EpiGenesis Name


Nyce Bio

Carbonyl Valley: New Jersey

Amanda Gillum

Adenosine’s Role in Asthma

Potential Cancer Drug

Corrections or additions?

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

to "off."

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

lung cancer.

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.

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EpiGenesis Name

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

"messenger" RNA.

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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

this year.

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.

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Nyce Bio

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.

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Carbonyl Valley: New Jersey

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.

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Amanda Gillum

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.

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Adenosine’s Role in Asthma

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

patents pending.

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.

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Potential Cancer Drug

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.

EpiGenesis Pharmaceuticals, Box 7007, Princeton,

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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