Noble Financial BOCEMb 2012 Equity Conference January 17,...
Transcript of Noble Financial BOCEMb 2012 Equity Conference January 17,...
Noble Financial BOCEMb 2012 Equity Conference
January 17, 2012
This presentation includes forward-looking statements and predictions,
including statements about potential revenue-bearing transactions, the
market potential of CBLI’s technologies and product candidates, and the
potential value of pipeline products. These statements represent the
Company’s judgment as of the date of this presentation and are subject to
risks and uncertainties that could cause actual results of events to differ
materially from those expressed in such forward-looking statements. In
particular, CBLI faces risks and uncertainties that it may not be able to
sustain its business model, that revenues may be lower or expenses higher
than projected, that product sales may not increase, that development of
product candidates in the Company’s pipeline may not succeed or that
commercial transactions may not go forward as planned.
Safe-Harbor
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• Broad pipeline of drug candidates with multiple applications
• Accelerated commercialization through biodefense
• Open IND for oncology trials
• Strategic partnerships with Cleveland Clinic and Roswell Park Cancer Institute
• Track record of non-dilutive grants and contracts (~$100M, including $30M conditional purchase for CBLB502)
• Patents issued in US, Europe and Asia
Investment Highlights
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Product Pipeline
Product Research Pre-
clinical Ph I Ph II Ph III
CBLB502 Radioprotectant
(biodefense)
Direct anticancer
Supportive care
in oncology
CBLC102 Liver cancer
CBLC137 Broad anticancer
Cancer prophylaxis
CBLB612
Hematopoietic
SC* induction
& mobilization
File
BLA
*HSC: hematopoietic stem cells
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History, Partners, Joint Ventures
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•Protectan CBLB502•Biodefense•Oncology•Ischemia
•Protectan CBLB612•HP stem cells
•Curaxins
•Mobilan•Revercom•Antimycon•Arkil•Xenomycin
Clever drugs
2003
2007
2010
2011
Basic Proprietary Concepts Behind CBLI’s Drugs
organism
Apoptosis
TumorNormal tissues
radiation
Imitating tumor antiapoptoticmechanisms: inhibition of p53
(Pifithrins) and activation of NF-kB (Protectans)
• Komarov et al., 1999. Science 285, 1733 • Burdelya et al., 2008. Science 320: 226
Necrosis, senescence, mitotic catastrophe
p53
NF-kB
bone marrow
lymphoid organs
small intestine
hair follicles
Restoring apoptosis in tumor cells by simultaneous activation of p53 and
inhibition of NF-kB (Curaxins)
• Gasparian et al., 2011. ScienceTransl Med 3(95): 95ra74
Understanding tumor mechanisms leads to new innovative approaches to cancer treatment and
normal tissue protection 6
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CBLB502 Radiation Countermeasure
Supportive Care against cancer therapy side effects Immunotherapy against cancer
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Radiation Countermeasure Opportunity
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• Nuclear attack identified by US and global leaders as number one security threat
• Reauthorization of Pandemic All hazards Preparedness Act includes radiation as top priority
• Terrorist attack with a 10 KT device will kill 400,000 people in NYC most of them via ARS (Institute of Medicine Report, June 2009)
• Fukushima disaster highlights risk of nuclear industry
• There are no FDA licensed countermeasures for ARS
CBLB502 uniquely positioned as therapeutic against ARS
CBLB502 as Medical Radiation Countermeasure Origin & Mechanism of Action
• Protein of bacterial origin (flagellin) modified to reduce immunogenicity and toxicity and improve production
• Acts through multiple mechanisms mediated by activation of pro-survival NF-kB signaling pathway
• Selectively protects normal tissues (but not malignant tumors) from radiation
• Increases survival of stem cells and early progenitors of hematopoietic system and stimulated regeneration of different HP lineages
• Reduces radiation damage to and stimulate regeneration of crypts, villi and lamina propria of GI tract
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Development of CBLB502 for Licensure as Countermeasure via FDA’s Animal Rule
• Efficacy in animal models that mimic human disease
• Human safety
• Well understood mechanism of action to justify selection of objective indicators (biomarkers) in humans
Drug candidates, efficacy of which cannot be directly tested in humans due to ethical reasons, are developed according to Animal Rule:
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CBLB502 is efficacious in mice and monkeys in protecting and mitigating regimens
27 studies with non-human primates; >180 studies (with multiple strains of mice, types of irradiation,
survival, HP, GI and other endpoints)
N IH S w is s m ic e , 1 3 G y o f to ta l b o d y ir ra d ia t io n
t im e a fte r ir ra d ia t io n , d a y s
0 2 4 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 2 4 2 6 2 8 3 0
an
ima
l s
urv
iva
l, %
0
2 0
4 0
6 0
8 0
1 0 0 C B L B 5 0 2 (n = 5 0 )
a m ifo s t in (n = 1 3 * )
s a lin e (n = 2 5 )5 -A E D (n = 5 )
Mice
0
10
20
30
40
50
60
70
80
90
100
0 5 10 15 20 25
Days after TBI
Su
rviv
al
(%),
n=
40
7.5 Gy, + 16h, PBS/Tween80
8 Gy, + 16h, PBS/Tween80
7.5 Gy, + 16h, CBLB502 40 µg/kg
8 Gy, + 16h, CBLB502 40 µg/kg =25%
=37%=37%
protection mitigation
Days after 6.5 Gy gamma-TBI0 10 20 30 40
% o
f su
rviv
ors
0
20
40
60
80
100
vehicle (PBS), n=8
CBLB502 @ +16h, n=12
CBLB502 @ +25h, n=10
CBLB502 @ +48h, n=12
Survival of rhesus monkeys after 6.5 Gy -TBI
Days after irradiation
0 10 20 30 40
% o
f s
urv
ivo
rs
0
20
40
60
80
100
120
Vehicle (N=8) at -45'
CBLB502, 0.04 mg/kg (N=11) at -45'
protection mitigationNHPs
Days after 6.5 Gy gamma-TBI0 10 20 30 40
% o
f su
rviv
ors
0
20
40
60
80
100
vehicle (PBS), n=8
CBLB502 @ +16h, n=12
CBLB502 @ +25h, n=10
CBLB502 @ +48h, n=12
Survival of rhesus monkeys after 6.5 Gy -TBI
Days after irradiation
0 10 20 30 40
% o
f s
urv
ivo
rs
0
20
40
60
80
100
120
Vehicle (N=8) at -45'
CBLB502, 0.04 mg/kg (N=11) at -45'
protection mitigationNHPs
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Summary of CBLB502 Efficacy Features in NHPs
• Species: rhesus monkey, Macaca mulatta (best-studied primate model in ARS); both sexes, young adults
• Doses of radiation tested: from LD10/40 to LD75/40 TBI in survival studies and LD90-100 TBI in GI morphology studies
• Efficacious times of treatment: at least from -45’ to >48 hours (treatment at 120 hours is not efficacious)
• Efficacious doses of CBLB502: >=10 ug/kg efficacious at all time points and radiation doses tested, as single intramuscular injection
CBLB502 increases survival (up to 3 times); reduces severity and duration of thrombocytopenia;
reduces severity of neutropenia; reduces morphological damage in BM, GI tract, spleen, thymus and lymph nodes
Almost 1,000 non-human primates
Completed Steps in Production of CBLB502
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• Full industrial-scale production process based on recombinant DNA technology
• Single fermentation generating hundreds of thousands of doses
• Reproducibility demonstrated in multiple GMP runs
• Stable as a frozen liquid and in lyophilized form
• Release assays validated
CBLB502 Human Trial Program Summary
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• Total of 150 human volunteers received range of doses of CBLB502 in 2 studies
• Dose limiting toxicity (DLT) defined (manifested as flu-like syndrome)
• Calculated efficacious dose in humans below DLT
• Adverse event profile predictable and directly related to mechanism of action of CBLB502
• Methodology established to determine projected human efficacious dose (based on biomarkers)
• All biomarkers project similar human dose
CBLB502-Biodefense Path to Licensure Remaining Tasks
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Completed Remaining steps
CMC
GMP process developed and tested, drug suitable for clinical trials released
Additional consistency runs
Efficacy
Data from ~1,000 primates demonstrates dramatic survival benefits and accelerated
recovery
Pivotal animal studies
Human safety
Two trials: 50-subject dose-escalation and 100-subject study completed
Definitive safety study
FDA process
Open IND, Fast Track Status, Orphan Drug Status
Coordinating study protocols, BLA submission
CBLB502 Federal Contract Funding
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GRANT/CONTRACT TITLE AMOUNT DATES
DoD /DTRA, Med. Chem. & Biol.
Defense Res. Program
Radioprotective Mechanisms of
CBLB502 $1,300,000 3/07-3/10
DoD/CBMS-JPEO
Chemical Biological Medical
Systems Joint Project Mgt.
BAA-07-01- Advanced
Development of a Medical
Radiation Countermeasure
$10,340,000 3/08-10/09
NIAID (NIH)
BioShield Program
CBLB502 mitigation of radiation
induced thrombocytopenia $1,230,000
9/08-3/10
BARDA (HHS)
BioShield Program
BAA-08-08 -Development of
CBLB502 of mitigation of HP
syndrome
$15,800,000 9/08-10/10
NIH/NIAID
Grand Opportunities (GO) Grant Protectan CBLB502 $5,300,000 9/09-9/11
DoD/CBMS-JPEO
Chemical Biological Medical
Systems Joint Project Mgt.
RFP W9113M-09-R-0010
Advanced Development of a
Medical Radiation
Countermeasure
$45,000,000
(15,000,000 +
30,000,000)
9/10-9/13
DoD /DTRA, Med. Chem. & Biol.
Defense Res. Program
Radioprotective Mechanisms of
CBLB502 $1,589,106 1/11-4/12
DoD/CBMS-JPEO
Chemical Biological Medical
Systems Joint Project Mgt.
RFP W9113M-09-R-0010
Advanced Development of a
Medical Radiation
Countermeasure
$1,343,759 6/11-9/13
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CBLB502 Medical Applications
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CBLB502 in Preclinical Model of Local Irradiation
Toll-like Receptor 5 Agonist Protects Mice from Dermatitis and Oral Mucositis Caused by Local Radiation: Implications for Head
and Neck Cancer Radiotherapy.
(Int. J. Rad. Onc. Biol. Phys., in press)
Result:
• CBLB502 efficacious against radiation-induced mucositis and dermatitis
Significance:
• Strong preclinical support of CBLB502 as radiotherapy adjuvant
• Justification of new application (protection from radiation-induced dermatitis)
Approval of “CBLB502 as supportive care” trial protocol in head and neck cancer patients by Scientific Review Committee of Roswell Park
Head and neck irradiation model in mice
Extending Indications of CBLB502 Mitigation of chemotherapy side effects and direct antitumor action
Irinotecan and CBLB502 against Wart colon tumors in Fisher rats
CBLB502 displays both supportive care and direct antitumor activities in rat model of colon cancer
0 4 8 12 16 20 24 28 32Me
an
Tu
mo
r W
eig
ht
(mg
)
200
500
2000
5000
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1000
10000
Antitumor activity and toxicity of Irinotecan ± CBLB502
in rats bearingadvanced Ward colorectal carcinoma
Time (Days)
0 4 8 12 16 20 24 28 32
Me
an
Bo
dy
We
igh
t (%
)
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85
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95
100
105
110
Control
CBLB502 0.2 mg/kg x 5
Irinotecan 200 mg/kg x 3
CBLB502 0.2 mg/kg(5) + Irinotecan 200 mg/kg
CBLB502 0.2 mg/kg(3) + Irinotecan 200 mg/kg
Irinotecan 200 mg/kg + CBLB502 0.2 mg/kg
"Toxicity"
"Antitumor Activity"
Irinotecan daily x3, 200 mg/kg i.v. +/- CBLB502
0 4 8 12 16 20 24 28 32 36 40 44 48 52Me
an
Tu
mo
r W
eig
ht
(mg
)
200
500
2000
5000
100
1000
10000
Indivadual rat bearing advanced Ward colorectal carcinoma
response to CBLB502 0.2 mg/kg/day by i.p. daily x 5
Time (Days)
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Me
an
Bo
dy
We
igh
t (%
)
90
95
100
105
110
115
Rat # 1
Rat # 2
Rat # 3
Rat # 4
"Toxicity"
"Antitumor Activity"
0
CBLB502, x3 daily, 0.2 mg/kg
Irinitecan+CBLB502
placebo
Irinitecan alone
(all dead from GI toxicity)
CBLB502 rescues animals from Irinotecan toxicity with no
interference with its antitumor activity
CBLB502 caused complete regression of tumors in part
of the animals
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Open IND and Roswell IRB approval for first trial in advanced cancer patients
Prospective Clinical Trials of CBLB502 in Cancer Patients
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• Reducing severity of mucositis and enhancing efficacy of radiotherapy of H&N
cancer
• Reducing severity of bowel toxicity and enhancing efficacy of radiotherapy of
pancreatic cancer
• Reducing severity of diarrhea in colon cancer patients treated with Irinotecan
• Treating primary hepatocellular carcinoma (liver cancer)
• Treating liver metastasis of colon cancer
• Treating liver metastasis of breast cancer
• Pre-operational treatment of prostate cancer
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CBLB612 Stem Cell Inducing Agent
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CBLB612 is 6x more efficacious than G-CSF and induces both early and late progenitor cells
Effects of CBLB612 and G- CSF are synergistic
CBLB612 Induces Propagation of HSCs
CBLB612 or
G-CSF
CBLB612 or
G-CSF
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Principle efficacy assessment in Phase I = potential partnering
CBLB612 Product Development Strategy
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• 6-month Phase I safety study in healthy volunteers enables accurate estimate of induction and mobilization of stem cells in peripheral blood, a direct predictor of efficacy of the drug
• Zhejiang Hisun Pharmaceutical Co. Ltd. licensing deal of 2009 provides additional data and possibility of synergistic development
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Curaxins Anticancer drugs
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Curaxins
• Synthetic small molecules with proprietary structure
• Unique molecular target: simultaneously affect multiple signaling pathways commonly deregulated in cancer cells
• Efficacious in a broad spectrum of preclinical tumor models
• Mechanism of action enables additional clinical indications beyond cancer treatment (anti-inflammatory, anti-infective)
• Recent peer review publications: • Science Translational Medicine (2011) • Journal of Virology (2010) • Cell Cycle (2009) • Oncogene (2009)
•Protectan CBLB502•Biodefense•Oncology•Ischemia
•Protectan CBLB612•HP stem cells
•Curaxins
•Mobilan•Revercom•Antimycon•Arkil•Xenomycin
Clever drugs
2003
2007
2010
2011
Incuron, LLC
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Incuron, LLC – JV for Curaxin Development
• 50/50 joint venture with BioProcess Capital Partners LLP, Moscow
• ~$18M to reach inflection points for primary molecules
• CBLI oversees mechanistic studies and formal development
• Phase Ib trial for prototype CBLC102 in gastrointestinal and liver cancer patients started October 2010 in Russia
• Phase I trial with oral formulation of next generation CBLC137 in solid tumors planned for 2012 in Russia
• Optimization of IV formulation of next generation CBLC137 for future trial in US ongoing
•Protectan CBLB502•Biodefense•Oncology•Ischemia
•Protectan CBLB612•HP stem cells
•Curaxins
•Mobilan•Revercom•Antimycon•Arkil•Xenomycin
Clever drugs
2003
2007
2010
2011
Panacela Labs, Inc.
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Panacela Labs, Inc.
• Joint venture with Open Joint Stock Company “RUSNANO”, $10B Russian Federation fund
• Commitment of up to $26M over four years • Portfolio of five compounds entering formal pre-clinical
development or hit-to-lead optimization Mobilan Revercom Xenomycins Antimycons Arkils
• Development for licensure in Russian market
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Milestones
CBLB502 Defense • Start of pivotal animal efficacy studies • Start of definitive safety/dose validation trial in healthy
volunteers
CBLB502 Medical • Trial as single agent in advanced cancer patients • Trial as supportive care in head and neck cancer patients
Incuron • Completion of CBLC102 trial in Russia • Phase I trial next generation Curaxin CBLC137
General • High profile peer reviewed publications
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Financial Summary
• Shares Outstanding: 35M common, 52M fully diluted
• Government Grants & Contracts support CBLB502 for defense and limited medical applications: $13M unspent as of 9/30/11 (excl. $30M option for first purchase)
– Continually seeking new grants and contracts as well as modifications to existing grants and contracts to maximize availability of non-dilutive financing
• Pro forma cash at September 30, 2011: $34 million
– Recognizes $9 million investment made by Rusnano in majority owned subsidiary Panacela Labs, Inc. on October 4, 2011
• Other: – $5 million Russian government Skolkovo grant to Incuron, LLC
subsidiary – $7 million milestone investment into Incuron, LLC subsidiary,
pending opening of Russian IND for clinical study of CBLC137
• Scientist and entrepreneur
• Founder of The Fellowship for Interpretation of Genomes (FIG)
• Founder and Former CEO of Integrated Genomics, Inc. (‘97-03)
Michael Fonstein, PhD
Chief Executive Officer & President
• SVP of Basic Science, Roswell Park Cancer Institute
• Former Chair, Dept. Molecular Biology at Cleveland Clinic
• 30+ issued patents
• 150+ research publications
Andrei Gudkov, PhD, D.Sci
Chief Scientific Officer
• 30 years of financial and operations management and accounting experience
• 6 years as CFO of a public biotech company
• 15 years experience in federal contracting
Neil Lyons, CPA
Chief Financial Officer
• Former Director of Business Development at Integrated Genomics, Inc.
• Expert in technical sales and contract negotiations
Yakov Kogan, PhD, MBA
Chief Operating Officer
Senior Management Team
• 25 years global oncology drug development experience
• Senior positions in clinical operations at CROs
• Led clinical development in several publicly traded biotech companies
Michael Kurman, MD
Chief Medical Officer
• Over 20 years of regulatory experience at large and small pharma
• Multiple successful NDAs, MAAs, sNDAs, advisory committees
Ann Hards, PhD
Executive Vice President, Regulatory Affairs and Quality Assurance
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Scientific Advisory Board
George R. Stark, PhD Chairman of SAB, Member of NAS, Former Director of Lerner Research Institute of Cleveland Clinic, Scientific Advisor to Amersham and Genentech, pioneered numerous major research technologies
Inder Verma, PhD Member of NAS, Professor of Salk Institute, Founder and Scientific Advisor to Cell Genesys, Signal Pharmaceuticals, UroGenesys, Ventana Pharmaceuticals, Quark Biotech. Internationally recognized leader in cancer biology and inflammation
Bruce Blazar, MD Professor, Chair in Transplantation Immunology of University of Minnesota. Member of the FDA Advisory Committee, SAB member of BioMarin Pharmaceutical, Seattle Genetics, etc.
Board of Directors
Independent Directors
Bernard L. Kasten, MD Former CEO, SIGA Technologies David Hohn, MD Former President of Roswell Park Cancer
Institute James Antal, CPA, MBA Former CFO and CIO of Experian
Paul DiCorleto, PhD Chairman Lerner Research Institute,
Cleveland Clinic
Management
Michael Fonstein, PhD CEO & President, Cleveland BioLabs, Inc. Andrei Gudkov, PhD, DSci CSO, Cleveland BioLabs, Inc. Yakov Kogan, PhD, MBA COO, Cleveland BioLabs, Inc.
Boards
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