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