inovio - corporate presentation
TRANSCRIPT
Revolutionizing the Fight
Against Cancers and
Infectious Diseases
Dr. J. Joseph KimPRESIDENT & CEO NASDAQ: INO
It’s All About the T-Cells
Forward Looking Statement
Our commentary and responses to your questions may containforward-looking statements, including comments concerningclinical trials and product development programs, evaluation ofpotential opportunities, the level of corporate expenditures,the assessment of Inovio’s technology by potential corporatepartners, capital market conditions, timing of events, cashconsumption and other subjects. Information concerningfactors that could cause actual results to differ materially fromthose set forth in our Annual Report on Form 10-K for the yearended December 31, 2014, our Form 10-Q for the quarterended March 31, 2015, and other regulatory filings from timeto time.
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A Compelling Weapon: T Cells
Cytotoxic T lymphocyte
T cell
Target cell
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A Compelling Weapon: T Cells
Cytotoxic T lymphocyte
T cell
Target cell
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• T cells: vital to fighting
disease
But…
• Can we help T cells
recognize evasive cancers
or mutating infectious
diseases?
• Can we enhance their
targeting, speed and
magnitude?
• Great strides in new
immunotherapy technology
• Just scratching the surface
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Is There an “Ideal” T Cell-Generating Immunotherapy?
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. Does not bypass the immune system’s inherent capabilities and controls.
Effective, efficient, safe…
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, enabling them to produce antigen
T cells eliminate cells displaying disease-specific antigen
Immune system activates antigen-specific T cells
Effective, efficient, safe in vivo T cell activation
Cellular machinery uses the DNA code to produce one or more of the disease antigens coded by the DNA plasmid
ANTIGENIC PROTEINS
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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 infectionImmune 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
cancersTherapeutic
Prostate cancer Therapeutic
Head & Neck Cancer Therapeutic
Cervical Cancer Therapeutic
Cervical dysplasia Therapeutic
Preventive/
Therapeutic
Ebola
Aerodigestive Cancer TherapeuticINO-3106
INO-4212
Preventive
INTERNALLY FUNDED
HPV programs
Pennvax®- B hiv
Pennvax®-GP hiv
Preventive/
Therapeutic
Preventive/
Therapeutic
Ino-8000 Hepatitis C Therapeutic
INO-3112Cervical Cancer 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
Phase II: Study Design
• 148 subjects: 18-55 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: HistopathologicRegression of CIN2/3 to CIN1 or Normal
30.6%(11/36)
Statistically significant difference(p=0.017; strata-adjusted)
Post-Hoc Analysis: Regression of CIN2/3 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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VGX-3100 Generates HPV-16 and HPV-18 T Cell Responses
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N=140
Regression of CIN3 to Normal and HPV Clearance Observed in VGX-3100 Treated Patient (via IHC) Over 36 Weeks
Wee
k 0
: CIN
3 p
ath
olo
gy
IHC Staining: HPV
Wee
k 3
6: N
o s
ign
ific
ant
pat
ho
logy
IHC Staining: CD814
Powerful Impact of VGX-3100 Phase II Efficacy Data
• Non-surgical option for the treatment of CIN2/3
• Simple 3 monthly injections generated CD8 killer T cells• Measured in blood• Observed in cervical tissue (tissue infiltrating T cells)• Direct correlation found between CD8 T cells and efficacy
• Demonstrated phase II efficacy and safety• Regressed disease to normal• Cleared virus which caused the disease
• Disease regression: expand into other HPV-caused diseases • Advance other anti-cancer therapies (lung, breast, pancreas, prostate)
• Virus (HPV) clearance supports other antiviral therapies (HBV, HCV, HIV)
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VGX-3100: Next Steps
EXPANSION OF HPV PROGRAM TO RELATEDCANCERS AND PRE-CANCERS• Cervical cancer (Ph I/IIa initiated)
• Head & neck (Ph I/IIa initiated)
• Anogenital cancers• VIN, PIN
PREPARED SCIENTIFIC PAPER FOR PEER REVIEW• Completed 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 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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• 126 women with cervical carcinoma• Safety & progression free survival at 18
months• INO-3112 administered during standard
chemo-radiotherapy (CRT) or during and after standard CRT as an adjuvant
• Funded by the EORTC
• 20 women with cervical carcinoma• Safety, tolerability, immunogenicity• Cervical histology • Treat after chemoradiation
HPV-Associated Cervical Cancer Studies: INO-3112
Two clinical trials for cervical cancer: INO-3112 (VGX-3100 + IL-12 DNA immune activator)
HPV 16/ 18 related disease
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Phase I/II Cervical Cancer Phase II Cervical Cancer
• 20 men/women • Safety, tolerability, immunogenicity • Anti-tumor effects & progression free survival• Arm #1: treat before/after tumor resection• Arm #2: treat after chemoradiation
HPV-Associated Head & Neck Cancer Studies: INO-3112
Phase I/IIa clinical trialINO-3112 (VGX-3100 + IL-12 DNA immune activator)
HPV 16/ 18 related disease
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Head & Neck Squamous Cell Carcinoma
Phase I: INO-1400 +/- IL-12 DNA immune activator
Human telomerase reverse transcriptase (hTERT), associated with cancer cell survival
hTERT-Associated Cancers Study: INO-1400
• hTERT overexpressed in 85% of cancers - potential “universal” cancer therapy • 54 patients• Safety, tolerability, immunogenicity• Anti-tumor effects and progression free survival • Trial launched: 4Q 2014
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Breast, Lung, or Pancreatic Cancers
• 126 patients• Safety, tolerability, immunogenicity • Trial started: 2Q 2015• Roche paying all development costs plus milestones• 240M+ global market opportunity
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Hepatitis B Study: INO-1800
Phase I: INO-1800 +/- IL-12 DNA immune activator
Multi-antigen: HBV pan-clade surface antigens & core antigens
Chronic Hepatitis B Virus
Louis Pasteur
Peter KiesCFO• Ernst & Young
• Experience with growth companies
Mark L. Bagarazzi, MDCMO• Clinical research experience incl. Merck
• Led clinical/regulatory for shingles and rotavirus vaccines; DNA vaccine expert
J.Joseph Kim, PhDPresident & CEO
• Decades of biotechnology/ pharma management
• Merck: hepatitis A and B vaccines manufacturing; HIV
vaccine (Ad5) R&D
Niranjan Y. Sardesai, PhDCOO
• 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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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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Nancy Wysenski , MBA• Former COO of Endo
Pharmaceuticals and Vertex Pharmaceuticals
Louis PasteurStanley 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, PhDChairman
•“Father of DNA vaccines”
• Dept. of Pathology & Laboratory Medicine, University of Pennsylvania
Scientific Advisory Board
Financial Information
Cash, cash equivalents & short-term investments3 $ 81.0 M
Debt3 0 M
Cash runway 4Q 2018
Shares outstanding2 71.8 M
Recent share price1 $7.23
Market cap1 $ 519.1 M
NASDAQ: INO
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1July 23, 2015 2May 8, 2015 3 March 31, 2015 4 May 5, 2015
Net cash from financing4 $ 82.1 M
INTERNALLY FUNDED EXTERNALLY FUNDED
Ino-14002016Report interim data
Breast, Lung, And
Pancreatic Cancer
Vgx-31002015 Publish data in med journalEarly 2016 Initiate phase IIICervical dysplasia
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Value Drivers
INO-31122H 2015Report interim data
Head & Neck and
Cervical Cancer
Ino-80002015Report interim phase I data
Hepatitis C
Ino-18002Q 2015Initiated phase I
Hepatitis B
Ebola2Q 2015Initiated phase I
INO-4212
Ino-51503Q 2015Initiated phase I
Prostate cancer
PennVAX® 3Q 2015 Initiate PENNVAX-GP phase I
HIV
INO-3112December 2015Initiate phase II Cervical Cancer
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 technology
Validating partnership with Roche
Lead product achieved phase
II efficacy endpoints
Investor Highlights
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