Cleveland BioLabs Announces Publication of Studies Identifying Biomarkers of CBLB502's Efficacy as a Radiation Countermeasure
Definition of Biomarkers Key to Animal Rule Development
BUFFALO, N.Y., Aug. 1, 2012 (GLOBE NEWSWIRE) -- Cleveland BioLabs, Inc. (Nasdaq:CBLI) today announced the online publication of studies identifying biomarkers of CBLB502's efficacy as a radiation countermeasure in the Journal of Pharmacology and Experimental Therapeutics, a leading peer-reviewed research journal in the field of pharmacology. The reported studies were conducted by scientists of Cleveland BioLabs in collaboration with researchers at the Armed Forces Radiobiology Research Institute and the F. Edward Hebert School of Medicine at the Uniformed Services University of the Health Sciences, and Roswell Park Cancer Institute.
CBLB502 is a Toll-like receptor 5 (TLR5) agonist currently under development as a radiation countermeasure. Development for this indication is guided by the U.S. Food and Drug Administration's (FDA) Animal Rule, one requirement of which is data or information on the kinetics and pharmacodynamics of the product or other relevant data that will allow projection of human efficacious doses from animal efficacy data.
The published work identified two cytokines, granulocyte
colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), as
biomarkers of CBLB502 efficacy that satisfy the conditions set by
the FDA for this aspect of the Animal Rule. Findings relevant to
these required conditions include: (i) for both G-CSF and IL-6,
induction by
CBLB502 was shown to be strictly drug target (TLR5)-dependent and
dependent on the dose of CBLB502 administered, (ii) G-CSF and IL-6
were strongly induced by CBLB502 within its efficacious dose range
in both non-irradiated and irradiated mammals, (iii) the identified
biomarkers were found to be critically important for the ability of
CBLB502 to rescue irradiated animals from death, and (iv) G-CSF and
IL-6 can be readily measured in humans using validated assays.
Notably, the majority of the reported studies were conducted in
non-human primates (NHP), the animal model of acute radiation
syndrome closest to humans.
Andrei Gudkov, Ph.D., D.Sci., Chief Scientific Officer of
Cleveland BioLabs, Senior Vice President of Basic Science at
Roswell Park Cancer Institute and corresponding author of the
paper, commented:
"Identification of biomarkers for CBLB502 represents a key step
along the critical development path for CBLB502 as a radiation
countermeasure. Our ability to define efficacy biomarkers for
CBLB502 reflects a greater understanding of the drug's mechanism of
action and builds a more solid platform for determination of the
human efficacious dose of CBLB502. Several publications have
highlighted the individual radioprotective effects of G-CSF and
IL-6. The ability of our drug to induce both of these cytokines
partially explains its potency as a radiation antidote."
Ann Hards, Ph.D., Executive Vice President of Regulatory Affairs and Quality Assurance for Cleveland BioLabs, stated, "Identification of efficacy biomarkers is one of the key elements of our strategy for accurately predicting the human efficacious doses of CBLB502, an important step in its development as a radiation countermeasure. We have submitted the results of the major experiments that formed the basis for this paper to the FDA, and as previously reported, have received concurrence from the agency that these biomarkers do play important roles in the mechanism of CBLB502-induced radioprotection."
The work reported in the publication was funded by the US Department of Defense (DoD) Defense Threat Reduction Agency; the US DoD Chemical Biological Medical Systems; the US Department of Health & Human Services Biomedical Advanced Research and Development Authority; and the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health.
"This publication is an indication of the success of an ongoing
collaboration between CBLI and the Armed Forces Radiobiology
Research Institute in developing new radiation countermeasures,"
added Dr.
Gudkov. "Sponsorship of these studies by government funding
agencies responsible for radiation countermeasure development
emphasizes the significance of biomarker identification to the
Animal Rule."
The Company recently announced survival results for its
randomized, blinded, placebo-controlled efficacy study of CBLB502
in 179 NHPs conducted under Good Laboratory Practice with elements
of Good Clinical Practice, as required by the FDA's Animal Rule.
This study demonstrated with a high degree of statistical
significance that a single dose of
CBLB502 given 25 hours after exposure of Rhesus macaques to a 70%
lethal dose of total body irradiation improved animal survival by
nearly three-fold compared to control. Dose-dependence of CBLB502's
efficacy was demonstrated with doses above the minimal efficacious
dose establishing a plateau at approximately 75% survival at 60
days after irradiation, as compared to 27.5% survival in the
placebo-treated group.
The Journal of Pharmacology and Experimental Therapeutics
publication may be found online at:
http://jpet.aspetjournals.org/content/early/recent
About Cleveland BioLabs, Inc.
Cleveland BioLabs, Inc. is a clinical-stage biotechnology company leveraging deep mechanistic understanding of the cell death process, apoptosis, to develop a robust pipeline of compounds primarily focused on oncology applications and mitigation of radiation injury. The Company's lead compound is being developed as both a radiation countermeasure and a cancer treatment. The Company has two operating subsidiaries, Incuron, LLC, and Panacela Labs, Inc., and strategic relationships with the Cleveland Clinic, Roswell Park Cancer Institute, the Children's Cancer Institute Australia and the Armed Forces Radiobiology Research Institute. To learn more about Cleveland BioLabs, Inc., please visit the Company's website at http://www.cbiolabs.com.
The Cleveland BioLabs, Inc. logo is available at
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This press release contains forward-looking statements within
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1995.
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See also the "Risk Factors" and "Forward-Looking Statements"
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Posted: August 2012
