Revolutionizing Vaccines Dr. J. Joseph Kim President & CEO NYSE MKT: INO
Revolutionizing Vaccines
Dr. J. Joseph Kim President & CEO NYSE MKT: INO
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, and other regulatory filings from time to time.
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2013: Dynamic Year • Best T cell responses in published clinical studies • Validating license deal with Roche in 2013
2014: Transformative Year
• Phase II efficacy and immunogenicity data from lead drug mid-year
• More cancer trials starting (cervical, head & neck, prostate, breast, lung, pancreatic cancers)
• Additional pharma discussions on-going
Inovio: Global Leader in Active Immune Therapy
• Collaborating with a global leader in innovative cancer drugs • Develop and commercialize Inovio’s prostate cancer (INO-5150)
and hepatitis B (INO-1800) immunotherapies • $10 million up-front payment • Roche funding all ongoing development costs as well as funded
research for new prostate cancer antigens • $412.5 million milestone payments for certain development and
commercial events • Roche may pay other development milestone payments if it
pursues other indications with INO-5150 or INO-1800 • Up to double-digit royalties on sales of a marketed product
Validating Partnership with Roche (September 2013)
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Broad Medical and Market Opportunities
Product Name
INTERNALLY FUNDED
Indication Preclinical Phase I Phase II
Vgx-3100
Ino-5150
Ino-1400
EXTERNALLY FUNDED
pennvax®
Ino-3510
Ino-8000
ino-1800
malaria MaV-12
Phase III
Preventive
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INO-3112
INO-3112
Preventive
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
• Are safe and tolerable
• Requires a directive to attack
T cells: Inovio Commands the Body’s SWAT Team
T cell Cytotoxic T lymphocyte
Target cell
Provided by Dr. Philip Greenberg Hutchinson Cancer Research Center
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• T cells are vital to clearing cancerous or infected cells
• Active immuno-therapies: harnessing the power of T cells
• Inovio’s DNA immunotherapies displaying best-in-class T cells
• Functional killing effect • Safe and well tolerated • >400 patents globally
T cells: Inovio Commands the Body’s SWAT Team
Antigen- specific T cell Cytotoxic T lymphocyte CD8+ T cells
Target cell and antigen(s)
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Checkpoint Inhibitors Alone are Good but Not Good Enough
• Inovio cancer vaccines greatly
increase T cells
• Overwhelm cancer cells as monotherapy
• Potential to combine with checkpoint inhibitors to increase efficacy
• Potential to improve safety and tolerability
• Unprecedented efficacy • Melanoma • Lung cancer
• Validate potential of T cell active
immunotherapies
• Evidence suggests that non-responders do not have sufficient pre-existing T cell levels
• Concerns re: safety/tolerability
• Projected $24 billion market Source: Citi
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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Optimized DNA Plasmid + EP: Better Antigen Expression
Ref: Sardesai & Weiner Curr. Opin. Immunol. 2011
1000x enhancement in cellular uptake and antigen expression
Intramuscular Intradermal
12 EP = electroporation
Inovio DNA/EP Beats Previous Gold Standard (Merck Ad5 Viral Vector) for T Cell Generation (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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PENNVAX®: Highest CD8+ T Cell Responses for HIV Vaccine
Ref: Kalams et al JID 2013 14
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
Inovio’s Lead Program
VGX-3100: • Capitalizes on Inovio’s ability to generate T cells • Immunotherapy for pre-cancers and cancers caused by
human papillomavirus (HPV) • Targeting E6/E7 oncogenes
• Phase II on-going: high grade cervical pre-cancers (CIN 2/3 dysplasia)
• Efficacy and immunogenicity data: mid-2014
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Inovio’s Lead Product Targets All HPV-caused Diseases
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Incidence rates in the U.S.
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
Bagarazzi, Yan, Morrow et al, Science Trans. Med. (2012)
HPV16-, HPV18-Specific IFN-γ Production
Multi-parameter flow cytometry: CD4, CD8 activation phenotype
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-VGX3100 PBMC are targets, post-VGX3100 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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VGX-3100 Phase II Study Design
Phase II Data Impact on Medical and Market Opportunities
• Efficacy data • Path forward to phase III for CIN 2/3 • Expansion of product use to other HPV-related indications
(cervical cancer, head/neck cancer, and anogenital cancer) • Seek orphan designation potential
• T cell and safety data
• Broader platform validation for all Inovio immunotherapy products in the pipeline
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INO-1400: Potential Universal Cancer Therapy
Yan J et al., Cancer Immunol Res. (2013) 23
Dharmapuri et al., Mol Ther. (2009)
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
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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 development of diagnostics for mesothelioma, bladder cancer, and ovarian
cancer for Fujirebio Diagnostics
Management
anthrax Louis Pasteur
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
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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
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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Thomas S. Edgington, MD • Founded multiple biotech companies;
extensively published • Emeritus Professor, Scripps
Research Institute
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 investments3 $ 52.6 M
Debt3 0 M
Cash runway 4Q 2017
Shares outstanding2 239.6 M
Recent price1 $3.42
Market cap1 $ 819.4 M
NYSE MKT: INO
1Mar 17, 2014 3 Dec 31, 2013 27
Additional cash after year end4
$ 69.3 M
2Mar 7, 2014 4 Mar 14, 2014
INTERNALLY FUNDED EXTERNALLY FUNDED
Ino-5150 1H 2014 Initiate phase I Prostate cancer
Vgx-3100 Mid-2014 Phase II study data Cervical dysplasia
INO-3112 1H 2014 Initiate phase I/IIa
Head & Neck Cancer
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Upcoming Value Drivers
INO-3112 1H 2014 Initiate phase I/IIa
Cervical Cancer
Ino-1400 2H 2014 Initiate phase I/IIa
Breast/lung/ Pancreatic Cancer
PennVAX® 2H 2014 Initiate PENNVAX -GP phase I HIV
Ino-8000 2015 Report phase I data
Hepatitis C
Ino-1800 Early 2015 Initiate phase I/IIa Hepatitis B
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Investor Highlights • Break-through active immune therapy with the
power to save lives and maximize shareholder value
• Targeting broad range of diseases and billion dollar markets • Best-in-class T cells to prevent, treat & cure cancers and infectious diseases
• Phase II efficacy data coming
• Validating partnership with Roche with more deals in the works
The Opportunity
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