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 17, 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 17, 1998 the Company issued the press release attached hereto
as Exhibit 99.1.
ITEM 7. EXHIBIT
99.1 Press Release dated June 17, 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 17, 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 ANNOUNCES THE ISSUANCE OF TWO PATENTS DIRECTED TO
HIGH POTENCY ANTISENSE COMPOUNDS THAT TARGET THE
PRODUCTION OF DISEASE CAUSING pre-RNA
San Diego, CA, June 17, 1998 --- Genta Incorporated (NASDAQ:GNTA) today
announced that it has received notification from the U.S. Patent and Trademark
Office that two patents have been issued for Genta's next generation antisense
backbone constructions. Backbone constructions are the chemical links between
the different bases of oligonucleotides. The normal backbone of DNA and RNA
molecules is subject to metabolism by the body when administered as a drug;
therefore, scientists in this field have sought to develop more stable
constructions.
Genta's new backbone constructions, when used in Genta's Anticode(TM) brand
antisense oligonucleotides, demonstrated a thousand-fold higher binding affinity
for target RNA in cellular and cell-free assay systems than currently used
phosphorothioate-backbone antisense oligonucleotides. "The protection this
patent provides will allow future development of Genta's next generation
antisense molecules," stated Robert E. Klem, Ph.D., Vice President, Genta
Incorporated.
The first of these patents describes a series of compounds containing new
backbone constructions that enhance the antisense effect by increasing the
binding affinity of the drug to the disease causing pre-RNA. The other patent
describes methods for the preparation of antisense oligonucleotides containing
these new backbone constructions.
These new compounds have significantly higher binding affinity for pre-mRNA than
phosphorothioate antisense oligonucleotides, and consequently, form much
stronger duplexes with the target RNA. Once bound, the duplex interrupts the
formation of mature mRNA thereby interfering with the production of the specific
target protein. The company demonstrated in its laboratories that their new
antisense oligonucleotides can markedly reduce mRNA replication in cellular and
cell-free assay systems. In addition, the amount of antisense drug required to
cause this significant reduction was lower by one to two orders of magnitude
over the currently used phosphorothioate backbone constructions.
Correspondingly, a reduction in overall cellular toxicity was observed in
contrast to currently utilized phosphorothioate oligonucleotides of the same
concentration.
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These new oligonucleotide constructions are anticipated to have reduced toxicity
and enhance the desired therapeutic effect while lowering the amount of
oligonucleotide that must be administered.
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 cells' sensitivity to apoptotic
stimuli, including many chemotherapeutic agents (an effect that has been termed
"chemosensitization").
In February 1998, a report of such chemosensitization appeared in Nature
Medicine, a peer-reviewed, scientific journal, 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
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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. 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. Examples of
such risks and uncertainties 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 any forward-looking statements.
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