Revolutionizing the Fight Against Cancers and Infectious Diseases

Revolutionizing
the Fight Against Cancers
and Infectious Diseases
Dr. Joseph Kim
President & CEO
NYSE MKT: INO
Forward Looking Statement
Our commentary and responses to your questions may contain
forward-looking statements, including comments concerning
clinical trials and product development programs, evaluation of
potential opportunities, the level of corporate expenditures,
the assessment of Inovio’s technology by potential corporate
partners, capital market conditions, timing of events, cash
consumption and other subjects. Information concerning
factors that could cause actual results to differ materially from
those set forth in our Annual Report on Form 10-K for the year
ended December 31, 2013, our Form 10-Q for the quarter
ended March 31, 2014, and other regulatory filings from time
to time.
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Inovio: Global Leader in Active Immune Therapy
2013: Dynamic Year
• Best T cell responses in published clinical studies
• Validating license deal with Roche in 2013
2014: Transformative Year
• Phase II meets efficacy endpoints: breakthrough for active
immunotherapy field
•
•
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More cancer trials starting (cervical, head & neck, prostate,
breast, lung, pancreatic cancers)
Working toward additional pharma partnerships
Phase II Data: Meets Efficacy Endpoints With Robust T Cells
• Efficacy data meets primary and secondary efficacy endpoints
VGX-3100
Placebo
P Value
CIN 2/3 Regression to
CIN 1 or No Disease
49.5%
53 of 107
30.6%
11 of 36
<0.025
HPV Clearance AND
CIN 2/3 Regression to
CIN 1 or No Disease
40.2%
43 of 107
14.3%
5 of 35
<0.025
• Induces regression of a cervical intraepithelial neoplastic process
• Eliminates HPV
• Robust HPV-specific T cell responses in majority of treated
subjects, as in phase I study
• Treatment well-tolerated; administration site redness
• Detailed data will be submitted for publication in
peer-reviewed journal
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Phase II Data: Clinical and Technology Validation
• Significant step toward providing women and physicians a nonsurgical treatment for pre-cancerous lesions
• Advance VGX-3100 for precancerous dysplasias and HPVassociated cervical, head and neck, and anogenital cancers
• SynCon® immunotherapy technology can activate immune
system to fight chronic infections, pre-cancers — and ultimately
cancers
• De-risk product and business development strategy for VGX-3100
and broad pipeline of SynCon® active immune therapy products
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Broad Medical and Market Opportunities
Product Name
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Indication
Preclinical
Vgx-3100
Cervical dysplasia
Therapeutic
INO-3112
Cervical Cancer
Therapeutic
INO-3112
Head & Neck Cancer
Therapeutic
Ino-5150
Prostate cancer
Therapeutic
Ino-1400
Breast/lung /
Pancreatic cancers
Therapeutic
pennvax®
hiv
Preventive/
Therapeutic
Ino-3510
influenza
Preventive
Ino-8000
Hepatitis C
Therapeutic
ino-1800
Hepatitis B
Therapeutic
Preventive
MaV-12
malaria
Preventive
INTERNALLY FUNDED
EXTERNALLY FUNDED
Phase I
Phase II
Phase III
T cells: Inovio Commands the Body’s SWAT Team
Target cell
T cell
Cytotoxic T lymphocyte
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Provided by Dr. Philip Greenberg
Hutchinson Cancer Research Center
T cells: Inovio Commands the Body’s SWAT Team
Target cell and
antigen(s)
Antigen-specific T cell
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Cytotoxic T lymphocyte
CD8+ T cells
• T cells are vital to
clearing cancerous or
infected cells
• Active immunotherapies: harnessing
the power of T cells
• Inovio’s DNA
immunotherapies
displaying best-in-class
T cells
• Functional killing effect
• Safe and well tolerated
• >400 patents globally
T Cells by Design: Antigen-Specific, Optimized, Best-in-Class
Antigen Y
Antigen Y
Antigen Y
Strain 2
Strain X
Identify gene sequence
of selected antigen(s) from
chosen strains/variants of
the virus/cancer
Strain 1
Synthetically create optimal
consensus gene sequence for
the selected antigen – PATENTABLE
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Designed to Break Tolerance or Provide Universal Protection
Insert SynCon® gene
sequence for selected
antigen into DNA plasmid.
Antigen
consensus
sequence
SYNCON®
DNA
SynCon DNA plasmid ready
to manufacture.
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DNA
Plasmid
Electroporation Delivery Plays a Vital Role
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SynCon®+ Electroporation: Significant Antigen Expression
1000x increase in
cellular uptake and
antigen production/
expression
Intramuscular
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Ref: Sardesai & Weiner Curr. Opin. Immunol. 2011
Intradermal
Inovio DNA/EP Beats Previous Gold Standard (Merck Ad5 Viral
Vector) for T Cell Generation (Non-Human Primates)
SIV Model: UPenn/Merck/Inovio Assay: Data Co-Published
T Cell ELISpot Assay
DNA + EP
Ad5
T Cell Proliferation Assay
DNA + EP
Ad5
Flow Cytometry Assay
Ad5
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DNA + EP
Ref: Hirao et al. Molecular Therapy, August 2010
Ad5
DNA + EP
PENNVAX®: Highest CD8+ T Cell Responses for HIV Vaccine
Dosing Schedule
(Months)
0 1 2 3 4 5 6 7 8 9
• Best CD8+ T cell response in HIV
clinical studies
• Durable T cell memory
responses
• Safe and well tolerated
A: 3X vaccination without EP
B: 4X vaccination without EP
C: 2x vaccination with EP (month 2)
D: 3x vaccination with EP (month 4)
E: Memory response (month 9)
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A
B
C
D
Ref: Kalams et al JID 2013
E
VGX-3100 Induces Robust and Durable T Cell Responses
Dosing Schedule
(Months)
0 1 2 3 4 5 6 7 8 9
ELISpot Assay
Individual Dose Cohorts
Combined Cohorts
• 14/18 (78%) subjects responded to at least one antigen
• 13/18 (72%) responded to at least two antigens
• 9/18 (50%) responded to all four antigens
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Bagarazzi, Yan, Morrow et al. Sci Transl Med 4, 155ra138 (2012)
HPV16-, HPV18-Specific IFN-γ Production
Multi-parameter
flow cytometry:
CD4, CD8
activation
phenotype
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Bagarazzi, Yan, Morrow et al, Science Trans. Med. (2012)
HPV16-, HPV18-Specific CD107a, Granzyme B, Perforin
CD8
cytolytic
phenotype
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Bagarazzi, Yan, Morrow et al, Science Trans. Med. (2012)
VGX-3100 Flow Cytometry – Functional Killing Assays
•
•
•
•
Patient pre-VGX-3100 PBMC are targets, post-VGX-3100 PBMC are effectors
Quantitative - PBMC added irrespective of Ag-specific CD8 frequency
Qualitative - PBMC normalized to account for Ag-specific CD8 frequency
Measure granzyme B delivery to targets
Qualitative Assay
Quantitative Assay
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Bagarazzi, Yan, Morrow et al. Sci Transl Med 4, 155ra138 (2012)
Inovio Confidential
Checkpoint Inhibitors: T Cell Validation; Combination Potential
• Unprecedented efficacy
• Melanoma, lung cancer
• Inovio cancer vaccines greatly
increase T cells
• Validate potential to enhance T
cell capabilities
• Potential to overwhelm cancer
cells as monotherapy
• Evidence suggests non-responders • Potential to combine with
do not have sufficient pre-existing
checkpoint inhibitors to increase
T cells
efficacy
• Projected $24 billion market (Citi)
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Inovio’s Lead Program
VGX-3100:
• Capitalizes on Inovio’s ability to generate T cells
• Immunotherapy for pre-cancers and cancers caused by
human papillomavirus (HPV)
• Targeting E6/E7 oncogenes
• Phase II completed: high grade cervical pre-cancers
(CIN 2/3 dysplasia)
• Top-line efficacy data reported
• In-depth data to be submitted to peer-reviewed journal
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Inovio’s Lead Product Targets All HPV-caused Diseases
Incidence rates
in the U.S. + EU5
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Sources: CDC, www.hpvcentre.net;
WHO IARC
VGX-3100 Phase II Study
• Placebo-controlled, randomized, doubled blind
• 148+ subjects: females 18-55
• Histologically confirmed HPV16 or 18-associated CIN 2/3 or 3
• 3:1 VGX-3100/electroporation vs. placebo/electroporation
• Two plasmids: Type 16 and Type 18, each encoded for E6/E7
antigens; 3 mg/ml per plasmid; treatment at months 0, 1, 3
• Primary endpoint month 9
• Regression of CIN 2/3 to CIN 1 or no disease
• Secondary endpoints
• Clearance of HPV 16 or 18 AND CIN 2/3 regression
• Immunogenicity
• Safety
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INO-1400: Potential Universal Cancer Therapy Targeting
hTERT (overexpressed in 85% of cancers)
T-cell generation: older generation
DNA vaccine and electroporation
device
SynCon® T-cell generation with
CELLECTRA® electroporation device
Dharmapuri et al., Mol Ther. (2009)
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Yan J et al., Cancer Immunol Res. (2013)
Management
J.Joseph Kim, PhD
President & CEO
• Decades of biotechnology/pharma
management
• Merck: hepatitis A and B vaccines
manufacturing; HIV vaccine (Ad5) R&D
Niranjan Y. Sardesai, PhD
COO
• Extensive biotech management and product
development experience
• Led development of diagnostics for
mesothelioma, bladder cancer, and ovarian
cancer for Fujirebio Diagnostics
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Peter Kies
CFO
• Ernst & Young
• Experience with growth companies
anthrax
Louis Pasteur
Mark L. Bagarazzi, MD
CMO
• Clinical research experience incl. Merck
• Led clinical/regulatory for shingles and
rotavirus vaccines; DNA vaccine expert
Board of Directors
Morton Collins, PhD
Avtar Dhillon, MD
• General Partner, Battelle Ventures and
Innovations Valley Partners
Chairman, BOD
• Former President & CEO,
Inovio Biomedical
Simon X. Benito
• Former Senior Vice President,
Merck Vaccine Division
Angel Cabrera, PhD
• President, George Mason University
• Former President, Thunderbird School of
Global Management
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anthrax
Louis Pasteur
J.Joseph Kim, PhD
• President & CEO, Inovio
Adel Mahmoud, PhD
• Professor, Princeton University
• Former President, Merck Vaccines
• Responsible for Gardasil®, Zostavax®,
Proquad® and Rotateq®
Scientific Advisory Board
Philip Greenberg, MD
David B. Weiner, PhD
• Expert in T cell immunology
• Head, Immunology Program, Fred
Hutchinson Cancer Research Center
Chairman
•“Father of DNA vaccines”
• Dept. of Pathology & Laboratory Medicine,
University of Pennsylvania
Thomas S. Edgington, MD
• Founded multiple biotech companies;
extensively published
• Emeritus Professor, Scripps
Research Institute
Anthony W. Ford-Hutchinson, PhD
• Former SVP, Vaccines R&D, Merck
• Oversaw development: Singulair®, Januvia®,
Gardasil®, Zostavax®, Proquad® and Rotateq®
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anthrax
Louis Pasteur
Stanley A. Plotkin, MD
• Developed rubella and rabies vaccines
• Oversaw Sanofi flu vaccine
• Emeritus Professor, Wistar Institute &
University of Pennsylvania
Financial Information
NYSE MKT: INO
Recent price1
$11.14
Shares outstanding3
60.0 M
$ 668.4 M
Market cap1
Cash, cash equivalents
$ 116.8 M
2
& short-term investments
Cash runway
4Q 2017
Debt2
1July
27
0M
22, 2014
2Mar
31, 2014
3March
31 (reflecting
June 6th 1:4 reverse
split)
Upcoming Value Drivers
Cervical dysplasia
Phase II meets efficacy
endpoints
Cervical Cancer
2Q 2014
Initiated phase I/IIa
INO-3112
Head & Neck Cancer
2Q 2014
Initiated phase I/IIa
Ino-5150
Prostate cancer
3Q 2014
Initiate phase I
Vgx-3100
INO-3112
Ino-1400
Breast/lung/
Pancreatic Cancer
PennVAX®
HIV
4Q 2014
Initiate PENNVAX -GP phase I
Ino-1800
Hepatitis B
Early 2015
Initiate phase I/IIa
Ino-8000
Hepatitis C
2015
Report phase I data
INTERNALLY FUNDED
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2H 2014
Initiate phase I/IIa
EXTERNALLY FUNDED
Investor Highlights
• Phase II data meets efficacy endpoints
• Break-through active immune therapy with the
power to save lives and maximize shareholder
value
• Targeting broad range of diseases and
billion dollar markets
• Best-in-class T cells to prevent, treat & cure
cancers and infectious diseases
• Validating partnership with Roche with
more deals in the works
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Revolutionizing
the Fight Against Cancers
and Infectious Diseases
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