Public Release:  Onconova Therapeutics presents new data demonstrating radioprotection by Ex-RAD at RRS annual meeting

Orally administered Ex-RAD (ON 01210.Na) is radioprotective in pre-exposure prophylaxis and post-exposure mitigation animal models

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Newtown, PA, September 27, 2010 - Onconova Therapeutics, Inc. is presenting new data in five posters and an oral presentation this week summarizing several studies with the company's radioprotectant Ex-RAD® at the 56th Annual Meeting of the Radiation Research Society (RRS), September 25-29 in Maui, Hawaii. In vivo studies show that Ex-RAD®, upon oral administration, produced a significant increase in survival versus placebo-treated groups in mice exposed to lethal whole body irradiation (WBI), for both prophylactic pre-treatment and mitigation post-treatment. Ex-RAD® is the only known oral radioprotectant that has shown such activity in animal model systems.

Collectively, these presentations demonstrate the ability of Ex-RAD® to provide radioprotective benefit by injection and oral delivery, an in-depth understanding of the kinetics and metabolism of Ex-RAD®, and radioprotective benefit to human bone marrow, as well as the gastrointestinal and hematopoietic systems in mice.

Onconova, a biopharmaceutical company developing novel chemical entities to treat cancer and protect normal cells, is developing Ex-RAD®, a novel radioprotectant with potential utility in bio-defense or bio-terrorism, which could prove useful as a prophylactic agent for first-responder protection from the harmful effects of radiation from nuclear accidents or weapons of mass destruction (WMD).

These presentations result from an on-going Onconova collaboration among investigators at a number of institutions: AFRRI, (The Armed Forces Radiobiology Research Institute) a part of the Uniformed Services University of the Health Sciences (USUHS); Georgetown University, Department of Biochemistry and Molecular & Cellular Biology; Long Island University, Arnold & Marie Schwartz College of Pharmacy; and the Department of Oncological Sciences, Mt. Sinai School of Medicine.

Summary of Oral Ex-RAD® Findings

The results from a prophylactic radioprotection study in mice demonstrated that Ex-RAD® dosed orally or by injection prior to lethal whole body irradiation (WBI) produced significant enhancement in survival for both Ex-RAD® treated groups versus placebo.

Results from the radiomitigation experiment (where the drug is administered after exposure to lethal radiation), using both injection and oral methods of delivery demonstrated that Ex-RAD® treated animals had comparably high rates of survival in both groups.

Hence, oral Ex-RAD® was found to be effective in both prophylactic pre-treatment and mitigation post-treatment settings.

"Years of collaborative work are resulting in great progress with Ex-RAD® in the laboratory and the clinic and Ex-RAD® is the focus of several posters and a key presentation within the RSS scientific and educational track," said Manoj Maniar, PhD, Senior Vice President for Product Development of Onconova. "We are very excited to see the acceleration and new developments within radioprotection, specifically in oral prophylaxis and treatment. Ex-RAD® holds a unique position among developing products with the potential to benefit people exposed to whole body radiation."

Onconova oral presentation and poster sessions on Ex-RAD® at the Radiation Research Society meeting:

Oral Presentation

WEDNESDAY, SEPTEMBER 29, 2010

  • No. MS701 (Mini-Symposium Presentation, 10:15 AM-12:15 PM) -- Radioprotection and Radiomitigation Properties of Ex-RAD® Upon Oral Administration Manoj Maniar1, Ramesh Kumar1, Bo-Hyun Moon2, David Taft3, Kamal Datta2; 1Onconova Therapeutics, Inc., 2Georgetown University, Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, 3Long Island University, Arnold & Marie Schwartz College of Pharmacy

Poster Sessions - Radiation Protection - Protection / Mitigators / Treatment

SUNDAY, SEPTEMBER 26, 2:00 pm-2:45 pm, 2010, Haleakala Foyer

  • PS.1.56 -- Radioprotection and Radiomitigation Properties of Ex-RAD® Upon Oral Administration Manoj Maniar1, Ramesh Kumar1, Bo-Hyun Moon2, David Taft3, Kamal Datta2; 1Onconova Therapeutics, Inc., 2Georgetown University, Department of Biochemistry and Molecular & Cellular Biology and Lombardi Comprehensive Cancer Center, 3Long Island University, Arnold & Marie Schwartz College of Pharmacy

  • PS1.10--Recovery from radiation-induced hematopoietic and gastrointestinal sub-syndromes by Ex-RAD™ in murine model, Sanchita P. Ghosh1, Shilpa Kulkarni1, Michael W. Perkins1, Kevin Hieber1, Ethery Amari1, Kristen Gambles1, Manoj M. Maniar2, Thomas Seed1, and K. Sree Kumar1; 1Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, 2Onconova Therapeutics Inc.

  • PS1.73--Radioprotection of human bone marrow by ON 01210.Na (Ex-RAD ®) through AKT-mediated signaling pathway Anthony D. Kang1,2, Stephen C.Cosenza1,3, Ramana Reddy1,3, E. Premkumar Reddy1,3 1Fels Institute for Cancer Research and Molecular Biologyand 2Armed Forces Radiobiology Research Institute, 3Department of Oncological Sciences, Mt. Sinai School of Medicine

Poster Sessions - Experimental Therapeutics and Translational Research

WEDNESDAY, SEPTEMBER 29, 5:30 PM-6:15 PM, 2010 Haleakala Foyer

  • PS7.64 --Disposition of Ex-RAD® (ON 01210.Na), a new radioprotectant, in the isolated perfused rat liver model; Chen Ren1, Mitalee Tamhane2, David Taft2, Manoj Maniar1, 1Onconova Therapeutics, Inc., 2Long Island University

  • PS7.20--Metabolic disposition of Ex-RAD® (ON 01210.Na), a novel radioprotectant Chen Ren1, Mitalee Tamhane2, Glenn Fegley1, David Taft2, Manoj Maniar1; 1Onconova Therapeutics, Inc., 2Long Island University, Brooklyn, NY

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About Ex-RAD®

Ex-RAD® is a novel radiation protection drug developed in collaboration with the U.S. Department of Defense to protect against (when given pre-exposure) and provide treatment for (when given post-exposure) lethal radiation in models of tissue and whole body radiation injury. Unlike most radiation protectors, Ex-RAD® is not a free-radical scavenger, chelator or cell cycle arrestor - instead, Ex-RAD® accesses a novel mechanism for radiation protection involving intracellular signaling, damage sensing, and DNA repair pathways. Ex-RAD-treated cells sustain less DNA damage upon exposure to irradiation.

Two Phase I safety trials of Ex-RAD® have been completed in healthy human volunteers. The development of Ex-RAD® is advancing according to the FDA Animal Rule, under which approval is based upon establishing safety in human volunteers coupled with demonstration of efficacy in well-characterized animal models.

About Onconova Therapeutics, Inc.

Onconova, based in Newtown, PA and Princeton, NJ, discovers and develops novel small molecule therapeutics targeting signal transduction, cell-cycle regulation, and DNA repair. Onconova has a novel discovery platform focusing on non-ATP kinase inhibitors directed at validated and novel targets, and the company is also exploring a new immunoconjugate technology (comprising potent active compounds and proprietary linkers) for arming monoclonal antibodies for cancer therapy. These products, technologies and candidates are derived internally from a proprietary library of new chemical entities and non-ATP competitive chemotypes. In addition to Ex-RAD®, Onconova is also developing ESTYBON™ (ON 01910.Na, in Phase 3), an injectable and oral anti-cancer agent, as well as inhibitors of Plk2, ALK, CDK, JAK, and Bcr-Abl pathways. Currently, Onconova is conducting clinical trials at major centers in the USA and abroad for three product candidates. For additional information, please visit http://www.onconova.com.

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