• Actelion Ltd., of Allschwil, Switzerland, is paying CHF60 million (US$45.5 million) to purchase privately held Axovan AG, of Basel, Switzerland. With the full due diligence completed, a binding letter of intent has been signed, with the integration process expected to start by the end of this month. Included in the acquisition is clazosentan, an intravenous endothelin receptor antagonist optimized for treating cerebral diseases such as vasospasms occurring as a consequence of subarachnoid hemorrhage. In that indication, clasozentan recently finished a Phase IIa study. Upon achieving development milestones, as well as registering and marketing the drug on a global basis, Actelion will make further payments to Axovan shareholders that could potentially raise the total acquisition price to up to CHF252 million in the coming years. Actelion, which reported cash reserves of CHF124.7 million as of June 30, said it might finance the initial acquisition consideration entirely from its existing cash balance, though it and further payments could be financed through the issuance of equity-linked instruments such as a convertible bond.

• Advanced Biotherapy Inc., of Los Angeles, reported data at last week's International Cytokine Society meeting in Dublin, Ireland, confirming the beneficial effects of using antibodies to block interferon-gamma to treat severe rheumatoid arthritis. The company sponsored a randomized, double-blinded trial in Moscow that followed 55 patients with severe rheumatoid arthritis unresponsive to other anti-arthritic treatments. The patients were given a short course of antibodies to interferon-gamma, a short course of antibodies to tumor necrosis factor-alpha, or placebo. Analysis at four weeks, using ultrasound measurement of the thickness of the inflamed knee-joint lining, established that anti-interferon-gamma resulted in a significant reduction in membrane thickness in patients. Also at four weeks, using criteria for measuring therapeutic responses established by the American College of Rheumatology, the number of patients achieving the maximum level of response was found to be greater in the patients receiving antibodies to interferon-gamma.

• ArQule Inc., of Woburn, Mass., began the first clinical trial of CO-501, the first clinical-stage compound derived from its biology platform, Activated Checkpoint Therapy. The small-molecule anticancer drug is intended to selectively kill cancer cells and spare normal cells by restoring and activating cellular checkpoints known to be defective in cancer.

• Bioenvision Inc., of New York, presented research at the 8th Nottingham International Breast Cancer conference in which Modrenal demonstrated clinical benefit rates of 55 percent in advanced, progressing breast cancer patients who had become resistant to existing therapies. An overall clinical benefit rate of 35 percent was observed among all patients' doses. The studies were performed at 11 sites involving more than 700 patients.

• Celera Diagnostics, of Alameda, Calif., reported its discovery of genetic markers associated with an increased risk for myocardial infarction at the International Symposium on Atherosclerosis in Kyoto, Japan. Selected findings from one of its cardiovascular disease studies were presented. The retrospective study identified a collection of genetic variations known as single nucleotide polymorphisms that are predictive of increased risk for heart attack.

• Connetics Corp., of Palo Alto, Calif., reported positive findings from a Phase III trial of Actiza, a formulation of 1 percent clindamycin delivered in the company's Versafoam delivery system, as a potential topical treatment for acne. The 12-week, double-blinded, active- and placebo-controlled trial included 1,026 patients at 18 centers across the U.S. The trial was designed to demonstrate that Actiza was not inferior to Clindagel as measured by the primary endpoints of Investigator's Static Global Assessment and percent reduction in lesion counts from baseline to week 12. Success was defined as achieving non-inferiority to Clindagel for two out of three lesion counts and for ISGA.

• Cubist Pharmaceuticals Inc., of Lexington, Mass., said an independent data monitoring committee recommended continuing its Phase III trial of Cubicin (daptomycin for injection) for infective endocarditis and bacteremia caused by Staphylococcus aureus. The committee made its recommendation after completing a review of the first group of patients enrolled in the ongoing international study examining the compound's safety and efficacy.

• DeCode Genetics Inc., of Reykjavik, Iceland, said it received a milestone payment after identifying a gene that in one form predisposes to obesity and in another form predisposes to thinness as part of its alliance with Merck & Co. Inc., of Whitehouse Station, N.J. DeCode said it isolated the gene through genotypic analysis involving more than 1,000 female participants in its obesity program, information the companies are using in their joint obesity drug discovery program. DeCode's stock (NASDAQ:DCGN) gained 44 cents Tuesday, or 10.3 percent, to close at $4.70.

• Elusys Therapeutics Inc., of Pine Brook, N.J., addressed the FDA's Arthritis Advisory Committee this week, urging it to recognize autoantibodies to double-stranded DNA as biomarkers to demonstrate that a drug is effective for systemic lupus erythematosus. The company is developing a drug candidate, ETI-104, that is designed to reduce the frequency and severity of kidney flares and resulting damage in lupus patients. Elusys noted that a large percentage of patients exhibit double-stranded DNA autoantibodies at some point in their disease.

• EntreMed Inc., of Rockville, Md., selected the final formulations of Panzem, its lead drug in Phase II oncology trials. The company expects to transition the reformulated Panzem into new clinical trials in early 2004. The new formulations are orally administered and are designed to increase the amount of Panzem that circulates in the patient's bloodstream by increasing absorption.

• Epoch Biosciences Inc., of Bothell, Wash., said that Qiagen NV, of Venlo, the Netherlands, launched QuantiTect Custom Gene Expression Assays, probe and primer sets for quantitative real-time PCR based on Epoch's MGB Eclipse technology. The custom assays permit a user to design and order assays to measure the expression of any gene from any organism in minutes, using software developed by Epoch and available on Qiagen's website.

• Guava Technologies Inc., of Hayward, Calif., entered a research alliance with the department of chemical engineering at the University of Birmingham in the UK, which will explore how Guava's benchtop micro-volume cell-analysis systems can accelerate the department's monitoring of cell culture or apoptosis. Guava's cell-analysis systems, the Guava PCA and Guava PCA-96, are designed to streamline cell-analysis research and the research and development process by enabling scientists to perform a variety of whole-cell assays at their benchtops.

• Lorus Therapeutics Inc., of Toronto, said it expanded its Phase III trial of Virulizin in advanced pancreatic cancer to include sites in Europe and South America. The multicenter, double-blind trial is comparing Virulizin in combination with gemcitabine to gemcitabine and placebo in the first-line treatment setting. The study's primary endpoint is survival, and it includes a second-line treatment component involving Virulizin in combination with 5-FU, vs. 5-FU and placebo.

• MedImmune Inc., of Gaithersburg, Md., gained a non-exclusive license to antibody phage display libraries from Dyax Corp., of Cambridge, Mass., for the discovery of therapeutic antibodies. Dyax will receive up-front and annual technology license fees, clinical milestone payments and royalties on net sales of products that result. In other news, MedImmune induced a protective immune response against three childhood respiratory viruses in a preclinical study incorporating intranasal vaccine technology similar to that used to develop FluMist. The study involved parainfluenza virus type 3, respiratory syncytial virus and human metapneumonovirus.

• Micrologix Biotech Inc., of Vancouver, British Columbia, said it completed treatment of all patients in its Phase IIb trial of MBI 594AN, its antimicrobial peptide for acne. More than 250 patients were enrolled in the randomized, double-blinded efficacy study, which tested two doses of the compound twice daily for 12 weeks vs. placebo. Results are expected in five weeks to eight weeks.

• Nabi Biopharmaceuticals, of Boca Raton, Fla., assigned some projects to Integrity Healthcare Communications, of Woodbridge, N.J., including one for StaphVAX, a vaccine in a Phase III trial to prevent Staphylococcus aureus bacteremia in end-stage renal disease patients. Integrity will develop prelaunch programs for StaphVAX and will develop direct mail and interactive marketing materials for an existing Nabi account, WinRho SDF, an intravenous Rho immune globulin treatment for acute, chronic and HIV-related immune thrombocytopenia purpura.

• Net Force Systems Inc., of St. John's, Antigua, acquired a controlling interest in Sinovac Biotech Co. Ltd., of Beijing. In conjunction with the acquisition, Net Force's management and directors resigned while Wei Dong Yin was appointed president and Lily Wang was named chief financial officer. Both also were appointed to the board, as was He Ping Wang. Privately held Sinovac is developing human vaccines for hepatitis A, combined hepatitis A and B, influenza and severe acute respiratory syndrome, while Net Force said it is shifting its focus toward the Chinese biotechnology industry.

• Nobex Corp., of Research Triangle Park, N.C., said it completed a Phase I trial of Apaza for inflammatory bowel disease. The compound was evaluated in 16 healthy volunteers in a randomized, single-blinded, placebo-controlled, dose-escalation study, which showed that Apaza is safe at the doses studied. Analysis of blood and urine samples provided evidence of little absorption into the body of the intact Apaza molecule, the chemical bond between the two drugs was broken in the colon to release each drug, and blood and urine levels of the anti-inflammatory and the immune modulator and their metabolites were low.

• Oxigene Inc., of Waltham, Mass., began a Phase I/II combination trial of its lead anticancer agent, Combretastatin A4 Prodrug (CA4P), with the iodine-labeled antibody A5B7 in patients with advanced colorectal cancer. About 35 patients are expected to be recruited for the trial, which Oxigene said would be the world's first human study combining a vascular targeting agent with radioimmunotherapy.

• Paradigm Genetics Inc., of Research Triangle Park, N.C., entered a research collaboration with the University of North Carolina at Chapel Hill to identify biomarkers indicative of choline deficiency, a physiological state that has been implicated in the onset of liver damage. The school will supply serum and urine samples collected as part of its research to determine the required daily amount of choline, on which Paradigm will perform biochemical analyses to identify the pathways and mechanisms that may be involved. Financial terms were not disclosed.

• Peninsula Pharmaceuticals Inc., of Alameda, Calif., and Takeda Chemical Industries Ltd., of Osaka, Japan, reached a licensing agreement for antibiotic TAK-599. Peninsula gains exclusive rights, including sublicense rights, to develop and market TAK-599 in all territories outside Japan. Takeda will manufacture the product for worldwide distribution. Financial terms were not disclosed.

• Peregrine Pharmaceuticals Inc., of Tustin, Calif., reported preclinical data at the Angiogenesis: New Opportunities & Solutions for Drug Development conference in Cambridge, Mass., highlighting phosphatidylserine (PS) as a potential treatment for cancer. Treatment of mice with one of the anti-PS antibodies resulted in 90 percent, 65 percent, 50 percent and 70 percent growth retardation of various tumors - both small (0.1 cm diameter) and well established (0.3 cm diameter) tumors were inhibited. Anti-PS treatment induced long-term, complete remissions in 50 percent of mice with Meth A fibrosarcomas and 30 percent of mice with MBA-MD-231 breast tumors. The anti-PS antibodies have shown no toxicity in preclinical in vivo studies.

• Progen Industries Ltd., of Brisbane, Australia, reported data at the Strategic Research Institute conference held in Cambridge, Mass., showing that PI-88 produced a partial response and some disease stabilization for three months to over two years in patients with advanced cancers for which there are few or no effective treatment options. PI-88 is in an international Phase I/II trial program in the U.S., Australia and Taiwan.

• Proneuron Biotechnologies Inc., of Los Angeles, said preclinical results published in last month's issue of the Journal of Neuroimmunology show that its macrophage therapy (ProCord) may effectively help improve the function and preserve the integrity of a damaged spinal cord. ProCord consists of autologous activated macrophage therapy for the treatment of patients with acute complete spinal cord injury within 14 days of damage.

• Regeneration Technologies Inc., of Alachua, Fla., lowered its third-quarter revenue guidance to $20 million, down from a previous forecast of $22 million to $24 million. The company, a processor of orthopedic, cardiovascular and other allograft implants, blamed the shortfall on lower spinal implant orders than previously expected. Its stock (NASDAQ:RTIX) fell $4.52 Tuesday, or 33.4 percent, to close at $9.

• Reliant Pharmaceuticals LLC, of Liberty Corner, N.J., raised $115 million through the initial closing of its Series D convertible preferred units (including the exchange of $37 million of existing secured debt). The privately held company also reserved the right to raise up to an additional $140 million by way of the financing (excluding debt exchange), which would bring the aggregate financing to $220 million (excluding debt exchange). The initial closing was led by Invemed Catalyst Fund LP, and also included investments by Bay City Capital Fund III LP, business interests of the Pritzker family, BayStar Capital and the family interests of Ernest Mario, Reliant's chairman and CEO.

• Stanford University in Palo Alto, Calif., said researchers from its medical center published findings in this month's issue of the American Journal of Psychiatry of their identification of a genetic marker, the 5HT2a gene, which can explain why some people experience side effects to common antidepressants while others do not. They also found that CYP2D6, a key liver enzyme involved in breaking down these antidepressants, played no role in the development of side effects nor in how well the drugs worked. The findings may lead to fewer side effects for patients undergoing antidepressant drug therapy.

• Targeted Genetics Inc., of Seattle, converted all of its outstanding convertible debt into equity under a collaborative agreement established in 1999 with Elan Corp. plc, of Dublin, Ireland, and its affiliates. Targeted Genetics converted about $9.4 million in outstanding loans and interest payable to Elan into about 5.2 million shares of restricted and unregistered common stock. The conversion consists of $2 million in debt into 1.6 million shares of common stock at conversion prices determined at the time of borrowing, and $7.4 million in debt being converted into 3.5 million shares of common stock at a price of $2.09 per share.

• The University Hospital in Homburg, Germany, reported findings at the European Respiratory Society meeting in Vienna, Austria, showing that patients taking ciclesonide, a new inhaled corticosteroid for bronchial asthma, attained a significantly greater improvement in lung function than those taking budesonide, a current standard therapy. More specifically, the randomized, double-blinded, parallel-group, multicenter study demonstrated that on average, participants who received a once-daily treatment of ciclesonide (320 ug) during the 12-week study recorded significantly greater improvements in their forced expiratory volume and vital capacity as compared with budesonide (400 ug). Ciclesonide also showed an earlier onset of treatment benefits (at the third day) vs. budesonide (at two weeks). The study's lead researcher was Rudiger Nave, who works for Altana Pharma AG, of Bad Homburg, Germany.

• The University of Pittsburgh was awarded $18 million from the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health in Bethesda, Md., for the construction of a regional biocontainment laboratory. The biosafety facility, which is scheduled to be completed by the summer of 2005, will be dedicated to research on agents that cause naturally occurring and emerging infections, as well as potential agents of bioterrorism. The NIAID award follows on several others reported a day earlier. (See BioWorld Today, Sept. 30, 2003.)