Squibb, Phyton to Commercialize Paclitaxel Process
As part of Bristol-Myers Squibb (BMS) Company's continuing quest to develop improved production processes for paclitaxel (Taxol), the company will commercialize a proprietary plant cell fermentation process for the drug developed by Phyton Inc. (Ithaca, NY). Phyton originally licensed this technology to BMS exclusively in 1995. Under the current agreement, BMS retains the rights to produce taxol and related compounds using plant cell fermentation. But tiny Phyton (72 employees) could turn into a major pharmaceutical player by licensing its production methods for other products, which the company is now discussing with two other drug firms.
Taxol is marketed by BMS in the United States and abroad for the treatment of ovarian and breast cancers. Recent studies have shown that Taxol may prevent breast cancer in at-risk women, but the drug's toxicity clouds this potential indication in significant risk.
Plant Cell Fermentation
Taxol was originally isolated from the pacific yew tree, but the extraction process is costly and environmentalists object to destroying the slow-growing trees to obtain the drug.
Total synthesis is out of the question except as an academic exercise. Since 1994 BMS has been using a semisynthetic method of producing paclitaxel from an intermediate derived from renewable biomass such as the twigs and needles of yew trees. This process involves isolating taxol-like molecules and performing several chemical steps on them. Again, this technique is time-consuming and expensive because the taxol structure is so complex and labile.
Because of taxol's complex structure, commercial-scale total synthesis is impractical
Phyton's plant cell fermentation technology (PCF) represents a potentially large-scale method of producing paclitaxel and related taxene molecules without synthesis and without harvesting the product from cultivated plants. "PCF exploits a plant's production of secondary metabolites in response to stress," said CEO Kris Venkat. "Our technology involves selecting cell lines from the right yew species, growing them in ways that do not induce the cells to differentiate into plants, and introducing the right environmental factors to favor production of taxol over other phytochemicals."
Plant cell fermenters could produce large
quantities of taxol, saving hundreds of
dollars per dose compared with semi-
synthetic production while sparing the
pacific yew
Towards this end Phyton has devoted 250 person-years. The company's fermentation facility, located in Germany, uses a 75,000 liter fermenter (the largest PCF in the world), capable of producing hundreds of kilograms of taxol in a single batch.
"The large scale is essential," Venkat told Pharmaceutical Online, "Because taxol is a high-dose drug. This isn't like monoclonal antibodies, which are often produced in a 20-liter fermenter or in a modest mouse colony."
To date, Bristol-Myers Squibb has invested more than $25 million to develop PCF technology with Phyton (taxol sales should surpass $1 billion in 1998). Phyton will receive further funding, milestone payments, and royalties on TAXOL product sales.
For more information: Kris Venkat, CEO, Phyton, Inc., 125 Langmuir Laboratory, 95 Brown Rd., Ithaca, NY 14850-1257. Tel: 607-257-5058.
By Angelo DePalma