maxim group growth conference september 29,...
TRANSCRIPT
Maxim Group Growth Conference September 29, 2009
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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CBLI is developing two families of drugs:
Protectans: protect healthy tissues fromradiation damage
Curaxins: kill tumor cells
Mission
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CBLI Target Product Market Opportunities
• CBLB502: Protection from Acute Radiation Syndrome (ARS) (accelerated pathway to licensure)
– $500 million + annually
• CBLB502: Reduction of cancer treatment side effects~$20 billion market (70% of patients experience regimen-limiting toxicity )
• CBLB612: Stem cell induction, mitigation of cancer treatment side effects
– Potential to compete with G-CSF ($5+ billion drug from Amgen) or other hematopoietic growth factors
• Curaxins: Broad range anti-cancer drugs – $50 billion + growing market
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CBLI Summary
IP
• Cleveland Clinic (CCF)• Roswell Park Cancer Institute (RPCI)
Partnerships
• Money raised from capital market $51 million• Federal grants and contracts >$50 million
Funding History
• Incorporated in June 2003 Spin-off from the Cleveland Clinic• HQ - Buffalo, NY 32 employees (majority PhDs & MDs)
• ~20 patent applications filed• First CBLB502 US patent granted
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Protectan CBLB502ARS and cancer treatment side effects
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There is no approved drug which can effectively protect from radiation injury
The Threat - Nuclear Attack
• A nuclear or radiological event has been identified by US Congress as a number one security threat
• A terrorist attack with a 10 KT device will kill 400,000 people in NYC (Institute of Medicine Report, June 2009)
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Recent Milestones – CBLB502
• Phase I ascending-dose safety trial successfully concluded June 2009
• Department of Defense Sources Sought Notice for Nuclear Medical Countermeasures - May 2009
• $23 million in development contracts from DoD and BARDA/HHS and NIAID/NIH received in 2008 (~$13 million left)
• Comparable levels of new funding applied for 2009-2010 (~$8 million received September 2009)
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CBLB502 Fits Desirable Countermeasure Profile
Highly efficacious- Increases survival of primates from 20% to >70%
Safe- Completed initial human Phase I safety trial
Easy to use in multiple real-life scenarios – Single intramuscular injection for self- or hospital administration- Effective from 24 hr before to 72 hr after exposure to radiation
Easy to produce & store- Established high-yield cGMP manufacturing process- Stable at room temperature
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A New Principle of RadioprotectionDiscovery of unique radio-protectant Protectan CBLB502 published in Science magazine received attention from the world scientific community
• Published on April 11,2008
• Validates mechanisms of action of the drug and protective effect on mice & primates
• First publication on radioprotection in more than 30 years
Selected as one of top 10 science advances for research funded by NIAID in 2007- 2008
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CBLB502: Mechanism of Action
CBLB502 protects from both gastrointestinal and hematopoietic components of radiation death
NF-kBCBLB502 TLR5IAPs, Bcl-2SOD2, ferritinCytokines
Suppress apoptosisInactivate ROSPromote regeneration
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CBLB502 mobilizes multiple mechanisms of radiation defense, all stemming from TLR5
activation
TBI, Gy Injections N total
N survivors % survival P‐value vs.
vehicle
6.5 CBLB502, 0.04 mg/kg @+1h‐+48h (pooled) 44 30 68.2% 0.0026.5 Vehicle (PBS) @+1h, +25h (pooled) 18 4 22.2% ‐
Days after 6.5 Gy gamma-TBI0 10 20 30 40
% o
f sur
vivo
rs
0
20
40
60
80
100
vehicle (PBS), n=8CBLB502 @ +16h, n=12CBLB502 @ +25h, n=10CBLB502 @ +48h, n=12
CBLB502 Efficacy: Survival (Mitigation) after LD70 IR
Effective when injected up to 48 hours after radiation
Non-human primates
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CBLB502: Organ and tissue recovery of lethally irradiated primates
Pathology data demonstrates protection of GI tract, blood, immune system and skin
50% subjects have no observed abnormalities on the day 40
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Animal Efficacy Rule – Path to FDA licensure
Established FDA pathway to approve drugs where efficacy is unethical to test in humans
Dramatically reduces development time and costs
• Compliance with standard CMC requirements
• Efficacy in two animal species (e.g. mice and rhesus macaques) using survival as endpoint
• Safety in healthy humans
• Well understood mechanism of action (to provide biomarkers of efficacy)
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Cell Bank
Test ResidualsQC protocols, stability
Formulation
Bioassay
ManufacturingProduction Strain, DSP
Preclinical & ClinicalStudies
Laboratory Strain
FermentationImprovement
MBF
CBLB502 – ARS: CMC Effort
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Time relative to TBI (if applicable)TBI Dose Parameter
‐45' +1h +16h +25h +48h +72hSurvival benefit +40% +45% +45% +40%‐60% +45% TBDThrombocytopenia reduction +++ +++ +++ +++ +++ +++
Neutropenia reduction + ++ ++ ++ + +
Improved BM, spleen, thymus +++ +++ +++ +++ +++ TBD
Improved GI mucosa ++ +++ Ongoing Ongoing Ongoing TBD
Cytokine release (G‐CSF, IL‐6, etc.) +++ +++ +++ +++ +++ TBD
LD60‐70
Data on dose dependence of efficacy √ √ TBD Ongoing TBD TBD
Thrombocytopenia reduction +++ +++ +++ +++ +++ ++
Neutropenia reduction + ++ ++ ++ + +
Cytokine release (G‐CSF, IL‐6, etc.) +++ +++ +++ +++ +++ ++LD10‐20
Data on dose dependence of efficacy Ongoing √ TBD TBD TBD TBD
Increased platelet levels +++
Increased neutrophil levels ++
Cytokine release (G‐CSF, IL‐6, etc.) +++No TBI
Data on dose dependence of efficacy √
+++: strong effect; ++: moderate effect; +: minor effect; √: data collected
CBLB502 – ARS: Summary of Primate Studies
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19 studies with over 700 primatestested dose-dependence for the drug, efficacy time window and
effects of various radiation doses
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• 50 human volunteers in groups of 6 received ascending doses of the drug
• Trial completed; database locked mid-July
• Dose limiting toxicity (DLT) defined
• Adverse event profile described; predictable and related to the known pharmacology of CBLB502
• Predicted safe dose in humans exceeds protective dose in primates (based on biomarkers)
• All biomarkers project similar human dose
Summary of Phase I trial of CBLB502
CBLB502 - ARS: Developmental Status
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COMPLETED (2006-2009)• Multiple meetings with FDA laying out the development path
• Animal efficacy for multiple regimens, radiation doses and time points
• Phase IA trial to determine MTD in humans
• Establish and characterize efficacy biomarkers in humans
PENDING (2009-2010)• FDA meeting finalizing protocols for Phase IB and pivotal NHP studies (4Q
2009)
• Phase IB (4Q 2009 – late summer 2010)
• Pivotal NHP study (2009 – early 2010)
• Manufacturing consistency runs and extended product stability (2009-2010)
• FDA submission (late 2010)18
CBLB502 - ARS Market Potential “Back of the Envelope”
• 1‐2 million doses for US army
• 5‐20 million doses for protection of US civilians
Initial sales targets: Need understood, concepts of use developed, high degree of financial commitment, relations with CBLI in place
Secondary sales targets : Serious public concern, policies being developed
Projected addressable market ~$500 M/yearNo competing products today
May 2009 RFI from DoD indicates official start of new procurement cycle
• Israel, UK, Canada, India, China, Japan, S. Korea
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Total Body Irradiation • Acute leukemia - reduction of lethality and improved recovery of patients
from allogenic bone marrow transplantation
Local Irradiation• Head and neck cancer - reduced radiotherapy side effects (mucositis of
mouth, throat and esophagus, larynx and dental caries)
• Prostate cancer - protection of GI (rectal bleeding, diarrhea, bladder damage)
• Lung cancer - protection of healthy lung tissue from inflammation
Chemotherapy• Multiple drugs and cancers - reduction of dose limiting adverse effects
of chemotherapeutic drugs (myelosuppression, GI toxicity, nephrotoxicity, etc.)
CBLB502 - Medical ApplicationsReducing Cancer Treatment Side Effects
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CBLB502 as Radiation Therapy Adjuvant (protection from total body irradiation)
• Rescues animals from radiation toxicity
• Potentiates effect of radiotherapy
• Allows radiation dose escalation
• Does NOT protect tumor
Survival
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CBLB502: Protection from Local Irradiation
Strong mitigation of radiological damage of healthy tissues shown in mouse model of head-and-neck
damage directly supports first medical trial
3x10 Gy daily with CBLB502 pretreatment
0 5 10 1560
70
80
90
100
110 10 Gy x3 (CBLB502 + 10 Gy) x3
Days
Bod
y w
eigh
t, %
3x10 Gy daily
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CBLB502: Phase I/II Head & Neck Human Trial
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• Open IND
• Funded by $5.3 million stimulus grant received September 2009
• Protocol submitted to IACUC
• Planned to start at Roswell Park Cancer Institute 2009/2010
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Protectan CBLB612Stem Cell Inducing Agent
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CBLB612: Potential Applications
• Recovery from myelosuppression associated with chemotherapy (breast cancer, leukemia, lymphomas, etc.)
• Donor treatment in bone marrow transplantation (improvement or replacement of aphaeresis)
• All other clinical applications of G-CSF (e.g.,myelodysplasticsyndrome)
Opportunity for combination with or substitute for G-CSF
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Dramatic improvement of blood recovery during Cyclophosphamide treatment in mice
CBLB612: Supportive Care During ChemotherapyWBC
0.00
5.00
10.00
15.00
20.00
25.00
30.00
10x3
/ul
CBLB612 10.33 2.66 3.09 14.73
PBS 9.65 1.98 0.43 7.21
day -5 day7 day14 day22
White Blood Cells
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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-CSFCBLB612 or G-CSF
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CBLB612: Product Development Strategy
6-month Phase I safety study in healthy volunteers enables full assessment of induction and mobilization of stem cells in peripheral blood, a direct predictor of efficacy of the drug
Principle efficacy assessment in Phase I = potential partnering
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Zhejiang Hisun Pharmaceutical license for China signed Sept. 2009
($1.65M upfront development, 10% royalties)
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Curaxin Product LineAnti-cancer drugs
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Curaxins: Overview
• First-in-class broad-spectrum anticancer drugs
• Small molecules suitable for oral administration
• Novel mechanism of action – simultaneous targeting three major pathways deregulated in cancer
• Composition of matter patent applications
• Efficacy in multiple animal models of major cancer types including breast and prostate cancer
• Proof of concept Phase II trial in prostate cancer
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Broad Spectrum in vivo Efficacy
Comparable efficacy in:- hormone refractory prostate cancer- advanced breast carcinoma- renal cell carcinoma
HCT116 sc xenograft model
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800
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
days of treatment
Tum
or v
olum
e (m
m3)
MCCBL0137
DLD1 tumors
02468
101214161820
1 2 3 4 5 6 7 8 9 10 12 13 14
days of treatment
incr
ease
in tu
mor
vol
ume
MC
CBL0137
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Complete cure of mouse fibrosarcomas treated by combination of Curaxin and HSP90 inhibitor (DMAG).
Same effect is shown in B16 melanoma model.
Synergistic Effects with Heat Shock Inhibitors
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INOCURON – JV for Curaxin Development
• 50/50 joint venture with Bioprocess Ventures, Moscow
• >$15M to reach Phase II for new generation of Curaxins
• Term sheet signed
• Definitive documents expected to be signed in September/October
• Scientist and serial entrepreneur
• Founder of Dia-M and The Fellowship for Interpretation of Genomes (FIG)
• Founder and Former CEO of Integrated Genomics, Inc. (‘97-03)
Michael Fonstein, PhDChief Executive Officer & President
• SVP of Basic Science, Roswell Park Cancer Institute
• 30+ issued patents
•150+ research publications
Andrei Gudkov, PhD, D.SciChief Scientific Officer
• 20 years of financial and accounting experience
• 8 years as a corporate controller of a public company
Jack Marhofer, MBA, CMA, CFMChief Financial Officer
• Former Director of Business Development at Integrated Genomics, Inc.
• Expert in technical sales and contract negotiations
Yakov Kogan, PhD, MBAChief Operating Officer
CBLI Management Team
• 25 years of global oncology drug development experience
• Senior positions in clinical operations at CROs
• Led clinical development in several publicly traded biotech companies
Michael Kurman, MDChief Medical Officer
• 30 years of Pharma experience
• Former Director of Drug Safety at TAP Pharmaceuticals, Inc.
Farrel Fort, PhD, MBA, DABTVice President, Drug Development
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Scientific Advisory BoardGeorge R. Stark, PhD
Chairman of SAB, Member of NAS, Former director of LRI, Scientific Advisor to Amersham and Genentech, pioneered numerous major research technologies
Inder Verma, PhDMember 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, MDProfessor, Chair in Transplantation Immunology of University of Minnesota. Member of the FDA Advisory Committee, SAB member of BioMarin Pharmaceutical, Seattle Genetics, etc.
Board of DirectorsIndependent Directors
Bernard L. Kasten, MDFormer CEO, SIGA Technologies
Daniel Perez, MDFormer CEO & President of Berlex Biosciences, a Division of Bayer AG
James Antal, CPA, MBAFormer CFO and CIO of Experian
Paul DiCorleto, PhDChairman, Lerner Research Institute
ManagementMichael Fonstein, PhD
CEO & President, Cleveland BioLabs, Inc.
Andrei Gudkov, PhD, DSciCSO, Cleveland BioLabs, Inc
Yakov Kogan, PhD, MBACOO, Cleveland BioLabs, Inc
CBLI Boards
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Maxim Group Growth Conference September 29, 2009