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Noble Financial BOCEMb 2012 Equity Conference January 17, 2012

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Page 1: Noble Financial BOCEMb 2012 Equity Conference January 17, …content.stockpr.com/cbiolabs/media/51558d306a27188bcf02ca543536d3df.pdfinnovative approaches to cancer treatment and normal

Noble Financial BOCEMb 2012 Equity Conference

January 17, 2012

Page 2: Noble Financial BOCEMb 2012 Equity Conference January 17, …content.stockpr.com/cbiolabs/media/51558d306a27188bcf02ca543536d3df.pdfinnovative approaches to cancer treatment and normal

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

2

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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

3

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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

4

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History, Partners, Joint Ventures

5

•Protectan CBLB502•Biodefense•Oncology•Ischemia

•Protectan CBLB612•HP stem cells

•Curaxins

•Mobilan•Revercom•Antimycon•Arkil•Xenomycin

Clever drugs

2003

2007

2010

2011

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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

7

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Radiation Countermeasure Opportunity

8

• 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

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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

9

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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:

10

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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

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Completed Steps in Production of CBLB502

13

• 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

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CBLB502 Human Trial Program Summary

14

• 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

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CBLB502-Biodefense Path to Licensure Remaining Tasks

15

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

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CBLB502 Federal Contract Funding

16

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

17

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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

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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

100

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 (%

)

80

85

90

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)

0 4 8 12 16 20 24 28 32 36 40 44 48 52

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

22

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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)

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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

Incuron, LLC

26

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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

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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

Panacela Labs, Inc.

28

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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

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• 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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