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, 2015 and other
regulatory filings from time to time.
2
3. Inovio Highlights
3
VGX-3100
Phase II clinical proof of concept in pre-cancer
First to show CD8+ T cells generated in vivo
can clear disease
Published in The Lancet
Two pharma partnership deals
(~$1 billion in milestone payments)
Over $130M in non-dilutive
grants/contracts in last six years
$163.0M in cash and short-term
investments, Dec. 31
Highly experienced management
team, board of directors, and
scientific advisory board
DNA-based immunotherapy and cancer vaccine technology
Cancers | Infectious Diseases
5. Immune Activating Technology
• Genetic sequence encoded for specific
immune mechanism
• Activates target immune functions
directly in the body
• Highly optimized DNA plasmids
• Novel sequences patentable
Core Technology Leverages Synthetic Biology
5
Up-regulate
desirable immune
mechanisms
Optimize
manufacturing,
safety, with in vivo
mechanism
To fulfill unmet needs in:
CANCER | INFECTION
7. What Have We Accomplished?
A N T I G E N G E N E R AT I O N / T C E L L A C T I VAT I O N
8. What does an Effective T Cell Activating Immunotherapy
Need to Accomplish?
8
Target cell
T Cell
Cytotoxic T lymphocyte
Must be CD8+ killer T cells
Induce significant T cells in vivo
Antigen-specific
Activated with killing function
Go to diseased tissue
Seek and destroy diseased cells
9. The Proof: VGX-3100 Phase II in HPV Cervical Dysplasia
9
Placebo-Controlled,
Randomized, Double Blind
• Targets: HPV 16/18 E6/E7
oncogenes
• 167 subjects
• 18-55 year old females
• High-grade cervical
dysplasia (CIN2/3)
• HPV 16 and/or
18 positive
• 3:1 randomization
Primary Endpoint
• Regression of CIN2/3 to
CIN1 or normal
(6 months post third
dose: week 36)
Secondary Endpoint
• Regression of CIN2/3 to
CIN1 or normal and
clearance of HPV
10. Best-in-Class Functional T Cell Responses
Activated In Vivo…
10
Phase II study of VGX-3100 HPV antigen generating
immunotherapy in high grade cervical dysplasia
*Statistically significant; bars are 95% Cl
VGX-3100800
600
400
200
0
0 5 10 15 20 25 30 35 40
Placebo
Study Week
VGX-3100SpecificTCells
(SFU/106PBMCsAboveBaseline)
Treatment at wks 0, 4, & 12
* * * *
• 167 subjects
• Paper published in The Lancet September 2015
11. Phase II Achieves Endpoints: Clinically Significant Efficacy
11
• Efficacy correlates to immune responses
• PP and mITT p-values equal
• 167 subjects
• Paper published in The Lancet September 2015
Regression high grade
to low grade cervical
dysplasia or normal
Dysplasia regression
to low or normal AND
HPV clearance
Lesion
regression
to normal
VGX-3100 49.5% 40.2% 40.2%
Control 30.6% 14.3% 16.7%
Difference 18.9% 25.9% 23.5%
P-Value
p=0.017
strata-adjusted
p=0.001
strata-adjusted
p=0.006
strata-adjusted
Groups
Primary
Endpoint
Secondary
Endpoint
Primary –
Post Hoc
12. VGX-3100 Efficacy Visualized:
Lesion/HPV Clearance and Tumor Infiltrating T Cells
12
Week0:CIN3pathology
IHC Staining: Lesion/HPV
Week36:Nosignificantpathology
IHC Staining: CD8 +
Regression: CIN3/HPV to Normal Persistent Presence of Killer CD8s
Significant increase
of infiltrating
CD8+ T Cells
13. Proof of Principle: Technology and VGX-3100 Product
- A “First Ever” Result
13
Effective immune activating treatment
• Select and encode any antigen
• Simple injections into arm
• Generate antigen-specific CD8+ killer T cells
• Measurable in blood and observed in diseased tissue (tissue infiltrating T cells)
• Regress disease to normal
• Clear virus causing the disease
• Direct correlation between CD8+ T cells and efficacy
Immune system’s disease fighting
mechanisms are common across
all diseases
• Data supports utility of SynCon® products
across cancers and infectious diseases
Favorable safety profile
shown in over 600 treated
subjects (without serious
adverse events)
14. Data Supports Advancing HPV Immunotherapy
• Potential as first non-surgical
treatment option for cervical dysplasia
• First-line therapy preceding surgery
Phase III
• Scaling biologic and
electroporation device
production
• End-of-phase-II FDA
meeting 1H 2016
• Market, pricing and
payor research
• Planned start 2016
• Targeting other HPV-caused
neoplasia indications
14
15. EU: 15,000
HPV 16/18-Caused Pre-Cancer Annual Incidence
15
US: 195,000
EU: 233,000
US: 13,400
EU: 2,514
Annual incidences: US EU31
HIGH GRADE CERVICAL DYSPLASIA
(CIN2/3)
HIGH GRADE VULVAR NEOPLASIA
(VIN)
HIGH GRADE ANAL NEOPLASIA
(AIN)
Sources: Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B, Valencia S, Brotons M, Mena M, Cosano
R, Muñoz J, Bosch FX, de Sanjosé S, Castellsagué X. ICO Information Centre on HPV and Cancer (HPV
Information Centre). Human Papillomavirus and Related Diseases in United States of America. Summary Report
2015-03-20., Henk et al J Low Genit Tract Dis (2010), Insigna et al, Am J Obs Gyn (2004), Hartwig et al.
Papillomavir. Res (2015), CDC, www.hpvcentre.net, WHO IARC
US: 23,000
16. Strategic Implications for Immuno-Oncology
A minority of tumors have T cell responses that can respond to immune checkpoint
inhibition – and even against those tumors, checkpoint inhibitors are only realizing
20 - 40% response rates
16
Leveraging the encouraging results of checkpoint inhibitors and taking
immuno-oncology to the next level requires better T cell generation
“You can block all the
PD-L1 in the world but it
means nothing without
infiltrating T cells”
— Roy Herbst, Yale
“In the majority of patients,
T cells either need to be trafficked
to the tumor, T cells need to be
generated or both in order to see
higher response rates with the
checkpoints”
— Michael Atkins, Georgetown
17. Immuno-Oncology Clinical and Commercialization Strategy
17
Monotherapies | Single agent, multi-antigen T cell
activating immunotherapies targeting early stage or slowly
progressing cancers
1
Combination Therapies With Partners | Combine Inovio
antigen-generating immunotherapies with third party checkpoint
inhibitors or other immuno-oncology products
2
Combination Therapies In-House | Combine Inovio antigen-
generating immunotherapies with proprietary checkpoint inhibitors
or other immuno-oncology products based on DNA-based
monoclonal antibodies (dMAbs). Keep product development, IP, and
downstream profit under one roof; strategic power/flexibility
3
18. Validating Immuno-Oncology Partnership
18
Products
INO-3112 HPV-driven cancer
+ 2 new R&D products
Upfront
Payment
$27.5 million
Development
Costs
All development costs
Milestone
Payments
$700 million
Royalties
Up to double digit tiered royalties on INO-3112 +
royalties for additional cancer vaccine products
AstraZeneca/MedImmune
(August 2015)
MedImmune intends to study INO-3112 in combination with
selected immuno-oncology molecules within its pipeline
20. Antigen-Generating/T Cell Activating SynCon® Products
20
Product Name Indication Preclinical Phase I Phase II
VGX-3100
INO-5150
INO-1400
Phase III
INO-3112
Breast/Lung/Pancreatic
Cancers
Therapeutic
Prostate Cancer Therapeutic
Cervical and Head & Neck
Cancer Therapeutic
Cervical Dysplasia Therapeutic
INO-1800 Hepatitis B Therapeutic
EbolaINO-4212
Preventive
PENNVAX®-GP HIV
Preventive/
Therapeutic
INO-8000 Hepatitis C Therapeutic
Preventive/
Therapeutic
EXTERNALLY FUNDED
Infectious Disease
Programs
INTERNALLY
FUNDED
Cancer Programs
EXTERNALLY
FUNDED
Cancer Programs
GLS-5300 MERS
Preventive/
Therapeutic
INO-5400 Cancer Target Therapeutic
Zika
Preventive/
Therapeutic
GLS-5700
21. Multi-Antigen Products Position Inovio to be a Leader in
Immuno-Oncology
21
Develop multi-antigen
cancer immunotherapies
based on scientific rationale,
unmet need, and
commercial attractiveness
Create DNA plasmids for
multiple antigens to target
heterogeneous tumors
50+ well
characterized
antigens known to
have high levels of
over-expression in
cancer cells
Partnership with
MedImmune to develop
two new cancer products
Inovio will initiate a
new multi-antigen
cancer program in
2016
Plan strategic
checkpoint inhibitor
combinations
23. 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
Management
23
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
24. Board of Directors
24
Nancy Wysenski, MBA
• Former COO of Endo
Pharmaceuticals and
Vertex Pharmaceuticals
Simon X. Benito
• Former Senior Vice
President, Merck
Vaccine Division
Avtar Dhillon, MD
Chairman, BOD
• Former President
& CEO, Inovio
Biomedical
Morton Collins, PhD
• General Partner,
Battelle Ventures and
Innovations Valley
Partners
Angel Cabrera, PhD
• President, George
Mason University
• Former President,
Thunderbird School of
Global Management
J. Joseph Kim, PhD
• President & CEO,
Inovio
Adel Mahmoud, PhD
• Professor, Princeton University
• Former President, Merck
Vaccines
• Responsible for Gardasil®,
Zostavax®, Proquad® and
Rotateq®
25. Scientific Advisory Board
25
Anthony W. Ford-
Hutchinson, PhD
• Former SVP,
Vaccines R&D, Merck
• Oversaw
development:
Singulair®, Januvia®,
Gardasil®,Zostavax®,
Proquad® and
Rotateq®
Stanley A. Plotkin, MD
• Developed rubella
and rabies vaccines
• Oversaw Sanofi
flu vaccine
• Emeritus Professor,
Wistar Institute
& University of
Pennsylvania
David B. Weiner, PhD
Chairman
• “Father of DNA
vaccines”
• Dept. of Pathology
& Laboratory
Medicine, University
of Pennsylvania
Philip Greenberg, MD
• Expert in T cell
immunology
• Head, Immunology
Program, Fred
Hutchinson Cancer
Research Center
26. Financial Information
26
1March 9, 2016 2December 31, 2015
Cash & short-term investments2
$163.0 M
0 MDebt2
Shares outstanding2
72.2 M
Recent share price1 $7.02
Market cap1
$506.8 M
27. Value Drivers and Milestones
34
2016
VGX-3100
End-of-Phase II
FDA meeting
INO-3112 cervical cancer
phase II study initiation with
MedImmune and EORTC
VGX-3100 phase III
study initiation
Report Ebola vaccine
phase I immunogenicity
and safety data
27
INO-3112
Conduct checkpoint
inhibitor combo study
28. Value Drivers and Milestones
34
2016
Initiate clinical studies for
new cancer targets:
HTERT + 2 new antigens
Report INO-5150
prostate immunogenicity
data (interim)
Report INO-1400
hTERT immunogenicity
data (interim)
Submit IND for first
dMAb phase I trial
28
Report on MERS vaccine
phase I immunogenicity
and safety study
Report Zika large
animal data
29. Value Drivers and Milestones
34
Additional corporate
development deals
Additional external
funding
BEYOND
29
30. Investment Summary
30
Mono- & combo
therapy strategy
with DNA multi-
antigen & mAb
products
Best-in-class
efficacy data
from in vivo
immunotherapy
Missing link
to take T cell
therapies to
the next level
Multi billion dollar
potential across
all cancers
and infectious
diseases
Entering
phase III
3rd party
validation:
MedImmune,
Roche, DARPA,
NIAID, Lancet
Taking immunotherapy to the next level
32. SynCon® Immune Control: Antigens and T Cells by Design
32
Identify pertinent disease-specific
antigens for target disease
Encode a DNA plasmid with genetic
code for each targeted antigen
T cells eliminate cells displaying
disease-specific antigen(s)
Immune system recognizes
“foreign” antigens; activates antigen-
specific T cells and antibodies
Effective, efficient, safe in vivo T cell and antibody activation
Cellular machinery uses genetic code
to produce encoded disease antigens
ANTIGENIC
PROTEINS
Deliver plasmids into human
cells using electroporation
33. Perforin
Granulysin
GranzymeA
GranzymeB
• Lytic phenotype: patient PBMCs stimulated 120 hours in vitro with antigen. No co-
stimulation; no cytokine added at any time.
• Activation markers: CD38, CD69, CD137
• Lytic proteins: perforin, granzyme A, granzyme B, granulysin
INO-3112 Drives Antigen Specific CD8+ T Cells with Lytic
Phenotype in Patient with HPV16/18 Head & Neck Cancer
33
34. HPV 16/18
Specific CD8+
T Cell
Activation and
Expression of
Lytic Proteins
HPV 16/18
Specific
Binding
Antibody
Titers
10 of 10 patients show
cellular responses
to INO-3112
10 of 10 patients show
humoral responses
to INO-3112
Inovio Pharmaceuticals: Proprietary Data; Sardesai et al. Presentation at World Vaccine Congress, Washington DC (2015)
INO-3112 CD8+ Activation, Lytic Protein Synthesis, and Humoral Immune
Responses to HPV 16/18 Head & Neck Cancer Patient
34
35. dMAB™ Products: Development Milestones and Catalysts
35
> 6 new
publications
expected in the
next year
Two dMAb
scientific
publications
to date
Technology
development
fueled by two
DARPA grants
totaling $57M
Advance a
portfolio of over 30
dMAb products
(cancer, checkpoint
inhibitors, infectious
diseases, others)
First clinical
study planned for
2016
37. Promising Preclinical dMAb Data
DARPA awards $57M to advance dMAb application and develop products for Ebola,
influenza and antibiotic resistant bacteria
37
0%
20%
40%
60%
80%
100%
TumorClearance(%)
Cancer dMAb
Prostate cancer model in mice
(Unpublished data)
dMAb (7 of 10) Control (0 of 10)
70%
0%
0%
20%
40%
60%
80%
100%
ProtectioninChallengewithDengue
Virus(%)
Dengue dMAb
(Nature Scientific Reports 2015)
dMAb (10 of 10) Control (0 of 10)
100%
0%
