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): June 18, 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
Item 7. Exhibit
Signature
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ITEM 5. OTHER EVENT
On June 18, 1998 the Company issued the press release attached hereto
as Exhibit 99.1.
ITEM 7. EXHIBIT
99.1 Press Release dated June 18, 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.
GENTA INCORPORATED
Date: June 18, 1998 /s/ Kenneth G. Kasses, Ph.D.
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Kenneth G. Kasses, Ph.D.
President and Chief
Executive Officer
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FOR IMMEDIATE RELEASE
Contact: Robert E. Klem, Ph.D.
Vice President
805-544-8524
GENTA TO COMMENCE PHASE I/IIa MALIGNANT MELANOMA TRIAL
OF bcl-2 ANTISENSE COMPOUND IN COMBINATION WITH A CHEMOTHERAPEUTIC DRUG
PRE-CLINICAL STUDIES SHOWED SIGNIFICANT TUMOR REDUCTION
IN MOUSE TRANSPLANT MODEL OF HUMAN MELANOMA
SAN DIEGO, CA, JUNE 18, 1998 -- Genta Incorporated (Nasdaq: GNTA) today
announced that it will initiate a new Phase I/IIa study of its lead development
compound G3139 at the University of Vienna, Austria. This study will examine the
effects of G3139 in the treatment of Stage III and IV metastatic malignant
melanoma in combination with dacarbazine (DTIC), a commonly used chemotherapy
drug. The principal investigators in this study, Dr. Burkhard Jansen and Dr.
Hubert Pehamberger, were also the key investigators in a preclinical study of
the same combination in an animal model of human melanoma. This new clinical
trial is designed to examine the effectiveness of the same combination in about
thirty patients by measuring the impact on both the production of the Bcl-2
protein and on tumor volumes.
PRE-CLINICAL STUDIES SHOWED SIGNIFICANT TUMOR REDUCTION
The results of the animal study, which were published in the February 1998 issue
of Nature Medicine, a leading scientific peer-reviewed journal, demonstrated the
effectiveness of Genta's G3139 antisense compound as a chemosensitizer. This
preclinical study examined the effect of G3139 on dacarbazine (DTIC) sensitivity
in a human melanoma transplant in immuno-compromised mice compared to three
control groups: a saline control, a reverse sequence antisense oligonucleotide
and a mismatched pair oligonucleotide. When DTIC, the most widely used
chemotherapeutic agent in melanoma, was administered to the animals, the mean
tumor weights in all three control groups were not significantly different but
the G3139 group had a mean tumor weight close to zero and the tumor was
completely ablated in ten out of thirteen animals. In a separate experiment, the
authors also demonstrated that the antisense compound, G3139, alone had a
significantly greater effect in reducing tumor growth
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Genta Incorporated June 18, 1998
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than did the three control treatments.
"When we were presented with these results by our colleagues in Vienna, we
became very interested in pursuing the clinical examination of this combination
therapy," stated Kenneth G. Kasses, President and Chief Executive Officer of
Genta. "We have theorized that G3139, by downregulating the Bcl-2 protein,
should resensitize the cells to chemotherapy and cell death. This Phase I/IIa
study, which is about to commence, will be our first effort to test our
hypothesis in patients."
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, cell types 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,
designed 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
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Genta Incorporated June 18, 1998
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cells' sensitivity to apoptotic stimuli, including many chemotherapeutic agents
(an effect that has been termed "chemosensitization").
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. Other clinical studies are also in
development and should be initiated beginning very shortly.
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 and 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 expressions 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, including the following: the results obtained in pre-clinical
studies may not be indicative of results that will be obtained in clinical
trials; all of Genta's potential products are at an early stage of development;
neither Genta nor, to its knowledge, any other company, has successfully
completed human clinical trials of a product based on antisense technology;
there can be no assurance that Genta will receive regulatory approvals to
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Genta Incorporated June 18, 1998
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commence or continue clinical trials of product candidates or to market any
products or that delays in completion of clinical trials as a result of delays
in patient enrollment or other factors will not occur; and there can be no
assurance that Genta will be able to obtain adequate funding to achieve its
objectives. The Company does not undertake to update any forward-looking
statements.
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