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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the
Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): January 13, 1998
GERON CORPORATION
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(Exact name of registrant as specified in its charter)
Delaware
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(State or other jurisdiction of incorporation)
0-20859 75-2287752
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(Commission File Number) (IRS Employer Identification No.)
200 Constitution Drive, Menlo Park, CA 94025
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(Address of principal executive offices) (Zip Code)
Registrant's telephone number, including area code: (650) 473-7700
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N/A
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(Former name or former address, if changed since last report)
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ITEM 5. OTHER EVENTS
On January 13, 1998, Geron Corporation, a Delaware corporation (the
"Company") and the University of Texas Southwestern Medical Center at Dallas
reported the successful extension of the life-span of normal human cells using
the enzyme telomerase. Further details regarding this announcement are contained
in the Company's press release dated January 13, 1998 attached as an exhibit
hereto and incorporated by reference herein.
ITEM 7. FINANCIAL STATEMENTS, PRO FORMA FINANCIAL INFORMATION AND EXHIBITS.
(c) EXHIBITS.
Exhibit 99.1 Geron Corporation Press Release dated January 13, 1998.
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934,
the Registrant has duly caused this report to be signed on its behalf by the
undersigned thereunto duly authorized.
GERON CORPORATION
(Registrant)
Dated: February 10, 1998 By: /s/ David L. Greenwood
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David L. Greenwood
Chief Financial Officer, Treasurer and
Secretary (Principal Financial and
Accounting Officer)
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INDEX TO EXHIBITS
Exhibits.
99.1 Geron Corporation Press Release dated January 13, 1998.
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EXHIBIT 99.1
Geron Corporation
200 Constitution Drive
Menlo Park. CA 94025
Tel: (650) 473-7700
Fax: (650) 473-7750
PRESS RELEASE
EXTENSION OF HUMAN CELL LIFE-SPAN REPORTED IN SCIENCE
Telomerase Rewinds the Clock of Cell Aging
Menlo Park, CA -- January 13, 1998 -- Geron Corporation (NASDAQ: GERN) and the
University of Texas Southwestern Medical Center at Dallas reported today the
successful extension of the life-span of normal human cells using the enzyme
telomerase. In a paper published in the journal Science, January 16, 1998,
scientists explain that the introduction of an active telomerase gene into
normal mortal cells resulted in the lengthening of telomeres and a marked
increase in the life-span of the cells, making the cells potentially immortal.
"This paper is a monumental advance in the understanding of the molecular
genetics of aging," remarked Leonard Hayflick, Ph.D., professor of anatomy at
the University of California, San Francisco, School of Medicine and the
discoverer of human cellular aging. "The telomerase gene will likely have many
important applications in the future of medicine and cell engineering."
Telomerase is an "immortalizing" enzyme that imparts replicative immortality
when expressed in reproductive and cancer cells. Conversely, cells that do not
express the enzyme are mortal. The gene for the telomerase protein was recently
isolated by Geron and collaborators at the University of Colorado at Boulder.
Previous research by Geron and its collaborators has shown that the aging of
mortal cells appears to be controlled by a molecular clock consisting of
telomeres - a chain of repeated DNA segments found at the ends of the
chromosomes. Each time a mortal cell divides, a small segment of telomeric DNA
is lost, and in the absence of telomerase, the shortened telomeres signal the
cell to become senescent and stop dividing. Cells that have no replicative
limit, such as reproductive cells, express telomerase, which synthesizes
telomeres, allowing replicative immortality. Telomeres can therefore be
envisioned as "molecular clocks" that limit the life-span of cells, and
telomerase can be envisioned as the "key" that "rewinds" the telomere clocks.
In the report today in Science, researchers at Geron Corporation and the
University of Texas Southwestern Medical Center at Dallas collaborated to test
the effects of the immortalizing gene. "We couldn't be more excited about the
results," stated Woodring E. Wright, M.D., Ph.D., professor in the Department of
Cell Biology and Neuroscience at the University of Texas Southwestern Medical
Center at Dallas and one of the senior authors of the paper, "I think this
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finally nails down the fundamental cause of cell aging, and provides a direct
means of altering the clock of cell aging for therapeutic effect."
Geron is exploring applications of the telomerase gene to extend the life-span
of many different types of human cells, including skin cells, blood vessel
endothelial cells, retinal cells, immune cells, and others. "We believe that the
extension and perhaps immortalization of human cells will have many important
applications for the treatment of age-related diseases," remarked Calvin B.
Harley, Ph.D., chief scientific officer at Geron.
In addition to its role in aging, telomerase has previously been shown to be
abnormally active in all types of cancer examined and not expressed in most
normal tissues. Telomerase is therefore thought to be unique among anti-cancer
targets because it is universal across cancers and highly specific to cancer
cells. Because telomerase is required for cancer cells to proliferate
indefinitely, Geron is seeking to discover compounds designed to inhibit
telomerase. Such drugs are expected to lead to the death of the cancer cells
through resumed telomere shortening, with little to no effect expected on normal
body cells and tissues.
Significantly, the expression of telomerase in normal mortal cells extends their
life-span without transforming them into malignant cancer cells, demonstrating
that telomerase makes tumor cells immortal, but that other genetic alterations
are responsible for the malignant characteristics of cancer cells. "This is the
best of all outcomes from our perspective" said Ronald Eastman, Geron's chief
executive officer. "These results suggest that we have a gene that is both an
important target for cancer and for the treatment of age-related disease."
Senior authors of the Science article, "Extension of Life-Span by Introduction
of Telomerase into Normal Human Cells" are Dr. Woodring E. Wright from
University of Texas Southwestern Medical Center at Dallas and Dr. Serge
Lichtsteiner of Geron Corporation. Co-authors from Dr. Wright's group include
Drs. Shawn E. Holt, Michel Ouellette, and Jerry W. Shay. Co-authors from Geron
are Drs. Andrea G. Bodnar, Choy-Pik Chiu, Maria Frolkis, Calvin B. Harley, and
Gregg B. Morin.
Geron Corporation is a biopharmaceutical company focused on discovering and
developing therapeutic and diagnostic products to treat cancer and other
age-related diseases based upon the company's understanding of telomeres and
telomerase, fundamental biological mechanisms underlying aging and cancer.
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BACKGROUNDER
ACTIVATION OF TELOMERASE IN NORMAL HUMAN CELLS
EXTENDS THEIR LIFE-SPAN
IMPORTANT IMPLICATIONS FOR MEDICINE
Extension of the life-span of normal human cells is a critical milestone on
Geron's path to discovering treatments for age-related disorders that strike at
a fundamental mechanism of aging: cell senescence. This achievement, which was
accomplished by introducing the enzyme telomerase into normal mortal cells,
provides definitive evidence that the triggering mechanism for aging, or
senescence, in human cells is telomere shortening. The demonstration that
telomerase activity can extend cell life-span identifies a central mechanism and
a point for intervention in age-related diseases at the cellular level.
Telomerase, Telomeres, and the Extension of Cell Life-Span
Most normal human cells can divide only a finite number of times. Cells from
various tissues in the body, such as osteoblasts in the bone, endothelial cells
in the blood vessels, retinal pigment epithelial cells in the eye, fibroblasts
in the skin, and lymphocytes in the blood are mortal, that is to say, they
divide 20-100 times (depending on the tissue and age of the donor) and then
cease dividing in a process called cell senescence. This phenomenon of cell
aging was first described by Leonard Hayflick in 1961, and therefore the limit
of cell proliferation is often called the "Hayflick Limit." Since it is widely
believed that we age in large part because our cells age, the National Institute
on Aging has sponsored a significant amount of research into the biological
mechanisms of cell aging.
In the decades that followed Hayflick's discovery that human cells are mortal
and age in the laboratory dish, a theory for the mechanism of a cellular clock
that counts how many times a cell has divided has emerged, called the telomere
hypothesis. According to this theory, the clock of cellular aging resides at the
linear ends of the DNA molecule, a region called the telomere (tea'-low-meer).
The linear end of each DNA strand ends with a sequence of DNA (TTAGGG) that
repeats hundreds of times, effectively "capping" the ends of chromosomes in a
manner similar to the way the plastic on the ends of shoelaces "caps" and
protects the shoelaces from unraveling. The telomere hypothesis proposes that as
mortal cells divide, terminal DNA or telomeres are progressively lost with each
cell division, shortening like a burning fuse. When a critical amount of
telomere shortening has occurred, the genetic program of cell senescence, or
cell aging, is triggered.
Among normal cells, only the reproductive cells do not senesce; the telomere
clock does not "tick," telomeres do not shorten, and the cells can apparently
divide indefinitely, a characteristic referred to as immortality. Cellular
immortality does not mean that the cells cannot die; like all cells, they must
be carefully nourished to remain viable. Instead, immortality refers to the fact
that these cells are not limited to a finite number of doublings. Immortal
cells, provided they are properly fed and maintained, can divide indefinitely.
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Geron Scientific Discoveries
Geron and collaborators have discovered that the capacity of reproductive cells
to divide in an immortal fashion is due to the presence of a protein, telomerase
(tel-om'-er-ase). This enzyme is actually a complex of at least two distinct
molecules, one made of RNA and another made of protein. The RNA component is
designated hTR (human Telomerase RNA), and the protein component is designated
hTRT (for human Telomerase Reverse Transcriptase). Telomerase uses the RNA
component to direct the synthesis of the repeated sequence (TTAGGG), and the
fusion of the building blocks of DNA is accomplished by the catalytic compound
hTRT. The combination of hTR and hTRT makes active telomerase that can lengthen
telomeres, "rewind the clock" of cell aging, and extend the replicative
life-span of cells.
Geron, in collaboration with Cold Spring Harbor Laboratory, reported the
isolation of the RNA component of telomerase in 1995 (Science September 1, 1995)
and has received a U.S. patent on the molecule on December 10, 1996. Geron and
the University of Colorado at Boulder were the first to report the isolation of
the protein component hTRT (Science August 15, 1997). Geron has filed for
patents to protect this discovery. While the RNA component is present in both
mortal and immortal cells, the catalytic protein component is observed to be
expressed only in immortal cells, leading to the logical question - what would
happen if the telomerase hTRT gene were introduced into mortal cells in an
active form? In the December 1, 1997 issue of Nature Genetics, Geron, in
collaboration with the University of Texas Southwestern Medical Center at
Dallas, demonstrated that the expression of hTRT in normal human cells is
sufficient to produce active telomerase. The final questions were would it
extend telomeres and would that reverse the aging of human cells?
In a breakthrough accomplishment, Geron and its collaborators have now reported
in Science (January 16, 1998) that the introduction of hTRT into mortal cells
leads to the extension of telomeres and also the extension of cell life-span. As
of the writing of the paper, three different types of cells were observed to
substantially pass their normal limits of replicative life-span. These cells are
continuing to grow and may be immortal.
Implications of Cell Life-Span Extension for Age-Related Disorders
Senescent cells are not only incapable of dividing, they also exhibit an altered
pattern of gene expression, leading to a number of changes in their structure
and function. The effects of senescence on cell function can damage the
surrounding tissues, contributing to age-related pathologies. For example,
senescent skin fibroblasts produce lesser amounts of important skin matrix
elements such as collagen and elastin and elevated levels of enzymes such as
collagenase that break down the skin matrix. These changes contribute to atrophy
of the skin and, ultimately, age-related skin disorders. Similarly, metabolic
changes in senescent retinal pigmented epithelium cells, and the loss of
proliferative capacity and overexpression of hypertensive and thrombotic factors
in endothelial cells are considered contributors to the pathologies of
age-related macular degeneration (AMD) and atherosclerosis, respectively.
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Skin disorders, AMD, and atherosclerosis are major diseases in the aging
population. Skin atrophy, for example, affects virtually all aging individuals,
with 40 percent of the population over 75 years of age seeking treatment for at
least one skin disorder. These disorders range from photoaging and wrinkling to
increased wounding and, ultimately, skin ulceration. The latter disease can be
life-threatening. The major class of drugs for treating age-related skin
disorders, the retinoids, produces mainly palliative or "cosmeceutical" effects.
In the case of AMD, one third of the population at age 70 is affected and, in
most patients, the disease is currently untreatable. The delay or prevention of
cell senescence through the extension of cell life-span is expected to have
important beneficial effects in diseases to which cell senescence contributes.
In addition to skin disorders, AMD and atherosclerosis, this group is thought to
include osteoporosis, immune dysfunction, arthritis, and neurodegenerative
disorders. The improvement in the health of the elderly through the more
effective treatment of age-related diseases is expected to increase the length
of healthy life. There is no evidence that this will translate into an extension
of the maximum human life-span, which is now believed to be about 120 years.
Implications of Life-Span Extension in Other Health-Related Areas
In addition to the application of cell life-span extension to the development of
therapeutics for age-related disorders, there are other health-related uses of
this technology which could be pursued in a much shorter time frame. These uses
relate to extension of the life-span of cells grown outside of the body. Cell
senescence was, in fact, first described by Hayflick in human cells grown in the
laboratory.
Laboratory culturing of human cells is the basis of several important current,
and anticipated, therapies. One example is reconstitution of the blood and
immune system following high-dose chemotherapy for cancer. In this approach,
cells removed from the patient before the therapy or obtained from a donor are
increased in number (expanded) by culturing in the laboratory, and reimplanted
into the patient after the chemotherapy. Following reimplantation, the cells
undergo further divisions to replace the blood and immune cells destroyed by the
chemotherapy. Other cell therapy, as well as gene therapy approaches, also
require cell expansion both in culture and after reintroduction in order to be
effective.
Because of the large number of cell divisions required by cell and gene therapy
approaches, cell senescence is a significant limiting factor in their success.
For example, in reconstitution of the blood and immune system after
chemotherapy, the cells exhaust the equivalent of an estimated 40 years of their
life-span. This restricts the use of this approach in older patients, reduces
the number of courses of therapy which can be given, and may produce problems in
blood and immune functions for recipients later in life. The ability to extend
the life-span of normal human cells in culture, preventing the loss of
replicative capacity that now accompanies cell and gene therapy approaches,
should dramatically increase their utility and probability of success.
Senescence in normal human cells also has a significant impact on the production
of human biological material for medical use. Many human biological products are
made in "transformed" cell lines derived from cancer or virally infected cells
because they do not senesce. Whenever normal human cells are used, cultures must
be replaced every time senescence occurs. These
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methods for production of biological materials introduce the risk of
contamination of viral products or other pathogens, result in high production
costs, and may affect the quality of the material produced, particularly when
transformed cells are used. Normal human cell strains with an extended life-span
can replace the cells currently used to produce biological materials, resulting
in safer, economical, and more efficacious therapeutics.
Telomerase, Telomeres and Cancer
Activation of telomerase does not transform normal cells into cancer cells. As
described in the January 16, 1998 Science paper, cells maintain normal growth
characteristics following the activation of telomerase. In fact, there are
certain types of cells in the body, such as the reproductive cells, in which
telomerase is normally activated. Conversely, lack of telomerase activity does
not prevent cells from becoming transformed into cancer cells, as has been
demonstrated in "knockout" mice. Telomerase activation, if done in a transient
fashion, would simply allow normal cells to undergo more divisions, under normal
growth conditions, before they become senescent. Inhibition of telomerase
activity in cancer cells, on the other hand, causes them to stop growing and die
once their telomeres become so short that their chromosomes are unstable.
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Note: This release moved over Business Wire January 13, 1998.
The Company desires to take advantage of the "safe harbor" provisions of the
Private Securities Litigation Reform Act of 1995. Specifically, the Company
wishes to alert readers the matters discussed in this press release may
constitute certain forward-looking statements that are dependent on certain
risks and uncertainties. Actual results may differ materially from the results
anticipated in these forward-looking statements. Additional information on
potential factors that could affect the Company's results are included in the
Company's Quarterly Report on Form 10-Q for the quarter ended September 30,
1997.
Contact:
Ronald Eastman Carole Melis / Mike Jackman
President & CEO StratiPoint Group
415 473-7700 415 326-0420
