rodman & renshaw 14th annual healthcare...
TRANSCRIPT
Rodman & Renshaw 14th Annual Healthcare Conference
NASDAQ: CBLI
September 10, 2012
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
Protectan CBLB502 (Entolimod™)
Radiation Countermeasure Targeted Biologic for Cancer Therapy
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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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)
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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)
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved. 18
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved. 19
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)
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
CBL0137 Efficacy in Mouse Tumor Models
• Effective against breast, prostate, pancreatic, melanoma models • Effective against chemotherapy sensitive and resistant tumors
0
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Mea
n fo
ld tu
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siz
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control
CBL137
* * * **
Vehicle control
30mg/kg CBLC137
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n fo
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Vehicle control
30mg/kg CBLC137
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Vehicle control30 mg/kg CBL013740 mg/kg
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Mea
n fo
ld tu
mor
siz
e 40 mg/kg Sunitinib
** * * * * *0
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Vehicle control30 mg/kg CBL013740 mg/kg
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** * * * * *
02468
101214161820
1 5 7 10 12 14 16 19 21 23 25 28
Vehicle control30mg/kg CBL137
* * * * * * * * * *02468
101214161820
1 5 7 10 12 14 16 19 21 23 25 28
Vehicle control30mg/kg CBL137
* * * * * * * * * *
Days following treatment initiation
kidney colon
melanoma pancreas
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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
Protectan CBLB612 Biologic Mobilizer of Hematopoietic Stem Cells
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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
Preclinical Cancer Therapeutics & Anti-infectives
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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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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Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved. 33
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved. 34
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved. 35
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
Copyright 2012 © Cleveland BioLabs, Inc. All rights reserved.
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
36