CBLB502 Medical and Curaxins OverviewInvestor DayJune 8, 2011

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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Scientific and Clinical Program Goals

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Support Animal Rule-driven development of CBLB502 for biodefense applications• Mechanism of action studies: rational choice of biomarkers

• Defining CBLB502 efficacy range

• Determination and validation of human dose

Moving CBLB502 to oncology clinic• Radiotherapy adjuvant (local irradiation models)

• Chemotherapy adjuvant

• Effect on tumors

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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)

Goal:

• Justification of use of CBLB502 as a supporting care radioprotection adjuvant

Results:

• CBLB502 is efficacious against radiation-induced mucositis and dermatitis

Significance:

• Strong preclinical support of use 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 CBLB502Mitigation of chemotherapy side effects and direct anticancer 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

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Antitumor activity and toxicity of Irinotecan ± CBLB502

in rats bearingadvanced Ward colorectal carcinoma

Time (Days)

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t (%

)

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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

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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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t (%

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Rat # 1

Rat # 2

Rat # 3

Rat # 4

"Toxicity"

"Antitumor Activity"

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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

Granulocyte colony formation in vitro by mouse BM cells irradiated

in vivo in vitroCBLB502CBLB502

Radioprotective Effect of CBLB502 is Indirect

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Histological Atlas of CBLB502 ActivityIdentification of Target Organs

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-5

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Liver Smallintestine

Largeintestine

Kidneys Lungs Brain Spleen

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cif

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se f

old

in

du

cti

on

CBLB502

LPS

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NFkB reporter induction in various tissues

NFkB reporter mice

vehicle CBLB502liver

control CBLB502

NF-kB

DNA

Liver is the primary target

organ of CBLB502

Balb/C-Tg(IkBa-luc)Xen mice

NF-kB activation in livers

Inta

ct

CBLB

502

PBS

PBS

CBLB

502

CBLB

502

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Liver isolation

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NF-kB activation in livers

Inta

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PBS

CBLB

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CBLB

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Liver isolation

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Step 1. Occluding the hepatoduodenalligament containing hepatic artery and portal vein with a non-traumatic clamp.

Step 2. CBLB502/PBS injections.

Step 3. The blood supply occluded for 30 minutes then clamp released and blood circulation restored.

Step 4. Mice were irradiated immediately after the surgery with 10 Gy TBI.

Step 5. Bone marrow cells isolated from femura and total colony formation estimated using MethoCult media and standard protocol for CFU assay.

Assessing Role of Hepatocytes in Radioprotection:surgical exclusion of liver from blood circulation

Step 1. Occluding the hepatoduodenalligament containing hepatic artery and portal vein with a non-traumatic clamp.

Step 2. CBLB502/PBS injections.

Step 3. The blood supply occluded for 30 minutes then clamp released and blood circulation restored.

Step 4. Mice were irradiated immediately after the surgery with 10 Gy TBI.

Step 5. Bone marrow cells isolated from femura and total colony formation estimated using MethoCult media and standard protocol for CFU assay.

No liver = No radioprotection of bone marrow

Liver is the source of endogenous HP-protecting factors mobilized by CBLB502

BMC-CFU

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Liver isolation

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BMC-CFU

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No surgery

Liver isolation

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x1

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BM

Cs

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TLR5 Activation Protects Liver from Fas

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TLR5 Agonist Protects Mice from Fas

Caspase activation

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Intact Fas CBLB502 CBLB502+Fas

Ca

sp

ase

3,7

activity

Liver enzymes

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Intact CBLB502

Se

rum

AL

T (

U/L

)

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Intact CBLB502Fas

Se

rum

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T (

U/L

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CBLB502

+Fas

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Days

Anim

al s

urv

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%)

Mouse survival

PBS (n=16)

CBLB502, 0.5 h (n=16)

CBLB502, 2 hs (n=10)

CBLB502, 6 hs (n=10)

Liver condition

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Intact

Anti-Fas

CBLB502 + anti-Fas

con

tro

lC

BLB

50

2

• CT26, TLR5-negative syngeneiccolon cancer, was grown as liver metastases in Balb/c mice

• Tumor growth was monitored using luminometer imager (tumors express luciferase)

• Tumor suppressive effect of CBLB502 is associated with tumor infiltration with immunocytes

CBLB502 against liver metastases of colon cancer in mice

livermetastase

liver

metastase

Control (no drug) CBLB502, 5hrs post injection

CT26 tumor-free mice (liver)

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100 Intact, n=15

CBLB502, n=19log rank p=0.0067

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Direct Anti-tumor Effects of CBLB502

healthy

TLR5- tumors in liver

TLR5+ tumors in liver

TLR5+ tumors

TLR5- tumors

CB

LB5

02

No toxicity

Tumor suppression

Tumor suppression

Tumor suppression

No antitumor effect

TLR5-negative tumors

TLR5-positive tumors

• Identification of target tissues enables rational choice of indications and regimens

• Phase I/II “CBLB502 as a single agent” trial protocol was approved by Scientific Review Committee of Roswell Park

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CBLB502 as Direct Antitumor Agent

• Has direct suppressive effect in several animal models of TLR5-positive tumors (lung, colon cancer, melanoma)

• Effective against liver metastases regardless of TLR5 status of the tumor

• Acts by mobilizing antitumor immunity

• Expected to provide anti-tumor vaccination

• Fits several clinical trial scenarios, including liver metastasis of colon cancer, liver cancer, bladder cancer, H&N cancer, etc.

Many of these trials enable assessment of both supportive care and direct anti-tumor activity of CBLB502

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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CBLB502: Major Scientific and Clinical Updates

Demonstration of CBLB502 efficacy in preclinical model of local irradiation• Approval of Phase I/II “CBLB502 as supportive care” trial in head and neck cancer

patients by Scientific Review Committee of Roswell Park

Discovery of direct anticancer action of CBLB502: from “supportive care only” drug to combined “supportive care and anticancer” drug• Approval of Phase I/II “CBLB502 as a single agent” trial by Scientific Review

Committee of Roswell Park

Demonstration of radiomitigating efficacy of CBLB502 against GI manifestation of acute radiation syndrome in primates that received extremely high radiation doses• Critical result for justifying extended indications of CBLB502

Building of Histological Atlas of CBLB502 activity, identification of target organs• Path to optimal indications and regimens

Completion of Phase Ib human dose validation trial

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CuraxinsAnticancer drugs

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Curaxin’s Targets р53, NF-kB, HSF1 in Cancer

Normal cell response

to stressesinfection

DNA damage

t0

death survival

CANCER

target for activation (doxorubicin, 5FU, cisplatin, etc.)

target for inhibition (bortezomib)

target for inhibition (geladanomycin)

survival

survival

death or

arrest

Normal cell response

to stressesinfection

DNA damage

t0

death survival

CANCER

target for activation (doxorubicin, 5FU, cisplatin, etc.)

target for inhibition (bortezomib)

target for inhibition (geladanomycin)

survival

survival

death or

arrest

Curaxins Target FACT-dependent Transcription

+ Curaxin

Trap of FACT on chromatin blocks FACT-dependent transcription and

causes CK2-mediated p53 activation

NF-kB-dependent transcription requires FACT

Gasparian et al., Science Translational Research, in final revision

Curaxinactivator

inhibitor

inhibitor

live tumor cell dead tumor cell

Non-genotoxic anticancer drug candidates with triple

mechanism of action suitable for use in combinations with

conventional drugs

Antitumor Effects of Curaxins

Curaxins: Safe Multi-targeted Drugs

p53 activation

NF-kB inhibition

Heat shock inhibition

Genotoxicity

CuraxinsConventional

drugsProperty

p53 activation

NF-kB inhibition

Heat shock inhibition

Genotoxicity

CuraxinsConventional

drugsProperty

yes

no

no

yes

yes YES

no yes

Curaxins in Cancer Prophylaxis

50% reduction in breast tumor incidence in transgenic MMTV-neumice that were maintained on drinking water with non-toxic doses of curaxinCBLC137 during 10 months

Lack of genotoxicity, combined with p53 activation and NF-kBand HSF1 suppression, opens the opportunity of using

Curaxins as cancer preventing agents

Appearance of palpable tumors

in mice of different groups

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Age (weeks)

tum

or-

free a

nim

als

(p

rop

ort

ion)

Control

CBL137, 0.1mg/ml

CBL137, 0.2mg/ml

p=10-5

p=0.0001

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Curaxins

Synthetic small molecules with proprietary structure

Unique mechanism of action: simultaneously affect multiple molecular targets in cancer cell

Efficacious in a broad spectrum of preclinical tumor models

Mechanism of action enables additional clinical indications beyond cancer treatment (anti-inflammatory, anti-infective)

First generation Curaxin CBLC102 is in clinical trial in patients with liver metastases

New generation Curaxin CBLC137 is at advanced stage of preclinical development

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Incuron – JV for Curaxin Development

50/50 joint venture with Bioprocess Ventures, Moscow

~$18M to reach Phase II for new generation of Curaxins in US and Russia and conduct human trials in liver cancer in Russia for CBLC102

CBLI oversees mechanistic studies and formal development

Phase Ib trial for CBLC102 in liver started October 2010

IND-enabling studies for new generation of Curaxins on track for IND

Demonstrates feasibility of model combining advantages of US and Russian development platforms

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Milestones

• Start of pivotal animal efficacy studies for CBLB502 defense

• Start of definitive safety/dose validation trial in healthy volunteers for CBLB502 defense

• Start of CBLB502 Phase I/II trial in head and neck cancer patients for supportive care indication

• Start of CBLB502 Phase I/II trial in advanced liver metastases patients for safety/antitumor effect

• Completion of CBLC102 trial in liver cancer patients in Russia

• Filing of IND for studies of new generation curaxins

• Top level peer reviewed publications