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Flipping off the Asthma Switch
This article by Monica J. Guendner was published in U.S. 1 Newspaper
on March 17, 1999. All rights reserved.
To Jonathan Nyce, the difference between curing asthma
his way and the traditional way can be likened to stopping the gears
on a piece of machinery. Traditional therapies throw a monkey wrench
in a "machine" that is doing harm. You stop the gears, but
you have not eliminated the problem. With Nyce’s "antisense"
therapies, he can go to the back of the machine and flip the switch
Nyce, CEO and founder of EpiGenesis Pharmaceuticals, says that these
therapies have been called "the pharmacology of the future."
He hopes to tap the potential that sequencing of the human genome
has promised for so long.
Nyce’s company is one of the most recent arrivals to the Princeton
biotech community; EpiGenesis moved from North Carolina to Exit 8A
last fall. By using antisense therapies to disable the harmful genes,
he is working on making the treatment of respiratory diseases as easy
as flipping a genetic switch. Early this week EpiGenesis floated its
second private placement, for $6 million.
The key, according to Nyce, is to deliver the drug directly to the
target tissue; this makes the drug less toxic and more potent. Only
EpiGenesis Pharmaceutical, he says, can rapidly and accurately reduce
disease genes in the respiratory tract. It is working to discover
the genetic basis for an amazing array of diseases, starting with
asthma — a $9 billion worldwide market — plus chronic obstructive
pulmonary disease, chronic bronchitis, respiratory infections, and
Once it finds a genetic target for a particular disease it can try
to treat these diseases by delivering RASONS (respirable antisense
oligonucleotides) to the target. Of three clinical candidates already
in the pipeline, the first one might go into Phase 1 clinical trials
within a year.
"We are focusing on medically unmet needs," says Nyce. Of
his three candidates for clinical trials, two are for asthma and one
is for cancer.
The name EpiGenesis implies something that is "near to" genes
that does not mutate genes. If DNA is the road map, says Nyce, and
EpiGenesis reads the road map. Or, DNA is the score, and when a musician
plays out of tune (as with disease), EpiGenesis corrects the musical
discord by teaching the pianist how to play better. The antisense
oligonucleotides that EpiGenesis uses can block the disease gene’s
The firm’s "cash cows" or revenue sources are its database
of genes and its "Target Validation" technology — for
which Nyce was unwilling to give specific projections, saying only,
"it will be very significant." In addition to Nyce’s personal
money, the company already had a private placement of stocks with
$2.5 million in cash and another $2.5 million in warrants to be exercised
this year. Last year it received a National Institutes of Health Phase
I Small Business Innovation Award, and Nyce heard in early February
that it will receive approximately $1 million with a Phase II award
Although the money from the NIH is a victory, it is
the attention the science is receiving that Nyce cherishes more. "The
most important thing was the scientific validation for RASONs,"
said Nyce. "The reviewers made embarrassingly nice comments."
The NIH even went as far as to ask permission to include EpiGenesis’s
research in its report to Congress this year.
Nyce has a personal interest in the success of his products: as a
child he and his brother both suffered from asthma. Recently he experienced
a severe reoccurrence — coughing fits while he was trying to give
a paper at a professional meeting. Thus he can empathize first-hand
with asthma sufferers. Citing that each year approximately 7,000 people
die from asthma, he adds, "It’s hard to imagine something worse
than not being able to breathe."
Nyce, 44, is the son of a machine designer who worked in Collegeville,
Pennsylvania. "My father influenced me because of something he
didn’t do," says Nyce. "He worked around the clock one night
to design the machinery to knit the first pair of pantyhose. But because
he had a new family, he was unable to capitalize on that discovery,
whereas his partner was able to run with it. He told me that if I
were ever in a similar position, to be sure I could capitalize on
The first of his family to attend college, Nyce soon discovered a
knack for doing dissections in biology labs. His undergraduate degree
is from Temple University, and he earned his PhD from the Fels Research
Institute at Temple University’s School of Medicine. He did post graduate
work in the Children’s Hospital of Los Angeles and then moved to the
Kenneth Norris Cancer Center in Los Angeles. In 1987 he returned to
the East Coast, this time to North Carolina, as assistant professor
at the School of Medicine, East Carolina University. He reached full
professor there in the department of molecular pharmacology and therapeutics.
On his board of directors are Ron Stanton (an alumnus of Glaxo Wellcome),
researcher Allen Cato, and George Muzinich and Karen Giroux, both
with Muzinich & Co. in New York, which is doing the private placements.
The scientific advisory board includes Peter Barnes of Imperial College
in London; James Metzger, director of the Asthma & Allergy Center
of Eastern North Carolina; Gioria Feuerstein, director of cardiovascular
pharmacology at SmithKline Beecham; Ken Lloyd of Salk SIBIA in La
Jolla; and Genoviffa Franchinni of National Institutes of Health in
David J. Sorin and Perry Pappas of Buchanan Ingersoll in Princeton
are the firm’s attorneys, and Michael McGinnis is the accountant.
Today Nyce lives with his wife and three young children in Princeton.
The only drawback to the business so far has been the separation from
his family during frequent business trips. "My driving force,"
said Nyce of his work, "is that I want to help sick people."
After three years in Greenville and Durham, North Carolina felt too
small and had too few opportunities for the growing company.
Nyce thinks the corridor between New York and Maryland is conducive
to the growth of pharmaceutical companies both big and small. He compares
it to California’s Silicon Valley, saying that this corridor is earning
the nickname "Carbonyl Valley" (carbonyl being an organic
ingredient often used in pharmaceutical products).
Proximity to potential clients and strategic partners was only part
of the appeal of the area. As the company poised to expand from its
facility in Greenville, it found sufficient lab space a daunting goal.
With the help of Tom Sullivan (of CB Richard Ellis) and Bruce Simons
(representing Eastern Properties’ holdings of more than a million
square feet at Exit 8A) it found its current space of between 5,000
and 6,000 square feet. When it expands again to 15,000 to 20,000 square
feet — as soon as next year — New Jersey will again be able
to offer appropriate facilities, Nyce believes.
Expanding again was built into the initial thinking of the move up
north, says Nyce. The search for employees to fill that space will
more than triple the company’s employee roster in the next year. Seven
PhD and two technical positions will add to the six scientists now
in the laboratory. Nyce is also actively interviewing for a president
and will be looking for a full time chief financial officer soon.
Nyce’s vice president of operations, Amanda Gillum, returned to biomedical
research when she accepted the position at EpiGenesis Pharmaceuticals
last July. She had studied chemistry at Indiana University before
gaining her Ph.D. in biochemistry at MIT with post doctoral work at
Stanford. She worked at Squibb, Kodak, Sterling Winthrop, and MDL
Information Systems. She and her husband have lived in Pennington
for 20 years, and they have two high school-age daughters.
The company recognizes the important role adenosine plays in the condition
of asthma. With an asthmatic lung, there is an overabundance of receptors
for adenosine, and the lung makes more adenosine for all the receptors.
Too much adenosine can shut the lung down, making it impossible to
Drugs break down in tissue, and any antisense oligonucleotide
containing adenosine would produce free adenosine — toxic to the
asthmatic lung. Virtually all of the oligonucleotides in the company’s
library do not have adenosine, and so Epigenesis can avoid such toxic
effects. EpiGenesis has the intellectual property rights to all those
"adenosine lacking" sequences for the asthma gene and has
One of EpiGenesis’s three candidates for clinical trials, EPI-2010,
knocks out the receptor that causes the adenosine problem. Tests so
far have shown that EPI-2010 may be available as a drug administered
weekly, which may help in supervision of pediatric patients. It also
has the potential of being the only single drug to address all three
common problems of asthmatic lungs: inflammation, bronchoconstriction,
and "drying out" of lung tissue, known as surfactant reduction.
Instead of taking a pill or getting a shot this drug can be administered
with an aerosol: you breathe in the medication and the lung actually
helps to deliver the drug. "The lung is kind enough to repackage
it for us and distribute it," says Nyce.
This repackaging also uses the therapies more effectively, resulting
in a smaller dose, possibly 1,000 times smaller than the usual. Other
companies’ attempts to administer antisense oligonucleotides into
the blood stream have used such a large amount that random reactions
and toxicity have become major problems. The use of this therapy is
also more the way nature stops the machinery too, says Nyce. Cells
use the same antisense techniques, so the main problem for scientists
is how to get the antisense into the cells and let the cells do their
work. Lipids in the cells aid the antisense oligonucleotides across
the barrier of the cell wall and into the cell.
Another company, Isis, is also delivering antisense oligonucleotides
directly to the target tissue, but to a different organ, the eye.
Isis’ Fomivirsen, an antisense oligonucleotide for the treatment of
drug-refractory CMV retinitis in AIDS patients, is injected into the
eye. Fomivirsen has been approved as a new drug and helps to prove
Nyce’s point about the effectiveness of local delivery.
EpiGenesis’s second clinical trial candidate, the more traditional
EPI-12322 asthma therapy, shows the good therapeutic features of glucocorticoids
(traditional antiinflammatory steroids) but without their side effects.
Coupled with the technology to find and then validate genes for asthma,
the company also has an improved animal model to continue development
of their drugs in the pipeline. This model should dramatically improve
the ability to predict drug efficacy in humans, according to the firm.
The third potential drug is EpiCyte (EP1163) which is supposed to
take advantage of cancer cells "over expressing" an enzyme.
Unlike other anticancer drugs, EpiCyte is completely non toxic until
it is activated by the enzyme. Once activated it suppresses tumor
Overall, the company has two issued patents, three allowed and seven
applications pending in the US and abroad.
If imitation is the sincerest form of flattery then the scientists
at EpiGenesis Pharmaceuticals must be blushing from all the attention.
Although EpiGenesis is an innovator in antisense therapeutics for
respiratory diseases, many companies, such as Boehringer Ingleheim
and Novartis have expressed their intent to work in this area, which
James Watson (discoverer of the structure of DNA) says is "the
next great wave of the biotechnology revolution."
"These companies immediately let us know that, `this is a great
idea and we’re going to do it too," says Nyce. "Our work has
not gone unnoticed." No fewer than 12 other companies are working
on other new genetic approaches to asthma treatment, according to
Genetic Engineering News (March, 1998).
What gives EpiGenesis Pharmaceuticals the edge and Nyce his confidence
of success is that his company has been the only one with the proven
ability to selectively attack a particular "villain" gene
in the respiratory system — to knock out the target gene.
08543-7007; 2005 Eastpark Boulevard, Cranbury, NJ 08512-3515. 609-409-6080;
fax, 609-409-6126. Home page: http://www.epigene.com.
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