Couldn't see an active ISIS thread. Perhaps this drug entering the clinic is of interest here....
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First Drug From Isis Pharmaceuticals and Lilly's Drug Discovery Alliance Enters Phase 1 Clinical Trials in Cancer
prnews
CARLSBAD, Calif., Nov. 17 /PRNewswire-FirstCall/ -- Isis Pharmaceuticals,
Inc. (Nasdaq: ISIS) announced today that LY2181308, the first antisense drug
to emerge from its drug discovery alliance with Eli Lilly and Company
(NYSE: LLY), has moved into Phase 1 clinical trials in cancer patients,
marking a significant milestone in the partnership. For the accomplishment of
this milestone, Isis earned a $1.5 million payment from Lilly. This is the
second milestone Isis has achieved in the development of this
second-generation antisense drug, which was licensed to Lilly in April 2003,
and the third milestone achieved in the collaboration overall. Recently, Isis
announced that Lilly licensed a second anti-cancer drug LY2275796 for clinical
development. The companies' oncology collaboration, initiated in June 2002
and extended earlier this year, is part of the companies' broad, strategic
alliance to discover antisense drugs.
"Moving LY2181308 into clinical trials is an important event for the
Isis-Lilly collaboration. It demonstrates that we are realizing the goal of
the partnership, which is to discover new RNA-based drugs for cancer as well
as for inflammatory and metabolic diseases," said C. Frank Bennett, Ph.D.,
Isis' Vice President, Antisense Research. "LY2181308 is the first drug to
successfully inhibit survivin, a molecule that has received considerable
attention in the cancer community and the pharmaceutical industry."
LY2181308 was selected by Lilly for clinical trials based on compelling
preclinical data. Specifically, it has:
* Demonstrated consistent activity in human xenograft tumor models and
multiple cancer cell lines derived from the lung, colon, breast,
prostate, ovary, cervix, skin and brain;
* Produced anti-tumor activity in animals that is associated with
selective inhibition of survivin protein expression with no effects on
other anti-apoptotic proteins;
* Shown additive effects with several chemotherapeutic agents, and
* Confirmed an antisense mechanism of action for the drug in cell
culture and in animals.
LY2181308 targets survivin, a molecule that supports the survival of cells
that would normally die through programmed cell death or apoptosis. Survivin
helps in the abnormal growth of cancer cells, and is abundant in many types of
cancers, including colon, brain, lung, skin and others, but nearly nonexistent
in normal cells and tissues.
"Lilly has made a substantial commitment to antisense through our broad
research partnership, the largest RNA-based drug discovery alliance in the
industry. We are pleased that this collaboration is successfully producing
new drugs for Lilly's high quality and innovative product portfolio,"
continued Dr. Bennett. "We will continue to apply the strength of our
technology, experience and expertise in multiple antisense mechanisms,
including RNase H, siRNA and RNA splicing, and advanced chemistries to
discover additional antisense drugs that can add significant value to Lilly's
pipeline."
ISIS' ANTI-CANCER DRUG DISCOVERY AND DEVELOPMENT PARTNERSHIPS
The entry of LY2181308 into the clinic further strengthens Isis' robust
cancer franchise that is supported through both strategic partnerships and
internal research and development. In addition to Isis' drug discovery
partnership with Lilly, the company has several ongoing collaborations that
are focused on identifying new antisense drugs for the treatment of a variety
of tumors.
With Isis' assistance, OncoGenex Technologies is developing OGX-011, an
inhibitor of clusterin. Clusterin is a cell survival protein that, when
overproduced, prevents cancer cell death and counters the effectiveness of
standard anti-tumor treatments.
OGX-011 is a second-generation antisense drug being developed to sensitize
tumors resistant to existing treatments such as chemotherapy, hormone ablation
therapy and radiation therapy. The companies have reported results from a
Phase 1 study showing that once-weekly intravenous administration of OGX-011
is well-tolerated, achieves excellent drug concentration in target tissue, and
produces up to a 91% dose-dependent down-regulation of its target, clusterin,
in prostate cancer.
In 2003, Isis and OncoGenex expanded their antisense drug development
partnership to include the development of the second-generation antisense
anti-cancer drug candidate, OGX-225. The compound is the first bi-specific
antisense inhibitor, a single-stranded antisense drug designed to inhibit the
production of two proteins simultaneously, to enter preclinical development.
OGX-225 targets both insulin-like growth factor binding protein-5 (IGFBP-5)
and insulin-like growth factor binding protein-2 (IGFBP-2), two molecules
involved in the development of metastatic disease in hormone-regulated tumors
such as prostate and breast.
Isis is also working with Ercole Biotech, a company focused on discovering
antisense drugs that regulate alternative RNA splicing. Through this
collaboration, Ercole received a license to Isis' Bcl-x preclinical antisense
drug. This drug inhibits the production of splice variants of the Bcl-x gene,
which is involved in the regulation of apoptosis, or programmed cell death.
Additionally, Isis continues its internal drug discovery efforts in
oncology, recently adding ISIS 345794 to its clinical development pipeline.
ISIS 345794 is a second-generation antisense drug that targets STAT-3, a
protein known to be an important transcription factor that turns on genes
required for the division, growth and death of cells. Activation of STAT-3 is
known to contribute to the formation and development of tumors.
ABOUT ISIS PHARMACEUTICALS, INC.
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