1. Revolutionizing the Fight
Against Cancers and
Infectious Diseases
Dr. J. Joseph Kim
PRESIDENT & CEO NASDAQ: INO
It’s All About the T-Cells
2. 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, 2014, our Form 10-Q for the quarter
ended March 31, 2015, and other regulatory filings from time
to time.
2
4. A Compelling Weapon: T Cells
Cytotoxic T lymphocyte
T cell
Target cell
4
• T cells: vital to fighting
disease
But…
• Can we help T cells
recognize evasive cancers
or mutating infectious
diseases?
• Can we enhance their
targeting, speed and
magnitude?
• Great strides in new
immunotherapy technology
• Just scratching the surface
5. 5
Is There an “Ideal” T Cell-Generating Immunotherapy?
Attributes
• Well-targeted, antigen-specific
• Not dependent upon being patient specific
• Functional, with “killing tools” granzyme and perforin
• Robust in magnitude
• Persistent and durable over time
• No unwanted immune response against a vector
• No toxic inflammatory response
• Capable of breaking tolerance
The ideal T cell generator would be an active immunotherapy. Does not bypass the
immune system’s inherent capabilities and controls.
Effective, efficient, safe…
6. DNA Immunotherapies: Disease-Specific T Cells by Design
IT’S ALL
ABOUT THE
T CELLS
Identify pertinent
disease-specific antigen(s)
Encode DNA
plasmid with genetic
code for antigen
Deliver plasmids
into cells, enabling them
to produce antigen
T cells eliminate cells
displaying disease-
specific antigen
Immune system
activates antigen-
specific T cells
Effective, efficient, safe in vivo T cell activation
Cellular machinery uses
the DNA code to produce
one or more of the
disease antigens coded
by the DNA plasmid
ANTIGENIC
PROTEINS
7. 7
• Activate disease-specific CD8+ killer T cells and
antibodies
Antigen targeting
immunotherapies &
vaccines
• Enhance immune response activation
• Impact durability of immune responses
• Drive immune responses to sites of infection
Immune activators
• Simplified design, product stability, better
manufacturing, dosing, and cost effectiveness
• Rapidly activates sufficient quantities of specific
antibodies
Monoclonal
antibodies
(DNA-based)
DNA Immunotherapy Platform: Multiple Applications
8. Broad Medical and Market Opportunities
Product Name
INTERNALLYFUNDED
OTHERCancerPrograms
Indication Preclinical Phase I Phase II
Vgx-3100
Ino-5150
Ino-1400
EXTERNALLYFUNDED
InfectiousDiseasePrograms
Ino-3510
ino-1800
Phase III
8
INO-3112
INO-3112
HepatitisB Therapeutic
influenza
Breast/lung/Pancreatic
cancers
Therapeutic
Prostatecancer Therapeutic
Head&NeckCancer Therapeutic
CervicalCancer Therapeutic
Cervicaldysplasia Therapeutic
Preventive/
Therapeutic
Ebola
AerodigestiveCancer Therapeutic
INO-3106
INO-4212
Preventive
INTERNALLYFUNDED
HPVprograms
Pennvax®-B hiv
Pennvax®-GP hiv
Preventive/
Therapeutic
Preventive/
Therapeutic
Ino-8000 HepatitisC Therapeutic
INO-3112 CervicalCancer Therapeutic
9. 9
Cervical Dysplasia: Schiffman et al. Arch Pathol Lab Med (2003), Public Health England Cervical Cancer Screening Programme,
Stoler et al. Anatomic Path (2011), Castle et al. JNCI (2005), Mayrand et al. NEJM (2007)
Cancers: CDC, www.hpvcentre.net, WHO IARC
LOWGRADE
CERVICAL
DYSPLASIA
(CIN1)
US:
1,400,000
EU5:
1,300,000
HIGHGRADE
CERVICAL
DYSPLASIA
(CIN2/3)
US:
270,800
EU5:
267,400
CERVICAL
CANCER
US:
11,818
EU5:
14,043
ORO-
PHARYNGEAL
CANCER
US:
11,726
EU5:
13,932
Anogenital
cancer
Annual incidences: US and EU5
HPV-Caused Pre-Cancers & Cancers
US:
9,530
EU5:
15,288
10. Phase II: Study Design
• 148 subjects: 18-55 year old females with
high-grade cervical dysplasia (CIN2/3)
• HPV 16 and/or 18 positive
• 6 mg VGX-3100 or placebo(IM followed by EP)
at weeks 0, 4, and 12
Placebo-Controlled,
Randomized, Double
Blind
• Regression of CIN2/3 to CIN1 or normal at six
months post third dose (Week 36)Primary Endpoint
• Regression of CIN2/3 to CIN1 or normal and
• Clearance of HPV 16 and/or 18 genotype
detected during screen
Secondary Endpoint
10
11. 0
10
20
30
40
50
60
Phase II: Regression of Cervical Lesions to CIN 1 or Normal
Pre-Specified 1° Endpoint: Histopathologic
Regression of CIN2/3 to CIN1 or Normal
30.6%
(11/36)
Statistically significant difference
(p=0.017; strata-adjusted)
Post-Hoc Analysis: Regression of CIN2/3
to Normal
0
10
20
30
40
50
60
40.2%
(43/107)
16.7%
(6/36)
Percent
VGX-3100 Placebo VGX-3100 Placebo
Statistically significant difference
(p=0.006; strata-adjusted)
Overall Histopathologic Regression Incidence
Per-Protocol Population (N=143)
11
49.5%
(53/107)
Percent
12. Phase II: Clinically Significant Efficacy; Achieves Endpoints
49.5%
(53/107)
30.6%
(11/36)
Histopathologic Regression to CIN1 or Normal
AND Virological Clearance (HPV16 or 18) (n=143)
0
10
20
30
40
50
60
40.2%
(43/107)
14.3%
(5/35)
Percent
VGX-3100 Placebo
Statistically significant difference
(p=0.001; strata-adjusted)
12
14. Regression of CIN3 to Normal and HPV Clearance Observed in
VGX-3100 Treated Patient (via IHC) Over 36 WeeksWeek0:CIN3pathology
IHC Staining: HPV
Week36:Nosignificant
pathology
IHC Staining: CD814
15. Powerful Impact of VGX-3100 Phase II Efficacy Data
• Non-surgical option for the treatment of CIN2/3
• Simple 3 monthly injections generated CD8 killer T cells
• Measured in blood
• Observed in cervical tissue (tissue infiltrating T cells)
• Direct correlation found between CD8 T cells and efficacy
• Demonstrated phase II efficacy and safety
• Regressed disease to normal
• Cleared virus which caused the disease
• Disease regression: expand into other HPV-caused diseases
• Advance other anti-cancer therapies (lung, breast, pancreas, prostate)
• Virus (HPV) clearance supports other antiviral therapies (HBV, HCV, HIV)
15
16. VGX-3100: Next Steps
EXPANSION OF HPV PROGRAM TO RELATED
CANCERS AND PRE-CANCERS
• Cervical cancer (Ph I/IIa initiated)
• Head & neck (Ph I/IIa initiated)
• Anogenital cancers
• VIN, PIN
PREPARED SCIENTIFIC PAPER FOR PEER REVIEW
• Completed immunological analysis to characterize T cell subsets.
Phase II data adds to phase I data, which was extensively
characterized (Bagarazzi, et al. Sci Transl Med 2012)
• Manuscript prepared for submission
PHASE III PLANNING FOR EARLY 2016 LAUNCH
• Clinical and regulatory
• Scale up immunotherapy production
• Market research
• Supply chain strategy
• EP device production
• Pricing & reimbursement
16
17. • 126 women with cervical carcinoma
• Safety & progression free survival at 18
months
• INO-3112 administered during standard
chemo-radiotherapy (CRT) or during
and after standard CRT as an adjuvant
• Funded by the EORTC
• 20 women with cervical carcinoma
• Safety, tolerability, immunogenicity
• Cervical histology
• Treat after chemoradiation
HPV-Associated Cervical Cancer Studies: INO-3112
Two clinical trials for cervical cancer:
INO-3112 (VGX-3100 + IL-12 DNA immune activator)
HPV 16/ 18 related disease
17
Phase I/II Cervical Cancer Phase II Cervical Cancer
18. • 20 men/women
• Safety, tolerability, immunogenicity
• Anti-tumor effects & progression free survival
• Arm #1: treat before/after tumor resection
• Arm #2: treat after chemoradiation
HPV-Associated Head & Neck Cancer Studies: INO-3112
Phase I/IIa clinical trial
INO-3112 (VGX-3100 + IL-12 DNA immune activator)
HPV 16/ 18 related disease
18
Head & Neck Squamous Cell Carcinoma
19. Phase I:
INO-1400 +/- IL-12 DNA immune activator
Human telomerase reverse transcriptase (hTERT), associated with cancer cell
survival
hTERT-Associated Cancers Study: INO-1400
• hTERT overexpressed in 85% of cancers - potential “universal” cancer therapy
• 54 patients
• Safety, tolerability, immunogenicity
• Anti-tumor effects and progression free survival
• Trial launched: 4Q 2014
19
Breast, Lung, or Pancreatic Cancers
20. • 126 patients
• Safety, tolerability, immunogenicity
• Trial started: 2Q 2015
• Roche paying all development costs plus milestones
• 240M+ global market opportunity
20
Hepatitis B Study: INO-1800
Phase I:
INO-1800 +/- IL-12 DNA immune activator
Multi-antigen: HBV pan-clade surface antigens & core antigens
Chronic Hepatitis B Virus
21. Louis Pasteur
Peter Kies
CFO
• Ernst & Young
• Experience with growth
companies
Mark L. Bagarazzi, MD
CMO
• Clinical research experience
incl. Merck
• Led clinical/regulatory for
shingles and rotavirus vaccines;
DNA vaccine expert
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 diagnostics development
for mesothelioma, bladder
cancer, and ovarian cancer for
Fujirebio Diagnostics
Management
21
22. J.Joseph Kim, PhD
• President & CEO, Inovio
Adel Mahmoud, PhD
• Professor, Princeton University
• Former President, Merck Vaccines
• Responsible for Gardasil®,
Zostavax®, Proquad® and Rotateq®
Morton Collins, PhD
• General Partner, Battelle
Ventures and Innovations Valley
Partners
Simon X. Benito
• Former Senior Vice President,
Merck Vaccine Division
Angel Cabrera, PhD
• President, George Mason
University
• Former President, Thunderbird
School of Global Management
Avtar Dhillon, MD
Chairman, BOD
• Former President & CEO,
Inovio Biomedical
Board of Directors
22
Nancy Wysenski , MBA
• Former COO of Endo
Pharmaceuticals and Vertex
Pharmaceuticals
23. Louis Pasteur
Stanley A. Plotkin, MD
• Developed rubella and rabies
vaccines
• Oversaw Sanofi flu vaccine
• Emeritus Professor, Wistar Institute
& University of Pennsylvania
Philip Greenberg, MD
• Expert in T cell immunology
• Head, Immunology Program, Fred
Hutchinson Cancer Research Center
23
Anthony W. Ford-Hutchinson,
PhD
• Former SVP, Vaccines R&D, Merck
• Oversaw development: Singulair®,
Januvia®, Gardasil®, Zostavax®,
Proquad® and Rotateq®
David B. Weiner, PhD
Chairman
•“Father of DNA vaccines”
• Dept. of Pathology & Laboratory
Medicine, University of Pennsylvania
Scientific Advisory Board
24. Financial Information
Cash, cash equivalents
& short-term investments3 $ 81.0 M
Debt3 0 M
Cash runway 4Q 2018
Shares outstanding2 71.8 M
Recent share price1
$7.23
Market cap1 $ 519.1 M
NASDAQ: INO
24
1July 23, 2015 2May 8, 2015 3 March 31, 2015 4 May 5, 2015
Net cash from financing4 $ 82.1 M
25. INTERNALLYFUNDED EXTERNALLYFUNDED
Ino-1400 2016
Report interim data
Breast,Lung,And
PancreaticCancer
Vgx-3100
2015 Publish data in med journal
Early 2016 Initiate phase IIICervicaldysplasia
25
Value Drivers
INO-3112
2H 2015
Report interim data
Head&Neck and
Cervical Cancer
Ino-8000
2015
Report interim phase I data
Hepatitis C
Ino-1800 2Q 2015
Initiated phase I
Hepatitis B
Ebola
2Q 2015
Initiated phase I
INO-4212
Ino-5150 3Q 2015
Initiated phase I
Prostatecancer
PennVAX® 3Q 2015
Initiate PENNVAX-GP phase I
HIV
INO-3112
December 2015
Initiate phase IICervical Cancer
26. Best-in-class
immune
responses to
fight cancers
and infectious
diseases
Targeting broad
range of billion
dollar disease
markets
Breakthrough
in vivo T cell
generating
technology
Validating
partnership
with Roche
Lead product
achieved phase
II efficacy
endpoints
Investor Highlights
26