MultiCell Technologies, a drug-development company based in Lincoln, RI, announced this week that it has licensed its Fa2N-4 immortalized human hepatocyte cells and MFE culture media for ADME/Tox applications to Eisai, which the company will use at its Tsukuba Research Laboratories in Japan.
In addition to selling hepatocytes for drug discovery, MultiCell also runs a therapeutics business that is currently focused on autoimmune diseases. MultiCell CEO Stephen Chang estimated that two thirds of the company’s business is therapeutics and the remaining third is the cell-lines business. He also said that MultiCell hopes to grow the drug-discovery side of the company.
According to Chang, Eisai had been using MultiCell’s Fa2N-4 cell line and culture media for several years under a sublicense granted by XenoTech, the previous licensee for this technology. The XenoTech agreement was terminated in February 2006 after XenoTech failed to pay royalty obligations to MultiCell. (see CBA News, 2/10/06)
Chang said that MultiCell then decided to license the cell line to Eisai for five years. It has similar licensing agreements with Bristol-Myers Squibb and Pfizer. As Chang pointed out, “Most people do not realize that Pfizer actually was our partner early on. They helped develop the technology and funded its development. They currently use the technology extensively in-house.”
Chang said that independent studies by pharmaceutical companies suggest that MultiCell’s immortalized hepatocytes are the only cells of their kind suitable for CYP 450 induction studies.
“The cells have unusual cytochrome p450 function, which you do not find in other immortalized hepatocytes that are available,” Chang said. “Other hepatocyte cell lines that have been isolated over the years make only a few liver enzymes. And to our knowledge, ours make at least 10 to 12 liver enzymes.”
Using the immortalized cells, drug makers can standardize their ADME/Tox studies, which would enable the companies to monitor and control them more easily, said Chang.
Chang went on say that the cell lines are similar to functioning in vivo hepatocytes. The only competition is primary hepatocytes, though the availability of these cells is very limited and their quality is very variable, he said.
According to Chang, the market for immortalized hepatocytes is growing. “Anything that can eliminate a drug candidate from continued clinical development is worthwhile,” Chang said. “A molecule that can do that in any way, shape, or form on the basis of toxicity or adverse effects is certainly value-added to the drug-development process.”
Chang also said that drug discovery is migrating towards using human hepatocyte cell lines as opposed to animal hepatocytes. He said the fact that a human system is available that can replicate a lot of the human issues with toxicity makes using it a “no-brainer.” He said that such a system will become further integrated into the drug-discovery process as the field grows.
Chang said that MultiCell does not currentlyhave the IP to expand its business to other types of cell lines. It is currently maintaining the focus of its cell line business on its existing immortalized hepatocyte cell lines, Fa2N-4 and Ea1C-35. However, “if a turnkey business became available for certain types of cell lines in what we felt was a potential growth market, we may consider it,” he said.
A possible growth driver could be a pending decision by the FDA to change its toxicity testing recommendations from the use of three primary hepatocyte cell lines to one immortalized hepatocyte cell line and two primary cell lines. That proposal is currently out for public comment.
“Any molecule that can eliminate a drug candidate on the basis of toxicity or adverse effects is certainly value-added to the drug development process.”
In addition, Chang said that MultiCell is looking to use its cells and cell lines “for the potential induction of novel proteins. There are currently several certified human cell lines that are used for the manufacture of recombinant proteins.”
Chang said that MultiCell investigators have been able to introduce recombinant DNA into the cells, and in turn, the recombinant DNA plasmid can manufacture proteins.
Chang said these proteins are likely appropriate for biomanufacturing. He said researchers have been using Chinese hamster ovary cells for this purpose, as well as some of the early recombinant protein technology using E. coli.
MultiCell’s technology represents “another platform … [that] allows those who are interested in protein manufacturing using an alternative cell substrate,” said Chang. “That’s what we perceive as the next potential use for this technology.”
Two in One
Chang explained that MultiCell is actually two businesses: a San Diego-based therapeutics business, which researches treatments for autoimmune disease, and a Lincoln, RI-based shop that sells hepatocytes for drug discovery.
All of MultiCell’s revenues are from the cell-line business. The company posted $679,881 in revenues from this business in its 2006 fiscal year.
Chang said MultiCell was a drug-discovery tools operation that morphed into a therapeutics business. “I guess to increase shareholder value we went into the therapeutics side,” he said. He added that the company plans to grow as a drug maker.
“Our core technology was based on cells for drug discovery,” he said. “Within that technology, however, was central IP technology that allowed us to segue into therapeutics opportunities.”
At the moment, MultiCell has a phase 2 drug for the treatment of fatigue in autoimmune multiple sclerosis that should enter phase 2B sometime later this year, Chang said.
Although MultiCell primarily deals in immortalized human hepatocyte lines, the company also has an inventory of immortalized rat and pig hepatocytes, Chang said.
He said the company employs eight people “and probably a much greater number of consultants.”