BUFFALO, NY--(Marketwired - Feb 9, 2016) - Cleveland BioLabs, Inc. (NASDAQ: CBLI) and Roswell Park Cancer Institute (RPCI) today announced the publication of studies elucidating immunotherapeutic mechanisms through which entolimod suppresses metastasis. The data were published 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, based on studies conducted by scientists at RPCI and CBLI.

Entolimod is a pharmacologically optimized flagellin derivative and Toll-like receptor 5 (TLR5) agonist currently under development by CBLI as both a medical radiation countermeasure and an oncology immunotherapy. Previous studies showed that treatment with entolimod led to extensive mobilization of innate and adaptive immunity to the liver, and significantly prolonged survival in experimental models of liver metastasis. 

The studies presented in the PNAS publication reveal the cascade of cell-signaling events that are triggered by entolimod activation of the TLR5 pathway in the liver. The data also define the functional roles of natural killer (NK), dendritic, and CD8+ T cells in the drug's activity as a suppressor of metastasis. The studies demonstrate that entolimod administration induces chemokines that attract NK cells to the liver via a CXCR3-dependent mechanism. Once in the liver, NK cells, which are components of the innate immune system, engage an adaptive antitumor immune response through dendritic cell activation. This NK-to-dendritic cell interaction generates CD8+ T-cell-dependent antitumor memory that results in tumor rejection upon animal re-challenge with tumor. Importantly, localized antitumor effects in the liver combine with systemic responses that enable suppression of metastasis to the lung.

NK cells are effectors of innate immunity that provide an early host response against viruses, bacteria and tumors and play a pivotal role in bridging the innate and adaptive arms of the immune response. CXCR3 is a chemokine receptor that is highly expressed on both NK and effector T cells and plays an important role in cell trafficking to tissues. CD8+ T cells are lymphocytes of the adaptive immune system that destroy virus-infected cells and tumor cells, and are also implicated in transplant rejection. T cells can persist long after an initial exposure, quickly expanding to large numbers upon rechallenge, thus providing protective immunological "memory" against viruses or tumors.

Andrei Gudkov, Ph.D., D.Sc., Chief Scientific Officer of CBLI, Senior Vice President of Basic Science at RPCI, and a corresponding author of the study, said, "These observations have elucidated the mechanisms of entolimod's immunotherapeutic activity. These data define the drug as an organ-specific, immunoadjuvant characterized by mobilization of innate and adaptive branches of immunity to the liver. Moreover, this work suggests that entolimod enables vaccination against tumor cells residing in the liver through a mechanism that does not require identification of a particular tumor antigen."

Langdon Miller, M.D., President and Chief Medical Officer of CBLI, noted, "Together with the established safety profile of entolimod, the mechanistic findings of the work reported here support the clinical evaluation of entolimod in patients with a high risk of liver metastases."

The liver is a common site of cancer metastases for many cancers, including cancers of the gastrointestinal tract. CBLI recently announced the start of dosing in a single-blinded, randomized, placebo-controlled clinical study of the safety and tolerability of entolimod as a neo-adjuvant therapy in treatment-naïve patients with primary colorectal cancer. The study is being conducted in the Russian Federation. The primary objective of the study is to determine the optimal dose and dosing regimen for treatment of these patients with entolimod prior to surgery. Secondary objectives include evaluation of pharmacodynamic parameters, including immune response to single or double administrations of entolimod at varying dose levels. 

This work was supported by National Institutes of Health grants (R01GM095874, R01AI080446, R01CA140622 and R01CA172105), a grant from the Department of Defense (W81XWH-15-1-0081), funding from Cleveland BioLabs, Inc., and grants from the Roswell Park Alliance Foundation.

The publication can be found online at: http://www.pnas.org/content/early/2016/01/27/1521359113.full.pdf

About Cleveland BioLabs, Inc.
Cleveland BioLabs, Inc. is an innovative biopharmaceutical company developing novel approaches to activate the immune system and address serious medical needs. The company's proprietary platform of Toll-like immune receptor activators has applications in radiation mitigation, oncology immunotherapy, and vaccines. The company's most advanced product candidate is entolimod, which is being developed for a biodefense indication and as an immunotherapy for oncology and other indications. The company conducts business in the United States and in the Russian Federation through a wholly-owned subsidiary, BioLab 612, LLC and a joint venture with OJSC Rusnano, Panacela Labs, Inc. The company maintains strategic relationships with the Cleveland Clinic and Roswell Park Cancer 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. Founded in 1898, RPCI is 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 www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or email askrpci@roswellpark.org. Follow Roswell Park on Facebook and Twitter.

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 do not relate strictly to historical or current facts. Words and phrases such as "potential," "may," "future," "will," "plan," "anticipate," "believe," "intend" and similar expressions are intended to identify forward-looking statements. These statements include, but are not limited to, statements regarding the company's future financial position, business strategy, new products, budgets, liquidity, cash flows, projected costs, regulatory approvals or the impact of any laws or regulations applicable to the company, and plans and objectives of management for future operations. 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 risks inherent in the early stages of drug development and in conducting clinical trials; the company's plans and expectations with respect to future clinical trials and commercial scale-up activities; the company's ability to attract collaborators with development, regulatory and commercialization expertise and the financial risks related to those relationships; the company's ability to comply with its obligations under license agreements; the company's inability to obtain regulatory approval in a timely manner or at all; the commercialization of the company's product candidates, if approved; the company's plans to research, develop and commercialize its product candidates; future agreements with third parties in connection with the commercialization of any approved product; the size and growth potential of the markets for the company's product candidates, and its ability to serve those markets; the rate and degree of market acceptance of the company's product candidates; 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; regulatory developments in the United States and foreign countries; the performance of the company's third-party suppliers and manufacturers; and the success of competing therapies that are or may become available. 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.

Cleveland BioLabs, Inc.
Rachel Levine, Vice President, Investor Relations
T: 917-375-2935
E: rlevine@cbiolabs.com

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