inovio - revolutionizing the fight against cancers and infectious diseases
DESCRIPTION
September 2014TRANSCRIPT
Revolutionizing the Fight Against Cancers and Infectious Diseases
Dr. Joseph Kim President & CEO NASDAQ: 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, our Form 10-Q for the quarter ended June 30, 2014, and other regulatory filings from time to time.
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Inovio: creating the path to an active immunotherapy with broad clinical utility
• Lead DNA immunotherapy product, VGX-3100, meets phase II efficacy endpoints; technology breakthrough for active immunotherapy field
• First clinically meaningful efficacy from T cells generated EXCLUSIVELY in vivo
• De-risking of pipeline products
• Best T cell responses in published clinical studies
• Favorable safety profile
• Validating partnerships
First-in-Class Efficacy from an Active Immunotherapy
Human Papillomavirus
Low Grade Cervical
Pre-cancer (CIN 1)
High Grade Cervical
Pre-cancer (CIN 2/3)
VGX-3100 Phase II Data: Building New Market Opportunity
• Treat HPV-associated pre-cancers and cancers • Phase II controlled trial regressed high grade
cervical pre-cancer and cleared HPV • Fulfill unmet need, providing non-surgical
alternative for pre-cancerous lesions • Potential elimination of residual HPV in
untreated tissue • Advance into phase III for cervical pre-cancer
(CIN 2/3) in 2016 • Dominate post-HPV infection therapeutic
markets • Advance other HPV-associated pre-cancers
(vulvar, vaginal and anogenital neoplasias) and cancers (cervical, head and neck, and anogenital)
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Disease Progression
Cervical Cancer
VGX-3100 Phase II Study Design
• Placebo-controlled, randomized, double blind o 148+ subjects: females 18-55 o Histologically confirmed HPV16 or 18-
associated CIN 2/3 or CIN3 o Randomized 3:1: VGX-3100 vs. placebo; both
with electroporation o Two plasmids: HPV Types 16 and 18; encoded
for E6/E7 antigens o Treatment at months 0, 1, 3 • Primary endpoint month 9 o Regress CIN 2/3 to CIN 1 or no disease • Secondary endpoints o Clearance of HPV 16 or 18 AND CIN 2/3
regression o Immunogenicity o Safety
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Phase II Data: Clinical Efficacy With Robust T Cells
• Efficacy data meets primary and secondary efficacy endpoints
• High level of complete CIN 2/3 clearance • Robust HPV-specific T cell responses in majority of treated subjects, as in
phase I • Treatment well-tolerated with only administration site redness • Data being published • Expect to initiate phase III trial in 2016
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VGX-3100 Placebo P Value
CIN 2/3 regression to CIN 1 or no disease
49.5% 53 of 107
30.6% 11 of 36 <0.025
HPV clearance AND CIN 2/3 regression to CIN 1 or no disease
40.2% 43 of 107
14.3% 5 of 35 <0.025
DNA Immunotherapies: Disease-Specific T Cells by Design
It’s all about the T cells!
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T cell Antigen-specific killer T cell
Target cell
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It’s All About the T Cells
• Inovio immunotherapies display best-in-class T cells in HIV and HPV human studies:
o Magnitude o Durability (memory) o “Killing tools”: granzyme and
perforin o Functional killing effect
• A new paradigm for generating
clinically relevant immune responses and efficacy
• Safe and well tolerated
9 Sources: CDC, www.hpvcentre.net; WHO IARC
Incidence rates in the U.S. + EU5
HPV-Caused Pre-Cancers & Cancers: VGX-3100
HPV-Associated Cancer Treatments Already Enrolling
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 • Treated after chemoradiation
Head & Neck Squamous Cell Carcinoma • 20 men/women • Safety, tolerability, immunogenicity • Anti-tumor effects & progression free
survival • Arm #1: treated before/after tumor
resection • Arm #2: treated after chemoradiation
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hTERT-Associated Cancers: INO-1400
• Antigen: human telomerase reverse transcriptase (hTERT), an enzyme associated with cancer cell survival; overexpressed in 85% of cancers - potential “universal” cancer therapy
• (+/- IL-12 DNA immune activator)
• Phase I/IIa: 54 patients with breast, lung, or pancreatic cancers
• Safety, tolerability, immunogenicity
• Anti-tumor effects and progression free survival
• Trial launch: 4Q 2014
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Prostate Cancer: INO-5150
• Antigens: PSA + PSMA
• Phase Ia/Ib: multi-arm study design
• Targeting castrate resistant prostate cancer
• Additional prostate cancer antigens being developed with Roche
• Roche immuno-modulatory drugs including checkpoint inhibitors
• Trial launch: 2015
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Checkpoint Inhibitors: Potent Combination Potential
Active immunotherapies: • Inovio immunotherapies greatly
increase T cells
• Potential to overwhelm cancer cells as monotherapy
• Potential to combine with checkpoint inhibitors to increase efficacy
Checkpoint inhibitors: • Unprecedented efficacy o Melanoma, lung cancer
• Validate potential to enhance T cell
capabilities
• Evidence suggests non-responders do not have sufficient pre-existing T cells
1 + 1 = ?
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 diagnostics development 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 investments2 $ 109.0 M
Debt2 0 M
Cash runway 4Q 2017
Shares outstanding2 60.3 M
Recent share price1 $10.67
Market cap1 $ 643.4 M
NASDAQ: INO
1Sept 12, 2014 2Jun 30, 2014
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Recent insider buying $2.75M
INTERNALLY FUNDED EXTERNALLY FUNDED
Ino-5150 2015 Initiate phase Ia/Ib Prostate cancer
Vgx-3100 2016 Initiate phase III Cervical dysplasia
INO-3112 2Q 2014 Initiated phase I/IIa
Head & Neck Cancer
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Value Drivers
INO-3112 2Q 2014 Initiated phase I/IIa
Cervical Cancer
Ino-1400 2H 2014 Initiate phase I/IIa
Breast/lung/ Pancreatic Cancer
PennVAX®
4Q 2014 Initiate PENNVAX-GP phase I HIV
Ino-8000 2015 Report phase I data
Hepatitis C
Ino-1800 2015 Initiate phase I/IIa Hepatitis B
• Phase II data shows clinically significant efficacy
• Breakthrough active immune therapy technology with potential to save lives and maximize shareholder value
• Best-in-class T cells to prevent, treat & cure cancers and infectious diseases
• Targeting broad range of diseases and numerous billion dollar markets
• Validating partnership with Roche; working toward more deals
Investor Highlights
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Revolutionizing the Fight Against Cancers and Infectious Diseases
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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PENNVAX®: Highest CD8+ T Cell Responses for HIV Vaccine
Ref: Kalams et al JID 2013 25
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)
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
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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INO-1400: Potential Universal Cancer Therapy Targeting hTERT (overexpressed in 85% of cancers)
Yan J et al., Cancer Immunol Res. (2013) 31
Dharmapuri et al., Mol Ther. (2009)
T-cell generation: older generation DNA vaccine and electroporation device
SynCon® T-cell generation with CELLECTRA® electroporation device