th annual bio ceo & investor conference february 9,...
TRANSCRIPT
12th Annual BIO CEO & Investor ConferenceFebruary 9, 2010
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
3
CBLI is developing two families of drugs:
Protectans: selectively protect healthy tissues from radiation damage
Curaxins: kill tumor cells
Mission
3
CBLI Target Product Market Opportunities
• CBLB502: Protection from Acute Radiation Syndrome (ARS)– >$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)
• Curaxins: Broad range anti-cancer drugs– $50 billion growing market
4
There is no approved drug which can effectively protect from ARS
The Threat - Nuclear Attack
• A nuclear 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)
5
Recent Milestones – CBLB502
• Phase I ascending-dose safety trial successfully concluded June 2009
• $23 million in development contracts from DoD and BARDA/HHS and NIAID/NIH received in 2008 (~$13 million left)
• $8 million in new funding in September 2009 including $5.3 stimulus GO grant (proposals for ~$30 million in additional funds pending)
6
7
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
7
CBLB502 mobilizes multiple mechanisms of radiation defense, all stemming from TLR5
activation
TBI, Gy InjectionsN
totalN
survivors% survival
P-value vs. vehicle
6.5 CBLB502, 0.04 mg/kg @+1h-+48h (pooled) 44 30 68.2% 0.002
6.5 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 radiat ion
Non-human primates
8
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 CMC requirements
• Efficacy in two animal species including rhesus macaques using survival as endpoint
• Safety in healthy humans
• Well understood mechanism of action (to provide biomarkers of efficacy)
9
Cell Bank
Test ResidualsQC protocols, stability
Formulation
Bioassay
ManufacturingProduction Strain, DSP
Preclinical & ClinicalStudies
Laboratory Strain
FermentationImprovement
MBF
CBLB502 – ARS: CMC Effort
10
GMP process developedDrug released
TBI Dose ParameterTime relative to TBI (if applicable)
-45' +1h +16h +25h +48h +72h
LD60-70
Survival benefit +40% +45% +45% +40%-60% +45% TBD
Thrombocytopenia reduction +++ +++ +++ +++ +++ +++
Neutropenia reduction + ++ ++ ++ + +
Improved BM, spleen, thymus +++ +++ +++ +++ +++ TBD
Improved GI mucosa ++ +++ Ongoing Ongoing Ongoing TBD
Cytokine release (G-CSF, IL-6, etc.) +++ +++ +++ +++ +++ TBD
Data on dose dependence of efficacy √ √ TBD Ongoing TBD TBD
LD10-20
Thrombocytopenia reduction +++ +++ +++ +++ +++ ++
Neutropenia reduction + ++ ++ ++ + +
Cytokine release (G-CSF, IL-6, etc.) +++ +++ +++ +++ +++ ++
Data on dose dependence of efficacy Ongoing √ TBD TBD TBD TBD
No TBI
Increased platelet levels +++
Increased neutrophil levels ++
Cytokine release (G-CSF, IL-6, etc.) +++
Data on dose dependence of efficacy √
+++: strong effect; ++: moderate effect; +: minor effect; √√√√: data collected
CBLB502 – ARS: Summary of Primate Studies
11
19 studies with over 700 primates tested dose-
dependence for the drug, efficacy time window and effects
of various radiation doses
12
• 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
13
- - Human safety is the last remaining developmental milestone: Phase IA study completed in Q3 2009
- - Expect to complete all other remaining requirement s needed for FDA in Q4 2010
Manufacturing&
Clinical/Regulatory
Formulation
Non-ClinicalSafety
Non-ClinicalEfficacy
Manufacturing of Consistency Lots
Reprotox Studies in Rabbits & Rats-Seg. II
Phase II Safety TrialPh IIA (100 subjects) & Ph IIB (~500 subjects)
Development & Stability Studiesof Lyophilized Formulation
Reprotox Studies in Rats-Seg. I&III
GMP manufacturing (>100,000 doses)
INDFiled
Pivotal GLP Mouse& Primate Efficacy Studies to support NDA filing
GLP Acute Mouse & PrimateToxicology Studies
Process validation
Dose EscalationTrial - Phase Ia(50 volunteers)
10/092004 Q4’10
Efficacy in Mice, Rats and Primates
� CompletedHuman Safety Data
BLAFiling
Federal grant support fromDoD and HHS/BARDA
Stability Studies of the Final Product
GLP 2-weekMouse & PrimateToxicology Studies
Mechanism of Action;Markers of Efficacy
13
Protectan CBLB502: Development Timeline
CBLB502 - ARS Market Potential “Back of the Envelope ”
• DoD - 2 million potential doses for US military
• BARDA/HHS - 5-20 million potential doses for protection of US civilians (Strategic National Stockpile)
Primary 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/year (w/penetration)
No competing products todayRFP from DoD indicates commitment to procurement
• Israel, UK, Canada, India, China, Japan, S. Korea
14
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
15
CBLB502: Phase I/II Head & Neck Human Trial
16
• Open IND
• Funded by $5.3 million stimulus grant received September 2009
• Protocol submitted to IRB
• Planned to start at Roswell Park Cancer Institute 1Q 2010
17
Protectan CBLB612Stem Cell Inducing Agent
17
Dramatic improvement of blood recovery during Cyclophosphamide treatment in mice
CBLB612: Supportive Care During Chemotherapy
WBC
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
18
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
19
Zhejiang Hisun Pharmaceutical license for China signed Sept. 2009
($1.65M upfront development, 10% royalties)
20
Curaxin Product LineAnti-cancer drugs
20
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
21
22
22
INCURON – JV for Curaxin Development
• 50/50 joint venture with Bioprocess Ventures, Moscow
• ~$18M to reach Phase II for new generation of Curaxins
• CBLI to serve as subcontractor to oversee mechanistic studies and clinical development
23
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)
• ~16 sets of patent applications filed• First CBLB502 US patent granted
23
24
24
Financial Summary
• Mcap (at 1/29/10): $78M
• Shares Outstanding:– 20M common
– 36M fully diluted
• Govt. Grants & Contracts committed to support CBLB502 for defense and medical applications (at 9/30/09): $21.8M
– Pending proposals for additional grants and contracts to support all CBLI programs: $37.5M
• CBLI Cash & Rcvbles (at 9/30/09): $5.2M
• Avg. Monthly Burn Rate (CBLI cash):– $200,000
• 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
• Former Chair, Dept. Molecular Biology at Cleveland Clinic
• 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 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
25
Scientific Advisory Board
George R. Stark, PhDChairman 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 Directors
Independent DirectorsBernard L. Kasten, MD
Former 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
26