GTx, Inc. Initiates Phase I Clinical Trial for Its Second SARM Ostarine
MEMPHIS, Tenn., February 01, 2005 /PRNewswire-FirstCall/ -- GTx, a
biopharmaceutical company dedicated to the discovery, development and
commercialization of therapeutics for serious men's health conditions,
today announced that it has initiated a Phase I clinical trial for
ostarine, GTx's second selective androgen receptor modulator (SARM)
compound to be tested in clinical trials.
"We are very excited about the promising preclinical ostarine data and are
pleased to initiate this clinical trial," stated Mitchell Steiner, M.D.,
Vice Chairman and CEO of GTx. "This shows that we have the proven ability
to create compounds in the laboratory and move them into the clinic as we
continue to position GTx as the lead SARM company."
The Phase I study will evaluate the safety, tolerability and
pharmacokinetic profile of ostarine using a single ascending dose, double-
blind, placebo-controlled design in healthy volunteers.
Ostarine is a nonsteroidal SARM that is designed to have positive anabolic
effects without having an impact on the prostate and is being developed
for andropause as well as other conditions associated with aging, such as
sarcopenia. Sarcopenia is defined as the loss of muscle mass associated
with aging leading to frailty and loss of independence.
As people age they undergo hormonal and metabolic changes. Each year after
age 30 people gain an average of a pound of fat every year and lose a half
a pound of muscle every year. Thus, men may lose 50% of muscle between the
ages of 30 and 90. Muscle provides strength and endurance, supports the
skeletal system and helps protect the body from illness. Loss of muscle
can cause frailty, loss of independence, and worsens other conditions such
as osteoarthritis and osteoporosis. There are 17 million Americans alive
over the age of 75 who suffer from sarcopenia and currently there are no
approved treatment options available.
GTx believes that the ability to selectively target and modulate the
androgen receptor will allow the development of many new drugs that are
crucial for men's health. In fact, different compounds within the SARM
class have demonstrated in preclinical studies unique pharmacologic
activities, with varying effects on endocrine feedback, prostatic
stimulation, spermatogenesis, muscle growth, bone growth and sexual
behavior, highlighting the untapped potential of these novel drugs for
treatment of other diseases, including benign prostatic hyperplasia (BPH),
male infertility, and low libido.
GTx is a biopharmaceutical company dedicated to the discovery, development
and commercialization of therapeutics for serious men's health conditions.
GTx's drug discovery and development programs are focused on small
molecules that selectively modulate the effects of estrogens and
androgens.
GTx currently has four clinical programs. In two of the
clinical programs, the company is developing ACAPODENE(TM), its most
advanced product candidate, through clinical trials for two separate
indications: (1) a pivotal Phase III clinical trial for the prevention of
prostate cancer in high risk men and (2) a pivotal Phase III clinical
trial for the treatment of serious side effects of androgen deprivation
therapy for advanced prostate cancer. [Link]
In its third clinical program, GTx
and its partner, Ortho Biotech Products, L.P., a subsidiary of Johnson &
Johnson, are developing andarine, a selective androgen receptor modulator
(SARM), which is expected to enter a Phase II clinical trial in 2005.
In
its fourth clinical program, GTx is developing its own SARM, ostarine, for
andropause and other conditions related to aging, including sarcopenia.
In
addition, GTx has a deep pipeline generated from its own discovery program
which includes specific preclinical product candidates prostarine, a SARM,
for benign prostatic hyperplasia (BPH), and andromustine, an anticancer
drug, for hormone refractory prostate cancer.
Nature says that after 50 a man will begin losing 2% of his natural testosterone
a year. His bones will thin, his muscles soften, his libido wilt.
Mitch Steiner is rewriting that script, and within a few years may have an oral
testosterone supplement that will help men remain beefy and sexually energetic
well into old age.
Steiner is a urologist and chairman of the Department of Urology at UT-Memphis.
He's also CEO of GTx, Inc., a biotech company that is developing commercial
applications of drugs invented at and patented by UT. One molecule in particular
is a SARM -- Selective Androgen Receptor Modulator. Invented by three UT
scientists, the basic form has the apparent ability to stimulate bone and muscle
growth without all the deleterious effects of other testosterone products.
"This is first-in-class, a new chemical entity," Steiner says. "There's nothing
else in the world even close."
One form of the drug, with the brand name Andarine, is finishing Phase I-B
clinical trials, in which multiple doses are given to determine safety. Phase
I-A was for the safety of single doses in healthy males. Those trials will be
complete by the end of the month, with Phase II trials for efficacy set to begin
by the end of 2003. Both Phase I trials involved 45-50 men.
Andarine was first developed as a treatment for wasting syndrome in cancer
patients. Cancer acts like a huge parasite, altering body chemistry so that no
matter how much food a person eats, the nutrient goes to the tumor while the
body wastes away.
"Chemotherapy is tough on a body," Steiner says. "The weaker you are the more
likely you are to get knocked off by the drugs than the disease."
Andarine works under the radar of the cancer, stimulating bone and muscle
growth. With 550,000 new cases each year in just lung and digestive cancers, the
potential market is huge. Down the road Andarine could also be useful in other
wasting conditions such as HIV/AIDS, end-stage renal disease, cystic fibrosis
and spinal cord injuries.
With cord injuries, muscles waste away because they aren't getting the
electrical signal to move and maintain themselves.
Phase II studies will give Andarine to 150 cancer patients for eight-10 months,
measuring their increase in muscle mass, as well as their ability to use that
new muscle.
"Most cancer patients lose 20 pounds before they even know anything is wrong,"
Steiner says. "Our goal is to give them five-10 pounds of lean muscle."
GTx hopes to get fast-track status for Phase III trials, since there are no
other drugs that fill this need. That could make Andarine commercially viable by
2005, at which time GTx would entertain suitors from large pharmaceutical
companies.
Most innovation companies run out of steam before Phase II and bring in a large
partner to help get the drug over the last hurdles. But by accepting that risk,
the major company also expects a pound of flesh. With all the clinical trials
complete and a clear application, GTx could negotiate the most lucrative deal
possible with an international pharmaceutical company.
GTx plans to market the drug for urology and oncology uses and let the partner
company handle the broader market. That would fuel GTx's efforts to develop its
own sales and marketing force.
Manufacturing is handled by a third party, under close controls using GTx's
processes.
What makes Andarine and its cousin drugs distinctive is that, unlike all other
testosterones, they lack the side effects.
Testosterone today is given through a dermal patch, releasing a slow trickle
into the bloodstream. The liver metabolizes the stuff in seconds, but not before
it causes a basket of complications. In women it produces facial hair, while men
go bald. In men, the natural testosterone levels plummet and their prostate
gland grows rapidly -- including cancerous cells.
The Andarine family has the ability to be highly selective; creating a version
that stimulates only bone growth is a matter of minor manipulation. Steiner
credits the inventors for this bit of handicraft. The drug was created by UT
scientists Duane Miller, Jim Dalton and Karen VeVerka. Dalton has since moved to
Ohio State University and VeVerka is now GTx director of the SARM program.
"It took our scientists over a decade to learn how to flip the chemical switch,"
Steiner says. "This is a unique chemical that sets us apart."
Most current research in the field focuses on kinases, a genetic approach
fraught with peril. Trying to find the right kinase is like standing before a
building with thousands of doors, each connecting to a hallway and with all the
hallways crisscrossing inside.
"One reason this is a safer investment is that we're taking advantage of an
age-old receptor; it's time tested," Steiner says. "It's one door and we know
what's inside."
GTx journey began as idea
Scott Shepard
Memphis Business Journal
March 8, 2004
It took eight months of discussions between urologist Mitch Steiner and Mark
Hanover of Equity Partners before they embarked on a venture both radical and
brave in 1997.
The result is GTx, Inc., a biotech company designed from the beginning as the
guinea pig for a series of businesses to come later. GTx will be the template
for producing a commercial biotech industry in Memphis, based on home-grown
technology. The company went public Feb. 3.
"I raised $53 million, I spent $38 million and after the IPO I've got $80
million in the bank," says Steiner, CEO of GTx.
The strategy worked because many people beyond Steiner and Hanover were
determined to see it through, for both economic and altruistic reasons. Over the
course of the startup, state laws were changed as scientists became business
minded, and businessmen came to understand science.
The result is a company that's designed to absorb new ideas from local academia,
nurture them and keep those that fit the profile of men's health. The rest will
be spun out into new small biotech firms, spawning an industry the way salmon do
their next generation.
"All along I could have gone to one of the coasts," Steiner says. "In San
Francisco the venture capitalists said that our science was so good that if I
moved to Silicon Valley all the money I needed would be waiting."
But Memphis is home for Steiner and Hanover. For plenty of personal and
practical reasons, neither wanted to move the company.
Also, as a professor and chairman of the Department of Urology at the University
of Tennessee Health Science Center, Steiner had become intimately aware of the
caliber of research going on in Memphis, though there was no company ready to
raise the serious cash it takes to bring a drug to market.
"Typically UT would license a discovery to Big Pharma, and then it disappears,"
Steiner says. "$400 million for development all gets spent in the Northeast or
California, but never in Memphis.
"Nobody had ever done what we were going to do, and looking back, I can say that
ignorance was bliss," he says. "We formed the company from the discoveries that
were coming out of my lab at UT."
At about that time, J.R. 'Pitt' Hyde was going through a personal epiphany. At
the top of the AutoZone empire he had built, Hyde was diagnosed with prostate
cancer and treated successfully by Steiner with a radical prostatectomy. After
his brush with mortality, Hyde became an angel investor in GTx with $1.4
million. His deep roots in Memphis guaranteed that the company would stay in one
place.
With Hyde's reputation behind GTx and other biotech efforts in Memphis,
successive rounds of cash pumped another $51 million into the company. Hyde was
also the driving force behind the creation of the Memphis Biotech Foundation,
which is redeveloping the old Baptist Medical Center property into a biotech
research park.
"Pitt has made all the difference," Steiner says. "In this region there are not
a lot of people who can afford to be an angel. VC money is geographic, so Pitt
organized Memphis Biomedical Venture Partners."
That local VC started in late 2001 and soon raised $22.5 million, against a goal
of $20 million.
"2002 was an incredibly challenging year for raising venture capital, and we
were trying to raise it for start-ups which was even more challenging," says
Gary Stevenson, managing partner in MB Venture Partners. "Still, we found a very
receptive audience by convincing local investors to keep their capital local
instead of sending it out of state."
An early hurdle for GTx came through state laws that prevented Steiner from
licensing the patents that he co-owned with UT.
"UT couldn't contract with an employee," he says. "We wanted to give the
university money but we couldn't."
The result of the change was Tri-Star, an entity within UT that negotiates
licensing agreements with university-owned technology. Since then the University
of Memphis, working with the Technology Resources Foundation, has created
IIDSystems to speed the commercialization of U of M discoveries.
The GTx strategy was to use Memphis' weaknesses as an advantage. With no biotech
competition, GTx gets the first look at the ideas pouring out of UT, the U of M
and St. Jude Children's Research Hospital. It's also a collegial scientific
community where most researchers know one another, do plenty of informal
collaboration and keep one another posted on advances.
In addition, the cost of living, wage rates and other overhead in Memphis are a
fraction of those in Silicon Valley. GTx could hire local talent and plow much
more money into research.
Memphis also has a seductive effect on newcomers -- many who could be involved
with GTx in the future.
"A place like St. Jude brings in very talented people, but after a four-year
post doc fellowship, St. Jude can't keep all of them," Steiner says. "Meanwhile,
they fall in love with the city and don't want to leave."
The Memphis allure gives GTx and its offspring another first-look opportunity at
freshly trained people who are ready to work today and will likely become
entrepreneurs here in the future.
GTx is already on that course, and named Karen Veverka as director of
pre-clinical development. A Kansas native, Veverka attended graduate school at
the Mayo Clinic in Minnesota and completed a doctorate in pharmacology and
bioanalytical chemistry. She came to Memphis in 1996 to work with Peter
Houghton, the chair of Molecular Pharmacology at St. Jude, where they studied
the receptors on the surfaces of cancer cells.
Meanwhile, her husband, Dan Swift, built a business here as a commercial general
contractor.
"After four years I was looking for something new, probably at a pharmaceutical
company on one of the coasts," she says. "But my family was very happy in
Memphis."
At a conference, Veverka became intrigued when a friend described GTx.
"A lot of their products are receptor mediated," she says. "What's very
attractive is the ability to get involved with a young company, energetic
management and a lot of opportunity for growth."
The company's first commercial drug, Acapodene, is slated to hit the market in
2006 so GTx is already putting together its sales and marketing team, finding
Memphis natives ready to bring their experience home. Recent hires have come
from Glaxo-Smith-Kline and Novartis.
Gary Bird is the new director of manufacturing, who most recently worked eight
years for Eli Lilly in Indianapolis. His moment came on the way out of town
after a family visit. He and his wife, Barbara, spent 20 minutes at a truck stop
in Arkansas mostly agreeing that they both wanted to return to Memphis after 25
years.
Before they got back on the road his phone rang with a job query.
"I would not have come back just to come back," Bird says. "I've been around a
lot of very intelligent people and those at GTx were on par with all of them.
For a small company you never hear them talk about product pipelines. Lilly
talks about the pipeline."
Two elements compelled the initial public offering. The drug Andarine has a $2.3
billion annual potential but needs access to cash to be fully developed. Also,
the investor market was ripe. After a dearth of biotech IPOs from 2001 to
mid-2003, there were suddenly five in a row.
"The IPO is a management decision," Stevenson says. "As soon as we saw a few get
out in '03 we could see that GTx was as good or better than the rest."
Steiner doesn't savor the idea of bringing in new ideas that eventually may not
fit his company profile because they drain resources. However, spun out of GTx,
he expects to retain a share.
"An opportunity that fits men's health, I want to keep," he says. "If we find
another application outside our area we can sell it or spin it off, but GTx
holds a piece. GTx throws off seeds."
All the elements are now in place, he says, to achieve that. There's a healthy
VC fund to vet concepts, and a university structure conducive to making it
happen. Within a few years the Memphis Biotech Foundation will have space ready
to catch the seeds.
The GTx pipeline right now has six drugs. At the core is the blocking or
stimulating of estrogen (SERM drugs) and androgenes (SARM drugs). In a man's
body both groups of hormones are associated with prostate cancer, enlarged
prostate and human wasting in cancer patients.
Acapodene is a compound already cleared by the FDA for a different use. GTx
licenses it from Orion for specific applications. With a safety database
complete it was a safer, more conservative approach for a young company.
Andarine was developed by two UT scientists, Duane Miller and Jim Dalton, who
has since moved to Ohio State. Originally it was designed to help chemotherapy
patients retain body mass so they could endure the treatments. Since then it's
been discovered that healthy men who take Andarine should enjoy the same
benefits: better muscle and bone mass.
Men over 50 lose their testosterone at a steady pace, but supplements have
plenty of unpleasant side effects absent in Andarine.
Thanks to a shorter time to market for cancer drugs, Andarine could quickly
generate revenue to get it labeled as a treatment for frailty in aging men. That
could lead to the ultimate lifestyle drug: Men could live past 90 with all the
vigor they enjoyed at 32. Women, Steiner notes, routinely take hormones to feel
young and strong.
"It may have an $8 billion-$15 billion global market as the population ages,"
Steiner says.
Prostarine was developed by Miller and UT's Eldon Geisert Jr. to treat benign
enlargement of the prostate without affecting bones or muscle.
Ostarine could be an even more powerful male enhancement drug than Andarine,
especially when it comes to preserving bone.
Andromustine is a chemotherapy drug that binds to a cancer cell in the
prostate and acts like a bomb to combat the disease.
Deep in the GTx pipeline is VSV, an assassin virus engineered at UT by Michael
Whitt and Clint Robinson. They created a virus that can be tagged with a
specific protein, say prostate cancer or HIV, which the virus uses like a mug
shot. Any cell with that protein is attacked and killed, but not before it's
used to manufacture more viruses that do the same thing.
Over seven years Steiner says he's learned a lot. The hardest lesson has been to
discipline the natural curiosity of a scientist, which is what made his company
possible in the first place.
"The lab is like a candy store with so many questions I want to ask," he says.
"The problem with that is that nothing gets done. There are a lot of questions
I'd like to ask, but I don't ask them unless it moves a product closer to a
patient."
[Link]
[Definitie:] "An ergogenic aid is any substance or phenomenon that enhances performance."
(Wilmore and Costill) 
