ARGUS PHARMACEUTICAL's AR-121 AIDS THERAPY IN PHASE I

ARGUS PHARMACEUTICAL's AR-121 AIDS THERAPY IN PHASE I trials to test the safety of the injectable drug, which combines the antifungal nystatin and a patented liposomal delivery system. Nystatin is currently available only in oral and topical formulations. In the Phase I study, which is being conducted at Twelve Oaks Hospital in Houston, 16 patients with AIDS-Related Complex (ARC) are receiving single (one-time) doses of AR-121. The study's principal investigator is Adan Rios, MD. In vitro studies indicate AR-121 "shows activity in the same range" as AZT, the company said. Argus believes the drug acts by "interfering with the lipid membrane that coats the HIV virus" in contrast to existing therapies that act on the replication mechanism of the virus. In animal models of fungal infections, AR- 121 demonstrated "enhanced effectiveness and fewer side effects, and may offer a broader spectrum of effectiveness" than currently marketed products, Argus said. AR-121 is the first product developed by Argus to enter human clinical trials. The focus of the two-year-old firm is the development of anti-infective and anti-cancer drugs using liposomes as carriers; the lipid formulations are intended to improve efficiency by increasing the amount of drug reaching the targeted macrophage cells and to allow larger doses due to limited toxicity. Argus received three patents in February covering the use of liposomal delivery systems for polyene antifungal compounds such as hamycin, filipin, lucensomycin, mepartricin, lagosin, and natamycin. Two of the patents deal with the use of liposomal systems to deliver higher doses of polyene antifungals for which the dosing is now limited due to toxicities that occur without a carrier. The third patent covers a process for producing powered polyene antifungals for later reconstitution and injection. In addition to AR-121, Argus is working on a retinoid liposome delivery drug, AR-623, with antitumor and antileukemia properties; preclinical studies have demonstrated "excellent activity with a significant reduction in toxicity," the company said. An antitumor compound, AR-522, is designed to "avoid the mechanism by which cells become resistant to antitumor compounds" and to reduce cardiotoxicity compared to the chemotheraphy agent Adriamycin (doxorubicin), the firm said. Argus has retained Vector Securities International to find potential corporate strategic partners. The firm is in the process of a second round of financing; the seed round, in August 1989, yielded $ 4.5 mil. Investors included Allstate Insurance, The Woodlands Venture Fund, Essex Venture Partners, Triad Ventures and the Genesis Fund. The Woodlands, Texas firm was formed out of the University of Texas M.D. Anderson Cancer Center. The company's founding technology was licensed from work led by Anderson's chief of immunobiology and its drug carrier section Gabriel Lopez-Beretein, MD. Argus President and CEO George Goldenberg was previously president of Moleculon, a drug delivery system company associated with the Massachusetts Institute of Technology. VP-R&D Robert Lenk was a founding scientist of The Liposome Company.