Cleveland BioLabs, Roswell Park Announce Publication of Studies Defining Role of Liver in Activity of Entolimod (CBLB502)

Anticancer agent generates immune response that may help to control or prevent liver metastasis
Wednesday, May 1, 2013

Buffalo, NY – May 1, 2013 – Cleveland BioLabs, Inc. (NASDAQ:CBLI) and Roswell Park Cancer Institute (RPCI) today announced the publication of studies identifying the liver as a key mediator of Entolimod’s tissue-protective and anticancer activities in Proceedings of the National Academy of Sciences of the United States of America (PNAS), the official journal of the United States National Academy of Sciences.  The reported studies were conducted by scientists at Roswell Park Cancer Institute and Cleveland BioLabs (CBLI) in collaboration with researchers at Attagene, Inc. and the Gamaleya Research Institute for Epidemiology and Microbiology in Moscow.

Entolimod is a Toll-like receptor 5 (TLR5) agonist currently under development by CBLI as both a radiation countermeasure and a cancer agent.  Previous work showed that the biological effects of Entolimod stem from TLR5-mediated activation of NF-kB, a transcriptional regulator that induces multiple genes encoding tissue-protective factors, such as inhibitors of programmed cell death, scavengers of reactive oxygen species, and cytokines that promote cell proliferation and differentiation.  The current studies were aimed at defining the mechanism of systemic response to Entolimod at the molecular and cellular levels.  The results showed that the liver is a major primary target organ of Entolimod.  The specific responsiveness of one particular type of liver cell, the hepatocyte, distinguishes TLR5 from other TLRs and provides plausible explanation for superior pharmacological properties of Entolimod compared to agonists of other TLRs.

A novel technique called Factorial™, developed by Attagene, was utilized to define molecular signaling pathways modulated by Entolimod in the liver.  This technique made it possible to simultaneously monitor the activity of close to 50 inducible transcription factors in the liver of treated animals.  In addition to the NF-kB pathway, Entolimod treatment was found to activate several other pro-survival and immunoregulatory signaling pathways in hepatocytes, culminating in induction of secreted cytokines and recruitment of immune cells to the liver.  In several animal models tested, this led to suppression of tumor cell growth in the liver regardless of whether the tumor cells expressed TLR5.  These results expand the potential anticancer applications of Entolimod beyond treatment of TLR5-expressing primary tumors to include prevention and/or treatment of metastases to the liver, irrespective of the primary tumor’s TLR5 status.  The liver is among the most common metastatic sites for several different types of cancer.  Of particular importance, while Entolimod treatment induced changes in the liver microenvironment that counteracted tumor cell growth, it also made normal liver cells resistant to a form of cell death commonly involved in hepatotoxicity.  This finding suggests that Entolimod may offer a new approach for liver protection in a variety of clinical scenarios.

Finally, by showing that occlusion of hepatic blood circulation eliminated Entolimod-mediated radioprotection of the hematopoietic system, the reported work strongly suggests that exposure of liver cells to Entolimod is essential for the drug’s radioprotective and radiomitigating activity.  Therefore, factors secreted by responsive hepatocytes appear to be responsible, at least in part, for the ability of Entolimod to protect and stimulate regeneration of the hematopoietic system in irradiated animals.   

Andrei Gudkov, Ph.D., D.Sci., Chief Scientific Officer of Cleveland BioLabs, Senior Vice President of Basic Science at RPCI and corresponding author of the paper, commented: “Entolimod continues to pleasantly surprise us.  The studies reported in this publication represent the first comprehensive work on TLR5 signaling conducted in vivo.  They provide new mechanistic insight into the radioprotection, radiomitigation and anticancer activities of Entolimod, strengthening both our understanding of the drug’s ability to mitigate radiation damage to the hematopoietic system and the hypothesis behind an ongoing clinical study with the drug in advanced cancer patients at Roswell Park Cancer Institute.  Moreover, the previously unanticipated effects of Entolimod on hepatocytes and the liver microenvironment defined in this work suggest that prevention or treatment of liver metastases and protection of the liver from various types of cell stress are additional areas of prospective clinical application for Entolimod.”

Jean Viallet, M.D., Chief Development Officer at Cleveland BioLabs, stated, “The intense liver-directed immune response induced by Entolimod resulted in the prevention of liver metastases in several experimental models.  Several types of human cancer show a strong predilection to metastasize to the liver.  The clinical implications are exciting, and our team is already developing clinical trials to bring these new concepts to patients.”

The work reported in the publication was supported by National Institutes of Health Grants R01AI080446 and RC2AI087616 and by Cleveland BioLabs, Inc., as well as by the Defense Threat Reduction Agency of the U.S. Department of Defense under Contract HDTRA1-11-C-0008 (to Cleveland BioLabs, Inc.).

The PNAS publication can be found online at: http://www.pnas.org/content/early/2013/04/25/1222805110.abstract

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.

About Roswell Park Cancer Institute:

The mission of Roswell Park Cancer Institute (RPCI) is to understand, prevent and cure cancer. RPCI, founded in 1898, was one of the first cancer centers in the country to be named a National Cancer Institute-designated comprehensive cancer center and remains the only facility with this designation in Upstate New York. The Institute is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers; maintains affiliate sites; and is a partner in national and international collaborative programs. For more information, visit RPCI’s website at http://www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci@roswellpark.org.

This press release contains certain forward-looking information about Cleveland BioLabs that is intended to be covered by the safe harbor for "forward-looking statements" provided by the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. Words such as "expect(s)," "feel(s)," "believe(s)," "will," "may," "anticipate(s)" and similar expressions are intended to identify forward-looking statements. These statements include, but are not limited to, statements regarding our ability to successfully develop and commercialize our therapeutic products; our ability to expand our long-term business opportunities; the conduct and results of our various clinical trials; financial projections and estimates and their underlying assumptions; and future performance. All of such statements are subject to certain risks and uncertainties, many of which are difficult to predict and generally beyond the control of the Company, that could cause actual results to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. 

These factors include, among others, the Company’s failure to successfully and timely develop new products; the Company’s collaborative relationships and the financial risks related thereto; the Company’s ability to comply with its obligations under license agreements; the risks inherent in the early stages of drug development and in conducting clinical trials; the Company’s inability to obtain regulatory approval in a timely manner or at all; the Company’s history of operating losses and the potential for future losses, which may lead the Company to not be able to continue as a going concern; the Company’s need for substantial additional financing to meet its business objectives; the potential for the loss of funding from the Company’s R&D grants and contracts and its ability to win additional funding under such grants and contracts. Some of these factors could cause future results to materially differ from the recent results or those projected in forward-looking statements.  See also the “Risk Factors” and “Forward-Looking Statements” described in the Company’s periodic filings with the Securities and Exchange Commission.

Contacts:

Rachel Levine, Vice President, Investor Relations
Cleveland BioLabs, Inc.
T: (646) 284-9439
E: rlevine@cbiolabs.com

Annie Deck-Miller, Senior Media Relations Manager
Roswell Park Cancer Institute
T: (716) 845-8593
E: annie.deck-miller@roswellpark.org

Media Contact: 

Annie Deck-Miller, Senior Media Relations Manager
716-845-8593; annie.deck-miller@roswellpark.org