• Acacia Research Corp., of Newport Beach, Calif., said its subsidiary CombiMatrix will collaborate with the Seattle Biomedical Research Institute to conduct a range of research activities based on flexible chip technology. The effort will use customized gene expression microarrays for investigating differential gene regulation of the Leishmania parasite life cycle. It also will apply CombiMatrix's RNA technology to develop pools of RNAi compounds to silence multiple genes in Trypanosoma brucei, Trypanosoma cruzi and Leishmania major.

• Accelr8 Technology Corp., of Denver, began trading on the American Stock Exchange under the ticker symbol "AXK." The company sells microarray slides and microtiter plates coated with its OptiChem activated surface chemistry.

• Aclara BioSciences Inc., of Mountain View, Calif., introduced the capabilities of its eTag technology for ADME/Tox analysis to the Japanese research community in a presentation made at the Toxicogenomics International Forum in Tokyo. Aclara has developed a library of genes associated with drug metabolism and toxicity for which eTag assays have been validated, the company said.

• Akorn Inc., of Buffalo Grove, Ill., completed a $40.5 million financing after entering a preferred stock and note purchase agreement with a group of insider and outsider investors. The financing consists of $25.7 million in Series A, 6 percent participating convertible preferred stock and warrants, a $2.8 million subordinated promissory note and up to $12 million in senior secured debt from LaSalle Bank National Association. Akorn, which manufactures and markets sterile specialty pharmaceuticals, will use the new capital to reduce its outstanding senior bank debt and is expected to provide up to $6 million in working capital. Leerink Swann & Co. served as Akorn's sole adviser.

• Alkermes Inc., of Cambridge, Mass., said its partner Janssen-Cilag SA, of Madrid, Spain, received approval from French authorities to market Risperdal Consta for schizophrenia. The product will be launched following negotiation of reimbursement pricing. Risperdal Consta is a long-acting injectable form of risperidone that was developed using Alkermes' Medisorb drug delivery technology. Janssen-Cilag is responsible for worldwide sales and marketing of the product. In the U.S., Johnson & Johnson Pharmaceutical Research & Development, of La Jolla, Calif., submitted additional data and analyses to the FDA to fulfill a complete response to the non-approvable letter issued by the FDA regarding the new drug application. (See BioWorld Today, April 30, 2003.)

• Arena Pharmaceuticals Inc., of San Diego, offered to pay about $23 million to purchase 3 million of its common shares from its largest stockholder, Biotechnology Value Fund LP and certain related entities, at $7.69 apiece. The per-share price reflects a 10 percent discount to the stock's $8.54 closing bid Oct. 7, when the offer was made. Under an amended stockholders agreement, the fund can accept or reject the initial offer by the earlier of 10 days following the notice of the offer or two business days after Arena requests a response. If the fund rejects the offer, Arena has the right during the next 10-business-day period to make a second offer for at least 3 million shares at a higher price. If the fund accepts either offer, or if the second offer is $8 or more per share, the standstill under the stockholders agreement would be extended until Dec. 31, 2004.

• Axcan Pharma Inc., of Mont Saint-Hilaire, Quebec, signed an agreement to pay $145 million to acquire the rights to a group of gastrointestinal products from Aventis SA, of Lyon, France. Axcan is gaining Carafate and Bentyl for the U.S. market and Sulcrate, Bentylol and Proctosedyl for the Canadian market, an acquisition the company said would be immediately accretive in generating more than 20 cents in earnings per share over the 12 months following closing. The total purchase price, about 3.5 times the net sales of the products for the trailing 12 months, will be funded by Axcan's cash reserves. The Carafate/Sulcrate drugs are indicated for the treatment of active duodenal ulcers. Bentyl/Bentylol are antispasmodic and anticholinergic drugs mainly used for the relief of gastrointestinal symptoms associated with irritable bowel syndrome. Proctosedyl is indicated for the reduction of swelling, pain and inflammation of hemorrhoids and other rectal lesions.

• Bayer Pharmaceutical Corp., a unit of Bayer AG, of Leverkusen, Germany, said data reported at the Fall Research Meeting of the Sexual Medicine Society of North America in Denver showed that treatment with Levitra (vardenafil HCl) resulted in a three times better chance of completing sexual intercourse successfully than placebo in erectile dysfunction patients who were historically unresponsive to Viagra (sildenafil citrate, Pfizer Inc.). More specifically, the trial showed that after 12 weeks, men were three times more likely to complete intercourse on Levitra than on placebo (46.1 percent vs. 16.1 percent). When compared with baseline, men were four times more likely to complete intercourse on Levitra (46.1 percent vs. 10.1 percent).

• Cellular Genomics Inc., of Branford, Conn., entered a research collaboration with Affymetrix Inc., of Santa Clara, Calif., to use the latter's GeneChip technology with the former's chemical genetics Analog Sensitive Kinase Allele technology to develop assays for kinase drug discovery. The research program also could show a new use for Affymetrix's GeneChip arrays in cell-based assay development and lead discovery. Financial terms were not disclosed.

• Collegium Pharmaceutical Inc., of Cumberland, R.I., relocated its corporate headquarters to a new facility at Highland Corporate Park in Cumberland. The site, which is about 25,000 square feet, incorporates all of Collegium's administrative functions as well as research and development, including analytical laboratories and formulation development.

• Cytomedix Inc., of Little Rock, Ark., raised gross proceeds of $2.5 million after closing a private offering of its common stock. The company, which said it would use the funding in connection with clinical trials and operations, produces a product called AutoloGel, an autologous platelet gel composed of multiple growth factors and a fibrin matrix used to treat chronic wounds.

• CytRx Corp., of Los Angeles, entered a pair of agreements to use its RNAi gene silencing technology to develop a drug that prevents, treats or cures amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease. With Massachusetts General Hospital in Boston, CytRx agreed to jointly begin a broad-based research program to use RNAi for ALS. The program will be led by a professor at Harvard Medical School. Separately, CytRx agreed to fund a sponsored research program at the University of Massachusetts Medical School to use RNAi for ALS. The company previously signed an exclusive, worldwide license agreement with the school to use RNAi technology for an ALS treatment.

• Durect Corp., of Cupertino, Calif., began to manufacture product for its anticipated pharmacokinetic study and other initial clinical studies in a Phase III program of Chronogesic (sufentanil), its pain therapy product, using its new terminal sterilization manufacturing process. The product, which is designed to deliver sufentanil continuously for three months, is intended to target patients with opioid-responsive chronic pain that results from a variety of causes. Chronogesic is the subject of a development and commercialization collaboration with Endo Pharmaceuticals Holdings Inc., of Chadds Ford, Pa., in a deal that includes milestones that could equal $52 million. Endo licensed exclusive promotional rights in the U.S. and Canada and would be responsible for marketing, sales and distribution. (See BioWorld Today, Nov. 12, 2002.)

• Eximias Pharmaceutical Corp., of Berwyn, Pa., received orphan drug designation in Europe for Thymitaq (nolatrexed) to treat hepatocellular carcinoma. The company already had orphan drug designation in the U.S. for the product, which is in Phase III trials.

• Flamel Technologies SA, of Lyon, France, reported that it closed its offering of about 4.5 million ordinary shares in the form of American Depository Shares at $33.25 per share. The offering included 2 million shares offered by the company, and 1.98 million shares offered by selling shareholders. The underwriters have an option to purchase 588,000 additional shares from the selling shareholders to cover overallotments. Flamel received proceeds of about $62.1 million from the issuance of 2 million shares. (See BioWorld Today, Oct. 6, 2003.)

• Genome Therapeutics Corp., of Waltham, Mass., said six poster presentations were reported at the Infectious Diseases Society of America meeting in San Diego related to its lead candidate, Ramoplanin. Among the findings, researchers showed that the antibacterial drug did not induce the two most common genes that cause vancomycin resistance (vanA and vanB). Licensed from Vicuron Pharmaceuticals Inc., of King of Prussia, Pa., Ramoplanin is in a Phase III trial for the prevention of bloodstream infections caused by vancomycin-resistant enterococci and a Phase II study for the treatment of Clostridium difficile-associated diarrhea.

• ICOS Corp., of Bothell, Wash., entered a manufacturing agreement with Protein Design Labs Inc., of Fremont, Calif. ICOS will manufacture PDL's M200, an antibody in Phase I studies. The antibody was initially developed by Eos Biotechnology Inc., of South San Francisco, and was manufactured by ICOS for early stage clinical trials. The manufacturing campaign is to be conducted during the first half of 2004.

• Indevus Pharmaceuticals Inc., of Lexington, Mass., reported data at the International Continence Society meeting in Florence, Italy, showing that treatment with trospium reduced urgency severity, a symptom among patients with overactive bladder. Trospium-treated participants in the 523-patient trial progressed from experiencing, on average, a moderate degree of urgency with each toilet void to experiencing a mild degree of urgency with each void (p<0.0001). Placebo patients had no notable change in the severity of their urgency. In addition, treatment with trospium achieved the coprimary endpoints in the trial by reducing both the frequency of urination (p<0.0001) and the number of urge urinary incontinence episodes (p<0.0001) per 24 hours, compared to treatment with placebo. The anticholinergic compound remains under FDA review. (See BioWorld Today, April 29, 2003.)

• ISTA Pharmaceuticals Inc., of Irvine, Calif., plans to sell up to 4 million shares after filing a registration statement with the SEC for a public offering. Another 500,000 shares were registered to be offered by selling stockholders. ISTA also granted the underwriters an overallotment option to purchase 675,000 shares. The lead managing underwriter is Thomas Weisel Partners LLC, with additional underwriting from Jefferies & Co. Inc., RBC Capital Markets and Roth Capital Partners LLC.

• Kyowa Hakko Kogyo Co., of Tokyo, entered an agreement with a U.S. pharmaceutical development venture, NovaCardia Inc., of San Diego, whereby Kyowa Hakko granted NovaCardia an exclusive license to develop and market, outside Asia and Japan, the adenosine-A1 receptor antagonist discovered and developed by Kyowa Hakko. Under the agreement, Kyowa Hakko will receive up-front and milestone payments, and could receive royalties. KW-3902 antagonizes the adenosine A1-receptor that is known to regulate renal function.

• Lorus Therapeutics Inc., of Toronto, reported preclinical results at the joint Human Proteome Organization and International Union of Biochemistry and Molecular Biology meeting in Montreal, showing that elevated levels of R1 protein, the large subunit of the ribonucleotide reductase complex, act as a tumor suppressor in experimental models of cancer. In the current study, R1 was incorporated into an adenovirus and delivered to tumor cells by infection. Overexpression of R1 resulted in a dramatic decrease in growth of tumor cells grown in culture. Moreover, tumor cells expressing high levels of R1 did not form tumors when implanted in mice, whereas a nonrelated gene was not effective in preventing tumor development in mice.

• Medarex Inc., of Princeton, N.J., reported data in collaboration with researchers from the Massachusetts Biologic Laboratories of the University of Massachusetts Medical School at the Infectious Disease Society of America meeting in San Diego, showing they have neutralized the severe acute respiratory syndrome virus in nonhuman tissue cultures. The breakthrough was accomplished using antibodies from genetically engineered mice immunized with a protein the SARS virus uses to infect cells. The researchers said the advance could lead to treatments to prevent infection with SARS after exposure, and potentially to therapeutic products to treat those already infected.

• Millennium Pharmaceuticals Inc., of Cambridge, Mass., initiated a Phase I/II trial of MLN2704 in patients with metastatic androgen-independent prostate cancer. MLN2704 is designed to deliver the maytansinoid chemotherapeutic agent, DM1, to prostate cancer cells through a targeted monoclonal antibody vehicle (T-MAV) that binds specifically to the prostate-specific membrane antigen. The study will involve about 46 patients.

• MorphoSys AG, of Munich, said preclinical studies of MOR101 and MOR102 demonstrated promising results of potency as anti-inflammatory antibodies. The data were presented at the Human Antibodies & Hybridomas Conference in Osaka, Japan. MOR101 and MOR102 target ICAM-1, a cell adhesion molecule involved in several inflammatory diseases.

• Novartis AG, of Basel, Switzerland, funded a study from which an international consortium of researchers from Seattle, London and Australia have reported the first use of a molecular test to measure the extent of remission or the likelihood of relapse in cancer patients being treated with Gleevec or a combination therapy consisting of interferon and cytarabine. The researchers said the test is more sensitive than any other test, making it a way to detect relapse earlier than before. A study on the subject was published in the Oct. 9, 2003, issue of the New England Journal of Medicine.

• Nuevolution A/S, of Copenhagen, Denmark, raised $15 million in a Series B financing led by Scandinavian Life Science Venture, of Copenhagen. The company has raised a total of $24 million since being founded in May 2001. Additional funds may be raised in a second closing, the company said. The company uses its Chemetics platform to identify drug candidates.

• ProMetic Life Sciences, of Montreal, and Arriva Pharmaceuticals Inc., of Alameda, Calif., opened a Phase II study to evaluate rAAT topical gel in atopic dermatitis. The companies are evaluating the product through their joint venture company, Arriva-ProMetic Inc. Alpha-1-antitrypsin is a glycoprotein primarily produced by hepatocytes and immune system cells.

• Regulome Corp., of Seattle, received $5.3 million in funding under the National Human Genome Research Institute's ENCODE project, which aims to lay the foundation for the next phase of the Human Genome Project. In collaboration with researchers at the University of Washington, privately held Regulome will apply its technology for locating and analyzing genetic sequences that control gene expression to a set of target regions that covers about 30 million DNA base pairs, or about 1 percent of the human genome. If the pilot effort proves successful, the project will be expanded to cover the entire genome, the company said.

• SIGA Technologies Inc., of New York, raised $9 million through the sale of stock and warrants to MacAndrews & Forbes Holdings Inc., a corporation wholly owned by Ronald Perelman and TransTech Pharma Inc., of High Point, N.C. In August, MacAndrews & Forbes invested $1 million in SIGA in exchange for 694,444 common shares at $1.44 apiece and warrants to purchase an additional 347,222 shares at an exercise price of $2 per share. MacAndrews & Forbes also was granted an option to make investments of up to $9 million for up to an additional 6.25 million shares and warrants for up to an additional 3.13 million shares on the same terms. MacAndrews & Forbes, immediately prior to the exercise of the option, assigned the right to invest up to $5 million to privately held TransTech Pharma, which is in a drug discovery collaboration agreement with SIGA.

• Tanox Inc., of Houston, said the FDA granted fast-track status to TNX-355 for patients with HIV-1 infection who have failed or are failing antiretroviral therapy. The humanized monoclonal antibody binds to domain 2 of the CD4 molecule, the primary receptor for HIV-1 that is present on the surface of certain cells (referred to as CD4+ cells). In that way, TNX-355 prevents the entry of HIV-1 into CD4+ cells.

• The Immune Response Corp., of Carlsbad, Calif., entered an agreement to license Amplivax from Hybridon Inc., of Cambridge, Mass. Immune Response will use the product, a second-generation immunomodulatory oligonucleotide also known as HYB2055, as an adjuvant to a vaccine candidate for HIV. The candidate, which the company said has demonstrated activity in laboratory experiments, combines the whole-killed vaccine technology employed in Remune, an immune-based HIV therapeutic vaccine being evaluated in Phase II trials, plus Amplivax. Immune Response will continue its development of Remune separately. Financial terms were not disclosed.