NASDAQ: INO

Taking Immunotherapy

to the Next LevelI T ’ S A L L A B O U T T H E T - C E L L S

J. Joseph Kim, Ph.D.

CEO

December 2016

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.

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 purposeDevelop

immunotherapies

and vaccines to

fight cancers and

infectious diseases

Executing “Inovio Vision 2020”

4

HPV-related pre-cancers

(VGX-3100)

Filed for marketing

approval

1Immuno-Oncology

Filed for marketing

approval or in

pivotal study

2Infectious diseases

Filed for marketing

approval or in

pivotal study

3

What We Do and

What We’ve Accomplished

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®

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.

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

VG

X-3

10

0 S

pe

cif

ic T

Ce

lls

1

Treatment at wks 0, 4, & 12

* * * *

• 167 subjects

• Published in The Lancet September 2015

• 1 Spot forming units/106 PBMCs above baseline

T Cells Infiltrate Diseased Tissue, Clear HPV

Virus and Lesion

10

We

ek 0

IHC Staining: Lesion/HPV

We

ek 3

6

IHC Staining: CD8 +

Regression of CIN3 &

HPV to normal

Increase and persistent

presence of infiltrating CD8+

killer T cells

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

Where Are We Going?

Inovio Vision 2020 Roadmap

13

1

Start PIII 1H17

Start PII 2017

VGX-3100, HPV-Related

Diseases

Filing for marketing approval by 2020

Cervical DysplasiaPhase II completed

Other HPV NeoplasiasPreparing 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 5.9% 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

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

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 CancerP1 enrollment completed

INO-5401 New Cancer TargetMulti-antigen immunotherapy + checkpoint inhibitor

INO-1400 hTERT9-cancer trial assessing immune responses

INO-3112 HPV CancerKiller T cells shown in phase I

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 ratesin most cancers

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

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

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

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

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

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

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

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

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

Appendix

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

1 x

10

-6 s

ple

en

ocy

tes

Immunized 3x with 15ug pNPresponses @2 wk post Imm

Display of GFP gene expression after

electroporation delivery into rabbit muscle

+EPE

P

Optim

ization

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 BenefitHIV 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 (%)

% R

es

po

nd

ers

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

What does an Effective T Cell Activating Immunotherapy

Need to Accomplish?

34

Target cell

T CellCytotoxic 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

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

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

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

Perforin

Gra

nu

lys

in

Gra

nzym

e A

Gra

nzym

e B

• 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

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

% C

D8

/CD

38

& C

D6

9 &

CD

13

7

B e fo r e

IN O -3 1 1 2

A fte r

IN O -3 1 1 2

Representative

patientBefore

INO-3112

After

INO-3112Before

INO-3112After

INO-3112

40

Representative IHC Image for CD8 and FoxP3

First Partnership to Initiate Immuno-Oncology Strategy

41

ProductsINO-3112 HPV-driven cancer immunotherapy

+ 2 new R&D products

Upfront

Payment$27.5 million

Development

CostsAll development costs

Milestone

Payments$700 million

RoyaltiesUp 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

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

dMAb™ Products: Multiple Immune Mechanisms & Products

Inovio’s DNA-based monoclonal antibody products target:

43

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

44

0%

20%

40%

60%

80%

100%

Tu

mo

r C

lea

ran

ce

(%

)

Cancer dMAbProstate cancer model in mice

(Unpublished data)

dMAb (7 of 10) Control (0 of 10)

70%

0%0%

20%

40%

60%

80%

100%

Pro

tec

tio

n in

Ch

all

en

ge w

ith

Den

gu

e

Vir

us

(%

)

Dengue dMAb(Nature Scientific Reports 2015)

dMAb (10 of 10) Control (0 of 10)

100%

0%

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 HIVPreventive/

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