Revolutionizing the Fight Against Cancers and Infectious Diseases

Dr. J. Joseph Kim PRESIDENT & CEO NASDAQ: INO

It’s All About the T-Cells

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, 2013, our Form 10-Q for the quarter ended September 30, 2014, and other regulatory filings from time to time.

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A Highly Compelling Weapon: T Cells

Cytotoxic T lymphocyte

T cell

Target cell

3

A Highly Compelling Weapon: T Cells

Cytotoxic T lymphocyte

T cell

Target cell

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Is There an “Ideal” T Cell-Generating Immunotherapy?

Effective, efficient, safe…

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. Do not bypass but enhances the immune system’s inherent strengths and controls.

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Inovio Active DNA Immunotherapies: It’s All About the T Cells

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 in the body (in vivo), enabling them to produce antigen

T cells eliminate cells displaying disease-specific antigen

Immune system activates antigen-specific T cells

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Effective, efficient, safe in vivo T cell activation

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• 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

Broad Medical and Market Opportunities

Product Name

INTERNALLY FUNDED OTHER Cancer Programs

Indication Preclinical Phase I Phase II

Vgx-3100

Ino-5150

Ino-1400

EXTERNALLY FUNDED Infectious Disease Programs

Ino-3510

ino-1800

Phase III

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INO-3112

INO-3112

Hepatitis B Therapeutic

influenza

Breast/lung / Pancreatic cancers

Therapeutic

Prostate cancer Therapeutic

Head & Neck Cancer Therapeutic

Cervical Cancer Therapeutic

Cervical dysplasia

Therapeutic

Preventive/ Therapeutic

Ebola

Aerodigestive Cancer Therapeutic

INO-3106

INO-4200

Preventive

INTERNALLY FUNDED HPV programs

Pennvax®- B hiv

Pennvax®-GP hiv

Preventive/ Therapeutic Preventive/ Therapeutic

Ino-8000 Hepatitis C Therapeutic

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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

LOW GRADE

CERVICAL DYSPLASIA

(CIN1)

US: 1,400,000

EU5: 1,300,000

HIGH GRADE

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

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Normal Cervical Intraepithelial Neoplasia

(CIN3) Invasive Cancer

If untreated, moderate/severe cervical dysplasia (CIN2/3) may progress to invasive cancer

Preventing Cervical Cancers: New Market Opportunity

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Non-Surgical Treatment of Cervical Dysplasia Desired

IARC Monograph 2003: Edited by J.W. Sellors and R. Sankaranarayanan

• LEEP (Loop Electrosurgical Excision Procedure) uses a high-voltage electrical arc at 100oC to vaporize a plane through the cervix • invasive, associated with pre-term births, does not fully clear HPV

• Market Research: Patient and physician desire for non-surgical first-line alternative • non-invasive; eliminate HPV in untreated tissue

Phase II: Study Design

• 148 subjects: 19-55 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

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0

10

20

30

40

50

60

Phase II: Regression of Cervical Lesions to CIN 1 or Normal

Pre-Specified 1° Endpoint: Histopathologic Regression to CIN1 or Normal

30.6% (11/36)

Statistically significant difference (p=0.017; strata-adjusted)

Post-Hoc Analysis: Regression to Normal

0

10

20

30

40

50

60

40.2% (43/107)

16.7% (6/36)

Perc

ent

VGX-3100 Placebo VGX-3100 Placebo Statistically significant difference

(p=0.006; strata-adjusted)

Overall Histopathologic Regression Incidence Per-Protocol Population (N=143)

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49.5% (53/107)

Perc

ent

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)

Perc

ent

VGX-3100 Placebo

Statistically significant difference (p=0.001; strata-adjusted)

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*Statistically significant; bars are 95% CI. IFN = interferon. .

IFN-γ ELISpot Analysis

VGX-3100 Generates HPV-16 and HPV-18 T Cell Responses

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800

600

400

200

0 0 5 10 15 20 25 30 35 40

Study Week

VGX-

3100

Spe

cific

T C

ells

(S

FU/1

06 PBM

Cs A

bove

Bas

elin

e)

* * * *

VGX-3100 Placebo

Treatment at wks 0, 4 & 12

N= 140 .

CD8 T Cells Clear Virus and Lesions in Cervical Tissue: Placebo W

eek

0: C

IN3

path

olog

y

IHC Staining: HPV

Wee

k 36

: CIN

3 pa

thol

ogy

IHC Staining: CD8 16

CD8 T Cells Clear Virus and Lesions in Cervical Tissue: VGX-3100 Treated Patients

Wee

k 0:

CIN

3 pa

thol

ogy

IHC Staining: HPV

Wee

k 36

: No

sign

ifica

nt

path

olog

y

IHC Staining: CD8 17

Powerful Impact of Successful VGX-3100 Phase II Efficacy Data

VGX-3100 is a non-surgical option for the treatment of CIN2/3

Simple 3 monthly injections generated CD8 Killer T cells

Measured in blood

Observed in cervical tissues (tissue infiltrating T cells)

Direct correlation found between CD8 T cells and efficacy

Demonstrated phase 2 efficacy and safety

Regressed disease to normal

Cleared virus which caused the disease

Disease regression - expand into other HPV-caused diseases

Other anti-cancer therapies (lung, breast, pancreas, prostate)

HPV clearance – antiviral therapies (HBV, HCV, HIV)

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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

PREPARING SCIENTIFIC PAPER FOR PEER REVIEW • Completing 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 being 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

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HPV-Associated Cancer Studies Enrolling: INO-3112

Phase I/IIa’s: INO-3112 (VGX-3100 + IL-12 DNA immune activator); HPV 16/ 18 related disease

Cervical Cancer • 20 women with cervical carcinoma • Safety, tolerability, immunogenicity • Cervical histology • Treat after chemoradiation

Head & Neck Squamous Cell Carcinoma • 20 men/women • Safety, tolerability, immunogenicity • Anti-tumor effects & progression free

survival • Arm #1: treat before/after tumor resection • Arm #2: treat after chemoradiation

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hTERT-Associated Cancers: INO-1400

• Antigen: human telomerase reverse transcriptase (hTERT), associated with cancer cell survival; overexpressed in 85% of cancers - potential “universal” cancer therapy

• +/- IL-12 DNA immune activator

• Phase I: 54 patients with breast, lung, or pancreatic cancers

• Safety, tolerability, immunogenicity

• Anti-tumor effects and progression free survival

• Trial launched: 4Q 2014

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• Multi-antigen: HBV clades A & C surface antigens & HBV core antigens

• +/- IL-12 DNA immune activator • Phase I/IIa: patients with chronic HBV

infection • Safety, tolerability, immunogenicity • Trial initiation: 1H 2015 • Trial initiation will trigger milestone

payment from Roche

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Hepatitis B: INO-1800

anthrax 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

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anthrax 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

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anthrax 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

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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

Financial Information

Cash, cash equivalents & short-term investments2 $ 100.9 M

Debt2 0 M

Cash runway 4Q 2017

Shares outstanding2 60.5 M

Recent share price1 $8.23

Market cap1 $ 497.9 M

NASDAQ: INO

1Feb 5, 2015 2Sep 30, 2014 3 From Q3 20142

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Insider buying3 > $2.75M

INTERNALLY FUNDED EXTERNALLY FUNDED

Ino-1400 4Q 2014 Initiated phase I

Breast, Lung, And Pancreatic Cancer

Vgx-3100 2016 Initiate phase III Cervical dysplasia

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Value Drivers

INO-3112 2015 Report interim data

Head & Neck and Cervical Cancer

Ino-8000 2015 Report interim phase I data

Hepatitis C

Ino-1800 1H 2015 Initiate phase I/IIa

Hepatitis B

Ebola 1H 2015 Initiate phase I INO-4200

Ino-5150 1H 2015 Initiate phase I

Prostate cancer

PennVAX®

1H 2015 Initiate PENNVAX-GP phase I HIV

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 platform

Validating partnership with Roche

Lead product met phase II

efficacy endpoints

Investor Highlights

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Revolutionizing the Fight Against Cancers and Infectious Diseases

It’s All About the T-Cells

Strain 1

Strain X

Strain 2

Antigen Y

Antigen Y Antigen Y

T Cells by Design: Antigen-Specific, Optimized, Best-in-Class

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Identify gene sequence of selected antigen(s) from chosen strains/variants of the virus/cancer

Synthetically create optimal consensus gene sequence for the selected antigen – PATENTABLE

Insert SynCon® gene sequence for selected antigen into DNA plasmid.

SYNCON® DNA

Antigen consensus

sequence

DNA Plasmid

Designed to Break Tolerance or Provide Universal Protection

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SynCon DNA plasmid ready to manufacture.

Electroporation Delivery Plays a Vital Role

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SynCon®+ Electroporation: Significant Antigen Expression

Ref: Sardesai & Weiner Curr. Opin. Immunol. 2011

• 1000x increase in cellular uptake and antigen production/ expression

• >500 patents globally

Intramuscular Intradermal

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Inovio Beats Previous Gold Standard for T Cell Generation DNA/Electroporation vs Merck Ad5 Viral Vector (Non-Human Primates)

SIV Model: UPenn/Merck/Inovio Assay: Data Co-Published

T Cell ELISpot Assay T Cell Proliferation Assay

DNA + EP Ad5 DNA + EP Ad5

Ref: Hirao et al. Molecular Therapy, August 2010

Flow Cytometry Assay

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Ad5 DNA + EP Ad5 DNA + EP

PENNVAX®: Highest CD8+ T Cell Responses for HIV Vaccine

Ref: Kalams et al JID 2013 35

A: 3X vaccination without EP B: 4X vaccination without EP C: 2x vaccination with EP (month 2) D: 3x vaccination with EP (month 4) E: Memory response (month 9)

A B C D E

• Best CD8+ T cell response in HIV clinical studies

• Durable T cell memory responses • Safe and well tolerated

0 1 2 3 4 5 6 7 8 9 Dosing Schedule (Months)

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HPV 16 E6 HPV 16 E7

VGX-3100: HPV16,18 E6/E7 Immunotherapy

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*Deletions or mutations important for p53 binding and degradation

Mutations in Rb binding site

pCon18E6E7

IgELS Endoproteolytic cleavage site

* * *

pCon16E6E7

HPV 18 E6 HPV 18 E7

IgELS Endoproteolytic cleavage site

* * *

Phase I summary: VGX-3100 is safe, tolerable and generates antigen-specific cellular responses

Bagarazzi et al., Sci Transl Med. (2012)

Safety: IM injection of VGX-3100 + CELLECTRA® EP – Well tolerated – No discontinuations, related SAEs, or grade 3 or 4 AEs Tolerability: Measured by visual analog scale (VAS) – Moderate pain (mean VAS score of 6 out of 10) experienced immediately after

injection; dissipates rapidly after 10 minutes

Immunogenicity: – High titers of antibody against all four antigens (ELISA, Western Blot)

– Antigen-specific cellular responses to HPV 16 and 18 E6/E7 (IFN-γ ELISpot)

– Cytotoxic T-lymphocyte (CTL) phenotype (Granzyme B/perforin release assay)

– No effect of pre-existing Treg cells – Primarily effector memory phenotype

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Combined Cohorts Individual Dose Cohorts

VGX-3100 Induces Robust and Durable T Cell Responses

Bagarazzi, Yan, Morrow et al. Sci Transl Med 4, 155ra138 (2012)

• 14/18 (78%) subjects responded to at least one antigen • 13/18 (72%) responded to at least two antigens • 9/18 (50%) responded to all four antigens

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ELISpot Assay

0 1 2 3 4 5 6 7 8 9 Dosing Schedule (Months)

Bagarazzi, Yan, Morrow et al, Science Trans. Med. (2012)

HPV16-, HPV18-Specific IFN-γ Production

Multi-parameter flow cytometry: CD4, CD8 activation phenotype

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HPV16-, HPV18-Specific CD107a, Granzyme B, Perforin

Bagarazzi, Yan, Morrow et al, Science Trans. Med. (2012)

CD8 cytolytic phenotype

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VGX-3100 Flow Cytometry – Functional Killing Assays

Inovio Confidential Bagarazzi, Yan, Morrow et al. Sci Transl Med 4, 155ra138 (2012)

Quantitative Assay

Qualitative Assay

• Patient pre-VGX-3100 PBMC are targets, post-VGX-3100 PBMC are effectors • Quantitative - PBMC added irrespective of Ag-specific CD8 frequency • Qualitative - PBMC normalized to account for Ag-specific CD8 frequency • Measure granzyme B delivery to targets

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Phase II: Study Timeline

Wk 6 -10 weeks to -1day (begins at initial biopsy)

S

Wk 2

Day 0

E

Wk 4 Wk 12

Wk 14 Wk 24 Wk 62 Wk 88

DC

Wk 36

Histopathology

Wk 40

21-month protocol • 3-month (0, 4, 12 week) regimen • +6 months to primary endpoint • +12 months long-term follow-up

DC = discharge; E = enrollment; S = screening; Wk = week. Data on file, Inovio. 42

INO-1400: Potential Universal Cancer Therapy Targeting hTERT (overexpressed in 85% of cancers)

Yan J et al., Cancer Immunol Res. (2013) 43

Dharmapuri et al., Mol Ther. (2009)

T-cell generation: older generation DNA vaccine and electroporation device

SynCon® T-cell generation with CELLECTRA® electroporation device