ChemGenex Investigators Report Omacetaxine Effective in Killing CML Stem Cells in Animal Model Studies
December 11 2007 - 7:00AM
Business Wire
ChemGenex Pharmaceuticals (ASX:CXS) (NASDAQ:CXSP) announced today
that pre-clinical data characterizing the mechanism of action of
omacetaxine mepesuccinate (formerly known as Ceflatonin�) were
presented yesterday at the American Society of Hematology (ASH)
Annual Meeting in Atlanta, Georgia. Study results demonstrate that
omacetaxine, down-regulating the key protein Mcl-1, had a direct
anticancer effect on leukemic stem cells that was not exhibited by
the tyrosine kinase inhibitor imatinib. The poster presentation was
authored by Dr. Shaoguang Li and colleagues from the Jackson
Laboratory in Maine, USA, as well as ChemGenex scientists. The
authors reported that omacetaxine reduced the number of leukemic
stem cells in the bone marrow by more than 80% in an animal model
of CML (mice with BCR-ABL-induced CML disease). In contrast, the
tyrosine kinase inhibitor imatinib mesylate (Gleevec�) did not
reduce the number of leukemic stem cells in the bone marrow.
Previous research by Dr. Li and his colleagues found that the
second generation tyrosine kinase inhibitor dasatinib (Sprycel�)
did not eradicate CML stem cells in the same model system (Hu et
al., 2006). Consistent with the killing of CML stem cells, the
authors reported that omacetaxine provided a significant survival
benefit to mice with two different types of leukemia;
BCR-ABL-induced CML and B cell acute lymphoblastic leukemia
(B-ALL). Scientists now believe that some cancers arise from a
small number of aberrant cells that, like adult stem cells, have
the ability to self-renew and differentiate into multiple cell
types. These cells often persist in cancer patients in low numbers
even following therapy, and can cause disease relapse. Therapies
that effectively kill cancer stem cells as well as differentiated
cancer cells may thus hold promise for improving the treatment of
cancer and increasing survival from the disease. The authors also
reported that omacetaxine inhibited cell proliferation and markedly
reduced the expression of the anti-apoptotic protein Mcl-1 in
leukemic cell lines. Mcl-1 is a key target protein in several types
of leukemias and other cancers, and is believed to be one of the
major targets through which omacetaxine causes clinical responses.
�Following-on from the clinical data presented over the weekend, we
are very pleased to be able to further articulate the underlying
biology of omacetaxine�s activity,� said Dr. Greg Collier,
ChemGenex�s Managing Director and Chief Executive Officer. �We can
now report that Mcl-1 is down-regulated by omacetaxine in CML, and
that in an animal model the drug acts directly on leukemic stem
cells in the bone marrow. These data suggest the potential of
omacetaxine to be utilized across a range of leukemias, and support
clinical application beyond CML, as well as the potential to extend
disease-free survival in this disease.� Dr. Collier will host an
investor conference call on Thursday, December 13 at 9:30am
Australian Eastern Daylight Time (Wednesday, December 12 in the USA
and Europe) to discuss the clinical results presented at ASH.
ChemGenex Conference Call Details Telephone Dial-in Numbers:
Australia: � � 1800 701 269 USA: 1866 242 1388 Guest PIN: 27707144
Dial-in numbers for other locations can be obtained by emailing
santoniou@bplifescience.com. Q&A Session At the completion of
his presentation Dr. Collier will invite participants to ask
questions. Instructions for asking questions will be given by the
operator prior to the Q&A session. Conference Call Timing
Australian Eastern Daylight Time � 9:30am � Thursday, December 13
US Pacific Time 2:30pm Wednesday, December 12 US Eastern Time
5:30pm Wednesday, December 12 Central European Time 11:30pm
Wednesday, December 12 If you are unable to participate in the live
session, please contact santoniou@bplifescience.com for dial-in
details to hear the conference call and Q&A session replayed.
Publication details Hu, Y. et al. (2006). Targeting multiple kinase
pathways in leukemic progenitors and stem cells is essential for
improved treatment of Ph+ leukemia in mice. PNAS. 103 (45),
16870-16875. Ceflatonin� is a registered trade-mark of ChemGenex
Pharmaceuticals Limited. Gleevec�/Glivec� is a registered
trade-mark of Novartis AG. Sprycel� is a registered trademark of
the Bristol-Myers Squibb Company. About ChemGenex Pharmaceuticals
Limited (http://www.chemgenex.com) ChemGenex Pharmaceuticals is a
pharmaceutical development company dedicated to improving the lives
of patients by developing personalized oncology medicines.
ChemGenex harnesses the power of genomics both to discover novel
targets and drug compounds, and in clinical trials to develop more
individualized treatment outcomes. ChemGenex�s lead compound,
omacetaxine mepesuccinate (formerly known as Ceflatonin�), is
currently in phase 2/3 clinical trials for chronic myeloid leukemia
(CML) where it has demonstrated single-agent efficacy against
drug-resistant disease, as well as synergistic activity with the
leading marketed compound. ChemGenex has a second anticancer
compound, amonafide dihydrochloride (formerly known as Quinamed�)
which is in phase 2 clinical development for various solid cancers,
and a portfolio of assets in pre-clinical development. ChemGenex
currently trades on the Australian Stock Exchange under the symbol
"CXS" and on NASDAQ under the symbol "CXSP". Safe Harbor Statement
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