To All:
The recent stock jump has been due to more great news from the company. I'll post a press release that i recieved from a friend by email below. The company also moved yesterday due to a new kind of laboratory mouse that was approved for use. This news about the mouse was released by DNX Corporation (DNXX), but it was co-developed with scientists from Isis Pharmaceuticals (ISIP).
Here is the press release:
ISIS ANTISENSE COMPOUND DEMONSTRATES POTENT,
SELECTIVE ANTI-TUMOR ACTIVITY IN MODELS OF HUMAN CANCER
CARLSBAD, Calif., June 4 -- Isis Pharmaceuticals (Nasdaq: ISIP) announces results of studies demonstrating that ISIS 5132/CGP 69846A demonstrated potent activity in inhibiting human tumor growth in both cell culture and in animals. ISIS 5132/CGP 69846A is a selective inhibitor of C-raf kinase gene expression that works through antisense to bind to a messenger RNA (mRNA) sequence unique to C-raf kinase to selectively inhibit the production of the C-raf kinase protein. Anti-tumor activity was demonstrated in multiple mouse xenograft models of human cancer including tumors generated from human breast, lung, and bladder, and at doses well below those known to be toxic. These studies also clearly demonstrate the ability of ISIS 5132/CGP 69846A to reduce C-raf kinase mRNA and protein in cell culture and in tumors in a dose-dependent, sequence-specific manner, thus providing strong evidence that the compound is working as an anticancer agent through an antisense mechanism of action.
These studies are published in the June issue of Nature Medicine, under the title, "Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C-raf kinase." The authors are Brett P. Monia and Joseph F. Johnston of Isis, and Thomas Geiger, Marcel Muller and Doriano Fabbro of Ciba-Geigy.
C-raf kinase is a member of the raf kinase gene family which is responsible for signal transduction processes that regulate cell proliferation. There is substantial evidence to suggest a direct role for raf kinases in the development and maintenance of a variety of human tumors. Working through an antisense mechanism, ISIS 5132/CGP 69846A has demonstrated selective inhibition of the production of C-raf kinase without inhibiting the production of other proteins in the raf kinase multi-gene family.
In the in vitro studies, multiple antisense compounds predicted to hybridize with human C-raf kinase mRNA were synthesized and tested against human tumor cell lines (e.g., bladder, lung) for activity. The most potent antisense inhibitor of C-raf kinase mRNA was ISIS 5132/CGP 69846A. Testing of mismatched control antisense compounds demonstrated that ISIS 5132/CGP 69846A completely eliminated expression of C-raf mRNA in a highly sequence-specific and target-specific manner. No effects were observed on the expression of any other cellular mRNAs examined in cells treated with ISIS 5132/CGP 69846A or the mismatched control, demonstrating the specificity of the compound. Studies to determine the effect of ISIS 5132/CGP 69846A on cell proliferation demonstrated dose- dependent antiproliferative effects as a direct result of the inhibition on C-raf gene expression by ISIS 5132/CGP 69846A.
In in vivo studies, the effects of ISIS 5132/CGP 69846A were studied using subcutaneously implanted tumor cell xenografts (lung, breast, bladder) in mice. ISIS 5132/CGP 69846A displayed potent inhibitory effects on the growth of tumors in mice while control antisense compounds displayed no effect. These effects on tumor growth were highly dose-dependent and the compound displayed potent antitumor activity at low doses. The studies conclude that the high level of specificity demonstrated by ISIS 5132/CGP 69846A for its molecular target and the demonstration of sequence-specific, dose-dependent anti- tumor activity provide evidence that the compound is achieving its biological effect through an antisense mechanism of action.
"The ability of both Ciba and Isis scientists to demonstrate in animals that significant antitumor activity can be achieved with this compound at low doses suggests that ISIS 5132/CGP 69846A may be a promising, novel treatment for cancer," said Stanley T. Crooke, M.D., Ph.D., Chairman and CEO, Isis. "We are encouraged by these results and are optimistic that the Phase I clinical trials currently underway will confirm the safety profile of this compound and provide some insight into its therapeutic potential in humans."
ISIS 5132/CGP 69846A is being evaluated in Phase I clinical trials in cancer patients with a broad range of solid tumors. The trials were initiated in April 1996. It is being developed as part of the antisense research and development collaboration between Isis and Ciba. ISIS 5132/CGP 69846A has demonstrated attractive pharmacokinetic properties in animals, similar to those exhibited by other systemically administered antisense compounds. In addition, because of its favorable preclinical toxicity profile and additive or synergistic effects with traditional anticancer drugs in nude mouse xenografts, ISIS 5132/CGP 69846A has significant potential as an agent to be used in combination chemotherapy regimens.
This press release contains forward-looking statements concerning ISIS 5132/CGP 69846A, an antisense compound in development as an anticancer agent. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics. Actual results could differ materially from those projected in this release. As a result, the reader is cautioned not to rely on these forward-looking statements. These and other risks are described in additional detail in Isis' Annual Report on Form 10-K for the year ended December 31, 1995 and in the Company's most recent quarterly report on Form 10-Q, which are on file with the U.S. Securities Exchange Commission, copies of which are available from the company.
Isis Pharmaceuticals, based in northern San Diego County, is engaged in the discovery and development of novel human therapeutic compounds. Isis has four compounds in human clinical trials: ISIS 2922, to treat CMV-induced retinitis in AIDS patients, is in Phase III clinical trials; ISIS 2302, an inhibitor of ICAM-1, is in Phase II clinical trials for renal transplant rejection, rheumatoid arthritis, psoriasis, Crohn's disease and ulcerative colitis; and ISIS 3521/CGP 64128A and ISIS 5132/CGP69846A, both anticancer compounds, are in Phase I clinical trials. The company also has several additional compounds in preclinical development. Isis' broad medicinal chemistry and biology research programs support efforts in both antisense and combinatorial drug discovery. |
