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NASDAQ: INO
Taking Immunotherapy
to the Next Level
I T ’ S A L L A B O U T T H E T - C E L L S
J. Joseph Kim, Ph.D.
President & CEO
March 2017
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 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, 2016 and other regulatory filings from time to
time.
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
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
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
1300 subjects and 3800 immunizations
Immune Responses by Design
5
SynCon
Immunotherapy
Optimized platform: SynCon® + CELLECTRA®
Inovio Vision 2020 Roadmap
6
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)
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 5.6% 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
7
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
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)
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
CD8+ 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
“Cold”
“Hot”
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
HPV Cervical Dysplasia Phase III
• Scaled biologic manufacturing to
commercial facility
• Completed CELLECTRA® commercial
delivery device design, manufacturing
process, production
• Phase III trial design similar to phase II
• < 400 total subjects
• Phase III trial package submitted. FDA
requested additional device-related
information; placed program on clinical hold
prior to initiation
• Aim to initiate phase III in 1H 2017
12
Goal: Commercialize first medical alternative focused on
preserving women’s reproductive health; regress HPV-
caused lesions and eradicate virus itself
Inovio Vision 2020 Roadmap
13
2Immuno-Oncology
One pivotal study
or filing for marketing
approval by 2020
IO combination
trial start 1H17
Preliminary data 1H17
Start PI/II 1H17
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
Checkpoint
inhibitors
combined with
Inovio’s cancer
vaccines
Two studies
starting in 2017:
- INO-3112 with
MedImmune
- INO-5401
Checkpoint
combinations
Modestly higher
response rates
Toxicity up
DRAMATICALLY
Holy Grail of Immuno-Oncology:
Turning “Cold” Tumors to “Hot” Tumors
Need presence of robust, antigen-
specific, functional CD8+ killer
T cells to leverage the capabilities
of checkpoint inhibitors: KOLs
14
Checkpoint
monotherapies
Few tumors
responsive.
Successes: only
15-20%
response rates
in most cancers
15
Turning “Cold” Tumors to “Hot” Tumors
Before treatment
with INO-3112
After treatment
with INO-3112
Control: FoxP3 CD8
Inovio Vision 2020 Roadmap
16
3Infectious Diseases
One pivotal study
or filing for marketing
approval by 2020
P1 data 2H17
Additional data
1H17
Immune response
data 1H17
Additional 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
Two phase I studies
Post Challenge (Days)
0 5 10 15 20 25 30
0
20
40
60
80
100
%Survival
ZIKV-prME (x1)
pVax1
n=10
2x106
X20
X20
X20
X40
X20
X20
iv
i ii
iii
pVax1 ZIKV-prME
v
vi
• ZIKV infection caused severe brain pathology in mice
• In contrast, vaccinated animals presented with normal histopathology in brain tissues
• Data supporting that protective antibodies induced by synthetic ZIKA-prME vaccine
could limit viral induced disease in the brain
GLS-5700 Zika Vaccine Protects from Death and Illness
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, Gates $8.8M
• Priority review voucher potential
• Stockpiling contracts: scale manufacturing
• Commercial opportunity for some diseases
18
DNA
Alternative Technologies
Design
DNA
Alternative Technologies
Manufacturing
Development Time Frames
Management & Financials
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
20
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
Board of Directors
21
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
Scientific Advisory Board
22
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
Financial Information
23
1March 10, 2017 2December 31, 2016
3 Due from ApolloBio Corp: up to $50M in signing
fee, milestone and equity investment, the latter two
contingent upon lifting of clinical hold
Cash & short-term investments2 3
$104.8 M
0 MDebt2
Shares outstanding2
74.1 M
Recent share price1 $6.68
Market cap1
$494.9 M
Publish Zika phase I
immune response and
safety data
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 (CIN)
phase III study
initiation
Report INO-5150
(prostate) immune
response and safety
data (interim)
Upcoming Value Drivers and Milestones
24
VGX-3100 (VIN)
phase II study
initiation
Investment Thesis: Inovio Positioned with Multiple
Transformational Steps as an Immunotherapy Leader
Taking immunotherapy to the next level
25
Powerful technology
platform
Best-in-class data
Entering phase III
Validation: partners,
publishing, grants
INO:
NASDAQ
Appendix
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
27
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.
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
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
CELLECTRA® 5PSP Electroporation Delivery Device
30
Array
Drug
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
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
† 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
antigens/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
First Partnership to Initiate Immuno-Oncology Strategy
34
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
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
35
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
36
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
dMAb™ Products: Multiple Immune Mechanisms & Products
Inovio’s DNA-based monoclonal antibody products target:
37
Cancers Infectious Diseases
• Influenza A
• Influenza B
• Pseudomonas
• MRSA/Staph
• Ebola
• MERS
• Dengue
• CHIKV
• Other infectious
diseases
• Checkpoint Inhibitors
(CI)
• PD-1
• PD-L1
• 4 additional CIs
• Herceptin
• Anti-Tregs
• Other anti-cancer
pathways
DARPA funded programs
Promising Preclinical dMAb Data
DARPA awards $57M to advance dMAb application and develop products for Ebola,
influenza and antibiotic resistant bacteria
38
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%
Antigen-Generating/T Cell Activating SynCon® Products
39
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

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Inovio Pharmaceuticals - Corporate Presentation

  • 1. NASDAQ: INO Taking Immunotherapy to the Next Level I T ’ S A L L A B O U T T H E T - C E L L S J. Joseph Kim, Ph.D. President & CEO March 2017
  • 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 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, 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
  • 5. 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 1300 subjects and 3800 immunizations Immune Responses by Design 5 SynCon Immunotherapy Optimized platform: SynCon® + CELLECTRA®
  • 6. Inovio Vision 2020 Roadmap 6 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)
  • 7. 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 5.6% 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 7 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
  • 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. CD8+ 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 “Cold” “Hot”
  • 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
  • 12. HPV Cervical Dysplasia Phase III • Scaled biologic manufacturing to commercial facility • Completed CELLECTRA® commercial delivery device design, manufacturing process, production • Phase III trial design similar to phase II • < 400 total subjects • Phase III trial package submitted. FDA requested additional device-related information; placed program on clinical hold prior to initiation • Aim to initiate phase III in 1H 2017 12 Goal: Commercialize first medical alternative focused on preserving women’s reproductive health; regress HPV- caused lesions and eradicate virus itself
  • 13. Inovio Vision 2020 Roadmap 13 2Immuno-Oncology One pivotal study or filing for marketing approval by 2020 IO combination trial start 1H17 Preliminary data 1H17 Start PI/II 1H17 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
  • 14. Checkpoint inhibitors combined with Inovio’s cancer vaccines Two studies starting in 2017: - INO-3112 with MedImmune - INO-5401 Checkpoint combinations Modestly higher response rates Toxicity up DRAMATICALLY Holy Grail of Immuno-Oncology: Turning “Cold” Tumors to “Hot” Tumors Need presence of robust, antigen- specific, functional CD8+ killer T cells to leverage the capabilities of checkpoint inhibitors: KOLs 14 Checkpoint monotherapies Few tumors responsive. Successes: only 15-20% response rates in most cancers
  • 15. 15 Turning “Cold” Tumors to “Hot” Tumors Before treatment with INO-3112 After treatment with INO-3112 Control: FoxP3 CD8
  • 16. Inovio Vision 2020 Roadmap 16 3Infectious Diseases One pivotal study or filing for marketing approval by 2020 P1 data 2H17 Additional data 1H17 Immune response data 1H17 Additional 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 Two phase I studies
  • 17. Post Challenge (Days) 0 5 10 15 20 25 30 0 20 40 60 80 100 %Survival ZIKV-prME (x1) pVax1 n=10 2x106 X20 X20 X20 X40 X20 X20 iv i ii iii pVax1 ZIKV-prME v vi • ZIKV infection caused severe brain pathology in mice • In contrast, vaccinated animals presented with normal histopathology in brain tissues • Data supporting that protective antibodies induced by synthetic ZIKA-prME vaccine could limit viral induced disease in the brain GLS-5700 Zika Vaccine Protects from Death and Illness
  • 18. 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, Gates $8.8M • Priority review voucher potential • Stockpiling contracts: scale manufacturing • Commercial opportunity for some diseases 18 DNA Alternative Technologies Design DNA Alternative Technologies Manufacturing Development Time Frames
  • 20. 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 20 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
  • 21. Board of Directors 21 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
  • 22. Scientific Advisory Board 22 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
  • 23. Financial Information 23 1March 10, 2017 2December 31, 2016 3 Due from ApolloBio Corp: up to $50M in signing fee, milestone and equity investment, the latter two contingent upon lifting of clinical hold Cash & short-term investments2 3 $104.8 M 0 MDebt2 Shares outstanding2 74.1 M Recent share price1 $6.68 Market cap1 $494.9 M
  • 24. Publish Zika phase I immune response and safety data 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 (CIN) phase III study initiation Report INO-5150 (prostate) immune response and safety data (interim) Upcoming Value Drivers and Milestones 24 VGX-3100 (VIN) phase II study initiation
  • 25. Investment Thesis: Inovio Positioned with Multiple Transformational Steps as an Immunotherapy Leader Taking immunotherapy to the next level 25 Powerful technology platform Best-in-class data Entering phase III Validation: partners, publishing, grants INO: NASDAQ
  • 27. 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 27 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.
  • 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
  • 30. CELLECTRA® 5PSP Electroporation Delivery Device 30 Array Drug
  • 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 antigens/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. First Partnership to Initiate Immuno-Oncology Strategy 34 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
  • 35. 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 35
  • 36. 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 36 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
  • 37. dMAb™ Products: Multiple Immune Mechanisms & Products Inovio’s DNA-based monoclonal antibody products target: 37 Cancers Infectious Diseases • Influenza A • Influenza B • Pseudomonas • MRSA/Staph • Ebola • MERS • Dengue • CHIKV • Other infectious diseases • Checkpoint Inhibitors (CI) • PD-1 • PD-L1 • 4 additional CIs • Herceptin • Anti-Tregs • Other anti-cancer pathways DARPA funded programs
  • 38. Promising Preclinical dMAb Data DARPA awards $57M to advance dMAb application and develop products for Ebola, influenza and antibiotic resistant bacteria 38 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%
  • 39. Antigen-Generating/T Cell Activating SynCon® Products 39 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