SOURCE: Cleveland BioLabs, Inc.

December 29, 2008 08:00 ET

Cleveland BioLabs Reports Advances in Curaxin Anticancer Program

Proof of Safety and Activity Demonstrated in Phase II Curaxin CBLC102 Trial Establishes Path to Clinic for Next Generation Lead Molecule Curaxin CBLC137; New Mechanistic Discoveries Enable Optimal Design of Treatment Regimens and Potential Combination Therapies

BUFFALO, NY--(Marketwire - December 29, 2008) - Cleveland BioLabs, Inc. (NASDAQ: CBLI) today announced several advances in the development of Curaxins, the leading class of drug candidates in the Company's anticancer drug discovery program.

Curaxins are synthetic small molecules designed to simultaneously target major stress response pathways that are frequently deregulated in cancer. Specifically, Curaxins cause powerful activation of tumor suppressor protein p53 (commonly inactive in cancer) and inhibition of pro-survival NF-kB signaling (constitutively active in the majority of tumors), thus successfully combining mechanistic properties of several existing anticancer drugs.

The founding molecule in the Curaxin program, CBLC102, was a previously known anti-malarial drug, quinacrine (Gurova et al., PNAS, 2005). Its record of safe use in humans as an anti-infective presented CBLI with an early opportunity to launch a Phase II clinical trial exploring the potential anticancer activity of molecules with this mechanism of action.

CBLI launched a Phase II study with CBLC102 in January 2007 to provide proof of safety and of anti-neoplastic activity in cancer patients and establish a foundation for clinical trials of CBLI's new proprietary Curaxin molecules, which have been designed and optimized for maximum anticancer effects, as well as for additional treatment regimens based on ongoing research into the precise molecular mechanisms of action of Curaxins.

Thirty-one patients were enrolled in a Phase II study of CBLC102 as a monotherapy in late stage, hormone-refractory taxane-resistant prostate cancer. All patients had previously received hormonal treatment for advanced prostate cancer and 28 of the 31 had also previously received chemotherapy. One patient had a partial response, while 50% of the patients exhibited a decrease or stabilization in PSA velocity, a measure of the speed of prostate cancer progression. CBLC102 was well tolerated and there were no serious adverse events attributed to the drug.

Michael Kurman, MD, clinical oncologist and Chief Medical Officer of CBLI, stated, "We are satisfied with the outcome of this trial, which demonstrated indications of activity and a remarkable safety profile in one of the most difficult groups of cancer patients. While clinical evidence indicates several opportunities for extending development of CBLC102 into other cancer types, dose escalation or use in combination with existing therapies, the rapid and fundamental advancement of CBLI's new generation of more powerful, proprietary Curaxin molecules with similar mechanisms of action justifies moving forward with the lead compound from this group for future clinical study."

CBLI has successfully completed a comprehensive hit-to-lead optimization program directed towards development of new proprietary Curaxin molecules simultaneously targeting p53 and NF-kB. Working in partnership with ChemBridge Corporation, a chemical libraries manufacturer and CBLI co-founder, the Company has developed CBLC137; which is a drug candidate with proprietary composition of matter intellectual property protection belonging to CBLI's next generation of highly improved Curaxins.

CBLC137 has demonstrated reliable anti-tumor effects in animal models of colon, breast, renal and prostate cancers. CBLC137 has favorable pharmacological characteristics, is suitable for oral administration and demonstrates a complete lack of genotoxicity. It shares all of the positive aspects of CBLC102, but significantly exceeds the former compound's activity and efficacy in preclinical tumor models. CBLC137 is currently undergoing manufacturing and preclinical toxicology studies in preparation for clinic trials in early 2010.

Another significant milestone in the Curaxin program was a recently achieved breakthrough in deciphering the finer details of the mechanism of action of these compounds. Successful identification of the exact cellular moiety that binds to Curaxins has provided a mechanistic explanation for the unprecedented ability of these compounds to simultaneously target several signal transduction pathways.

Andrei Gudkov, Ph.D., D. Sci., CBLI's Chief Scientific Officer and Senior Vice President of Basic Science at Roswell Park Cancer Institute, commented, "This new mechanistic knowledge enabled us to discover additional advantages of Curaxins and to rationally design treatment regimens and drug combinations, which have since been validated in experimental models. In addition, this understanding further strengthens our intellectual property position for this exciting class of principally new anticancer drugs." Specific details regarding CBLI's enhanced understanding of Curaxins' mechanisms of action have been included in a new patent application and will be described in a publication currently in preparation.

While CBLI is focusing immediate clinical development efforts on next generation compound CBLC137, additional potential uses for CBLC102 will be explored in conjunction with CBLI's strategic partners at Roswell Park Cancer Institute. The indications of activity and remarkable safety demonstrated in the CBLC102 Phase II trial, in conjunction with new mechanistic discoveries, point to additional potential treatment paradigms including combination therapies with existing drugs or prospective use as a cancer prevention agent.

James Marshall, Ph.D., Senior Vice President for Cancer Prevention and Population Sciences at Roswell Park Cancer Institute, noted, "The fact that CBLC102 and other Curaxins simultaneously target the most fundamental pathways underlying malignant transformation in a non-genotoxic manner opens a unique and exciting opportunity to consider these agents for cancer prevention. We are prepared to initiate a prevention trial of CBLC102 in patients with precancerous lesions in the colon and to consider similar directions in a number of other frequently observed tumor types such as prostate cancer. We are especially interested in the potential of CBLC102 to prevent or delay the transformation of pre-malignant lesions to cancer." Dr. Marshall is an internationally recognized expert in cancer prevention currently overseeing a multi-million dollar, inter-institutional cancer prevention program funded by the National Institutes of Health (NIH).

Michael Fonstein, Ph.D., President and Chief Executive Officer of Cleveland BioLabs, concluded: "We are very excited by the progress in our Curaxin program. Our Phase II study with CBLC102 has established proof of principle for a novel approach to killing tumors without the toxic effects of most existing cancer therapies. With this in hand, as well as a deeper understanding of Curaxins' mechanisms of action, we can move aggressively ahead with CBLC137, our more potent next generation lead molecule, and explore potential applications for CBLC102 in combination with existing drugs or as a cancer prevention agent with our strategic partners at Roswell Park."

About Cleveland BioLabs, Inc.

Cleveland BioLabs, Inc. is a drug discovery and development company leveraging its proprietary discoveries around programmed cell death to develop treatments for cancer and protection of normal tissues from exposure to radiation and other stresses. The Company has strategic partnerships with the Cleveland Clinic, Roswell Park Cancer Institute, ChemBridge Corporation 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.

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements reflect management's current expectations, as of the date of this press release, and involve certain risks and uncertainties. The Company's actual results could differ materially from those anticipated in these forward-looking statements as a result of various factors. Some of the factors that could cause future results to materially differ from the recent results or those projected in forward-looking statements include the "Risk Factors" described in the Company's periodic filings with the Securities and Exchange Commission.

Contact Information

  • Contact:
    Rachel Levine
    Director Corporate Development & Communications
    Cleveland BioLabs, Inc.
    T: (646) 284-9439
    E: rlevine@cbiolabs.com