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Feature Articles
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New York City Companies Work toward Novel Treatments for Cancer |
Jonathan Westring |
10/6/2006 |
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New York City Companies Work toward Novel
Treatments for Cancer
One-hundred-and-nine years ago Bayer scientist, Dr. Felix Hoffman,
first synthesized a stable form of acetylsalicylic acid from a naturally
occurring compound. Fifty years before the discovery, salicin was isolated as
the medicinal molecule in the willow tree, the bark of which Europeans had used
for thousands of years to alleviate pain and fever. Dr. Hoffman made the
decision to improve upon the ancient folk remedy at a time salicin-derived
compounds were achieving a limited success in arthritis pain treatment. Today
many biochemists are also pursuing research on classes of molecules that have
demonstrated only some success treating complex illnesses and for which the
underlying science is not well understood. As employees of public companies,
many biologists are funded by investors, who are keen to support research
efforts as long as there is steady progress. However, investors keep in mind
that previous healthcare successes have been found through unique science.
Eleven years after the establishment of Bayer’s pharmaceutical department,
acetylsalicylic acid was registered under the trademark, Aspirin, and became
one of healthcare’s most popular treatments.
Within the last thirty-years biotechnology companies have begun to replace
pharmaceutical departments as entities of drug discovery. Approximately
two-hundred new therapies and drugs have been created by the biotechnology
industry since Genentech, Inc. was founded in 1976, and the companies continue
to grow rapidly. Revenue from the United States biotech industry has increased
approximately ten times during the last fifteen years, according to data by
Ernst & Young. Also by the same source, New York is home to a little over
fifty publicly and privately-held companies, many of which are located in New
York City. Several companies, which have made New York City their headquarters,
have been founded upon unique ideas. For example, Keryx Biopharmaceuticals,
Inc. and Antigenics, Inc. both went public only a few years after they were
founded on novel academic work with applications in oncology. Another company
with executive offices in Manhattan is Bioenvision, which started-up to develop
a viral infection treatment as an anticancer drug.
Antigenics was founded twelve years ago by Dr. Pramod K. Srivastava to build
upon promising work in cancer vaccinations. As a graduate student Dr.
Srivastava successfully vaccinated mice against specific forms of cancer and
isolated the class of biomolecules, Heat Shock Proteins (HSP), as responsible
for conferring the immunity. The company’s start is similar to that of
Genentech, Inc., which was founded by Dr. Herbert Boyer on his concept that
bacterial plasmids could be used to synthesize human proteins, like insulin, in
large quantities; recombinant DNA technology is now fundamental to disease
research laboratories and pharmaceutical operations. Like Antigenics, Genentech
also held an Initial Public Offering only several years after the company’s
founding. Clearly, Antigenics had initial success in its cancer research
similar to the salicin molecule’s treatment of arthritis pain. Salicin
alleviated arthritis pain but caused severe stomach aches while HSP are shown
to vaccinate mice but not humans.
Heat Shock Proteins are transcribed in the cell during both periods of elevated
temperature and stress, which includes low oxygen levels, infection and
exposure to toxins. Under normal conditions HSP act as chaperones for other
proteins and serve general maintenance functions inside the cell. Dr.
Srivastava found that HSP bind to peptides originating from cells under stress
as well as those which have died by necrosis. Antigen-presenting cells and
T-lymphocytes then activate the immune system to search for diseased cells.
Antigenics is exploring the use of the technology against other types of
disease, like herpes; AG-707 is currently in evaluation for a Phase I clinical
trial. A second HSP compound is Oncophage. At the American Society of Clinical
Oncology annual meeting held in Atlanta this past June, Antigenics reported
that its Phase III study of Oncophage for metastatic melanoma did not improve
survival rates at a level that was statistically significant.
On August 1st the company posted second quarter financial losses that were
higher than expected due to greater research and development spending on the
Phase III trials for Oncophage. In addition, the company’s only revenue comes
from research and development contracts, in particular a licensing agreement
with GlaxoSmithKline for QS-21, a molecule used to augment the effectiveness of
vaccines. Analysts estimate with the 32 Million USD in cash and cash
equivalents the company had at the beginning of August will only fund
operations through the beginning of 2007.
While Antigenics has not made the level of achievement that Bayer had after
eleven years, the science behind cancer is significantly more complex and more
time will be needed if a breakthrough is possible. The company has diversified
its oncology program since going public to make itself more attractive for
investment by increasing the likelihood it will produce a revolutionary cancer
treatment. Currently, the company is working with a more traditional therapy
that has proven success in humans, platinum chemotherapeutic treatments. The
main compound developed from this approach is Aroplatin, which has shown some
effectiveness against colorectal cancer in a recent Phase II trial.
Another New York City biotechnology company is Keryx Biopharmaceuticals. The
company was founded approximately ten years ago in Jerusalem, but moved its
headquarters to New York in early 2003 after taking the company public on the
Nasdaq National Market. After it started-up the company began working with
scientist Shmeul A. Ben-Sasson from Hebrew University to develop a technology
platform that would create short peptides to bind and inhibit specific
serine-theronine kinases, a class of proteins that play a large role in cell
signaling pathways. Kinase inhibitors can have a broad range of applications in
medicine ranging from treatment of cardiovascular disease to oncology;
depending on the role of the signal transduction protein being inhibited. As
cancer is in its nature the uncontrolled growth of cells, the pathways which
instruct the cell to multiply play a critical role in the disease; in fact,
mutations in the DNA encoding for specific signaling proteins are the cause of
the disease. After successfully developing the technology with Hebrew
University, Keryx used the KinAce platform to create a pipeline of thirteen
drug candidates by the year 2000, which included KRX-123, a treatment for
hormone resistant prostate cancer.
As stated by Keryx Biopharmaceuticals, using technology that develops drug
candidates from human genomic data produces more compounds in less time and
does so with fewer side-effects. However, from company records it appears that
KRX-123 was never approved for clinical trials nor did any of the protein
kinase candidates proceed to advanced testing. Like Antigenics and Bayer,
Keryx’s approach initially held promise, but unlike the two companies their
founding work was placed to the side.
In February, 2004, the company acquired Access Oncology, which included in its
pipeline three oncology drugs. The most advanced of the compounds was given the
designation, KRX-0401. Already in Phase II trials during the time of
acquisition, KRX-0401 is an alkylphophocholine, a new class of signal
transduction pathway modulators designed to induce apoptosis, or gene-mediated
cell suicide, in cancer cells. It is through inhibition of the protein, Akt,
that cancer cells can either be killed or kept from growing. Akt is a specific
signal transduction molecule that has been known for many years within the cell
biology community. As a company, Keryx adapted to the concerns of investors by
purchasing drug candidates, which had already proven themselves in clinical
trials and represented a more traditional approach to cancer research.
Immediately prior to and after the announcement of the company’s acquisition,
Keryx’s share price and the volume of shares traded both increased
significantly. Keryx’s stock on the Nasdaq Market averaged approximately 2
dollars per share at the end of 2002 and beginning of 2003; by May of 2004 the
company’s share price was worth over 15 dollars. The positive investor response
indicates that belief in the original technology was only a partial reason for
initial investment.
Additionally, Keryx licensed a compound in development for the treatment
diabetic nephropathy before going public, diversifying its original pipeline.
Sulonex is currently in a single Phase III trial where its primary endpoint is
the regression of microalbuminuria. Demonstrated by this compound’s original
success in previous clinical trials Keryx could very well have offset declining
investment in the long term without the acquisition of Access Oncology.
However, KRX-0401 has generated short-term investment that can be used to
further develop candidates from its original technology.
Dr Christopher Wood is another scientist who has become an entrepreneur. In
Europe during the 1990’s Dr. Wood held leadership positions at Medeva PLC and
Eurobiotech, Inc, and in January of 1999 became CEO and Chairman of
Bioenvision. Prior to Dr. Wood’s arrival the company provided financial
services to clients. However, board members were dissatisfied with their
business model, and entered into an agreement with Southern Research Institute
to assume responsibility for the development of Clofarabine; subsequently,
executive offices were transferred to Manhattan. Clofarabine is a purine
nucleoside analog, which mimics the subunits of human genetic structure and
inhibits the DNA replication of tumor cells thereby stopping cancer growth.
Bioenvision was created with the initial intention to commercialize a
particular research discovery though was not founded by the discovering
researchers themselves. In this respect, the company is representative of many
start-up biotechnology companies and has proven to be equally successful.
Bioenvision’s stock price and average trading volume both tripled in 2004 after
Clofarabine was approved by the FDA for the treatment of pediatric acute
lymphoblastic leukemia.
Many younger biotechnology companies have demonstrated initial successes with
unusual approaches to cancer treatment that reflect similarities to the work
that led to Aspirin’s synthesis. Initial success of a compound is important for
a primary investment in a new approach, but the investors can be a company with
drug development capability as well as Wall Street financers. The untried
methods generate interest in part because they give hope that successful
treatments can be achieved where other lines of research are not producing
results quickly enough. However, companies need to produce results in order to
maintain investor confidence. New York City biotechnology companies have the
expertise and proper science in their approaches to create a breakthrough
cancer drug, though to satisfy investors’ expectations several companies have
made modifications to their oncology programs. The complexity of cancer is not
always appreciated and great ideas may need to be placed to the side if only
until a time when further successes will warrant secondary investment.
Considering cancer therapy research will take more time to achieve successes
made in other fields of medicine, New York is in a strong position to develop
and commercialize effective products in the long run.
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