inovio pharmaceuticals, inc. - corporate presentation

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Revolutionizing the Fight Against Cancers and Infectious Diseases Dr. J. Joseph Kim PRESIDENT & CEO NASDAQ: INO

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Page 1: Inovio Pharmaceuticals, Inc. - Corporate Presentation

Revolutionizing the Fight Against Cancers and Infectious Diseases

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

Page 2: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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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Page 3: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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• Industry first: clinically significant efficacy

from killer T cells generated in the body

• Lead DNA immunotherapy product meets phase II endpoints

• Favorable safety profile

First-in-Class Efficacy from an Active Immunotherapy

Page 4: Inovio Pharmaceuticals, Inc. - Corporate Presentation

T-cells: Inovio Commands the Body’s SWAT Team

Cytotoxic T lymphocyte

T cell

Target cell

• Best-in-class T cell generation in vivo: o Antigen-specific o Robust o Functional, with “killing

tools” granzyme and perforin

o Durable o No unwanted immune

response against vector o No toxic inflammatory

response

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Page 5: Inovio Pharmaceuticals, Inc. - Corporate Presentation

DNA Immunotherapies: Disease-Specific T Cells by Design

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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Page 6: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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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

Page 7: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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

Pennvax®- B

Ino-3510

Ino-8000

ino-1800

Phase III

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INO-3112

INO-3112

Hepatitis C Therapeutic Hepatitis B Therapeutic

influenza

Preventive

hiv

Preventive/ Therapeutic

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

Pennvax®-GP hiv

Preventive/ Therapeutic Preventive/ Therapeutic Preventive

INTERNALLY FUNDED HPV programs

Page 8: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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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

Page 9: Inovio Pharmaceuticals, Inc. - Corporate Presentation

Human Papillomavirus

Low Grade Cervical

Pre-cancer (CIN 1)

High Grade Cervical

Pre-cancer (CIN 2/3)

Preventing Cervical Cancers: New Market Opportunity

• Treat HPV-associated cervical pre-cancers

• Standard of care (LEEP): invasive, associated with pre-term births, does not fully clear HPV

• Patient and physician desire for non-surgical first-line alternative

• non-invasive • eliminate HPV in untreated tissue

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Disease Progression

Cervical Cancer

Page 10: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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)

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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Page 11: Inovio Pharmaceuticals, Inc. - Corporate Presentation

0

10

20

30

40

50

60

Phase II: Clinically Significant Efficacy; Achieves Endpoints

Histopathologic Regression from CIN2/3 to CIN1 or Normal (n=143)

49.5% (53/107)

30.6% (11/36)

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

Perc

ent

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 VGX-3100 Placebo Statistically significant difference

(p=0.001; strata-adjusted)

• Efficacy: high level of complete CIN2/3 clearance

• Robust HPV-specific CD8+ killer T cells in majority of treated subjects, as in phase I

• Well-tolerated with only administration site redness 11

Page 12: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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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Page 13: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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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Page 14: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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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Page 15: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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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Page 16: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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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Page 17: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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

Page 18: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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 $9.28

Market cap1 $ 561.4 M

NASDAQ: INO

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

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Insider buying3 > $2.75M

Page 19: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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

PennVAX®

1H 2015 Initiate PENNVAX-GP phase I HIV

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

Page 20: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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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Page 21: Inovio Pharmaceuticals, Inc. - Corporate Presentation

Revolutionizing the Fight Against Cancers and Infectious Diseases

Page 22: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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

Page 23: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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.

Page 24: Inovio Pharmaceuticals, Inc. - Corporate Presentation

Electroporation Delivery Plays a Vital Role

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Page 25: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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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Page 26: Inovio Pharmaceuticals, Inc. - Corporate Presentation

CIN 2/3

Immuno-oncology Strategy: CIN 2/3 & Beyond

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Page 27: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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

Ref: Kalams et al JID 2013 27

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)

Page 28: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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

Page 29: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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)

Page 30: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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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Page 31: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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

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

CD8 cytolytic phenotype

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Page 32: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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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Page 33: Inovio Pharmaceuticals, Inc. - Corporate Presentation

Surgical Standard of Care for CIN2/3: LEEP

• High-voltage electrical arc at 100oC vaporizes a plane through the cervix, then fulguration using a cautery

• Black, particulate “coffee ground” discharge for weeks

IARC monograph 2003:Edited by J.W. Sellors and R. Sankaranarayanan 33

Page 34: Inovio Pharmaceuticals, Inc. - Corporate Presentation

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

Yan J et al., Cancer Immunol Res. (2013) 34

Dharmapuri et al., Mol Ther. (2009)

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

SynCon® T-cell generation with CELLECTRA® electroporation device