LEXINGTON, MA, May 23, 2000
- Genta Incorporated (Nasdaq:
GNTA
) announced the presentation of clinical and laboratory results
that showed the biologic activity of Genasense
TM
(G3139), Genta"s lead investigational anticancer drug,
related primarily to its knocking out production of Bcl-2. These
key scientific findings were presented today by Dr. Justin Waters
from the Royal Marsden Hospital at the annual meeting of the
American Society of Clinical Oncology (ASCO) in New Orleans.
As an antisense molecule, Genasense is comprised of modified DNA
bases. The drug then combines in cancer cells that express the mRNA
that codes for Bcl-2 protein, a substance that contributes to the
ability of tumor cells to withstand anticancer treatment. By
inactivating the precursor mRNA, Bcl-2 production is thus halted,
and cancer cells then become markedly sensitized to the killing
effects of cancer therapy.
Recently, several groups have claimed that many antisense
compounds that contain so-called "CpG motifs" lack "true" antisense
activity, and that any positive actions relate to induction of
non-specific immune reactions. In the study presented today, Dr.
Waters presented in vivo data from studies in mice that lacked any
B- or T-lymphocytes or NK cells (i.e. SCID and NOD/SCID mice).
After these mice had been injected so that they developed a human
non-Hodgkin"s lymphoma, they were then treated with Genasense
therapy. Using sensitive tests for molecular detection of residual
disease, 20 of 24 mice were shown to be completely cured of
lymphoma. Moreover, in a related clinical trial of Genasense in
patients with advanced lymphoma, no evidence of non-specific immune
activation, including increased production of interleukin-2,
interleukin-4, and interferon-gamma, or NK activation, was
found.
Dr. Raymond P. Warrell, Jr., MD, Genta"s President and CEO
commented, "The data presented today by Dr. Waters complement
similar results reported by Dr. Jill Lacy from Yale University in
December (Blood (Suppl.) 94:386a,1999). Irrespective of reported
effects using other antisense drugs, the combined results from
these 2 studies confirm that the marked antitumor activity of
Genasense, which has been observed both preclinically and in
patients, is due to down-regulation of Bcl-2 production rather than
non-specific immune reactions."
