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GLYNN FAIRCLOTH - PharmaMar USA
President and CEO, PharmaMar USA
Vice-President of Preclinical Research and Development, PharmaMar
The Research: Drug Treatments from Ocean to Market
PharmaMar is the only commercial company in the world
dedicated entirely to the discovery of new pharmaceuticals from marine organisms. Based in Spain, PharmaMar
focuses mainly on identifying cancer treatments. It has the resources and facilities to handle the entire
drug development process, from collection of samples all the way to commercialization. PharmaMar focuses on
shallow water species, of which it has collected tens of thousands of samples. The company's greatest successes
to date have been with chemicals isolated from tunicates (sea squirts). One of the company's drugs, with the
trade name of Yondelis®, is rapidly nearing FDA
and equivalent approvals in the U.S. and Europe. Yondelis is likely to become the first commercially available
cancer treatment derived directly from a marine organism, and as such many in the marine biotechnology field
and elsewhere are excitedly following its progress. Beyond Yondelis, PharmaMar also has five other compounds
in U.S. and European human clinical trials.
PharmaMar is based in Madrid, Spain and has about 300 employees. Faircloth is the company's vice-president of preclinical research and development. However, he is based in the U.S. and is the president and CEO of PharmaMar USA, a PharmaMar subsidiary based in Cambridge, MA, with about 30 employees. PharmaMar USA is in charge of preclinical research for PharmaMar discoveries.
 PharmaMar USA's Place in the Pipeline
PharmaMar USA is responsible for preclinical research with compounds identified and purified by PharmaMar scientists in Madrid as having promising bioactivity. By the time a compound make's it to Cambridge, the Spain team will have already determined its chemical structure. However, the PharmaMar USA group has far more extensive assays--some 40 to 50cancer cell lines to work with--and so it does additional work to identify a compound's potential as completely as possible. Led by Faircloth the Cambridge group also tests a compound's toxicity, works to elucidate its mechanism of action, and conducts tests in animal models. If promising results continue, PharmaMar USA prepares the reports for the FDA and its foreign equivalents that are required before human clinical trials can begin. The group also works closely with Madrid colleagues to determine the optimal clinical formulation for human tests, but these clinical trials and the other final steps toward commercialization are handled in Madrid.
Yondelis®
Ecteinascidin 743, which PharmaMar is developing under the trade name
Yondelis, was first isolated in the 1980s from the Caribbean sea squirt Ecteinascidia turbinata, which is
common in some areas in mangrove roots. The compound was first isolated by Tom Holt, a gruduate student in
the late Kenneth Rinehart's laboratory at the University of Illinois, Urbana-Champaign. Together, the two
filed the first patent. Scientists at Harbor Branch Oceanographic Institution were later instrumental in
defining the compound's structure. The University of Illinois licensed Ecteinascidin 743 to PharmaMar,
which has focused the vast majority of its efforts on Yondelis in hopes of positively illustrating the
company and marine drug discovery's potential. This strategy has clearly paid off as PharmaMar is nearing
completion of Phase III human clinical trials with Yondelis as an ovarian cancer treatment. The compound
is also in Phase II trials for soft tissue sarcoma, and prostate and breast cancers, and it is in Phase I
trials to evaluate its potential use in combination with other chemotherapy treatments.
Yondelis has multiple novel methods of action. It interferes with a cancer cell's ability to repair mistakes
in the DNA replication process, causing cell death, it inhibits the transcription of genes, and it also slows
tumor cell division leading to programmed cell death. To produce enough of the compound to allow preclinical
work on Yondelis, PharmaMar developed a successful mariculture system for raising E. turbinata in waters off
Spain. Later, however, an acceptably efficient synthetic production method was established, which is how the
drug will be produced if it does indeed make it to market.
Other Success Stories
PharmaMar's most advanced compound behind Yondelis is also derived from a tunicate. Aplidin®
was originally isolated from Aplidium albicans, which was discovered near a very small uninhabited island off the
coast of Spain. Also like Yondelis, Aplidin is now obtained through total synthesis. In Phase II clinical trials, Aplidin's
mechanisms of action are not yet fully understood, but the compound rapidly causes programmed cell death in cancer cells
and also blocks cell division.
Other PharmaMar compounds in clinical trials are Kahalalide F, ES-285, Zalypsis, and PM02734.
A Shark as "Big as a House" and an Impish Seal
These days, not surprisingly, Faircloth's travels mostly involve trips back and forth to Madrid, Spain. Faircloth has dived around Spain, Morocco, and Portugal with the PharmaMar collection team, but says his most interesting dive tales go back to his days working with the Harbor Branch Oceanographic drug discovery program.
Once, during a wall dive off Belize, Faircloth's dive buddy came to him with big eyes and a little frantic. Faircloth clapped his hands together in the standard sign for shark to ask if that was the problem. His buddy vigorously shook her head no, and instead began clapping her whole arms together to convey that this was much larger than your average shark. Soon, the animal was pushing both divers up against the wall. "It was pretty terrifying," says Faircloth, "because it was as big as a house." As it turned out, their assailant was a basking shark, a species known for its resemblance to great white sharks, but also for being a docile filter feeder. Baskings can be over 30 feet long. They do have hundreds of teeth, but these are very small and harmless. Needless to say, the divers were relieved once they figured all this out.
During another Harbor Branch trip, this time to the Galapagos Islands, Faircloth was diving with Shirley Pomponi
and others near a small rock outcropping that turned out to be the home of a seal colony. The seals were swimming through the divers legs and coming up to their masks, so it wasn't terribly surprising when Pomponi signaled to Faircloth to surface and told him that a seal had taken his snorkel that he had secured to his leg. Later in the dive, Faircloth saw his snorkel sitting on a rock ledge, but when he reached for it, the playful seal grabbed it and swam away. The game continued through three or four rounds of this before Faircloth gave up and decided he'd have to sacrifice the snorkel. At the end of the dive, the team was back in a small boat about to return to their ship when, to everyone's astonishment, the snorkel popped up out of the water and into the boat. "We all just looked at each other in stunned silence," says Faircloth. A coincidence? Perhaps, but Faircloth is convinced the seal knew his playmate was leaving and thought he should give back the toy.
Education: Over Two Decades and No Regrets
As an undergraduate, Faircloth majored in biochemistry and physics at Harvard University. Afterwards he worked as a technician at Massachusetts General Hospital in the neurology group and then went on to get his Ph.D. in physiology at the Boston University Medical School. Faircloth joined the Harbor Branch Oceanographic drug discovery program as a postdoctoral immunologist when it was just beginning. His arrival at Harbor Branch, he says, was serendipitous, because he thought he was heading to MIT for a postdoc. However, the lab he was going to be working in lost its funding just a couple of months shy of Faircloth's arrival. "I really needed to scurry for a position," he says. He learned about the Harbor Branch program through a friend and decided to apply. From Harbor Branch, Faircloth went to work for PharmaMar and began the company's U.S. branch. As for his diversion from a more traditional biotech life to the marine variety, Faircloth says, "I've absolutely loved everything I've been doing. I haven't had a day I've regretted."
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