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Taking Immunotherapy to the Next level
- 1. NASDAQ: INO Taking Immunotherapy to the Next level I T ’ S A L L A B O U T T H E T - C E L L S Dr. J. Joseph Kim PRESIDENT & CEO
- 2. 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, 2014, our Form 10-Q for the quarter ended June 30, 2015, and other regulatory filings from time to time. 2
- 3. Inovio Highlights • Powerful DNA-based immunotherapy and vaccine platform • Lead product VGX-3100 to enter phase III in 2016 • All phase II efficacy endpoints met • Publication in major medical journal imminent • First to show CD8+ T cells generated in-vivo can clear disease • Large pipeline of oncology and infectious disease products • Protected by > 900 granted and pending patents • Two Big Pharma partnership deals in the last two years (~$1 billion in milestone payments) • Over $130 M in non-dilutive grants and contracts in the last six years • $70M in the last 12 months • Cash runway through 2018 3
- 4. What We Do
- 5. SynCon® Immune Control Technology • Highly optimized DNA plasmids • Genetic sequences encoded for specific targeted immune mechanism • Generates target immune functional components directly in the body One Core Technology: Leveraging Synthetic Biology 5 Up-regulation of desirable immune mechanisms Down-regulation or inhibition of detrimental immune mechanisms To fulfill unmet needs in: CANCER | INFECTION | INFLAMMATION
- 6. Multiple Immune Mechanisms, Products, Diseases. How? In-vivo generation of immune functional components capable of fighting disease 6 Generate • Antigens • Monoclonal antibodies Activating • CD8+ killer T cells • Polyclonal antibodies • Checkpoint inhibition • Tumor blocking pathways • Cytotoxicity Products • Monotherapies • Combination therapies • Prevention • Treatment Disease Targets • Cancer • Infectious diseases • Other Driving synthetic biology to achieve vital immune activation/control outcomes SynCon® DNA Plasmids:
- 7. What Have We Accomplished? A N T I G E N G E N E R AT I O N / T C E L L A C T I VAT I O N
- 8. In-Vivo Killer T Cell Generation is a Key Missing Link 8 Target cell T Cell Cytotoxic T lymphocyte Just scratching the surface Still notable unmet needs Great strides in new immuno-oncology therapy technologies enabling T cells to perform their function CD8+ T cells: targeted destroyer of cancer and infected cells in the body
- 9. Best-in-Class Functional T Cell Responses Activated In-Vivo… 9 Phase II study of VGX-3100 HPV antigen generating immunotherapy in high grade cervical dysplasia *Statistically significant; bars are 95% Cl. IFN = interferon VGX-3100800 600 400 200 0 0 5 10 15 20 25 30 35 40 Placebo Study Week VGX-3100SpecificTCells (SFU/106PBMCsAboveBaseline) Treatment at wks 0, 4, & 12 * * * *
- 10. Correlated to Clinically Relevant Efficacy 10 Phase II study of VGX-3100 HPV immunotherapy in high grade cervical dysplasia meets primary and secondary endpoints Groups Paper accepted for publishing in top tier medical journal Primary Endpoint Control VGX-3100 P-Value Regression From High Grade to Low Grade Cervical Dysplasia or Normal 49.5% 30.6% p=0.017 strata-adjusted
- 11. Implication: Broad Proof of Principle 11 Effective immune activating treatment • Select and encode any antigen • Simple injections into arm • Generate antigen-specific CD8+ killer T cells • Measurable in blood and observed in diseased tissue (tissue infiltrating T cells) • Regress disease to normal • Clear virus causing the disease • Direct correlation between CD8+ T cells and efficacy Immune system’s disease fighting mechanisms are common across all diseases • Data supports utility of SynCon® products across cancers and infectious diseases Favorable safety profile shown in over 600 treated subjects (without serious adverse events)
- 12. Strategic Implications for Immuno-Oncology A minority of tumors have T cell responses that can respond to immune checkpoint inhibition—and even against those tumors, checkpoint inhibitors are only realizing 20—40% response rates 12 Taking immuno-oncology to the next level, and leveraging the encouraging results of checkpoint inhibitors, requires better T cell generation “You can block all the PD-L1 in the world but it means nothing without infiltrating T cells” — Roy Herbst, Yale “In the majority of patients, T cells either need to be trafficked to the tumor, T cells need to be generated or both in order to see higher response rates with the checkpoints” — Michael Atkins, Georgetown
- 13. Immuno-Oncology Clinical and Commercialization Strategy 13 Monotherapies | Single agent, multi-antigen T cell activating immunotherapies: potential in specific scenarios such as early stage or slowly progressing cancers 1 Combination Therapies With Partners | Combine Inovio antigen-generating immunotherapies with third party checkpoint inhibitors or other immuno-oncology products 2 Combination Therapies In-House Using DNA-Based Monoclonal Antibodies (dMAbs) | Keep product development, IP, and downstream profit under one roof; strategic power/flexibility 3
- 14. Two Validating Big Pharma Partnerships in Two Years 14 Products INO-1800 Hepatitis B immunotherapy INO-3112 HPV-driven cancer + 2 new R&D products Upfront Payment $10 million $27.5 million Milestone Payments $400+ million $700 million Royalties Up to double digit tiered royalties Up to double digit tiered royalties on INO-3112 + royalties for additional cancer vaccine products Roche (September 2013) AstraZeneca/MedImmune (August 2015)
- 15. What We Are Doing Now P R I M A R Y F O C U S : A N T I G E N / T C E L L G E N E R AT I O N F O R I M M U N O - O N C O L O G Y
- 16. Antigen-Generating/T Cell Activating SynCon® Products 16 Product Name Indication Preclinical Phase I Phase II VGX-3100 INO-5150 INO-1400 Phase III INO-3112 Breast/Lung/Pancreatic Cancers Therapeutic Prostate Cancer Therapeutic Head & Neck Cancer Cervical and Head & Neck Cancer Therapeutic Cervical Dysplasia Therapeutic Aerodigestive Cancer TherapeuticINO-3106 INO-1800 Hepatitis B Therapeutic EbolaINO-4212 Preventive PENNVAX®-GP HIV Preventive/ Therapeutic INO-8000 Hepatitis C Therapeutic Preventive/ Therapeutic EXTERNALLY FUNDED Infectious Disease Programs INTERNALLY FUNDED Cancer Programs Externally FUNDED Cancer Programs GLS-5300 MERS Preventive/ Therapeutic
- 17. VGX-3100 Phase II Study: HPV Cervical Dysplasia 17 Placebo-Controlled, Randomized, Double Blind • Targets: HPV 16/18 E6/E7 oncogenes • 148 subjects • 18-55 year old females • High-grade cervical dysplasia (CIN2/3) • HPV 16 and/or 18 positive • 3:1 randomization Primary Endpoint • Regression of CIN2/3 to CIN1 or normal (6 months post third dose: week 36) Secondary Endpoint • Regression of CIN2/3 to CIN1 or normal and clearance of HPV
- 18. Phase II: Clinically Significant Efficacy; Achieves Endpoints 18 • Efficacy correlates to immune responses • PP and mITT p-values equal Regression High Grade to Low Grade Cervical Dysplasia or Normal Dysplasia Regression to Low or Normal AND HPV Clearance Lesion Regression to Normal VGX-3100 49.5% 40.2% 40.2% Control 30.6% 14.3% 16.7% Difference 18.9% 25.9% 23.5% P-Value p=0.017 strata-adjusted p=0.001 strata-adjusted p=0.006 strata-adjusted Groups Primary Endpoint Secondary Endpoint Primary – Ad Hoc
- 19. Data Supports Advancing HPV Immunotherapy HPV Dysplasias • Potential as first non-surgical treatment option for cervical dysplasia • First-line therapy to pre-empt surgery Phase III • Planned start 2016 • Scaling biologic and electroporation device production • End-of-phase-II FDA meeting by year end • Market, pricing and payor research • Planning other HPV anogenital dysplasia studies HPV Cancers • MedImmune assumes development of head & neck and cervical cancer studies under strategic cancer collaboration 19
- 20. US: 27,000 EU: 6,500 HPV-Caused Pre-Cancer Incidence 20 US: 220,000 – 270,000 EU: 260,000 US: 13,400 EU: 13,400 Annual incidences: US EU HIGH GRADE CERVICAL DYSPLASIA (CIN2/3) HIGH GRADE VULVAR NEOPLASIA (VIN) HIGH GRADE ANAL NEOPLASIA (AIN) 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
- 21. Cancer Programs 21 INO-3112 VGX-3100 + IL-12 HPV 16 & 18 driven cancers Antigens: E6 and E7 • Two phase I/II trials against cervical and head and neck cancer underway; planned phase II trial against cervical cancer sponsored by EORTC • Interim head & neck data: 3 of 4 patients w/ robust CD8+ T cell responses New cancer products partnered by MedImmune • Co-develop two additional DNA-based cancer vaccine products • MedImmune: exclusive rights to develop and commercialize INO-1400 Antigen: hTERT (+/- IL-12) • Human telomerase reverse transcriptase associated with cancer cell survival • Over-expressed in 85% of cancers—potential “universal” cancer therapy • Phase I trial in 54 patients with breast, lung, or pancreatic cancer INO-5150 Prostate cancer Antigens: PSA and PSMA (+/- IL-12) • Phase I trial in 60 men with biochemically relapsed prostate cancer InternallyFundedPartnerFunded
- 22. Infectious Disease Programs 22 INO-1800 Hepatitis B Antigens: Surface and core (+/- IL-12) • Phase I trial in 126 patients • Safety, immunogenicity & efficacy biomarkers • Roche paying all development costs plus milestones PENNVAX®-GP HIV Global subtype coverage Antigens: 2 env, gag & pol • Initiated phase I in collaboration with HVTN • $25M grant from NIAID completed; new $16M grant will allow further optimization research INO-4212 Ebola Antigen: GP protein • Phase I trial (~75 healthy patients) • Research funded by $45M DARPA award as part of multi- faceted approach to prevent and treat Ebola GLS-5300 MERS Antigen: Spike protein • Induced 100% protection from live virus challenge in monkeys • Three animal models, including camels, in preclinical study • Initiate phase I in 4Q 2015 in collaboration with GeneOne InternallyFundedPartnerFunded
- 23. Where Are We Going?
- 24. Many Target Antigens…Many Antigen Targeting Products 24 Encode for multiple antigens for best targeting and response to target disease SynCon® immune control technology can encode for any target antigen to activate cancer-destroying T cells – or against infectious diseases 50+ well characterized antigens known to have high levels of over-expression in cancer cells Developing multiple multi- antigen SynCon® cancer immunotherapies prioritized based on clinical unmet need, commercial attractiveness, and scientific rationale Inovio will launch a new multi-antigen product against a new cancer target in 2016 MedImmune to select sub-set of antigens to target two additional cancer products
- 25. Others (6) dMAbs™: Multiple Immune Mechanisms & Products Inovio’s DNA-based monoclonal antibody products target: 25 • Alzheimer's • Parkinson’s • Other Cancer (10) Infectious Diseases (14) • Influenza A • Influenza B • Pseudomonas • MRSA/Staph • Ebola • MERS • Dengue • CHIKV • Other infectious diseases • Checkpoint Inhibitors (CI) • PD-1 • PD-L1 • 4 additional CIs • Herceptin • Anti-Tregs • Other anti-cancer pathways DARPA funded programs
- 26. Promising Preclinical Data & Notable Third Party Support DARPA awards $57M to advance dMAb application and develop products for Ebola, influenza and antibiotic resistant bacteria 26 0% 20% 40% 60% 80% 100% TumorClearance(%) Cancer dMAb Prostate cancer model in mice (Unpublished data) dMAb (7 of 10) Control (0 of 10) 70% 0% 0% 20% 40% 60% 80% 100% ProtectioninChallengewithDengue Virus(%) Dengue dMAb (Nature Scientific Reports 2015) dMAb (10 of 10) Control (0 of 10) 100% 0%
- 27. dMAB™ Products: Development Milestones and Catalysts 27 > 6 new publications expected in the next year Two dMAb scientific publications to date Technology development fueled by two DARPA grants totaling $57M Developing an arsenal of over 30 dMAb products (cancer, checkpoint inhibitors, infectious diseases, others) First clinical study using dMAb product planned in 2016
- 29. 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 Management 29 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
- 30. Board of Directors 30 Nancy Wysenski, MBA • Former COO of Endo Pharmaceuticals and Vertex Pharmaceuticals Simon X. Benito • Former Senior Vice President, Merck Vaccine Division Avtar Dhillon, MD Chairman, BOD • Former President & CEO, Inovio Biomedical Morton Collins, PhD • General Partner, Battelle Ventures and Innovations Valley Partners Angel Cabrera, PhD • President, George Mason University • Former President, Thunderbird School of Global Management J. Joseph Kim, PhD • President & CEO, Inovio Adel Mahmoud, PhD • Professor, Princeton University • Former President, Merck Vaccines • Responsible for Gardasil®, Zostavax®, Proquad® and Rotateq®
- 31. Scientific Advisory Board 31 Anthony W. Ford- Hutchinson, PhD • Former SVP, Vaccines R&D, Merck • Oversaw development: Singulair®, Januvia®, Gardasil®,Zostavax®, Proquad® and Rotateq® Stanley A. Plotkin, MD • Developed rubella and rabies vaccines • Oversaw Sanofi flu vaccine • Emeritus Professor, Wistar Institute & University of Pennsylvania David B. Weiner, PhD Chairman • “Father of DNA vaccines” • Dept. of Pathology & Laboratory Medicine, University of Pennsylvania Philip Greenberg, MD • Expert in T cell immunology • Head, Immunology Program, Fred Hutchinson Cancer Research Center
- 32. Financial Information 32 1September 2, 2015 2June 30, 2015 3 Payable in Q3, 2015 Cash & short-term investments2 $154.6 M Debt2 0 M Cash runway 4Q 2018 Shares outstanding2 $71.8 M Recent share price1 $7.23 Market cap1 $519.1 M Upfront payment: MedImmune 3 $27.5 M
- 33. Value Drivers and Milestones 34 2015 Publishing of VGX- 3100 HPV phase II paper in top tier medical journal Launch MERS vaccine phase I immunogenicity and safety study Launched PENNVAX®-GP HIV vaccine phase I immunogenicity and safety study Report Ebola vaccine phase I immunogenicity and safety data End-of-phase II FDA meeting
- 34. Value Drivers and Milestones 34 INO-3112 cervical cancer phase II study initiation with MEDI and EORTC Initiate first dMAb phase I trial VGX-3100 phase III study initiation Report INO-1400 hTERT immunogenicity data (interim) Report INO-5150 prostate immunogenicity data (interim) 2016 Initiate clinical studies for new cancer targets
- 35. Value Drivers and Milestones 34 Additional corporate development deals Additional grant funding BEYOND
- 36. Investment Summary 36 Mono- & combo therapy strategy with DNA-based antigens & mAbs Best-in-class efficacy data from in vivo immunotherapy Missing link to take T cell therapies to the next level Entering phase III Applicable to all cancers and infectious diseases Validating partnerships with MedImmune and Roche Taking immunotherapy to the next level
- 37. Appendix
- 38. VGX-3100 Efficacy Visualized Through Tissue Stain 38 Week0:CIN3pathology IHC Staining: Lesion/HPV Week36:Nosignificantpathology IHC Staining: CD8 + Regression: CIN3 HPV to Normal Persistent Presence of Killer CD8s
- 39. SynCon® Immune Control: Antigens and mAbs by Design 39 Identify pertinent disease-specific antigens for target disease Encode a DNA plasmid with genetic code for each targeted antigen T cells eliminate cells displaying disease-specific antigen(s) Immune system recognizes “foreign” antigens; activates antigen- specific T cells and antibodies Effective, efficient, safe in-vivo T cell and antibody activation Cellular machinery uses genetic code to produce encoded disease antigens ANTIGENIC PROTEINS Deliver plasmids into human cells using electroporation