Exhibit 99.1
Geron and Hong Kong's Biotechnology Research Corporation Form Strategic Alliance
for Telomerase Activation Therapies
MENLO PARK, Calif. & HONG KONG--(BUSINESS WIRE)--March 2,
2005--Geron Corporation (Nasdaq:GERN) and the Biotechnology Research
Corporation (BRC) of Hong Kong announced today the formation of a new
company, TA Therapeutics Limited (TAT), in Hong Kong. The company will
conduct research and commercially develop products that utilize
telomerase activator drugs to restore the regenerative and functional
capacity of cells in various organ systems that have been impacted by
senescence, injury or chronic disease. Geron and collaborating
scientists have generated evidence that telomerase activation can
restore function in certain aged or diseased tissues.
TAT will be owned 50% by Geron and 50% by BRC, a company
established by the Hong Kong University of Science and Technology
(HKUST), Geron's research partner. Geron is contributing scientific
leadership, development expertise, intellectual property and capital
to the new company. BRC is also providing scientific leadership, a
research team, capital and laboratory facilities.
"We are very pleased to announce this important strategic event,"
said David L. Greenwood, Geron's executive vice president. "We first
initiated a scientific collaboration on telomerase activation with the
Biotechnology Research Institute of HKUST in 2000. It was productive.
Our teams have discovered two small molecule compounds that activate
telomerase in human in vitro models of chronic and infectious
diseases, including AIDS. The potential therapeutic opportunities are
numerous and large. We, and our partner, agreed to create and
capitalize a new company to aggressively pursue further research with
the intent of developing the compounds into commercial products."
"Our collaborative research with Geron was an important success,"
said Professor Roland Chin, Vice-President for Research and
Development of HKUST. "The drug discovery efforts have produced two
compounds that demonstrate telomerase activation broadly. We view this
arrangement with Geron to be an extraordinary opportunity to launch an
important biopharmaceutical company in Hong Kong that will immediately
begin preclinical development of a new therapeutic paradigm with
potential medical utility in multiple major chronic diseases. This is
a remarkable opportunity and we are very pleased to form this
venture."
Calvin B. Harley, Geron's chief scientific officer, noted that,
"Geron has been conducting research in telomere and telomerase biology
for years. Using telomerase gene transfer as a model, we have
demonstrated the biological utility of telomerase activation in over
20 different human cell types that could impact a broad array of
infectious and chronic degenerative conditions. With the discovery of
two small molecule telomerase activators, our objective now is to put
a substantial team to work testing these compounds in various models
of disease and organ dysfunction."
About HKUST and BRC
Officially opened in 1991, HKUST is a research university
dedicated to the advancement of knowledge, and to the economic and
social development of Hong Kong and the region through teaching,
research, and service. It was named the number 42 university in a
ranking of the world's top 200 universities by The Times, UK, in 2004.
It has gained international recognition for its groundbreaking
research achievements in nanotechnology, biotechnology, and for its
leadership in business education.
The Biotechnology Research Corporation (BRC) is wholly owned by
HKUST and is established with a contribution of HK$175 million by The
Hong Kong Jockey Club to develop potential drug candidates from the
laboratory into commercially viable drugs.
Website: www.ust.hk
About Geron Corporation
Geron is a biopharmaceutical company focused on developing and
commercializing therapeutic and diagnostic products for cancer based
on its telomerase technology, and cell-based therapeutics using its
human embryonic stem cell technology.
This news release may contain forward-looking statements made
pursuant to the "safe harbor" provisions of the Private Securities
Litigation Reform Act of 1995. Investors are cautioned that such
forward-looking statements in this press release regarding potential
applications of Geron's technology and compounds constitute
forward-looking statements that involve risks and uncertainties,
including, without limitation, risks inherent in the development and
commercialization of potential products, reliance on collaborators,
need for future capital and maintenance of our intellectual property
rights. Actual results may differ materially from the results
anticipated in these forward-looking statements. Additional
information on potential factors that could affect our results and
other risks and uncertainties are detailed from time to time in
Geron's periodic reports, including the annual report on Form 10-K for
the year ended December 31, 2004.
GERON CORPORATION
-- BACKGROUNDER --
THE POTENTIAL FOR TELOMERASE ACTIVATION THERAPIES
The strategic alliance between Geron and the Biotechnology
Research Corporation expands development efforts for telomerase
activator drugs for applications in AIDS, wound healing and other
chronic degenerative diseases.
TELOMERES AND TELOMERASE IN CELL AGING AND CANCER
Telomeres are essential genetic elements (DNA) that "cap" the ends
of our chromosomes. They are maintained in immortal cells, such as
normal germ cells (egg- and sperm-producing cells) and cancer cells,
by expression of the enzyme telomerase, which synthesizes telomeric
DNA (repeats of TTAGGG). Telomerase consists of two core subunits,
both cloned by Geron scientists and collaborators: hTR, the human
telomerase RNA component, and hTERT, the human telomerase reverse
transcriptase. In normal body cells, telomerase is "turned off," or is
present only transiently or at very low levels, and telomeres
gradually erode with time and cell division. Eventual loss of telomere
function on one or a few chromosomes triggers a complex response
associated with damaged DNA, leading to loss of normal cell function,
division capacity, and/or cell death. This process of "replicative
senescence" is now believed to play an important role in age-related
diseases (e.g. cardiovascular diseases, stroke, macular degeneration,
osteoporosis, and joint disease), and in conditions such as viral
infections or chronic stress (e.g. AIDS, liver diseases, and skin
ulcers).
Telomerase is constitutively active in the vast majority of
biopsies from all cancer types studied to date. However, telomerase
does not cause cancer. This has been shown by experiments in which
over-expression of telomerase causes no malignant changes in normal
cells (see below), and by the fact that in developing germ cells
(cells that produce oocytes and sperm), telomerase is highly activated
yet the cells remain normal. Cancer is characterized by abnormal cell
growth caused by mutations in oncogenes that regulate cell growth and
division. During early growth and expansion of mutated cells,
telomerase is typically inactive and telomeres continue to shorten
until telomerase is activated through one or more additional
mutations, conferring immortality to the cancer cell. Thus, even
though telomerase activation is important for cancer cell survival,
telomerase activation in normal human cells is expected to improve
their function without causing cancerous changes.
TELOMERES AND TELOMERASE IN DEGENERATIVE DISEASES
Evidence that suggests telomerase activation has potential in
treating degenerative disease comes from at least three lines of
research. First, a variety of human cell types grown in culture
exhibit little or no telomerase activity, gradual telomere loss, and a
finite lifespan culminating in replicative senescence associated with
loss of normal differentiated function. These cellular changes in the
laboratory dish mimic events seen with age and disease in vivo.
Introduction of the telomerase gene, hTERT, by gene transfer, into
human cells typically increases telomere length, extends cellular
lifespan, and restores (or prevents loss of) normal differentiated
function. Moreover, "telomerized" cells have normal growth control and
show no signs of malignant changes. In many cases, introduction of
active telomerase also increases the capacity of cells to withstand
stress due to high or low levels of oxygen, toxic molecules, or
abnormal growth conditions. This fact is important, as it suggests
that even non-dividing cells will benefit from telomerase activation.
Examples of human cells responding positively to telomerase gene
transduction in culture are listed below, and include 18 different
tissue systems and over 20 cell types.
Cells that Respond to Telomerase Gene Transduction with Improved
Replicative Capacity, Function, and/or Resistance to Stress
-- Bone: Osteoblasts
-- Brain and the nervous system: Neurons and neural progenitors
-- Breast: Mammary epithelial cells
-- Connective tissue: Chondrocytes
-- Endocrine system: Adrenocortical cells
-- Gum tissue: Gingival fibroblasts
-- Heart: Cardiomyocytes
-- Immune system (normal): Cytotoxic T cells
-- Immune system (impaired, e.g. HIV/AIDS): Cytotoxic T cells
-- Liver: Hepatocytes, cholangiocytes
-- Muscle: Skeletal myocytes
-- Ovary: Surface epithelial cells
-- Pancreas: Ductal stem or precursor cells
-- Eye: Retinal pigmented epithelial (RPE) cells
-- Uterus: Endometrial stromal cells
-- Skin: Keratinocytes, fibroblasts, microvascular endothelial
cells, melanocytes
-- Vasculature: Endothelial cells, smooth muscle cells
-- Other: Mesenchymal and hematopoietic stem cells
The second line of research linking telomere loss to cellular
aging and disease comes from in vivo studies in which hTERT-expressing
or control cells are injected into rodent models to assess functional
capacity. In the five model systems of tissue repair or regeneration
listed below, including a model of cancer immunotherapy, normal cells
which have been transduced with active telomerase form functional
tissue more readily than their normal (untransfected) counterparts.
In Vivo Models in Which Telomerase Activated (hTERT Transduced) Cells
Have Improved Function Over Control Cells
-- Wound healing (human skin reconstitution in mice): Human
fibroblasts and keratinocytes
-- Neovascularization (ischemic hind limb salvage in mice): Human
endothelial or endothelial progenitor cells
-- Bone formation (human cells or bone fragments injected into
mice): Human osteoblasts or mesenchymal stem cells
-- Dentin formation (rat cells into rat): Odontoblasts
-- Cancer immunotherapy (human melanoma in mice): Human cytotoxic
T cells specific for the implanted tumor cells
The third line of research supporting telomerase activation for
the treatment of disease involves injection of a telomerase gene into
diseased or wounded tissue in an animal. In two studies reported to
date, activation of telomerase in vivo by telomerase gene therapy
resulted in improved regenerative capacity and tissue repair. In the
first study, telomerase "knock-out" mice were created by deleting both
chromosomal copies of the murine telomerase RNA gene (mTR). When these
telomerase-negative mice were bred until their telomeres became
critically short, multiple degenerative changes were seen in
proliferative tissues (e.g. skin, gut, bone marrow, and liver).
Restoration of telomerase activity in the liver of these mice by mTR
gene therapy prevented lethal loss of liver function upon exposure to
toxic molecules. In a second study modeling human chronic ulcers, the
ears of old rabbits were made ischemic (deprived of oxygen) by
ligating ear arteries. Ears were then wounded, and the wounds treated
with the telomerase gene or control agents. The telomerase-treated
wounds regenerated in a more robust manner than the control-treated
wounds.
HUMAN EPIDEMIOLOGY AND GENETICS LINK SHORT TELOMERES TO DISEASE
In addition to experimental models illustrating the potential of
telomerase activation for improved cell or tissue function and repair,
multiple studies on human populations show an association between
shortened telomeres and disease. In epidemiological studies of broad
populations, individuals with short telomeres have been shown to be
statistically at higher risk for infections, stroke, and heart disease
compared to individuals with longer telomeres. A recent study has also
shown that telomeres tend to be shorter in women exposed to long-term
stress, a condition associated with increased susceptibility to
multiple diseases. Finally, human genetic disorders such as
Dyskeratosis Congenita that cause decreased telomerase activity in all
cells throughout life show shortened telomeres at birth and rapid
progression to diseases in highly proliferative tissues such as bone
marrow and skin.
POTENTIAL FOR SMALL MOLECULE ACTIVATION OF TELOMERASE IN DISEASE
THERAPY
Delivering the telomerase gene to cells or tissues by gene therapy
remains a viable approach for telomerase activation, but is not as
attractive as a small molecule drug which is simpler to manufacture
and control, and does not carry the same level of risk for genetic
modification to cells. Based on the research reviewed above, a small
molecule telomerase activator could find utility in the treatment of
essentially all age-related diseases that involve reduced cellular
proliferative capacity or sensitivity to stress related to lack of
telomerase activity or shortened telomeres. A partial list of diseases
that should respond to a telomerase activator drug follows:
Potential Therapeutic Uses of a Small Molecule Telomerase Activator
-- AIDS: Improved cytotoxic T cell elimination of HIV-infected
CD4 cells
-- Cardiovascular and heart diseases: Reduced ischemic damage,
improved neo-vascularization
-- Chronic ulcers: Improved wound healing
-- Joint diseases: Improved cartilage production
-- Infections in the elderly: Improved overall immune response
-- Liver disease: Improved hepatocyte growth and resistance to
stress
-- Macular degeneration: Improved RPE cell function; reduced
angiogenesis
-- Osteoporosis: Improved osteoblast function and bone generation
-- Stroke and neurodegenerative diseases: Reduced ischemic damage
and increased resistance to neurotoxins (e.g. amyloid)
SMALL MOLECULE TELOMERASE ACTIVATORS
Geron Corporation, in collaboration with the Biotechnology
Research Institute, Hong Kong University of Science and Technology,
conducted a screen for telomerase activators using human
keratinocytes. The source of material for the screen was natural
product extracts. In the course of the screen, several extracts were
discovered that reproducibly up-regulated the low, basal level of
telomerase in human keratinocytes. With analysis of the extract and
further testing, one compound in the extract, named GRN139951, was
identified as the key telomerase activator in the extract. It was
capable of activating telomerase in keratinocytes and other human cell
types (e.g. lymphocyte immune cells) at very low concentrations.
GRN140665, a derivative of GRN139951 also present in the extract but
at lower concentrations, was prepared and found to possess similar
telomerase activating properties. These molecules are under
development for the treatment of degenerative diseases by TA
Therapeutics, Limited. Other small molecule activators discovered
during the course of the research may also be developed for certain
disease indications.
ABOUT GERON CORPORATION
Geron is a biopharmaceutical company focused on developing and
commercializing therapeutic and diagnostic products for cancer based
on its telomerase technology, and cell-based therapeutics using its
human embryonic stem cell technology. For more information, please
visit our website at www.geron.com.
This news release may contain forward-looking statements made
pursuant to the "safe harbor" provisions of the Private Securities
Litigation Reform Act of 1995. Investors are cautioned that such
forward-looking statements in this backgrounder regarding potential
applications of Geron's technology and compounds constitute
forward-looking statements that involve risks and uncertainties,
including, without limitation, risks inherent in the development and
commercialization of potential products, reliance on collaborators,
need for future capital and maintenance of our intellectual property
rights. Actual results may differ materially from the results
anticipated in these forward-looking statements. Additional
information on potential factors that could affect our results and
other risks and uncertainties are detailed from time to time in
Geron's periodic reports, including the annual report on Form 10-K for
the year ended December 31, 2004.
CONTACT: Geron Corporation
David L. Greenwood, 650-473-7765 (EVP)
or
HKUST RandD Corporation Ltd.
Tony Eastham, 011-852-2358-7911 (President and CEO)