• ActivX Biosciences Inc., of La Jolla, Calif., and Kyorin Pharmaceutical Co. Ltd., of Tokyo, entered a collaboration to develop protein activity profiles for certain Kyorin compounds. ActivX agreed to use its technology to analyze specific protein activities in order to understand the biological activity of Kyorin's compounds and their potential to treat metabolic diseases. The companies first collaborated in May 2002 to identify and optimize drug candidates for Type II diabetes. Under the continuing collaboration, ActivX will be responsible for assay development, screening, profiling and selectivity analysis of hit and lead compounds. Kyorin will be responsible for medicinal chemistry and animal pharmacology, as well as clinical development.

• Affymetrix Inc., of Santa Clara, Calif., and Caliper Technologies Corp., of Hopkinton, Mass., entered a collaboration and supply agreement to develop and provide automated target-preparation instruments for the GeneChip probe array system, the new High Throughput Array system and future GeneChip platforms. The partners will develop products that leverage high-throughput automation and microfluidics knowledge at Caliper, now doing business as Caliper Life Sciences Inc., with Affymetrix's knowledge of microarray technology and applications. Affymetrix will market and distribute the line of automation products developed under the multiyear agreement. Caliper will manufacture the products and partner with Affymetrix to provide installation, training and field support for those new automated systems. Financial terms were not disclosed. Separately, Affymetrix released a Plasmodium/Anopheles Genome GeneChip array, which can be used to simultaneously study the entire expressed genomes of the host mosquito, Anopheles gambiae, and the malaria parasite, Plasmodium falciparum.

• Alnylam Pharmaceuticals Inc., of Cambridge, Mass., said its German affiliate, Ribopharma AG, granted three nonexclusive licenses to its RNA interference (RNAi) technology in a trio of deals that permit the use of short double-stranded RNAs to mediate RNAi. Invitrogen Corp., of Carlsbad, Calif., gained a nonexclusive license to provide research products and services under that particular RNAi patent family, which includes European Patent No. 1 144 623. Financial terms were not disclosed. Cell Signaling Technology Inc., of Beverly, Mass., also gained a nonexclusive license to the use of such technology in exchange for payment to Alnylam of an initial and annual license fees, as well as royalties on the sales of licensed products. Cenix BioScience GmbH, of Dresden, Germany, received a nonexclusive license to market research services under the patent in exchange for payment of annual fees and royalties.

• AnorMED Inc., of Vancouver, British Columbia, expanded the terms of its licensing agreement with Shire Pharmaceuticals Group plc, of Andover, UK, granting the latter exclusive rights to develop, manufacture, use and sell Fosrenol (lanthanum carbonate) worldwide for all potential human indications and veterinary uses. AnorMED will receive an up-front payment of about $180,000, followed by a royalty on sales and a percentage of net income received by Shire from any veterinary sub-licensees. Shire will begin a clinical study of the product, based on its ability to bind oxalate, as a treatment for kidney stones.

• Applied Molecular Evolution Inc., of San Diego, said the Federal Trade Commission granted early termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act relating to its proposed merger with Eli Lilly and Co., of Indianapolis, whereby AME will become a wholly owned subsidiary of Lilly. The proposed merger remains subject to other customary closing conditions, including the approval of AME's stockholders, who will meet Feb. 11.

• Archemix Corp., of Cambridge, Mass., entered a pair of development deals. A worldwide collaboration agreement with Nuvelo Inc., of Sunnyvale, Calif., aims to develop and commercialize Archemix's thrombin inhibitor, ARC183, for potential use in coronary artery bypass graft surgery, percutaneous coronary intervention and other acute anticoagulant applications. Archemix initially will lead development and be responsible for all clinical development activities. Nuvelo will have the option to lead commercialization efforts, in which both companies may participate. They will share equally all costs associated with ARC183 and will have 50/50 ownership of the compound. Archemix will receive an undisclosed up-front payment and additional development and milestone payments over the first year of the partnership and upon initiation of Phase II work. Additional financial terms were not disclosed. Separately, privately held Archemix entered a funded target-validation collaboration with Johnson & Johnson Pharmaceutical Research & Development LLC, of Raritan, N.J. The collaboration will focus on validating G protein-coupled receptor targets. Financial terms were not disclosed.

• Carrington Laboratories Inc., of Irving, Texas, reported the renewal of a raw materials supply agreement with Mannatech Inc., of Coppell, Texas. Under the 12-month renewal, Carrington will continue to provide its raw material, Manapol Powder, for use in Mannatech's nutraceutical products. Mannatech develops nutritional supplements, topical products and weight-management products.

• Cephalon Inc., of West Chester, Pa., began a Phase III program of R-modafinil, a single isomer of the active pharmaceutical ingredient contained in Provigil (modafinil), for the treatment of excessive sleepiness associated with narcolepsy and obstructive sleep apnea/hypopnea syndrome (OSA/HS). Earlier placebo-controlled trials demonstrated that the compound maintained wakefulness and had a longer duration of effect than Provigil, which received its first FDA approval in 1998 as an orphan drug for narcolepsy. It received an expanded label late last year to include use in improving wakefulness in people with excessive sleepiness associated with shift-work sleep disorder and in patients with OSA. The R-modafinil program's efficacy portion includes a pair of 12-week trials in OSA/HS patients and one in narcolepsy patients. The randomized, double-blind, placebo-controlled clinical trials are expected to include about 800 patients to test primary outcome measures of the Maintenance of Wakefulness Test and the Clinical Global Impression of Change-Clinician. The trials are being conducted at sites in the U.S., Europe, Canada and Australia. Cephalon said it remains on schedule to complete the OSA/HS program, and expects to file a new drug application for R-modafinil with the FDA in the fourth quarter. In addition, the company will begin a study of the compound in patients with shift-work sleep disorder early this year, and intends to file a supplemental NDA for that indication as well. (See BioWorld Today, Oct. 22, 2003.)

• ChemoCentryx Inc., of San Carlos, Calif., began a Phase I trial to evaluate its drug for the treatment of inflammatory bowel disease. Called Traficet-EN, the compound is an orally active anti-inflammatory agent that targets a chemokine receptor protein implicated in both Crohn's disease and ulcerative colitis. Initial pharmacokinetic, safety and toxicity data were presented at the JPMorgan Healthcare Conference in San Francisco. Two trials are being conducted in 72 healthy volunteers and are scheduled to be completed in the second quarter.

• Coley Pharmaceutical Group Inc., of Wellesley, Mass., began Phase I studies of Actilon (CPG 10101), a synthetic TLR9 agonist, targeted for patients with chronic hepatitis C infection. The studies will examine the safety, dose tolerability, immunological and antiviral activity of subcutaneous Actilon, first in healthy volunteers, and then in HCV-positive patients. Coley expects to enroll 40 healthy volunteers and 40 patients in the blinded, placebo-controlled, dose-escalation studies. The studies are scheduled to be completed in the first half of this year.

• Corautus Genetics Inc., of Atlanta, closed on $2.5 million of the $15 million convertible debt facility made available to the company by Boston Scientific Corp., of Natick, Mass., under a loan agreement established in July. The transaction, in addition to a recently reported $2.1 million private placement, brings Corautus' cash and short-term investment balances as of Dec. 31 to about $8.9 million.

• Crucell NV, of Leiden, the Netherlands, granted an exclusive license to Pfizer Inc., of New York, to develop and commercialize Crucell's West Nile virus veterinary vaccine for use in horses. Pfizer will pay Crucell an up-front license fee, milestones, annual fees and a royalty on sales of the vaccine. Further financial details were not disclosed.

• CytRx Corp., of Los Angeles, signed an agreement with the University of Massachusetts Medical School in which the company will fund research for the further development of gene silencing technology to use to treat diseases caused by cytomegalovirus (CMV), with an initial focus on CMV retinitis. CytRx will hold worldwide commercial rights to any products developed based on the technology.

• Diversa Corp., of San Diego, formed a collaboration with Bayer Animal Health, of Guelph, Ontario, to develop and market products to prevent infectious diseases in fish. Diversa and Bayer will collaborate to complete the development and registration of the existing pipeline of microbially produced vaccines for aquaculture previously developed by a Bayer venture. Those products will be manufactured by Diversa and exclusively marketed and distributed by Bayer in designated markets.

• D-Pharm Ltd., of Rehovot, Israel, reacquired full rights to DP-VPA from Shire Pharmaceuticals Group plc. The new chemical entity, a phospholipid derivative of the generic drug Valproic acid, significantly reduced the number of seizures in a Phase II study in patients with complex partial epilepsy. Financial terms were not disclosed.

• Entelos Inc., of Foster City, Calif., said it would develop a hematology model for Johnson & Johnson Pharmaceutical Research & Development LLC, of Raritan, N.J. In addition, Entelos will conduct an in silico research program upon completion of the model to support clinical development and Phase IV trial design.

• Esperion Therapeutics Inc., of Ann Arbor, Mich., entered a license agreement with Nippon Chemiphar Co. Ltd., of Tokyo, to develop small molecules based on peroxisome proliferators-activated receptor delta agonists. Esperion will have access to a range of PPAR delta agonists, which have been shown to elevate levels of HDL. Nippon Chemiphar will retain commercialization rights in Asia for any new products, while Esperion will have rights in the U.S., Europe and other markets outside Asia.

• Forest Laboratories Inc., of New York, said Namenda (memantine HCl) is available to physicians, patients and pharmacies nationwide. The product, developed in partnership with Neurobiological Technologies Inc., of Richmond, Calif., is the first and only medication approved for patients with moderate to severe Alzheimer's disease, the company said. It received FDA approval for moderate to severe Alzheimer's patients in the fall, and Forest said last week it would seek approval for an expanded label. (See BioWorld Today, Oct. 20, 2003.)

• Hemispherx Biopharma Inc., of Philadelphia, is conducting a new clinical program to treat severe acute respiratory syndrome in collaboration with Vanderbilt University in Nashville, Tenn. The program is designed to provide a rapid response to a SARS epidemic and to improve rapid diagnosis of the disease. The parties will study Hemispherx's lead drug, Alferon N Injection, and Alferon LDO (low-dose oral interferon) in the treatment and prophylaxis of SARS.

• Immunomedics Inc., of Morris Plains, N.J., raised $10 million after agreeing to issue convertible senior notes for a two-year period. The notes bear interest at a fixed annual rate of 3.25 percent to be paid semi-annually in arrears. Their unidentified holder may convert them at any time prior to the maturity date, with the conversion price fixed at the greater of 120 percent of the average volume-weighted average prices for the five business days immediately after the trade date or $5.33 per share. Immunomedics, which said it plans to use the funds for the development of its cancer and autoimmune disease therapeutics, intends to file for the notes' registration and applicable conversion shares within four months. The holder has a six-month option to purchase up to an additional $3 million of notes.

• Integrated BioPharma Inc., of Hillside, N.J., acquired intellectual property developed by the Center for Molecular Biotechnology of Fraunhofer USA Inc., of Newark, Del. It covers exclusive rights to property in the area of expression, engineering, testing, production and validation of human therapeutic proteins in plants. The agreement grants Integrated BioPharma exclusive rights and eventual ownership of all of the intellectual property and expertise in the field of vaccine, therapeutic protein and antibody production for human use. The company will pay the center cash and royalties in exchange for rights to the technology.

• Jerini AG, of Berlin, reported positive results from its POC Phase II study to evaluate its lead compound, Icatibant, for the treatment of acute attacks of hereditary angioedema. Symptoms resolved rapidly in all eight patients, and the treatment response was sustained over the observation period. The company said such data confirm that Icatibant can be of benefit in acute attacks of hereditary angioedema. Icatibant is a bradykinin receptor antagonist that, in contrast to other agents, acts directly on the effects of bradykinin causing rapid symptom relief.

• Kemin Pharma, of Herentals, Belgium, said it identified two molecules that appear to have good biological effects against hepatitis C virus. The first molecule, KPE02003002, is being tested in Phase II trials and was discovered in October 2002 through a collaborative effort with the National Institutes of Health in Bethesda, Md., and the Rega Institute for Medical Research in Leuven, Belgium. The second molecule, KPE00001113, was discovered last year as part of the same collaborative, in vitro, in an antiviral screening program.

• Meridian Bioscience Inc., of Cincinnati, will begin a program to redeem at par its outstanding issue of 7 percent convertible subordinated debentures due 2006. The first call for redemption, in the amount of $4 million, will take place soon after Jan. 28, when the holders lose their right to exchange their current debt for new debentures. They have until that date to exchange their debt for new 5 percent convertible subordinated debentures that mature on Sept. 1, 2013, cannot be called at par before Sept. 1, 2007, and have a lower conversion price than the current debentures. It is anticipated that the company will make additional redemptions, at par value, prior to the maturity date of the debentures.

• Metabasis Therapeutics Inc., of San Diego, formed a collaboration with Merck & Co. Inc., of Whitehouse Station, N.J., to research, develop and commercialize small-molecule therapeutics to treat hepatitis C virus infections. Merck will contribute drug candidates and Metabasis will apply its liver-targeting HepDirect prodrug technology. Merck also gains certain option rights to develop and commercialize drugs for HCV that might be discovered independently by Metabasis. Merck paid an execution fee and will fund Metabasis' efforts to synthesize HepDirect prodrugs of the Merck compounds. Merck has exclusive responsibility for further development and commercialization of HepDirect HCV drugs that result. Metabasis also may be entitled to milestone payments and royalties.

• Montreux Equity Partners, of Menlo Park, Calif., closed a new venture fund, MEP III, at about $83 million. The fund will co-invest alongside MEP II and together comprise a total of $160 million of venture capital funds. The closing brings more than $180 million in funds under management at Montreux, a venture capital firm focused on health care and life science investing.

• MorphoSys AG, of Martinsried, Germany, and Bayer Healthcare AG, a unit of Bayer AG, of Leverkusen, Germany, agreed to cross-license certain technology. MorphoSys will receive the human cell line HKB11 for production of HuCAL antibodies and for its own research, as well as an option for the commercial production of antibodies using the HKB 11 cell line. Bayer will switch its in-house research and development programs to the MorphoSys HuCAL GOLD antibody technology and will pay an installation fee to MorphoSys, which also will receive annual license payments and possibly milestone payments and royalties.

• Myriad Genetics Inc., of Salt Lake City, said its cancer compound, MPI-176716, is in the final stages of preclinical development. New data demonstrate the drug's potency in killing cancer cells and its ability to cause tumor regression in animal models of ovarian cancer, it said.

• Nadag AG, of Munich, Germany, agreed to merge with SiREEN AG, also of Munich, to form Sirenade Pharmaceuticals AG, a company with clinical and preclinical projects in central nervous system diseases and oncology. Following the merger, the company will begin a financing round to raise about €20 million in additional investments for the combined entity.

• Pharmacopeia Inc., of Princeton, N.J., reached a research milestone in its collaboration with AstraZeneca plc, of London, in which scientists identified lead compounds from Pharmacopeia's compound collection active against a gastrointestinal receptor target. The milestone was triggered by AstraZeneca's acceptance of the compounds identified from the collaboration. Pharmacopeia received an undisclosed payment for reaching the milestone.

• Progenics Pharmaceuticals Inc., of Tarrytown, N.Y., began a second pivotal Phase III trial of its investigational drug methylnaltrexone (MNTX) for the treatment of opioid-induced constipation in patients with advanced medical illness. The double-blinded, randomized, placebo-controlled study will measure the ability of MNTX to induce laxation within four hours in patients with advanced medical illness and opioid-induced constipation. The study also will evaluate the ability of MNTX to restore patients to a normal bowel schedule of three or more laxations per week.

• SkyePharma plc, of London, entered an agreement with Critical Therapeutics Inc., of Cambridge, Mass., to develop a controlled-release formulation of the oral asthma drug zileuton for asthma and chronic obstructive pulmonary disease, a drug the company would market in the U.S. with its own specialist sales force. A four-times-a-day, immediate-release version was marketed as Zyflo Filmtab (zileuton tablets) by Abbott Laboratories, of Abbott Park, Ill. SkyePharma developed a controlled-release formulation of zileuton, using its Geomatrix technology. Abbott completed Phase III development in asthma with the product.

• Spectrum Pharmaceuticals Inc., of Irvine, Calif., said it received waivers of the "product-triggered redemption right" from substantially all holders of the company's outstanding Series E convertible preferred stock. The company continues to have cash in excess of $25 million to fund its business strategy. In the event that Spectrum did not conclude the acquisition of a clinical-stage oncology product candidate by Dec. 26, the holders of Series E convertible preferred stock had the right to redeem, at their discretion, up to one-half of the preferred shares at face value, or up to $10 million, on or before Jan. 27.

• Sucampo Pharmaceuticals Inc., of Bethesda, Md., completed the second of two Phase III efficacy studies to support a new drug application for its chloride channel activator, SPI-0211, in treating constipation. The pivotal trial randomized 237 patients with documented constipation into two treatment groups. Sucampo's last open-label safety study is ongoing and will end in the third quarter. It also recently began a Phase II study of SPI-0211 in treating postoperative ileus.

• Tripos Inc., of St. Louis, and Chronogen Inc., of Montreal, formed a three-year collaboration to discover and optimize small-molecule therapeutics for cardiovascular disorders. Tripos will use its chemistry process to provide complete drug discovery chemistry services for Chronogen to support its biological knowledge in metabolic pathways related to aging. Chronogen will apply its in vivo screening technologies to select effective molecules.

• V.I. Technologies Inc., of Watertown, Mass., received $1.5 million in cash after reaching a settlement with Precision Pharma Services Inc., of Melville, N.Y., related to amounts due Vitex per the 2001 sale of its plasma operations to Precision. It also will return 4.4 million Vitex shares, or 75 percent of the shares it had acquired in a 2003 rights offering. The total value of the consideration to be received by Vitex, based upon the most recent closing price on Nasdaq, is $6.4 million. Vitex will release Precision from all obligations, which total $5.4 million as of fiscal 2003.

• ViaCell Inc., of Boston, appointed Vaughn Kailian its chairman. Kailian, the vice chairman of Millennium Pharmaceuticals Inc., of Cambridge, Mass., previously headed its commercial organization after serving as CEO, president and director of COR Therapeutics Inc., of South San Francisco, which merged with Millennium. ViaCell is a clinical-stage company with a cellular medicine pipeline focused on the areas of cancer, neurological diseases, diabetes and muscular dystrophy.

• Xencor Inc., of Monrovia, Calif., agreed to license its technology to Protein Design Labs Inc., of Fremont, Calif., as part of a collaboration to create monoclonal antibodies with enhanced potency. The multiyear arrangement will allow PDL to apply a number of its preclinical-stage antibodies against a number of its targets using Xencor's XmAb technology, which consists of a suite of engineered Fc domains that can be applied to any antibody to control the recruitment of the immune system's effector functions and for oncology applications to increase antibody-mediated tumor killing. Xencor will receive technology access and license fees, development milestones and royalties. PDL will be responsible for development and commercialization of resulting products. More specific financial terms were not disclosed.

• Zonagen Inc., of The Woodlands, Texas, said that based on final results of its self tender offer, about 6.5 million common shares, including about 61,000 issuable upon exercise of options tendered by directors for repurchase, were properly tendered and not withdrawn. The figure is about 300,000 shares less than originally expected.