rodman & renshaw 14th annual healthcare...

Rodman & Renshaw 14th Annual Healthcare Conference

NASDAQ: CBLI

September 10, 2012

Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.


Safe Harbor

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 CBLI’s judgment as of the date of this presentation and are subject to risks and uncertainties that could cause actual results 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.

The factors that could cause actual results to differ are discussed in more detail in

CBLI’s filings with the Securities and Exchange Commission, including its latest Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. These reports are available under the “Investors” tab on CBLI’s website at www.cbiolabs.com.

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Investment Highlights • Clinical stage oncology company with broad pipeline of proprietary,

novel products

• Pivotal-stage radiation countermeasure targeting BLA in 2014, with $30M conditional purchase order from Dept. of Defense

• Thought-leading science supported by peer-reviewed publications and alliances with Cleveland Clinic, Roswell Park Cancer Institute and Children’s Cancer Institute Australia

• Track record of non-dilutive development grants and contract awards in excess of $60M from US and foreign sources

• Experienced senior management and operational leadership

• Robust world-wide IP portfolio with expirations in 2023-2029

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CBLI Product Pipeline

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Animal Rule Research Pre-Clinical Ph I Pivotal BLA

CBLB502 (Entolimod™) Radiation Countermeasure

CBLI

Traditional Research Pre-Clinical Ph I Ph II Ph III

CBLB502 (Entolimod™) Advanced Solid Tumors (companion diagnostic)

CBL0137 Advanced Solid Tumors (oral)

Advanced Solid Tumors (IV)

CBL0102 Advanced Solid Tumors

CBLB612 Bone Marrow Transplantation

5 Preclinical Assets: Varied oncology and anti-infective compounds

CBLI

Incuron

Incuron

Incuron

CBLI

Panacela


Understanding tumor mechanisms leads to new approaches to cancer treatment and normal tissue protection

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Founding Technology Concepts

organism

Apoptosis

Tumor Normal tissues

radiation

Imitating Tumor anti-apoptotic mechanisms: 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 - κ B

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. Sci. Transl.

Med. 3, 95ra74


Protectan CBLB502 (Entolimod™)

Radiation Countermeasure Targeted Biologic for Cancer Therapy

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CBLB502 (Entolimod™)Mechanism of Action • Biologic: modified protein of Salmonella,

only known agonist of TLR5 • Activates NF-κB signaling in specific cell

types (i.e. liver, GI) • Directs innate immune response to

activated cells and tissues (cancer therapy) o Enables immune attack against TLR5-positive

tumors o Creates antitumor microenvironment in liver

and lungs

• Stimulates production of numerous endogenous tissue protective factors (radiation countermeasure, protection from side effects of cancer treatment): o Apoptosis suppressors (radioprotection) o Antioxidants (radioprotection) o Stimulators of regeneration (radioprotection

and mitigation)

Cytokines

G-CSF

IL6

IL8

IL10 NF-κB

NF-κB

IκBα

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/CBLB502

TLR5

Yoon et al. Science 335:859-64. 2012.

Antioxidants Anti-infectives Anti-apoptosis

Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved. 8

CBLB502 - Initial Validation and Revenues through Radiation Countermeasure Application

• Unmet Need: o Nuclear attack identified by US and global leaders as number one security threat o Fukushima disaster highlights risk of nuclear industry o US government stockpiled over $2B of countermeasures for various threats o No FDA licensed medical radiation countermeasures (MRC)

• Drug Profile Meets/Exceeds Requirements: o Significantly increases survival of irradiated NHPs (from ~20% to ~80% at LD80) o Reduces radiological damage in both HP and GI systems o Single intramuscular injection with broad application time window (-24h to +48h) o Completed two Phase I safety trials in total of 150 healthy subjects


FDA’s Animal Rule - Pathway to Approve Drugs Where Efficacy is Unethical to Test in Humans

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Efficacy and biomarkers in

relevant animal models

BLA

Correlation of biomarkers

between animals and humans =

dose conversion

CBLB502 (Entolimod™): • 27 studies with ~1,100 non-human primates • >200 studies in mice (with multiple strains, types of irradiation, survival and other

endpoints) • 150 healthy subjects received 2-50 µg per subject in 2 studies • Transient (lasting approx. 24 hrs.), mild-moderate flu-like syndrome most common AE

linked to up-regulation of cytokines (including biomarkers of efficacy) Transient changes in blood pressure and laboratory parameters also observed, without clinical sequelae

• Fast Track and Orphan Drug Status granted • Robust manufacturing process with 100,000s of dose equivalents on hand

Well understood

mechanisms of action yield

biomarkers of efficacy

Safety and biomarkers in

healthy subjects


Efficacy demonstrated at highest anticipated dose requested by FDA

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CBLB502 Efficacy: Randomized Blinded 179 NHP GLP Study

• Total Body Irradiation (TBI): LD70 • Drug/placebo administration: i.m., 25 hours post TBI • Monitoring: physiological parameters, biomarkers • Observation period: standard 60 days post-irradiation


CBLB502 (Entolimod™) MRC Path to Licensure Summary

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Completed Remaining Steps CMC

• GMP mfg. process developed • Clinical trial material released to support

animal and human studies • 100,000s dose equivalents on hand

• GMP process validation • Consistency runs

(to be done after BLA submission, in parallel with FDA review)

Efficacy

• 28 non-GLP studies with ~1,000 NHPs • >200 non-GLP studies with thousands of

mice of different strains • Pivotal GLP/GCP Survival Irradiated

NHP (LD70)

Pivotal animal studies • GLP/GCP Survival Irradiated NHP

(LD30 and LD50) • GLP/GCP Survival Irradiated Mouse • GLP/GCP PK/PD Non-Irradiated NHP • GLP/GCP PK/PD Non-Irradiated Mouse

Human Safety • 50-subject dose-escalation study • 100-subject study

• Safety study in approx. 300 hundred subjects

FDA Process

• Open IND • Fast Track and Orphan Drug Status • End of Phase II meeting

• Human database agreement • Dose conversion agreement • BLA package preparation • BLA submission(s)


CBLB502 is active against TLR5+ tumors and against TLR5+/- liver metastases

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CBLB502 Oncology: Mobilizing Innate Immunity to Attack Cancer

healthy

TLR5- tumors in liver

TLR5+ tumors in liver

TLR5+ tumors

No toxicity

Tumor suppression

Tumor suppression

Tumor suppression

No antitumor effect

TLR5 negative tumors TLR5 positive tumors

TLR5- tumors

Companion diagnostic

assay optimized

CBLB502vehicle

NFκB-responsive luciferase reporter mice


TLR5 Oncology Companion Diagnostic

• Created by CBLI in partnership with Roswell Park Cancer Institute

• Functional assay for TLR5 expression in various tumors

• Adaptation and optimization for use with biopsies in process

• Tumors identified to date expressing TLR5 Breast Colon Lung Others being tested and confirmed

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CBLB502 as a single agent can cause complete tumor regression of Wart colon tumors in Fisher rats

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Efficacy of CBLB502 Against TLR5+ Tumors*

Mea

n Tu

mor

Wei

ght (

mg)

Time (Days) CBLB502 3xdaily 0.2 mg/kg

* * *

* unpublished data


cont

rol

CB

LB50

2

Since the liver is a TLR5+ organ, a single injection of CBLB502 shows efficacy in mouse liver metastases

CBLB502 Against Liver Metastases of Colon Cancer*

Liver metastasis model of CT26 colon cancer

0 20 40 60 0

20

40

60

80

100 control, n=15 CBLB502, n=19 p=0.0067

Days

Perc

ent s

urvi

val

*unpublished data

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CBLB502 (Entolimod™) Oncology Phase I Trial

• Advanced Solid Tumors as a single agent

o Target enrollment 48 patients

o Enrolled first patient March 2012 – 2nd cohort dosed (as of Aug. 2012)

o No drug-related SAEs reported to date

o Roswell Park Cancer Institute (RPCI)

o PI: Alex Adjei, M.D., Ph.D., FACP, Chair of the Department of Medicine and Senior Vice President of Clinical Research at Roswell Park Cancer Institute

http://clinicaltrial.gov/ct2/show/NCT01527136?term=196111&rank=1.

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http://clinicaltrial.gov/ct2/show/NCT01527136?term=196111&rank=1


Curaxins CBL0137 & CBL0102

Small Molecule Cancer Therapeutics

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“These results introduce FACT as a novel target for anti-cancer therapy. The broad anti-tumor activity of Curaxins, their previously unidentified mechanism of action – which apparently does not rely on the induction of DNA damage – and their ability to affect multiple pathways fully justify a continued effort in evaluating them as anti-cancer agents that could possibly hit the clinic.”

- excerpt from 2011 STM Perspective by Giulio Draetta (Dana Farber Cancer Institute) and Ronald DePinho (President, Univ. of Texas MD Anderson Cancer Center)


Curaxins Simultaneously Modulate Three Pathways Important for Tumor Viability and Progression

p53 (apoptosis/growth arrest) • sensor and mediator of intrinsic stresses • commonly inactive in tumors

TARGET FOR ACTIVATION NF-kB (survival, resistance, growth)

• sensor and mediator of extrinsic stresses • commonly active in tumors

TARGET FOR SUPPRESSION HSF-1 (survival, resistance)

• sensor and mediator of proteotoxic stress • commonly active in tumors

TARGET FOR SUPPRESSION


Unique Molecular Target (FACT) and Mechanism of Action

Trapping of FACT on chromatin results in blocking FACT-dependent transcription and CK2-mediated p53 activation

+ Curaxin

NF - κ B - dependent transcription requires FACT

Gasparian et al., Sci. Transl. Med., 3: 95 ra74 (2011)


CBL0137 • Synthetic small molecule with proprietary structure

o New chemical space with fully characterized structure-activity relationship

• Efficacious in a broad spectrum of preclinical tumor models o RCC, colon, melanoma, pancreatic, non-small cell lung cancer, glioblastoma, head &

neck, lymphoma, leukemia, neuroblastoma

• To date, no CBL0137 resistant tumors found

• In vivo efficacy demonstrated for IV and oral routes o Open IND for oral administration in Russia (first patient in - 3Q12) o US IND for IV administration (targeting 1Q13)

• Lack of genotoxicity suggests safe applications including cancer prophylaxis o Koman et al. Cancer Prevention Research (Phila). 2012 Jun 11

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CBL0137 Efficacy in Mouse Tumor Models

• Effective against breast, prostate, pancreatic, melanoma models • Effective against chemotherapy sensitive and resistant tumors

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CBL137

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Vehicle control

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02468

101214161820

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Vehicle control30mg/kg CBL137

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Days following treatment initiation

kidney colon

melanoma pancreas

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Synergy of CBL0137 with Conventional Cancer Therapeutic: Activity Against Neuroblastoma in Mice*

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* unpublished data

CBL0137 given on top of standard therapy used for treatment of relapsed neuroblastoma turns partial tumor suppression into complete response


CBL0102 / Quinacrine

• Synthetic small molecule with history as WWII anti-malaria drug

o Pursue orphan indications and/or liver cancer o No other active cGMP manufacturing

• Same molecular target as CBL0137 (FACT)

• Efficacious in a broad spectrum of preclinical tumor models

• Ongoing Phase I trial in advanced cancer patients in Russia

o Dosed 5th cohort, may continue to cohort 6, then enroll efficacy arm

• Lack of genotoxicity suggests safe applications including cancer prophylaxis

• Primary clinical focus will be on orphan indications

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Incuron, LLC – JV for Curaxin Development

• Joint venture with BioProcess Capital Partners LLP, Moscow (CBLI holds 58.8% ownership)

• ~$15M to reach inflection points for primary molecules (CBL0137 & CBL0102)

• $5 million prestigious Russian government Skolkovo grant awarded September 2011

• CBLI oversees mechanistic studies and formal development

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Protectan CBLB612 Biologic Mobilizer of Hematopoietic Stem Cells

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CBLB612 Overview

• Biologic, synthetic analogue of Mycoplasma lipopeptide

• TLR2 agonist

• Powerful inducer and mobilizer of hematopoietic stem cells (HCS) when combined with standard of care o Works synergistically with G-CSF and AMD3100

o Potentially eliminates the need for aphaeresis during Bone Marrow Transplant (BMT)

• Potential clinical orphan and non-orphan applications:

o BMT with HSC

o Mitigation of neutropenia

• Development Strategy: Phase I safety study in healthy volunteers to enable estimates of induction and mobilization of stem cells in peripheral blood o $4M contract with Russian Ministry of Industry & Trade funds development through

this milestone

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Synergistic Effect of CBLB612, G-CSF, and AMD3100 on HSC Mobilization*

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Tota

l CFC

num

ber p

er 1

ml o

f PB,

x 1

000

CFC - colony-forming cells HSC - hematopoietic stem cell

4.4x increase over SoC for neutropenia

6.4x increase over SoC for bone marrow

transplant

Standard of Care

Neutropenia HSC transplant

* unpublished data


Preclinical Cancer Therapeutics & Anti-infectives

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Panacela Labs, Inc. – JV for Development of Early Preclinical Oncology and Anti-infective Assets

• Joint venture with Open Joint Stock Company “RUSNANO”, $7B Russian Federation fund

• IP Partners: Roswell Park Cancer Institute, Cleveland Clinic, Children’s Cancer Institute Australia

• Commitment from RUSNANO: $9M received, $17M over four years, based on milestones

• Portfolio of five compounds entering formal preclinical development or hit-to-lead optimization

• Strategy – to accelerate human data and licensure via Russian market and use Phase IV data to expedite approval in U.S. and RoW

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Panacela Portfolio

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Product Candidate Field Potential Indication(s) Development

Stage Efficacy Evaluation

Mobilan Oncology Renal cell carcinoma, ovarian

carcinoma, melanoma, glioblastoma

Formal preclinical Multiple animal models

Revercom Oncology Head & Neck, Bladder,

Melanoma, Breast, Prostate, Non-Small Cell Carcinoma

Formal preclinical Multiple animal models

Xenomycins (multiple)

Infectious diseases Fungal infections, malaria Formal preclinical Multiple animal models

Arkil Oncology Prostate, Breast Advanced Hit-to-lead In vivo proof-of-principle

Antimycon Oncology Broad range of solid tumors and hematological malignancies Advanced Hit-to-lead In vivo proof-of-principle


CBLI Milestones (2012/2013) CBLB502 (Entolimod™) Defense • Agreement with FDA on final program requirements for BLA filing • BARDA development contract • Remaining pivotal animal efficacy studies • Definitive safety/dose validation trial in healthy volunteers

CBLB502 (Entolimod™) Oncology • Continue/complete enrollment of Phase I advanced cancer trial

CBL0137 • Phase I trial of oral administration in Russia (first patient - 3Q12) • FiIe IND for IV administration in US (1Q13)

CBL0102 • Complete dosing of Phase I trial in Russia (1H13)

CBLB612 • Complete formal preclinical development and file IND in Russia (2Q13)

General • Secure additional non-dilutive grant funding • High profile peer reviewed publications

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Financial Summary

• Shares Outstanding: 36M common, 47M fully diluted

• Government Grants & Contracts help support CBLB502 for defense and limited medical applications:

o Continually seeking new grants and contracts as well as modifications to existing grants and contracts to maximize availability of non-dilutive financing

• Consolidated Cash & Investments at June 30, 2012: $22M • Proforma Consolidated Cash & Investments: $30M

o ~$4 million more available from Skolkovo grant to Incuron, LLC for Curaxins o ~$4 million contract for CBLB612 with Russian Ministry of Industry and Trade

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Senior Management Team Chief Executive Officer & Co-Founder Yakov Kogan, PhD, MBA • Negotiated and secured >$40M in project-

specific VC funding and >$50M in USG grants and contracts

• Closed significant R&D contracts with multi-national customers and increased revenues over 33% as former Director of Business Development at Integrated Genomics, Inc.

President & Co-Founder Michael Fonstein, PhD • Scientist and entrepreneur • Founder of The Fellowship for Interpretation

of Genomes (FIG) • Founder and Former CEO of Integrated

Genomics, Inc. (1997-2003)

Chief Scientific Officer & Co-Founder Andrei Gudkov, PhD, DSc • SVP of Basic Science, Roswell Park Cancer

Institute • Former Chair, Dept. Molecular Biology at

Cleveland Clinic • 30+ issued patents • 200+ research publications

Chief Financial Officer Neil Lyons, CPA • Over 20 years of financial executive

experience, including 7 years in life sciences • Advised on equity, debt and M&A transactions

of over $1 billion • Managed complex Federal contracting

operations in excess of $300 million, annually


Senior Operational Leadership Chief Medical Officer Michael Kurman, MD • Over 25 years global oncology drug

development experience • Senior positions in clinical operations at CROs • Led clinical development in several publicly

traded biotech companies

Vice President, Business Development Debra Bowes, MT • Over 30 years of biotechnology and

pharmaceutical experience • 5 major product deals • Managed and built 2 BD departments • Launched & marketed 4 biotech products (2 in

oncology)

Executive Vice President, Regulatory Affairs and Quality Assurance Ann Hards, PhD • Over 20 years of regulatory experience • Multiple successful NDAs, MAAs, sNDAs, advisory

committees • Responsible for regulatory aspects of development

and/or approval of 14 major new drugs/new indications, negotiated 12 of these NDA approvals, including drugs that have combined annual peak sales of over $30B (Lipitor, Plavix)

Vice President, Product Development Anna Muchnik, MS • Over 20 years of pharma and biotech drug

development experience • Strong comprehension of science, drug development,

project management, contract manufacturing, and regulatory affairs


Board of Directors Independent Directors Bernard Kasten, MD - Chairman Former CEO, SIGA Technologies James Antal, CPA Former CFO and CIO Experian Paul DiCorleto, PhD Chairman Lerner Research

Institute, Cleveland Clinic David Hohn, MD Former President, Roswell Park

Cancer Institute

Executive Directors

Yakov Kogan, PhD, MBA Chief Executive Officer Michael Fonstein, PhD President Andrei Gudkov, PhD, DSc Chief Scientific Officer


Summary • Clinical stage oncology company with broad pipeline of proprietary,

novel products

• Pivotal-stage radiation countermeasure targeting BLA in 2014, with $30M conditional purchase order from Dept. of Defense

• Thought-leading science supported by peer-reviewed publications and alliances with Cleveland Clinic, Roswell Park Cancer Institute and Children’s Cancer Institute Australia

• Track record of non-dilutive development grants and contract awards in excess of $60M from US and foreign sources

• Experienced senior management and operational leadership

• Robust world-wide IP portfolio with expirations in 2023-2029

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rodman & renshaw 14th annual healthcare...

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