Hank Wuh believes that 40 centuries of Asian medical traditionprovides just the sort of base of empirical knowledge that couldpoint his company to useful new drug candidates.
"We intend to harness the best technology has to offer to thisbody of empirical knowledge that offers very important cluesto new drug discoveries," said Wuh, the president and chiefexecutive of Pharmagenesis of Palo Alto, Calif., which has twopotential immunosuppression drugs in preclinical development.
The Chinese in 5 B.C. used the plant artemisia to treat what isnow known as malaria. Today, the plant's active compound,artemisinin, shows promise in clinical trials against malariaconducted by the World Health Organization and by Hoffmann-La Roche.
Modern medical explorers are combining traditional medicalknowledge with a set of biotechnologies to quickly move alongthe path to new drug discoveries. Technology can improve onthe traditional medications. It can also be used to build onideas suggested by traditional medicine, sparking researchersto attempt a whole new approach to a medical problem.
Wuh and Pharmagenesis aren't alone in their interest innatural sources for medicine. Several companies are checkingup on medical practices around the world, while a few aretramping the forests and other terrain for natural compoundsand organisms that have been overlooked as medical remedies.
Systematically evaluating plants believed to have therapeuticvalue reduces the randomness of drug screening and cansubstantially cut the costs of early-stage discovery, said LisaConte, president and chief executive of ShamanPharmaceuticals of San Carlos, Calif.
"It's a prioritization game," she said. "We're trying to boost theKhit' rate of the discovery process."
Companies can protect their investment since rights to a plant-derivative that may be the basis of a lead compound areprotected in the same way that those derived from any micro-organism are, said Conte.
Shaman's researchers live and work with medicine men intropical regions of South America, Africa and Southeast Asia.The investigators learn by observing how native medicine ispracticed and translate the symptoms of patients being treatedwith traditional medicine into a Western diagnosis.
Shaman's ethnobotanists look for plants with proven value thatare common to several locales H in different villages of thesame region, or even in similar plants in different continents.
Focusing on plants with potential anti-viral, anti-fungal,sedative or analgesic effects, Shaman found pharmacologicalpotential in about half of 70 plants it examined during its firstyear of operation.
Wuh, a medical doctor, also sees the value of observing localuses of herbal medicines, but has steered Pharmagenesis onto adifferent strategy than Shaman's. His staff in Asia bypassescontact with patients and "deals directly with Asian hospitalsand physicians to observe patients taking medicinal plants aspart of therapy," Wuh said.
He said environmental conditions unique to Asia stimulateattributes in plants that have been found to be effectiveagainst disease.
The useful compounds must be identified and their variationsscreened for pharmacological effects.
"What bioassays can provide you with is a Western-style drug,"said Jeff Labovitz, president and co-founder of CalyxPharmaceuticals Inc. of Palo Alto, Calif. "You
need a pure and simple compound with a well-characterizedmolecule to pass FDA standards in the U.S."
This approach to the process is crucial in screening for plant-derived compounds, said Labovitz. Calyx is developing its ownspecific bioassays to perform the initial screening. "Rapidscreening makes it feasible to test the abundance of potentialdrug candidates found in the Asian rain forests in a matter ofweeks or months, instead of years or decades," Labovitz said.
Third World Partners
All three companies agree that forging close workingrelationships with Third World nations is increasinglyimportant for the new drug explorers.
Pharmagenesis relies on its network of Asian contacts, whichstarted through its contact with its primary Asian investor,Wuh said. The local contacts have helped the company navigatecultural barriers.
As a result, Pharmagenesis has entered preclinical trials for PG3113 and PG 3028 for treating rheumatoid arthritis, systemiclupus erythematosis and organ transplant rejection. Thecompany plans to enter human clinical trials with one or moreof these compounds next year.
Calyx was aided by its established relationships with a varietyof Asian organizations, from government ministries thatmanage natural resources to medical research institutions,Labovitz said. The company is evaluating natural products foruse in treating skin diseases, including psoriasis, atopicdermatitis, wound healing, viral skin infections, acne anddiseases of aging skin.
Conte said Shaman's access to hundreds of reports and folkhistories of medicinal plants on three continents helped get itslead product into clinical trials in only 16 months. That firstdrug, Provir, is in clinical trials involving 40 patients fortreatment of respiratory viruses. The drug has shown activityagainst parainfluenza, influenza A and B, and respiratorysynctyial virus (RSV).
A second drug, now in Phase I/II clinical trials, is a topicaltreatment for herpes 1 and 2. The company has filed U.S.patents on two other drugs H one for use as an anti-fungalagent that comes from a plant that is taken orally in Africa totreat infections, and the other as an analgesic.
Shaman has attracted two rounds of venture capital fundingtotaling $13.1 million from a dozen firms, including DelphiaBioVentures, Sequoia Capital and the Walden Group. Beforeforming Shaman, Conte herself was a vice president atTechnology Funding, a venture capital firm that is invested inShaman.
-- Michelle Slade Associate Editor
(c) 1997 American Health Consultants. All rights reserved.