SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, DC 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): December 7, 1998
GENTA INCORPORATED
(Exact name of registrant as specified in its charter)
Commission file number 0-19635
Delaware 33-0326866
(State or other jurisdiction of (IRS Employer Identification Number)
incorporation or organization)
3550 General Atomics Court, San Diego, CA 92121
(Address of principal executive offices)
(Zip Code)
(619) 455-2700
(Registrant's telephone number, including area code)
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GENTA INCORPORATED
FORM 8-K
CURRENT REPORT
TABLE OF CONTENTS
Item 5. Other Event ..........................................................3
Item 7. Exhibit ..............................................................3
Signature .....................................................................4
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ITEM 5. OTHER EVENT
On December 7, 1998, the Company issued the press release attached as
Exhibit 99.1 below.
ITEM 7. EXHIBIT
99.1 Press Release dated December 7, 1998.
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SIGNATURE
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 hereunto duly authorized.
Date: December 8, 1998
GENTA INCORPORATED
/s/ Kenneth G. Kasses, Ph.D.
----------------------------
Kenneth G. Kasses, Ph.D.
Chairman of the Board of Directors,
President, Principal Executive Officer
and Principal Financial Officer
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FOR IMMEDIATE RELEASE Contact: Kenneth G. Kasses, Ph.D.
Chairman, President and CEO
(619) 455-2700
Report at American Association for Cancer Research Meeting
Presents Scientific Basis for Clinical Trial Now Underway at
British Columbia Cancer Agency
Bcl-2 Antisense Shows Potent Anti-Tumor Effects in Pre-Clinical
Models of Prostate Cancer
San Diego, CA, December 7, 1998 - Genta Incorporated (Nasdaq: GNTA) announced
that Dr. Martin Gleave, Associate Professor of Surgery/Urology at The University
of British Columbia and Vancouver General Hospital, presented research results
last Friday at the American Association for Cancer Research (AACR) sponsored
conference entitled, New Research Approaches in the Prevention and Cure of
Prostate Cancer. The research, conducted by Dr. Gleave and his associates, Drs.
Anthony Tolcher and Hideake Miyake, revealed a significant role of the Bcl-2
protein in the progression of hormone-resistant prostate cancer. Furthermore,
their work revealed potent effects of Genta's Bcl-2 antisense sequence on the
levels of Bcl-2 messenger RNA and protein levels in their pre-clinical models.
G3139, which is Genta's proprietary Anticode(TM) product targeted to Bcl-2, is
now in clinical development for treatment of prostate cancer, lymphoma, melanoma
and other malignancies.
Prostate cancer is the most common malignancy in men in North America, and the
second leading cause of cancer-related death behind lung cancer. While hormonal
therapy is initially very effective, the disease often progresses and becomes
hormone-resistant; outcome for patients is poor with available treatments. Dr.
Gleave reported that, using two models for human prostate cancer in mice, the
group made new progress in understanding the mechanisms for progressive prostate
cancer and its resistance to therapy. "We now have a better understanding of the
genetic changes linked to progressive prostate cancer, including the frequent up
regulation of the bcl-2 gene and increased production of related proteins which
appear to prevent tumor cell death (apoptosis), increasing the growth advantage
for prostate cancer cells despite therapy with hormones or drugs," reported Dr.
Gleave. "Using G3139 antisense product in the prostate cancer cells, we found
specific and consistent block of this Bcl-2 protein, linked to striking
inhibition of cancer cell growth both in cell culture and in mice."
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Results with Combination Therapy Leads to New Clinical Trial
Dr. Gleave also reported that they found that Bcl-2 antisense significantly
improved the anticancer action of paclitaxel and mitoxantrone, two drugs that
are widely used for clinical treatment of patients with metastatic prostate
cancer. "Supporting our prediction that Bcl-2 was linked to resistance by cancer
cells to chemotherapy, we found that antisense oligonucleotides could improve
the potency of these standard chemotherapies by over 10-fold in the prostate
cancer models," reported Dr. Gleave. "This is a dramatic improvement in potency
that could not be easily reproduced by other treatment strategies. Since G3139
is already in clinical studies and we know a great deal about patient tolerance
as a single agent, these findings contribute to a potential new approach for
combination therapy of prostate cancer."
Based on these results presented by Dr. Gleave, and other ongoing clinical
studies with G3139, a Phase I-II protocol has been started with Drs. Richard
Klasa and Kim Chi at the British Columbia Cancer Agency to treat patients with
progressive prostate cancer using G3139 in combination with mitoxantrone.
Background Information on Apoptosis, Cancer, Bcl-2 and G3139
The body's cells are normally programmed to detect damage in their genetic
makeup and to enter into a suicidal state when such alterations are detected.
This natural process, known as apoptosis or "programmed cell death," helps the
body regulate its own well being by destroying damaged cells. In many cancer
cells, however, this process of natural cell death is inhibited by the over
expression of a protein called Bcl-2, which is produced by a gene identified as
bcl-2. Consequently these cancer cells, even though damaged, resist dying and
continue multiplying.
In many cases, cells that over produce the Bcl-2 protein are also resistant to
chemotherapeutic agents, many of which act by stimulating apoptosis, and these
cancers have been associated with an unfavorable prognosis. For example, it has
been reported that Bcl-2 protein is over produced in virtually all
hormone-refractory, metastatic prostate cancer; 80-90% of
estrogen-receptor-positive breast cancer; 70-100% of follicular lymphomas; and
up to 90% of malignant melanomas. Bcl-2 has also been reported to be up
regulated in some lung, gastric and colorectal cancers.
Using a single drug based on the genetic sequence of the bcl-2 gene, Genta
Incorporated is developing a novel therapeutic approach to treating several
cancers. Genta developed this synthetic DNA-like molecule, identified as G3139,
to bind specifically to a small segment of the messenger RNA, which produces the
harmful Bcl-2 protein. Once bound to the messenger RNA, the messenger RNA is
destroyed, preventing the production of the Bcl-2 protein. (This type of
interference with the process, whereby genes produce proteins through their
messenger RNA, has been called "antisense.") The goal of this therapeutic
approach is to restore the diseased cells' sensitivity to apoptotic stimuli,
including many chemotherapeutic agents - an effect called "chemosensitization."
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In February 1998, a report of such chemosensitization appeared in Nature
Medicine, a peer-reviewed, scientific journal. In the report, G3139 was shown to
enhance the effect of a standard chemotherapeutic agent, DTIC or dacarbazine, in
a mouse model of human malignant melanoma. In two experiments with a total of 13
animals, 10 had no tumor after the combined treatment and the other three showed
an average reduction in tumor weight of 90% compared to the DTIC-alone treated,
control animals.
Genta is now in the clinical development phases of G3139. A Phase I study at the
Royal Marsden Hospital in London has been completed, and a Phase I/IIa study is
in progress at the Memorial Sloan-Kettering Cancer Center in New York City. A
preliminary report of the study at the Royal Marsden was published in The Lancet
in April 1997. Although this was primarily a safety study, the investigators
reported very encouraging biological clinical activity of the drug, including
one complete response to G3139 alone. The first combination drug trial using
G3139 and DTIC in malignant melanoma is in progress at the University of Vienna
conducted by the same investigators who published the work cited in Nature
Medicine, above. Another study has been initiated at the Sidney Kimmel Cancer
Center in San Diego to study longer durations of therapy and in combination with
androgen receptor blockade, the most common therapeutic approach to prostate
cancer. A study to examine the concurrent use of G3139 and mitoxantrone in
prostate cancer has recently started at the British Columbia Cancer Agency in
Vancouver as noted above. Other clinical studies are also in development and
should be initiated in the coming months.
Genta Incorporated (Nasdaq: GNTA) is a biopharmaceutical company focused on
building a product and technology portfolio based on its Anticode(TM)
(antisense) products intended to treat cancer at its genetic source.
The statements contained in this press release that are not historical are
forward-looking statements within the meaning of Section 27A of the Securities
Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934,
as amended, including statements regarding the expectations, beliefs, intentions
or strategies regarding the future. Without limiting the foregoing, the words
"anticipates," "believes," "expects," "intends," "may" and "plans" and similar
expectations are intended to identify forward-looking statements. The Company
intends that all forward-looking statements be subject to the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995. These
forward-looking statements reflect the Company's views as of the date they are
made with respect to future events, but are subject to many risks and
uncertainties, which could cause the actual results of the Company to differ
materially from any future results expressed or implied by such forward-looking
statements. For example, the results obtained in pre-clinical studies may not be
indicative of results that will be obtained in clinical trials; Genta has not
successfully completed human clinical trials of a product based on antisense
technology; and delays in the completion of clinical trials as a result of
delays in patient enrollment or other factors may occur. Examples of such risks
and uncertainties also include, but are not limited to: the obtaining of
sufficient financing to maintain the Company's planned operations; the timely
development, receipt of necessary regulatory approvals and acceptance of new
products; the successful application of the Company's technology to produce new
products; the obtaining of proprietary protection for any such technology and
products; the impact of competitive products and pricing and reimbursement
policies; and the changing of market conditions. The Company does not undertake
to update forward-looking statements.
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