Study Shows Coronado Biosciences' Bcl-2 Inhibitor, Apogossypol, Is More Efficacious, Less Toxic Than Gossypol In Animal Models

Main Category: Cancer / Oncology
Also Included In: Clinical Trials / Drug Trials;  Pharma Industry / Biotech Industry
Article Date: 29 Jan 2008 - 0:00 PDT

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Coronado Biosciences Inc. announced the publication of data demonstrating that the Bcl-2 inhibitor, Apogossypol, effectively killed a variety of cancer cells in vitro while demonstrating less toxicity than Gossypol in vivo in mice.

Published online in Blood (Jan. 17, DOI 10.1182/blood-2007-09-113647) by the Burnham Institute's president and CEO, John Reed, M.D., Ph.D., and collaborators, the paper summarized study findings demonstrating that mice treated with Apogossypol experienced less hepatotoxicity and gastrointestinal toxicity than those treated with Gossypol. The results support Coronado Biosciences' continued development of its lead candidate, CNDO103, as a cancer treatment.

"Apogossypol was rationally designed to eliminate the toxicities seen with Gossypol," said Reed. "This study provides strong evidence that Apogossypol is better tolerated by the animals without a compromise in potency in vitro. We hope these preclinical results translate to humans. If they do, Apogossypol can play a role in the treatment of many types of cancers."

Maurizio Pellecchia, Ph.D., a professor at the Burnham Institute of Medical Research, developed Apogossypol using NMR guided rational drug design. "Based on our molecular modeling, we predicted that Apogossypol would be equally potent in killing cancer cells but safer than the parent compound Gossypol," said Pellecchia. "It is gratifying that the exhaustive set of experiments reported in the paper support our predictions."

RJ Tesi, M.D., president and CEO of Coronado Biosciences, added: "The data reinforce our decision to push rapidly to the clinic with Apogossypol. We plan to perform IND-enabling preclinical studies for Apogossypol, CNDO103, in the first half of the year. If the toxicity profile in animals approximates what was shown in this work, we plan to file an IND in late 2008."

About CNDO103

CNDO103 is Apogossypol, a rationally designed derivative of Gossypol. Apogossypol targets the Bcl-2 family pro-survival proteins class -- inhibiting five of the six members of the Bcl-2 family. In preclinical studies, oral Apogossypol appears to have improved physiologic and pharmaceutical properties compared to other drugs in the same class. Apogossypol shows activity against both hematologic and epithelial tumors.

The Bcl-2 family of proteins control naturally occurring, programmed cell death called apoptosis. In cancer, increased levels of the Bcl-2 pro-survival proteins lead to abnormal apoptosis, uncontrolled cell growth and the development of resistance to standard therapies. The inhibition of Bcl-2 pro-survival proteins may normalize apoptosis, cause tumor shrinkage and make resistant tumors sensitive to standard treatments.

Burnham Institute for Medical Research

Burnham Institute for Medical Research conducts world-class collaborative research dedicated to finding cures for human disease, improving quality of life, and thus creating a legacy for its employees, donors, and community. The Institute is headquartered in La Jolla, Calif., where it was established as a nonprofit, public benefit corporation in 1976 and is now home to four centers: a National Cancer Institute-designated Cancer Center; the Del E. Webb Center for Neurosciences, Aging and Stem Cell Research; the Infectious and Inflammatory Disease Center and the Sanford Children's Health Research Center. In 2006, Burnham established a center for bionanotechnology research at the University of California, Santa Barbara. Burnham is currently establishing a campus at Lake Nona in Orlando, Florida that will focus on diabetes and obesity research and will expand the Institute's drug discovery capabilities. Today, Burnham employs more than 820 people and ranks consistently among the world's top 25 organizations for its research impact and among the top four research institutes nationally for NIH grant funding. For additional information about Burnham and to learn about ways to support its research, visit http://www.burnham.org.

About Coronado Biosciences Inc.

Coronado Biosciences Inc. is a clinical stage biopharmaceutical company that is focused on changing cancer care by improving current therapies. The company's pipeline consists of both clinical and preclinical compounds that will offer unique options to physicians and patients. By mitigating scientific, development and financial risk, the company increases the likelihood of developing marketable drugs with the potential for broad indications.

Coronado Biosciences Inc.
http://www.coronadobiosciences.com

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