HYBRIDON's FIRST ANTISENSE DRUG FOR AIDS COULD ENTER CLINICALS IN 1991

HYBRIDON's FIRST ANTISENSE DRUG FOR AIDS COULD ENTER CLINICALS IN 1991, Chairman Nigel Webb, PhD, maintained at a Jan. 9 press briefing by antisense companies during the BioEast '91 biotech conference in Washington, sponsored by the International Biotechnology Suppliers Association and Bioconferences International. "We believe we have potency and safety data in animals that warrant the generation of an IND and it is our intention . . . to submit to the FDA in 1991 an IND application," Webb said. The company's lead genetic targeting or "antisense" compound HBY-0047 is an oligonucleotide, a sequence of small molecules (nucleotides) bound to a phosphate-sugar (phosphothionate) backbone. The compound is designed to interfere specifically with replication and production of the AIDS virus by binding in a complementary way to HIV viral RNA, thereby blocking the production of proteins necessary for the virus to reproduce itself. Preliminary safety, pharmacokinetic and efficacy studies with HBY-0047 in animals have been encouraging, Webb said. In addition, the compound appears to have a long half-life in animals. There has been 'concern that such molecules will be susceptible to cleavage by enzymes in the human body. The firm was issued a patent in 1989 for the use of oligonucleotides in AIDS and has patents pending for the specific compound and manufacturing process. Hybridon is also developing an antisense compound, utilizing the same sugar backbone, for Haemophilus influenzae b virus. The compound is already being tested in animals and is expected to be in clinicals in two years. Another major company program is the development of antisense drugs which downregulate or inhibit certain proteins required to maintain diseases, such as Alzheimer's and diabetes. Those projects are two to three years away from clinical study. Farther down the road are oligonucleotides targeted to DNA control sequences. In this area, Hybridon has initiated a program for ex- vivo leukemia treatment, where bone marrow is removed from a patient, treated and reinfused into the body. Based in Worcester, Massachusetts, Hybridon was founded in February 1990 by Paul Zamecnik, MD, principal scientist at the Worcester Foundation for Experimental Biology. Hybridon's seed funding of $ 3 mil. came primarily from Medical Science Partners, L.P., a venture fund created by Harvard Medical School ("The Pink Sheet" July 30, T&G-8). Among Hybridon's advisors are former director of the National Institutes of Health James Wyngaarden and former FDA Center for Drugs and Biologics Assistant Director for Pharmacology and Toxicology Wayne Galbraith. San Diego-based Genta Chairman Thomas Adams, PhD, told the conference that his company will be prepared to enter the clinic by year-end with an antisense drug for chronic myelogenous leukemia (CML). Based on the company's proprietary Matagen oligomer technology, the drug "can actually kill Philadelphia chromosome-postive cells and not affect normal cells," Adams maintained. Genta was founded in February 1989 by Adams, previously a founder of Gen-Probe and a former VP of research for Hybritech. ISIS VP-Research Christopher Mirabelli, PhD, former director of molecular pharmacology at SmithKline & French, told the group that the company's first product, ISIS 1082, has shown activity against herpes simplex virus 1 and 2. The compound is being tested currently in animal models with stromal keratitis, he said, and it has shown activity equivalent to Burroughs-Wellcome's Viroptic, which is commonly used to treat the disease. In the papillomavirus area, Mirabelli said that ISIS is "going to be selecting a compound in the first quarter for development" for the treatment of genital warts. Based in Carlsbad, California and founded in March 1989, ISIS has signed major R&D agreements with Ciba-Geigy and Rhone-Poulenc ("The Pink Sheet" Nov. 5, T&G-9) and, most recently, with the Japanese firm Eisai. Gilead President Michael Riordan announced at the conference that his firm will launch a new program in aptamers, oligonucleotides that bind to target molecules that cause disease. The program is similar to the projects of the other antisense companies. Until now, Gilead, one of the oldest antisense startups founded in August 1987, has been focused on code blockers that inhibit the function of harmful genes, a technology considered to be more complex and farther from clinical use. Gilead entered into a $ 20 mil. R&D venture with Glaxo in July ("The Pink Sheet" July 30, T&G-6) and more recently hired former Bristol-Myers Squibb director of antiviral chemistry John Martin, PhD. Allendale, N.J.-based antisense start-up Pharmagenics, founded last summer, said it is finalizing an agreemnt with a major pharmaceutical company. Synthecell, a Rockville, Md.-based manufacturer of biomolecules for research and diagnostics, announced the creation of a new antisense company, Genetic MediSyn. The company will first develop antisense drugs to block simple viral replication. Baylor College of Medicine researcher and founder of Texas-based antisense company Triplex Pharmaceutical, Michael Hogan, PhD said his firm will focus on a triple helix approach to antisense therapy to inhibit viral growth and the expression of oncogenes in CML, other cancers, and psoriasis.