2. Forward Looking Statement
2
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, our Form 10-Q for the quarter
ended September 30, 2016, and other regulatory filings from time to
time.
3. Leading the Development of DNA-based Immunotherapies
to Commercialization
3
Powerful platform,
multiple products
Efficacy in
phase II study
Phase III and
immuno-oncology
combo studies starting 1H17
Major partnership:
MedImmune/AstraZeneca
Our purpose
Develop
immunotherapies
and vaccines to
fight cancers and
infectious diseases
4. Executing “Inovio Vision 2020”
4
HPV-related pre-cancers
(VGX-3100)
Filed for marketing
approval
1
Immuno-Oncology
Filed for marketing
approval or in
pivotal study
2
Infectious diseases
Filed for marketing
approval or in
pivotal study
3
6. CELLECTRA
5PSP Device
• SynCon® antigen genetic code enables
precise targeting of cancer or pathogen
• Designed to break tolerance and
cover mutating strains
• Highly optimized SynCon plasmid +
novel CELLECTRA delivery generate
optimal antigen production IN THE
BODY
• Activates robust functional CD8+ killer
T cell and antibody responses
• Phase II efficacy
• Highly favorable safety profile in over
1200 subjects and 3000 immunizations
Immune Responses by Design
6
SynCon
Immunotherapy
Optimized platform: SynCon® + CELLECTRA®
7. Right Immune Targets,
Genetic Sequences &
Delivery Method
Immune Responses
Validated in Humans
T Cell Related
Efficacy in Humans
Late Stage Development
& Commercialization
2005-2009 2010-2013 2014-2016 2017-2020+
Inovio Refines and Validates DNA Immunotherapies
Inovio has built leading knowledge capital and IP
7
Breakthrough in
vivo generation of
immune responses
in large animals.
Integrated technology
platform achieves
robust immune
responses in humans.
Killer T cells
generated in the
body correlated to
efficacy.
Strong immune
responses across
multiple diseases.
Launching P3 and
combo cancer studies.
Pursuing efficacy data
in multiple studies.
8. Demonstrated Efficacy in Phase II Trial of VGX-3100
8
Placebo-Controlled,
Randomized, Double Blind
• VGX-3100 SynCon® product
for HPV-related pre-cancers
• Targets HPV 16/18
subtypes, 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
• Dosing: week 0, 4, 12
Primary Endpoint
• Regression of CIN2/3
to CIN1 or normal
(week 36)
Secondary Endpoint
• Regression of CIN2/3
to CIN1 or normal and
clearance of HPV
(week 36)
9. Robust Functional Antigen-Specific T Cells
Measured in Blood
9
*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-3100SpecificTCells1
Treatment at wks 0, 4, & 12
* * * *
• 167 subjects
• Published in The Lancet September 2015
• 1 Spot forming units/106 PBMCs above baseline
10. T Cells Infiltrate Diseased Tissue, Clear HPV
Virus and Lesion
10
Week0
IHC Staining: Lesion/HPV
Week36
IHC Staining: CD8 +
Regression of CIN3 &
HPV to normal
Increase and persistent
presence of infiltrating CD8+
killer T cells
11. Phase II Achieves Primary and Secondary Endpoints
11
• Efficacy correlates to immune responses
• PP and mITT p-values equal
• 167 subjects
• Paper published in The Lancet September 2015
• 1Strata-adjusted
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-value1
p=0.017 p=0.001 p=0.006
Groups
Primary
Endpoint
Secondary
Endpoint
Primary –
Post Hoc
13. Inovio Vision 2020 Roadmap
13
1
Start PIII 1H17
Start PII 2017
VGX-3100, HPV-Related
Diseases
Filing for
marketing approval
by 2020
Cervical Dysplasia
Phase II completed
Other HPV Neoplasias
Preparing INDs (VIN, AIN)
14. Fulfill Unmet Treatment Needs of HPV Related Diseases
High Grade Cervical Dysplasia (CIN 2/3)
• Current CIN excisional and ablative
procedures increase risk of pre-term births
from 5.9% to 10.7%;
Kyrgiou et al meta-analysis published June 2016 in
British Medical Journal
• Existing procedures cannot eliminate HPV
outside treated area; recurrence risk post-
LEEP is 10 – 16%
• VGX-3100: potential first-line therapy; first
non-surgical treatment option
Vulvar & Anal Neoplasias
• No good existing treatments
• Surgery is disfiguring
14
EU: 15,000
US: 195,000
EU: 233,000
US: 13,400
EU: 2,514
CIN2/3
VIN
AIN
US: 23,000
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
Annual Incidence
15. HPV Cervical Dysplasia Phase III
• Scaled biologic manufacturing to commercial
facility
• Completed CELLECTRA® commercial
delivery device design, manufacturing
process, production
• Constructive end of phase II meeting with
FDA 2Q 2016
• Phase III trial design similar to phase II
• < 400 total subjects
• Trial package submitted to FDA in Sept.
• FDA requested additional device-related
information, including shelf life data; placed
program on clinical hold prior to initiation
• Aim to initiate phase III in 1H 2017
15
Goal: Commercialize first medical alternative focused on
preserving women’s reproductive health; regress HPV-
caused lesions and eradicate virus itself
16. Inovio Vision 2020 Roadmap
16
2Immuno-Oncology
One pivotal study
or filing for marketing
approval by 2020
IO combination
trial start 1Q17
Preliminary data 1H17
Start PI/II 1Q17
INO-5150
Prostate Cancer
P1 enrollment completed
INO-5401 New Cancer Target
Multi-antigen immunotherapy
+ checkpoint inhibitor
INO-1400 hTERT
9-cancer trial assessing
immune responses
INO-3112 HPV Cancer
Killer T cells shown
in phase I
17. Checkpoint
inhibitors
combined with
Inovio’s cancer
vaccines
?
Checkpoint
combinations
Modestly higher
response rates
Toxicity up
DRAMATICALLY
Progressing Checkpoint Inhibitors Points to Combination
with Active (and Safe) T Cell Generation
Need presence of robust, antigen-
specific, functional CD8+ killer
T cells to leverage the capabilities
of checkpoint inhibitors: KOLs
17
Checkpoint
monotherapies
Few tumors
responsive.
Successes: only
15-20%
response rates
in most cancers
18. Inovio Vision 2020 Roadmap
18
3Infectious Diseases
One pivotal study
or filing for marketing
approval by 2020
P1 data 2H17
Additional data
early 2017
Immune response
data 1H17
Possible efficacy
data 2017
Discuss
potential
regulatory
path 2017
CHRONIC INFECTIONS
INO-1800 HBV
P1 enrolling
INO-4212 Ebola
P1 expanded: 200 patients
EMERGING INFECTIONS
GLS-5300 MERS
P1 fully enrolled
GLS-5700 Zika
2nd P1: Puerto Rico
19. Emerging Disease Vaccine Development Opportunities
Rapid response technology platform
desired by health authorities to
fight emerging infectious diseases
• Inovio technology demonstrates rapid design,
manufacturing, and clinical development of
new vaccines, e.g. Zika
• Financial drivers
• Grants, such as DARPA $45M Ebola
award
• Priority review voucher potential
• Stockpiling contracts: scale manufacturing
• Commercial opportunity for some diseases
19
DNA
Alternative Technologies
Design
DNA
Alternative Technologies
Manufacturing
Development Time Frames
21. 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
21
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
22. Board of Directors
22
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
• Seasoned venture
capitalist and biotech
entrepreneur
Morton Collins, PhD
• General Partner,
Battelle Ventures and
Innovations Valley
Partners
Angel Cabrera, PhD
• President, George
Mason University
J. Joseph Kim, PhD
• President & CEO,
Inovio
Adel Mahmoud, PhD
• Professor, Princeton Univ.
• Former President, Merck
Vaccines
• Responsible for Gardasil®,
Zostavax®, Proquad® and
Rotateq®
David B. Weiner, PhD
• Executive VP, The
Wistar Institute;
Director, Vaccine
Center
23. Scientific Advisory Board
23
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”
• Executive VP, The
Wistar Institute;
Director, Vaccine
Center
24. Financial Information
24
1December 12, 2016 2September 30, 2016
Cash & short-term investments2
$119.7 M
0 MDebt2
Shares outstanding2
74.0 M
Recent share price1 $7.03
Market cap1
$520.2 M
ATM facility in place
25. Report Zika phase I
immune response and
safety data (interim)
Report MERS phase I
immune response and
safety data (interim)
Advance INO-5401
new cancer target
program
Publish Ebola clinical
data in peer-reviewed
manuscript
INO-3112
Initiate checkpoint
inhibitor combo study
VGX-3100 phase III
study initiation
Report INO-5150
(prostate) and INO-1400
(hTERT) immune
response and safety
data (interim)
Upcoming Value Drivers and Milestones
25
26. Investment Thesis: Inovio Positioned with Multiple
Transformational Steps as an Immunotherapy Leader
Taking immunotherapy to the next level
26
Powerful technology
platform
Best-in-class data
Entering phase III
Validation: partners,
publishing, grants
INO:
NASDAQ
28. Optimized DNA with Safe & Effective Delivery to Generate
Significant T Cells with Killing Activity
28
Synthetic
Consensus
DNA
Protective universal antibodies
and killer T-cells produced by
immune system against a virus
or cancer self-antigen
29. Enhanced Cellular Delivery:
Key Enabler of DNA Immunotherapies
• DNA plasmids must get through
protective membrane into a cell
to work
• Best method to enhance cellular
uptake is electroporation
• SynCon® DNA plasmid and
CELLECTRA® delivery device
are phase III ready
29
CELLECTRA® 5PSP Device
31. Natural Immune Activation in the Body
31
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 disease antigens
ANTIGENIC
PROTEINS
Deliver plasmids into human
cells using electroporation
32. 0
1000
2000
3000
4000
5000
T Cell Responses By ELISpot Assay
1x10-6spleenocytes
Immunized 3x with 15ug pNP
responses @2 wk post Imm
Display of GFP gene
expression after
electroporation delivery
into rabbit muscle
+EPEP
Optimization
Design + Delivery = Improved Immune Responses
32
33. † HVTN 080 (N = 48 total). Responses shown against
global peptides post-third dose, based on evaluable
responders.
‡ HVTN 070 (N = 120 total). Responses shown against
global peptides post-third dose, based on evaluable
responders.
Clinical Confirmation of Inovio Electroporation Benefit
HIV Antigen Response
• CD4 and CD8 intracellular
cytokine staining (IFN-γ, IL-2)
response associated with IL-12
and EP administration (2 clinical
studies) with HIV Gag, Pol, Env
plasmids
• Dosing at 0, 4, 12 weeks
• Performed by independent HVTN
Core Lab at University of
Washington in NIH-sponsored
Trials
0
10
20
30
40
50
60
70
80
90
- IL-12 + IL-12 - IL-12 + IL-12
CD4+ Responders (%) CD8+ Responders (%)
%Responders
33
+ EP
- EP
Spyros A. Kalams, et al., The Journal of Infectious Diseases 2013;208:818–29
Responses to three doses of vaccine
delivered with EP are greater than
responses to four doses of vaccine
delivered IM
P= 0.0003
P < 0.0001
34. What does an Effective T Cell Activating Immunotherapy
Need to Accomplish?
34
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
35. Zika: Growing Epidemic, Major Medical Impacts
Disease status
• 68 countries with local transmission: only 33 in February
• Mosquito transmission in multiple US areas
• Notable new outbreak in Singapore
• Sexual transmission
• No vaccine or treatment
Medical impacts
• Microcephaly
• Guillain-Barre
• Observations of other long term neurological
effects in children and adults
Opportunity
• Grants, priority review voucher, stockpiling
• Potential preventive vaccine market for travelers and
females prior to child-bearing years
35
36. Inovio: First Zika Animal Data, First Human Studies
WHO declares Zika emergency Feb. 1
Inovio: first positive animal data Feb. 17
First human study June 20
• Phase 1 open label study
• 40 healthy subjects
• 3 sites in US and Canada
• Assessing safety and immune responses
• Data by year end
First human study in epidemic region
36
Spreading Zika Image: HealthMap• Inovio’s second human study August 29
• Puerto Rico: CDC estimates infection rate to reach 25% by year end
• Unique opportunity to assess rate of infection in vaccinated subjects
• Randomized, placebo-controlled, double blind
• 80 in each of vaccine and placebo groups
• Safety, immune responses, preliminary efficacy signals
• Aim to discuss regulatory path with FDA in 2017
37. Building off the Initial Success of Checkpoint Inhibition
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
37
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
38. 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
38
39. HPV 16/18
Specific CD8+
T Cell
Activation
HPV 16/18
Specific CD8+
T Cell
Activation and
Expression of
Lytic Proteins
8 of 9 patients show
CD8+ responses
to INO-3112
Induction of CD8+ Activation, Lytic Protein Synthesis, and Humoral Immune
Responses to HPV 16 and 18 in INO-3112 Treated HNSCC Patient
39
0 .0
0 .2
0 .4
0 .6
0 .8
1 .0
IN O -3 1 1 2
%CD8/CD38&CD69&CD137
B e fo r e
IN O -3 1 1 2
A fte r
IN O -3 1 1 2
Representative
patient
Before
INO-3112
After
INO-3112
Before
INO-3112
After
INO-3112
41. First Partnership to Initiate Immuno-Oncology Strategy
41
Products
INO-3112 HPV-driven cancer immunotherapy
+ 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
(deal signed August 2015)
MedImmune intends to study INO-3112 in combination with
selected immuno-oncology molecules within its pipeline
42. dMAB™ Products: Development Milestones and Catalysts
42
> 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
2017
44. Promising Preclinical dMAb Data
DARPA awards $57M to advance dMAb application and develop products for Ebola,
influenza and antibiotic resistant bacteria
44
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%
45. Antigen-Generating/T Cell Activating SynCon® Products
45
Product Name Indication Preclinical Phase I Phase II
VGX-3100
INO-5150
INO-1400
Phase III
INO-3112
hTERT (antigen) Therapeutic
Prostate Cancer Therapeutic
HPV-Related Cancers Therapeutic
Cervical Dysplasia Therapeutic
INO-1800 Hepatitis B Therapeutic
EbolaINO-4212
Preventive
PENNVAX®-GP HIV
Preventive/
Therapeutic
INO-8000 Hepatitis C Therapeutic
Preventive
EXTERNALLY FUNDED
Infectious Disease
Programs
INTERNALLY
FUNDED
Cancer Programs
EXTERNALLY
FUNDED
Cancer Programs
GLS-5300 MERS Preventive
INO-5401 Cancer Target Therapeutic
Zika PreventiveGLS-5700
Hinweis der Redaktion
Three Phase II studies underway – interim data from two in 2012Three additional Phase I studies to report data by 1H 2012
Three Phase II studies underway – interim data from two in 2012Three additional Phase I studies to report data by 1H 2012
(cause 70% of cervical cancers)Powered to detect efficacyStudy timelineLaunched 1Q 2011; enrollment underway Enrollment: 1 – 1 ½ yearsPotential extension to CIN 1; cervical cancer; other anogenital and head & neck cancers; additional HPV types
222,000 deathsWilms' tumor gene 1 (WT1) is overexpressed in the majority (70-90%) of acute leukemias and has been identified as an independent adverse prognostic factor, a convenient minimal residual disease (MRD) marker and potential therapeutic target in acute leukemia.
SVR from SOC only for genotype 1 virus: typically 40-50%