Exovir Bets Future on Antiviral Mixtures Exovir is a lean company. With just five full-time employees and an of fice in the New York City suburb of Great Neck, the firm has no labora tories and no manufacturing facili ties. What it does have is an in triguing approach to the topical treatment of a variety of skin disor^ ders. If Phase III human clinical trials now under way prove success ful, at least one product—an oint ment for genital herpes—could be on the market as soon as late next year. Exovir's chief technological asset is a patented combination of α-in terferon with nonoxynol 9, a sur factant commonly used as the ac tive ingredient in spermatocides. Ac cording to Fred Rapp, a professor of microbiology at Pennsylvania State College of Medicine and one of the inventors of the ointment, the two ingredients interact synergistically, greatly increasing each component's activity against herpes simplex virus. "The nonoxynol appears to knock out the virus outside the cells, while the α-interferon prevents further replication of the virus inside the cells," explains Rapp, a shareholder in and consultant to Exovir. Exovir hopes to market its ExovirHZ gel not only to what the Cen ters for Disease Control estimate are 20 million to 25 million genital her pes sufferers in the U.S. but to the 10 million Americans with condylo mata, or genital warts, as well. For herpes, Exovir-HZ would compete chiefly with Zovirax, an acyclovir marketed by Burroughs-Wellcome. In its current form Zovirax is taken orally and, Rapp says, must be tak en constantly to prevent outbreaks. The gel, on the other hand, need be applied only at the onset of an out break, he says. In the case of con dylomata treatment, now being test ed on human beings, the ointment would replace the use of acid, sur gery, or cauterization. Exovir also has obtained promis ing results from in vitro tests in which the gel destroyed HTLV-III, the AIDS virus. In July, the compa ny received the go-ahead from the Food & Drug Administration for clinical trials. The gel does not cure AIDS but could be used in a con-
Powell:prevents transmission of virus dom to kill AIDS virus in semen. "In the absence of a vaccine or ef fective drug, the gel could prove beneficial in preventing the trans mission of the AIDS virus," says Maxwell M. Powell, company chair man. In the first part of the test program, scientific advisory board member Thomas C. Merigan Jr., chairman of the infectious diseases department at Stanford University's medical school, will survey possi ble side effects of the gel in a ho mosexual population, a high-risk group. A second program, awaiting approval by the board at Beth Israel Hospital in Brookline, Mass., will examine the effect of the gel in vitro on HTLV-III levels in the semen of AIDS patients. With this range of potential ap plications for the α-interferon/non oxynol pairing, Exovir is looking to other materials. The company was issued a patent (U.S. 4,507,281) on the combination of any interferon— natural or recombinant—in March and has applied for similar protec tion on the combination of nonoxy nol 9 with any single lymphokine or synergistic mixture of lymphokines—such as tumor necrosis fac tor, interleukin-2, and colony stim ulating factor. "There is going to be a massive search for combinations of immunomodulators that will be effective
against one or more serious diseas es for which there is no treatment at present," Powell comments. In cases for which topical treatment is possible, he says, Exovir's gel could be the delivery system of choice. "Those diseases include certain types of skin cancers, psoriasis, rheuma toid arthritis, keratitis, and others," he says. In that vein, Exovir signed a joint research and licensing agreement in April with Genentech to develop topical treatments for various viral diseases through the combination of nonoxynol 9 and two recombinantly produced cytokines, which, though not identified by the com panies, are commonly believed to be 7-interferon and tumor necrosis factor. Under the agreement, Gen entech gets the right to use combi nations of the substances in research and for commercial purposes, while Exovir would receive royalties based on a percentage of the net revenues from commercial sales of the prod ucts developed. Exovir, however, re ceives no upfront or milestone pay ments as part of the deal. Like other small firms, Exovir is in a race to get products on the market before its funds, raised most ly in a $3.8 million 1983 stock offer ing, run out. At midyear, it had about $1.8 million in cash and Trea sury bills. Exovir lost $839,178 in the first half of 1986, compared to a loss of $743,217 in the comparable 1985 period. Since the only income in first-half 1986 was $80,363 in in terest, most of the loss came right out of cash and marketables. Powell says the company has enough money to take it through clinical trials on the gel for the her pes and genital warts applications. After that, he says, Exovir will need more funds or partners or both. Ear lier this year, the company retained a firm to seek marketing agreements for its first two products with phar maceutical companies. Tina Rizopoulos, health care ana lyst at Arnhold and S. Bleichroeder, a Wall Street investment house, agrees that Exovir should be able to remain financially sound. "Their burn rate has been slow over the past three years," she says. "They've been conservative about it. They have a good time frame in mind." D October 13, 1986 C&EN
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