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Onconova Therapeutics Announces Presentation of Nonclinical Data on Lead Compound ON 01910.Na and New Jak 2/Bcr-abl Inhibitors at AACR.

NEWTOWN, Pa. -- Onconova Therapeutics, Inc. today announced the presentation of four scientific studies relating to its lead anticancer drug anticancer drug

see antineoplastic.

anticancer drug Chemotherapeutic, see there
 ON 01910.Na and a new class of anticancer compounds at the Annual Meeting of the American Association for Cancer Research Wikipedia is not the place for advertisement or self-advertising.

The American Association for Cancer Research (AACR) is an organization based in Philadelphia, Pennsylvania, that focuses on all aspects of cancer research including basic, clinical and translational
 (AACR AACR American Association for Cancer Research
AACR Anglo-American Cataloging Rules
AACR Australasian Association of Cancer Registries
AACR African Armed Conflicts Resolved
), being held April 18-22, 2009 in Denver.

The data will be presented in one oral presentation and three posters on Monday and Tuesday during the AACR meeting.

The oral presentation and two posters will focus on ON 01910.Na, a novel, targeted, small-molecule anti-cancer compound undergoing clinical trials at several major centers in the USA and abroad. In clinical studies ON 01910.Na has shown broad-spectrum anti-tumor activity against both solid tumors and hematological malignancies and in nonclinical studies has demonstrated remarkable synergistic activity when combined with several classes of conventional chemotherapeutic agents.

Extensive Phase I data from more than 125 patients with solid tumors recruited in eight different clinical protocols is now available and indicate a good tolerability profile. Onconova is conducting additional single agent trials and new combination therapy clinical trials of ON 01910.Na with leading investigators at major oncology clinical centers in the USA.

The third poster introduces a new Onconova drug candidate, ON 044580, which is a dual JAK2/BCR-ABL kinase inhibitor which has therapeutic potential to treat JAK2V617F positive myeloproliferative disorders (MPDs), other MPDs and imatinib- resistant chronic myeloid leukemia myeloid leukemia
n.
See myelogenous leukemia.
 (CML 1. CML - A query language.

["Towards a Knowledge Description Language", A. Borgida et al, in On Knowledge Base Management Systems, J. Mylopoulos et al eds, Springer 1986].
2. CML - Concurrent ML.
) and may provide an option for patients who develop resistance to current therapies.

AACR Presentations Relating to Onconova Compounds:

Tuesday, April 21, 11:55 AM -12:10 PM
Room 505-507, Colorado Convention Center
Session Title: Mechanisms of Drugs Targeting Cell Cycle Controls
[TABLE OMITTED]


Dr. Oussenko will report assessment of DNA DNA: see nucleic acid.
DNA
 or deoxyribonucleic acid

One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes.
 damage checkpoints throughout the cell cycle and effects on signaling molecules signaling molecules

substances synthesized by cells for purposes of extracellular communication between cells.
 upstream of Cdc25C following treatment with ON 01910.Na. These results suggest that effects on DNA damage checkpoint pathways may be a part of ON 01910.Na's multi-targeted mode of action.

Tuesday, April 21, 8:00 AM -12:00 PM
Hall B-F, Denver Convention Center
Session Title: Conjugates and Other Targeted Approaches
Poster Section: 33
Poster Board Number: 28
[TABLE OMITTED]


This study aimed to determine activity of ON 01910.Na in CLL CLL
abbr.
chronic lymphocytic leukemia


CLL,
n.pr See leukemia, chronic lymphocytic.

CLL 1. Chronic lymphocytic leukemia 2. Cholesterol-lowering lipid
 and investigate the mechanism of action because ON 01910.Na is a multi-kinase inhibitor. ON 01910.Na has anti-tumor activity in solid tumor models and is currently undergoing clinical testing in other cancers. Results of this study show that over expression of the antiapoptotic protein Mcl-1 is a central mechanism of CLL cell survival, and ON 01910.Na decreased Mcl-1 protein expression in leukemic cells and this preceded the onset of apoptosis. This suggests that a reduction of Mcl-1 expression could play an important role in the antileukemic activity of ON 01910.Na. These results support the development of ON 01910.Na in CLL, and a clinical trial for this indication is being developed.
Tuesday, April 21, 1:00 PM - 5:00 PM
Hall B-F, Denver Convention Center
Session Title: Novel Agents 3
Poster Section: 37
Poster Board Number: 27
[TABLE OMITTED]


This study was designed to determine the efficacy of the novel clinical stage mitotic inhibitor ON 01910.Na in head and neck cancer (HNC (HNC Software Inc., San Diego, CA) A software company that specialized in products that detect credit card fraud, manage merchant risk, automate lending decisions and home valuations and manage retail inventories. Founded in 1986 by Robert Hecht-Nielsen and Todd W. ), and to elucidate gene expression-based predictors of efficacy, in comparison with approved therapeutic agents. These results show that ON 01910.Na is a highly effective mitotic inhibitor active in a broad panel of HNC cell lines, with potency equivalent or superior to approved agents. Expression analysis revealed that sensitive strains had over-expression of the cell cycle pathway (providing further evidence of mechanisms relevant in the action of ON 01910.Na in HNC).
Tuesday, April 21, 8:00 AM -12:00 PM
Hall B-F, Denver Convention Center
Session Title: Kinase Inhibitors 3
Poster Section: 36
Poster Board Number: 1
[TABLE OMITTED]


A specific JAK2 mutation has been observed in about 95% of patients with the myeloproliferative disorder polycythemia vera (PV), and 50% of those with both essential thrombocythemia (ET) and primary myelofibrosis Myelofibrosis Definition

Myelofibrosis is a rare disease of the bone marrow in which collagen builds up fibrous scar tissue inside the marrow cavity.
 (PMF PMF,
n.pr See proprioceptive neuromuscular facilitation.
). This mutation has also been found in patients with non-classic MPDs such as refractory anemia with ringed sideroblasts associated with thrombocytosis (RARS-T), chronic neutrophilic leukemia Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder that features a persistent neutrophilia in peripheral blood, myeloid hyperplasia in bone marrow, hepatosplenomegaly, and the absence of the Philadelphia chromosome or a BCR/ABL fusion gene.  (CNL CNL CityNightLine (German Rail)
CNL Cancel
CNL Clinical Nurse Leader
Cnl Colonel
CNL Center for Naval Leadership
CNL Compensated Neutron Log (oil industry) 
), atypical chronic myeloid leukemia (CML) and chronic myelomonocytic leukemia (CMML CMML Chronic Myelomonocytic Leukemia
CMML Continuous Media Markup Language
CMML Civilian Manpower Management Letter
) at incidences of 50%, 20%, 20% and 3%, respectively. JAK2V617F has been found to confer erythropoietin-independent growth of the mutant cells in vitro due to deregulation Deregulation

The reduction or elimination of government power in a particular industry, usually enacted to create more competition within the industry.

Notes:
Traditional areas that have been deregulated are the telephone and airline industries.
 of signaling pathways downstream of JAK2. These findings have opened new avenues for the diagnosis and classification of patients with these disorders, and identify a new molecular target for drug discovery. These study results identify ON 044580 as a first in class dual Jak2/Bcr-abl inhibitor. The results suggest that ON 044580 may have therapeutic potential to treat JAK2V617F positive MPDs and CML and provide an option for patients who develop resistance to current therapies such as imatinib and dasatinib.

About Onconova's Product-Pipeline

Onconova is developing therapeutic candidates directed at critical targets involved in signal transduction, cell-cycle and DNA repair. These candidates are derived from the Company's proprietary library of new chemical entities and non-ATP competitive chemotypes. In addition to ON 01910.Na, Onconova is also developing Ex-RAD[TM], an injectable and oral radioprotectant, and inhibitors of Cyclin D, JAK and Bcr-abl pathways. These compounds were invented by Dr. E. Premkumar Reddy Dr. E. Premkumar Reddy is a biologist.

He obtained his Ph. D. in molecular biology in 1971 from the Osmania University, Hyderabad, India. After post-doctoral training in the United States of America at the UCLA School of Medicine and the National Cancer Institute (NCI), he
 and colleagues at the Fels Institute and are exclusively licensed to Onconova Therapeutics, Inc.

About Onconova Therapeutics, Inc.

Onconova, based in Newtown, PA, and Lawrenceville, NJ, discovers and develops novel small molecule therapeutic agents for cancer, radiation protection and hematological hematological, hematologic

pertaining to or emanating from blood cells.


hematological tests
total and differential white cell counts, hematocrit estimation, erythrocyte count.
 disorders. Currently, the Company is conducting clinical trials at major centers in the USA and abroad. The novel chemical library platform is permitting identification of non-ATP competitive kinase inhibitors directed at validated and novel targets, and a new immunoconjugate technology (comprising potent active compounds and proprietary linkers) for arming monoclonal antibodies for cancer therapy. All of the Company's products and technologies are being developed internally.

For more information on Onconova Therapeutics, Inc., please visit www.onconova.com.

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Publication:Business Wire
Article Type:Clinical report
Date:Apr 21, 2009
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