSA response data were recently announced from a trial in prostate cancer and encouraging early data have been presented from an ovarian cancer study. Antisoma is currently in talks with a number of companies with a view to licensing AS1404.



Spectrum Pharmaceuticals Announces Positive Phase 2 Data with Ozarelix in Patients with Benign Prostatic HypertrophySpectrum Pharmaceuticals, Inc. announced that its double-blinded, randomized, placebo-controlled, multi-center, dose-ranging Phase 2 trial with ozarelix in patients suffering from Benign Prostatic Hypertrophy (BPH) met the primary endpoint. The results were highly statistically significant (p<0.0001) in improving clinical symptoms of BPH as measured by the International Prostate Symptom Score (IPSS), the standard method of assessing BPH symptoms and the primary endpoint of the study. Other efficacy endpoints of the study, such as urine flow, residual urine volume, and quality of life were also met. In addition, the drug had an excellent safety profile. The trial was conducted in Europe in collaboration with Spectrum Pharmaceutical's partner AEterna Zentaris Inc.MacroChem Initiates Phase II Trial of EcoNail™ Topical Antifungal Lacquer
MacroChem Corporation has begun enrollment in a Phase II study of EcoNail™ in patients with onychomycosis, a fungal infection of the fingernail and toenail. MacroChem expects to enroll approximately 40 patients in this U.S. multi-center open label trial. Patients participating in the study, which is being conducted under MacroChem's U.S. IND, will receive 48 weeks of treatment and will undergo efficacy assessments using standard criteria of nail appearance and mycology. The study protocol also specifies an interim assessment after all patients complete 24 weeks of treatment. At both the interim and final assessments, MacroChem plans to utilize a panel of independent onychomycosis experts to assist with the efficacy evaluations.



Health Canada Grants Approval Of TYSABRI™
Biogen Idec Canada and Elan Corporation, plc announced that following a priority review process, Health Canada has granted approval to TYSABRI™ (natalizumab) for the treatment of relapsing-remitting multiple sclerosis (MS). TYSABRI is the first in a new therapeutic class of MS treatments (called selective adhesion molecule inhibitors) and has been shown to significantly reduce the rate of MS relapses as well as the progression of disability associated with the illness. A two-year, randomized, multi-centre, placebo-controlled, double-blind study (called AFFIRM) enrolled 942 patients and evaluated the effect of TYSABRI on the rate of clinical relapses and the progression of disability. The results found that TYSABRI reduced the rate of clinical relapses by 68 per cent relative to placebo, and the risk of sustained disability progression associated with MS by 42 per cent relative to placebo.







LAB International reports positive results from its LAB-CGRP Phase IIA study
LAB International Inc. ("LAB"), a drug development company focused on developing therapies for the inhalation market, announced positive results from the first Phase II clinical trial of its LAB CGRP product. LAB CGRP showed statistically significant broncho-protective effects compared to placebo and a similar safety profile to placebo except for transient and mild headaches and flushing in some of the patients. The objectives of this randomized, double blind, cross-over Phase II study were to investigate the protective efficacy of LAB CGRP on metacholine induced bronchial hyper-responsiveness in adult patients with mild to moderate asthma, to compare this efficacy to salbutamol and placebo and to evaluate the safety and tolerability of LAB CGRP in asthma patients. The trial enrolled a total of 12 patients and reached statistical difference. Each patient received one dose of LAB CGRP (5mg), one dose of Salbutamol sulphate (500(micro)g) and one dose of placebo. The doses were given in a randomized order and study agents were compared in terms of absolute provocative concentration (PC20) of methacholine causing at least 20% fall in forced expiratory ventilation volume. LAB CGRP increased PC20 in a majority of patients (7 out of 12) while Salbutamol and placebo respectively achieved 11 and 2 out of 12. On average, the PC20 with LAB CGRP was approximately two-fold as compared to placebo (geometric mean 1.97 mg/ml, and 0.95 mg/ml, respectively p<0.05).





The Medicines Company Commences Phase III Clinical Trial of CangrelorThe Medicines Company announced that the first patient has been treated in a Phase III clinical trial called CHAMPION PLATFORM to evaluate the safety and efficacy of cangrelor, a fast-acting, reversible intravenous (IV) antiplatelet agent for preventing platelet activation and aggregation during the clotting process. CHAMPION PLATFORM is a randomized, double-blind, placebo-controlled, parallel group study with a planned enrollment estimated at 4,400 patients. The primary objective of this study is to demonstrate that the efficacy of cangrelor plus usual care is superior to placebo plus usual care in patients requiring percutaneous coronary intervention (PCI). PCI, often referred to as coronary angioplasty, is a procedure conducted to clear blockages in arteries around the heart. Usual patient care during PCI includes a mix of IV and oral therapies that target the inhibition of blood clotting factors such as thrombin or platelets. The trials' co-primary investigators are Deepak Bhatt, MD of The Cleveland Clinic Foundation and Robert Harrington, MD of the Duke Clinical Research Institute.



Schering AG and Biogen Idec Announce Start of the ZEAL Phase III Clinical Trial With Anti-Cancer Drug Zevalin®Schering AG, Germany and Biogen Idec Inc. announced the start of Zevalin (Ibritumomab Tiuxetan) in Aggressive Lymphoma (ZEAL), a Phase III, international multi-center clinical trial. Approximately 400 patients will be enrolled in the trial. This is an open-label, prospective, randomized, two-armed, group-sequential study evaluating the efficacy and safety of Zevalin treatment vs. observation in patients with diffuse large-B-cell lymphoma (DLBCL) -- the most common type of aggressive non-Hodgkin's lymphoma (NHL) -- who are in complete remission (CR) or unconfirmed complete remission (CRu) after first-line CHOP-rituximab (CHOP-R) therapy. The trial is being conducted in 46 U.S. and 57 European, Asian and Canadian centers. The duration of treatment will consist of two treatment days one week apart followed by a 12-week safety follow-up period. The study duration will be approximately four years. Entry criteria include patients older than 60 years of age with DLBCL who are in CR or CRu after six or eight cycles of first-line treatment with CHOP-R. The primary endpoint for the trial is overall survival (OS), with disease-free survival and health-related quality of life as secondary endpoints. Once the final data from the trial is completed and analyzed, Schering AG and Biogen Idec expect to file an application seeking to expand the product's current label to include first-line therapy for patients with aggressive DLBCL.

FDA Approves New Indication for YAZ® to Treat Emotional and Physical Symptoms of Premenstrual Dysphoric Disorder (PMDD)
Berlex, Inc., a U.S. affiliate of Schering AG, Germany announced that the U.S. Food and Drug Administration (FDA) has approved YAZ® (3 mg drospirenone/20 mcg ethinyl estradiol) as the first and only oral contraceptive shown clinically effective for the treatment of the emotional and physical symptoms of premenstrual dysphoric disorder (PMDD) in women who choose to use an oral contraceptive as their method of contraception.

YAZ, which received FDA approval for the prevention of pregnancy in March, 2006, is the fastest growing oral contraceptive brand in the U.S.* PMDD is a condition in which women's emotional and physical premenstrual symptoms are disruptive enough to significantly impact relationships, social activities and work productivity. Symptoms of PMDD include mood swings, irritability, headaches, feeling anxious, bloating and food cravings. The symptoms regularly occur seven to 10 days before menstruation begins, and resolve within a few days of the onset of menses. While the symptoms of PMDD and premenstrual syndrome (PMS) are the same, women with PMDD experience five or more symptoms which are more severe.







deCODE Suspends Phase III Trial of DG031 to Improve Tablet Manufacturing
deCODE genetics announced that it is voluntarily suspending its Phase III clinical trial for DG031 (veliflapon), the company's developmental compound for the prevention of heart attack, in order to address an unexpected formulation problem with the tablets being used in the trial. Routine testing of clinical supplies has revealed that over time the tablets appear to dissolve more slowly. Pharmacokinetic data indicates that to date this has not affected drug exposure nor raised any safety concerns, but the company is concerned that this change may eventually cause the tablets to release too little drug, potentially limiting the effect of the compound and undermining the trial's chances of success. deCODE has presented the issue to the Food and Drug Administration (FDA) and is exploring alternative manufacturing processes.

SUBOXONE® (Buprenorphine/Naloxone) Approved In European Union for Treatment of Opioid Dependence
Schering-Plough Corporation announced that the European Commission has granted marketing approval to SUBOXONE® (buprenorphine hydrochloride/naloxone hydrochloride) Sublingual Tablets for the substitution treatment of opioid dependence, within a framework of medical, social and psychological treatment. The intention of adding the naloxone component is to deter intravenous misuse. SUBOXONE is intended for use in adults and adolescents 15 years of age and older who have agreed to be treated for addiction. SUBOXONE currently is the only centrally-approved product for treatment of opioid dependence in the European Union (EU). The approval results in Marketing Authorization with unified labeling that is valid in the current 25 EU member states as well as in Iceland and Norway. The approval follows a positive opinion recommending approval that was granted on July 27 by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA).





FDA Approves ZOLINZA™ (Vorinostat) for the Treatment of Cutaneous Manifestations in Patients with Cutaneous T-Cell Lymphoma Who Have Tried and Failed Other TherapiesMerck & Co., Inc. announced that the U.S. Food and Drug Administration (FDA) has approved oral ZOLINZA™ (vorinostat) 400 mg once daily for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL), a form of non-Hodgkin's lymphoma, who have progressive, persistent or recurrent disease on or following two systemic therapies. CTCL is a cancer of the T-cells, a type of white blood cell, which affects the skin. ZOLINZA is a histone deacetylase (HDAC) inhibitor. Based on in vitro studies, ZOLINZA inhibits the enzymatic activity of HDAC1, HDAC2, HDAC3 (Class I) and HDAC 6 (class II) at nanomolar concentrations (IC50<86 nM). In some cancer cells, excess amounts of the enzyme HDAC prevent the activation of genes that control normal cell activity. ZOLINZA is believed to decrease the activity of HDAC. Decreasing the activity of HDAC allows for the activation of genes that may help to slow or stop the growth of cancer cells. The exact mechanism of the anticancer effect of ZOLINZA has not been fully characterized. The approval is based on two open-label clinical studies in which CTCL patients with refractory CTCL were evaluated to determine their response rate to oral ZOLINZA. One study was a Phase IIb, single-arm pivotal clinical study and the other assessed several dosing regimens. In both studies, patients were treated until disease progression or intolerable toxicity.





Bristol-Myers Squibb, Gilead Sciences and Merck & Co. Submit Marketing Authorisation Application for ATRIPLA™ (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) to European Medicines AgencyBristol-Myers Squibb Company, Gilead Sciences, Inc. and Merck & Co., Inc. announced the submission of a Marketing Authorisation Application (MAA) for ATRIPLA™ (efavirenz 600 mg/ emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg) in the European Union to the European Medicines Agency (EMEA). The MAA will be reviewed by the Committee for Medicinal Products for Human Use (CHMP), subject to validation by the EMEA. ATRIPLA is a once-daily single tablet regimen approved in the United States for the treatment of HIV-1 infection in adults for use either as stand-alone therapy or in combination with other antiretroviral agents. The product contains 600 mg of efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI), 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate, both nucleoside reverse transcriptase inhibitors (NRTIs).



GlaxoSmithKline Seeks FDA OK For Cancer Drug Tykerb
GlaxoSmithKline PLC (GSK) submitted a new drug application to the Food and Drug Administration for approval to market Tykerb in combination with Xeloda for the treatment of advanced or metastatic breast cancer in women who have received prior therapy, including Herceptin. The London-based pharmaceutical company said the drug has been granted fast-track status by the agency for this particular patient population. GlaxoSmithKline Monday announced the submission of a Marketing Authorisation Application to the European Medicines Agency (EMEA) for approval to market Tykerb in combination with Xeloda, for the treatment of advanced or metastatic ErbB2 (HER2) positive breast cancer in women who have received prior therapy, including Herceptin.





Data from Protalex' Phase I Clinical Trial of PRTX-100 Presented at the American College of Clinical PharmacologyProtalex, Inc. announced that data from its Phase I clinical trial of PRTX-100 was presented at the American College of Clinical Pharmacology meeting in Boston, MA on September 17, 2006. The abstract was entitled: Phase I study of the safety and pharmacokinetics of staphylococcal protein A in healthy adults. PRTX-100 is in development for autoimmune disorders including rheumatoid arthritis and idiopathic thrombocytopenic purpura (ITP), a disorder in which the blood does not clot. As previously announced, the data demonstrated that in a single dose Phase I clinical trial, PRTX 100 was safe and well tolerated. There were no serious adverse events deaths and no major safety lab or vital sign abnormalities. All 36 volunteers who enrolled in the study completed the trial. The company plans to meet with the United States Food and Drug Administration during the fourth quarter and expects to file an investigational new drug application for PRTX-100 in ITP. Protalex anticipates proceeding to a Phase II clinical trial in the ITP indication in early 2007.



Theravance Initiates Phase 2 Clinical Program in Gastrointestinal Motility DysfunctionTheravance, Inc. announced that the first patient was dosed in a Phase 2 clinical study of TD-5108, an investigational compound for the treatment of chronic constipation and other disorders related to reduced gastrointestinal (GI) motility. The goal of this program is to develop a product with once-a-day oral dosing and improved efficacy relative to current therapy. TD-5108 is a selective 5-HT4 (5-hydroxytryptamine4) receptor agonist that has shown prokinetic activity in preclinical and clinical studies. Theravance initiated the Phase 2 program based on preclinical data and results from Phase 1 studies completed earlier this year which showed pharmacokinetics consistent with once-daily dosing. In these randomized,double-blind, placebo-controlled, single- and multiple-ascending dose Phase 1 studies which enrolled 77 healthy volunteers, TD-5108 demonstrated a dose-dependent prokinetic effect, with rapid onset at the higher doses, and a tolerability profile consistent with compounds in this class. The prokinetic effect of TD-5108 was observed, within the dose range studied, throughout the 14-day multiple-dose study. The Phase 2 multi-center, randomized, double-blind, placebo-controlled study is designed to evaluate the safety and efficacy of a range of TD-5108 doses administered once daily for 28 days. The Phase 2 study will be conducted in the United States with a goal of enrolling approximately 350 patients.



VIVUS SUBMITS APPLICATION FOR ESTRADIOL SPRAY
VIVUS has submitted a new drug application to the FDA for its investigational estradiol drug, EvaMist, being developed for the treatment of vasomotor symptoms associated with menopause.VIVUS announced positive results from its Phase III trial of EvaMist earlier this year. The study showed a statistically significant reduction in the number and severity of moderate and severe hot flashes for all three doses tested.The trial, conducted at 43 clinical sites in the United States, was a 12-week, randomized, double-blind, placebo-controlled study of 454 menopausal women. Patients were randomized into three treatment arms each administering a different dose with one, two or three sprays. Results showed that EvaMist decreased the number of hot flashes by 78 percent, from 10.8 hot flashes per day at baseline to 2.3 per day after treatment. This decrease was statistically significant compared with placebo. The reduction in frequency and severity of moderate to severe hot flashes was statistically significant over placebo for all three doses.EvaMist is a once-a-day transdermal spray that delivers estradiol, a naturally occurring estrogen, for the treatment of hot flashes in women. EvaMist is a small, hand-held spray that is designed to provide an easy and convenient means to deliver a preset dose of estradiol via the skin. Studies have shown that once administered, EvaMist's formulation is not affected by washing and does not transfer to other people.

MICROMET, SERONO PHASE II TRIALS DO NOT MEET MAIN ENDPOINT
Micromet and Serono have reported the outcome of two Phase II trials testing the activity of adecatumumab (MT201) in metastatic breast cancer and in prostate cancer. Adecatumumab, a fully human monoclonal antibody targeting tumor cells overexpressing the epithelial cell adhesion molecule (EpCAM), was assessed as a single agent for efficacy and safety in patients with EpCAM-positive metastatic breast cancer and in patients with prostate cancer. The studies tested adecatumumab at two dose levels in patients with high and low EpCAM expression. The results suggested dose-dependent activity of adecatumumab as well as a dependency on relevant levels of target expression.The first randomized, open-label study was conducted in five European countries at 26 centers. Patients were stratified according to EpCAM expression into two groups, one with low EpCAM expression and another with high EpCAM expression. Each group was then randomized into two arms treated every two weeks by intravenous infusion at either 2 or 6 mg adecatumumab per kilogram of body weight. Patients were treated until disease progression with full tumor assessments every six weeks according to standardized RECIST criteria. While the primary endpoint of the study (25 percent clinical benefit rate at week 24) was not reached, secondary endpoint analysis showed a significant prolongation of time to progression in patients treated with the higher dose of adecatumumab compared with patients receiving the lower dose.The second trial used serum PSA levels as the main readout for biological and clinical activity. The primary endpoint of this study was mean change in PSA at week 24 compared with baseline. While the primary endpoint was not reached, the analysis of the final data of the study indicated that treatment with 6 mg/kg adecatumumab had a beneficial trend when compared with placebo.



AVI BIOPHARMA REPORTS RESULTS FROM HCV TRIAL
AVI BioPharma has reported results from a Phase II multicenter study in patients with chronic active hepatitis C virus (HCV) infection. The trial was designed to assess the safety, tolerability, pharmacokinetics and viral and clinical response to treatment with AVI's proprietary Neugene antisense compound, AVI-4065, in HCV patients.AVI-4065 exhibited favorable safety and tolerability profiles in the 12 patients completing the clinical treatment phase of the protocol, with no serious drug-related adverse events or tolerability issues observed during treatment or follow-up. Consistent with the preliminary results, the therapeutic threshold required for efficacy of the drug was not achieved at the treatment dose used in this protocol. Significant differences were observed in the plasma PK in patients compared with what was noted in healthy volunteers: notably, a longer plasma half life (approximately 26 hours compared with 13 hours), a lower peak plasma concentration (initially 1.2 compared with 1.6 micrograms/mL) and a slower plasma clearance (approximately 15 compared with 40 mL/minute). These observations demonstrate a direct pharmacodynamic response to HCV infection.

SIRTRIS ANNOUNCES RESULTS FROM TRIALS OF SIRTUIN THERAPEUTIC
Sirtris Pharmaceuticals that the company's initial clinical candidate, SRT501, was found to be safe and well-tolerated when administered orally in two Phase I clinical studies. Based on this progress, Sirtris has initiated a Phase Ib study in patients with Type 2 Diabetes. SRT501 targets SIRT1, a member of the human sirtuin family of enzymes. Specifically, SRT501 acts by increasing the number and function of mitochondria and so is therapeutically targeted to address diseases of aging including metabolic diseases, such as diabetes and obesity.In the Phase I studies, SRT501 was administered orally once daily to 85 healthy male volunteers in separate study groups for seven days in order to evaluate dose, safety, tolerability and pharmacokinetics. SRT501 was found to be safe and well-tolerated, and there were no serious adverse events. The company has initiated a Phase Ib trial in patients with Type 2 Diabetes. The trial is designed to evaluate the safety and the pharmacokinetics of SRT501 in 90 patients using daily oral administration of SRT501 for 28 days.

3M'S DURAPREP SURGICAL SOLUTION WINS FDA APPROVAL
3M announced that the FDA has approved its new drug application (NDA) for 3M DuraPrep surgical solution (iodine povacrylex [0.7 percent available iodine] and isopropyl alcohol, 74 percent w/w) patient preoperative skin preparation. DuraPrep surgical solution has been available and used in more than 20 million preoperative patient skin preparation procedures since 1988.In 1994, the FDA published the Tentative Final Monograph for Healthcare Antiseptic Drug Products by which it regulates healthcare antiseptic solutions. In this monograph, the FDA limited the allowable form of iodophor used in patient preoperative skin preparations to povidone iodine. Because DuraPrep surgical solution uses a proprietary, film-forming iodine acrylate copolymer that differentiates it from treatments based on traditional povidone iodine, this monograph, when finalized, is not expected to cover DuraPrep surgical solution. After discussions with the FDA about the unique iodine acrylate copolymer in DuraPrep surgical solution, 3M decided to file an NDA to seek formal approval for the compound. As part of the NDA, 3M submitted data from six efficacy studies and two safety studies. Three studies involving healthy volunteers tested DuraPrep surgical solution's efficacy on the abdomen and groin. All three studies showed DuraPrep surgical solution was either generally equivalent or superior to Hibiclens cleanser, a chlorhexidine gluconate aqueous-based antimicrobial solution.