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Inovio Pharmaceuticals - Corporate Presentation
- 1. NASDAQ: INO Taking Immunotherapy tothe Next Level I T ’ S A L L A B O U T T H E T - C E L L S J. Joseph Kim, Ph.D. President & CEO March 2017
- 2. Forward Looking Statement 2 Ourcommentary 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 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, 2016 and other regulatory filings from time to time.
- 3. Leading the Developmentof DNA-based Immunotherapies to Commercialization 3 Powerful platform, multiple products Efficacy in phase II study Phase III and immuno-oncology combo studies starting 1H17 Major partnership: MedImmune/AstraZeneca Our purpose Develop immunotherapies and vaccines to fight cancers and infectious diseases
- 4. Executing “Inovio Vision2020” 4 HPV-related pre-cancers (VGX-3100) Filed for marketing approval 1 Immuno-Oncology Filed for marketing approval or in pivotal study 2 Infectious diseases Filed for marketing approval or in pivotal study 3
- 5. CELLECTRA 5PSP Device • SynCon®antigen genetic code enables precise targeting of cancer or pathogen • Designed to break tolerance and cover mutating strains • Highly optimized SynCon plasmid + novel CELLECTRA delivery generate optimal antigen production IN THE BODY • Activates robust functional CD8+ killer T cell and antibody responses • Phase II efficacy • Highly favorable safety profile in over 1300 subjects and 3800 immunizations Immune Responses by Design 5 SynCon Immunotherapy Optimized platform: SynCon® + CELLECTRA®
- 6. Inovio Vision 2020Roadmap 6 1 Start PIII 1H17 Start PII 2017 VGX-3100, HPV-Related Diseases Filing for marketing approval by 2020 Cervical Dysplasia Phase II completed Other HPV Neoplasias Preparing INDs (VIN, AIN)
- 7. Fulfill Unmet TreatmentNeeds of HPV Related Diseases High Grade Cervical Dysplasia (CIN 2/3) • Current CIN excisional and ablative procedures increase risk of pre-term births from 5.6% to 10.7%; Kyrgiou et al meta-analysis published June 2016 in British Medical Journal • Existing procedures cannot eliminate HPV outside treated area; recurrence risk post- LEEP is 10-16% • VGX-3100: potential first-line therapy; first non-surgical treatment option Vulvar & Anal Neoplasias • No good existing treatments • Surgery is disfiguring 7 EU: 15,000 US: 195,000 EU: 233,000 US: 13,400 EU: 2,514 CIN2/3 VIN AIN US: 23,000 Sources: Bruni L, Barrionuevo-Rosas L, Albero G, Aldea M, Serrano B, Valencia S, Brotons M, Mena M, Cosano R, Muñoz J, Bosch FX, de Sanjosé S, Castellsagué X. ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in United States of America. Summary Report 2015-03-20., Henk et al J Low Genit Tract Dis (2010), Insigna et al, Am J Obs Gyn (2004), Hartwig et al. Papillomavir. Res (2015), CDC, www.hpvcentre.net, WHO IARC Annual Incidence
- 8. Demonstrated Efficacy inPhase II Trial of VGX-3100 8 Placebo-Controlled, Randomized, Double Blind • VGX-3100 SynCon® product for HPV-related pre-cancers • Targets HPV 16/18 subtypes, E6/E7 oncogenes • 167 subjects • 18-55 year old females • High-grade cervical dysplasia (CIN2/3) • HPV 16 and/or 18 positive • 3:1 randomization • Dosing: week 0, 4, 12 Primary Endpoint • Regression of CIN2/3 to CIN1 or normal (week 36) Secondary Endpoint • Regression of CIN2/3 to CIN1 or normal and clearance of HPV (week 36)
- 9. Robust Functional Antigen-SpecificT Cells Measured in Blood 9 *Statistically significant; bars are 95% Cl VGX-3100800 600 400 200 0 0 5 10 15 20 25 30 35 40 Placebo Study Week VGX-3100SpecificTCells1 Treatment at wks 0, 4, & 12 * * * * • 167 subjects • Published in The Lancet September 2015 • 1 Spot forming units/106 PBMCs above baseline
- 10. CD8+ T CellsInfiltrate Diseased Tissue, Clear HPV Virus and Lesion 10 Week0 IHC Staining: Lesion/HPV Week36 IHC Staining: CD8 + Regression of CIN3 & HPV to normal Increase and persistent presence of infiltrating CD8+ killer T cells “Cold” “Hot”
- 11. Phase II AchievesPrimary and Secondary Endpoints 11 • Efficacy correlates to immune responses • PP and mITT p-values equal • 167 subjects • Paper published in The Lancet September 2015 • 1Strata-adjusted 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-value1 p=0.017 p=0.001 p=0.006 Groups Primary Endpoint Secondary Endpoint Primary – Post Hoc
- 12. HPV Cervical DysplasiaPhase III • Scaled biologic manufacturing to commercial facility • Completed CELLECTRA® commercial delivery device design, manufacturing process, production • Phase III trial design similar to phase II • < 400 total subjects • Phase III trial package submitted. FDA requested additional device-related information; placed program on clinical hold prior to initiation • Aim to initiate phase III in 1H 2017 12 Goal: Commercialize first medical alternative focused on preserving women’s reproductive health; regress HPV- caused lesions and eradicate virus itself
- 13. Inovio Vision 2020Roadmap 13 2Immuno-Oncology One pivotal study or filing for marketing approval by 2020 IO combination trial start 1H17 Preliminary data 1H17 Start PI/II 1H17 INO-5150 Prostate Cancer P1 enrollment completed INO-5401 New Cancer Target Multi-antigen immunotherapy + checkpoint inhibitor INO-1400 hTERT 9-cancer trial assessing immune responses INO-3112 HPV Cancer Killer T cells shown in phase I
- 14. Checkpoint inhibitors combined with Inovio’s cancer vaccines Twostudies starting in 2017: - INO-3112 with MedImmune - INO-5401 Checkpoint combinations Modestly higher response rates Toxicity up DRAMATICALLY Holy Grail of Immuno-Oncology: Turning “Cold” Tumors to “Hot” Tumors Need presence of robust, antigen- specific, functional CD8+ killer T cells to leverage the capabilities of checkpoint inhibitors: KOLs 14 Checkpoint monotherapies Few tumors responsive. Successes: only 15-20% response rates in most cancers
- 15. 15 Turning “Cold” Tumorsto “Hot” Tumors Before treatment with INO-3112 After treatment with INO-3112 Control: FoxP3 CD8
- 16. Inovio Vision 2020Roadmap 16 3Infectious Diseases One pivotal study or filing for marketing approval by 2020 P1 data 2H17 Additional data 1H17 Immune response data 1H17 Additional data 2017 Discuss potential regulatory path 2017 CHRONIC INFECTIONS INO-1800 HBV P1 enrolling INO-4212 Ebola P1 expanded: 200 patients EMERGING INFECTIONS GLS-5300 MERS P1 fully enrolled GLS-5700 Zika Two phase I studies
- 17. Post Challenge (Days) 05 10 15 20 25 30 0 20 40 60 80 100 %Survival ZIKV-prME (x1) pVax1 n=10 2x106 X20 X20 X20 X40 X20 X20 iv i ii iii pVax1 ZIKV-prME v vi • ZIKV infection caused severe brain pathology in mice • In contrast, vaccinated animals presented with normal histopathology in brain tissues • Data supporting that protective antibodies induced by synthetic ZIKA-prME vaccine could limit viral induced disease in the brain GLS-5700 Zika Vaccine Protects from Death and Illness
- 18. Emerging Disease VaccineDevelopment Opportunities Rapid response technology platform desired by health authorities to fight emerging infectious diseases • Inovio technology demonstrates rapid design, manufacturing, and clinical development of new vaccines, e.g. Zika • Financial drivers • Grants, such as DARPA $45M Ebola award, Gates $8.8M • Priority review voucher potential • Stockpiling contracts: scale manufacturing • Commercial opportunity for some diseases 18 DNA Alternative Technologies Design DNA Alternative Technologies Manufacturing Development Time Frames
- 19.
- 20. 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 20 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
- 21. Board of Directors 21 NancyWysenski, MBA • Former COO of Endo Pharmaceuticals and Vertex Pharmaceuticals Simon X. Benito • Former Senior Vice President, Merck Vaccine Division Avtar Dhillon, MD Chairman, BOD • Seasoned venture capitalist and biotech entrepreneur Morton Collins, PhD • General Partner, Battelle Ventures and Innovations Valley Partners Angel Cabrera, PhD • President, George Mason University J. Joseph Kim, PhD • President & CEO, Inovio Adel Mahmoud, PhD • Professor, Princeton Univ. • Former President, Merck Vaccines • Responsible for Gardasil®, Zostavax®, Proquad® and Rotateq® David B. Weiner, PhD • Executive VP, The Wistar Institute; Director, Vaccine Center
- 22. Scientific Advisory Board 22 AnthonyW. 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” • Executive VP, The Wistar Institute; Director, Vaccine Center
- 23. Financial Information 23 1March 10,2017 2December 31, 2016 3 Due from ApolloBio Corp: up to $50M in signing fee, milestone and equity investment, the latter two contingent upon lifting of clinical hold Cash & short-term investments2 3 $104.8 M 0 MDebt2 Shares outstanding2 74.1 M Recent share price1 $6.68 Market cap1 $494.9 M
- 24. Publish Zika phaseI immune response and safety data Report MERS phase I immune response and safety data (interim) Advance INO-5401 new cancer target program Publish Ebola clinical data in peer-reviewed manuscript INO-3112 Initiate checkpoint inhibitor combo study VGX-3100 (CIN) phase III study initiation Report INO-5150 (prostate) immune response and safety data (interim) Upcoming Value Drivers and Milestones 24 VGX-3100 (VIN) phase II study initiation
- 25. Investment Thesis: InovioPositioned with Multiple Transformational Steps as an Immunotherapy Leader Taking immunotherapy to the next level 25 Powerful technology platform Best-in-class data Entering phase III Validation: partners, publishing, grants INO: NASDAQ
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- 27. Right Immune Targets, GeneticSequences & Delivery Method Immune Responses Validated in Humans T Cell Related Efficacy in Humans Late Stage Development & Commercialization 2005-2009 2010-2013 2014-2016 2017-2020+ Inovio Refines and Validates DNA Immunotherapies Inovio has built leading knowledge capital and IP 27 Breakthrough in vivo generation of immune responses in large animals. Integrated technology platform achieves robust immune responses in humans. Killer T cells generated in the body correlated to efficacy. Strong immune responses across multiple diseases. Launching P3 and combo cancer studies. Pursuing efficacy data in multiple studies.
- 28. Optimized DNA withSafe & Effective Delivery to Generate Significant T Cells with Killing Activity 28 Synthetic Consensus DNA Protective universal antibodies and killer T-cells produced by immune system against a virus or cancer self-antigen
- 29. Enhanced Cellular Delivery: KeyEnabler of DNA Immunotherapies • DNA plasmids must get through protective membrane into a cell to work • Best method to enhance cellular uptake is electroporation • SynCon® DNA plasmid and CELLECTRA® delivery device are phase III ready 29 CELLECTRA® 5PSP Device
- 30. CELLECTRA® 5PSP ElectroporationDelivery Device 30 Array Drug
- 31. Natural Immune Activationin the Body 31 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 disease antigens ANTIGENIC PROTEINS Deliver plasmids into human cells using electroporation
- 32. 0 1000 2000 3000 4000 5000 T Cell ResponsesBy ELISpot Assay 1x10-6spleenocytes Immunized 3x with 15ug pNP responses @2 wk post Imm Display of GFP gene expression after electroporation delivery into rabbit muscle +EPEP Optimization Design + Delivery = Improved Immune Responses 32
- 33. † HVTN 080(N = 48 total). Responses shown against global peptides post-third dose, based on evaluable responders. ‡ HVTN 070 (N = 120 total). Responses shown against global peptides post-third dose, based on evaluable responders. Clinical Confirmation of Inovio Electroporation Benefit HIV Antigen Response • CD4 and CD8 intracellular cytokine staining (IFN-γ, IL-2) response associated with IL-12 and EP administration (2 clinical studies) with HIV gag, pol, env antigens/plasmids • Dosing at 0, 4, 12 weeks • Performed by independent HVTN Core Lab at University of Washington in NIH-sponsored trials 0 10 20 30 40 50 60 70 80 90 - IL-12 + IL-12 - IL-12 + IL-12 CD4+ Responders (%) CD8+ Responders (%) %Responders 33 + EP - EP Spyros A. Kalams, et al., The Journal of Infectious Diseases 2013;208:818–29 Responses to three doses of vaccine delivered with EP are greater than responses to four doses of vaccine delivered IM P= 0.0003 P < 0.0001
- 34. First Partnership toInitiate Immuno-Oncology Strategy 34 Products INO-3112 HPV-driven cancer immunotherapy + 2 new R&D products Upfront Payment $27.5 million Development Costs All development costs Milestone Payments $700 million Royalties Up to double digit tiered royalties on INO-3112 + royalties for additional cancer vaccine products AstraZeneca/MedImmune (deal signed August 2015) MedImmune intends to study INO-3112 in combination with selected immuno-oncology molecules within its pipeline
- 35. Perforin Granulysin GranzymeA GranzymeB • Lytic phenotype:patient PBMCs stimulated 120 hours in vitro with antigen. No co- stimulation; no cytokine added at any time. • Activation markers: CD38, CD69, CD137 • Lytic proteins: perforin, granzyme A, granzyme B, granulysin INO-3112 Drives Antigen Specific CD8+ T Cells with Lytic Phenotype in Patient with HPV16/18 Head & Neck Cancer 35
- 36. HPV 16/18 Specific CD8+ TCell Activation HPV 16/18 Specific CD8+ T Cell Activation and Expression of Lytic Proteins 8 of 9 patients show CD8+ responses to INO-3112 Induction of CD8+ Activation, Lytic Protein Synthesis, and Humoral Immune Responses to HPV 16 and 18 in INO-3112 Treated HNSCC Patient 36 0 .0 0 .2 0 .4 0 .6 0 .8 1 .0 IN O -3 1 1 2 %CD8/CD38&CD69&CD137 B e fo r e IN O -3 1 1 2 A fte r IN O -3 1 1 2 Representative patient Before INO-3112 After INO-3112 Before INO-3112 After INO-3112
- 37. dMAb™ Products: MultipleImmune Mechanisms & Products Inovio’s DNA-based monoclonal antibody products target: 37 Cancers Infectious Diseases • 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
- 38. Promising Preclinical dMAbData DARPA awards $57M to advance dMAb application and develop products for Ebola, influenza and antibiotic resistant bacteria 38 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%
- 39. Antigen-Generating/T Cell ActivatingSynCon® Products 39 Product Name Indication Preclinical Phase I Phase II VGX-3100 INO-5150 INO-1400 Phase III INO-3112 hTERT (antigen) Therapeutic Prostate Cancer Therapeutic HPV-Related Cancers Therapeutic Cervical Dysplasia Therapeutic INO-1800 Hepatitis B Therapeutic EbolaINO-4212 Preventive PENNVAX®-GP HIV Preventive/ Therapeutic INO-8000 Hepatitis C Therapeutic Preventive EXTERNALLY FUNDED Infectious Disease Programs INTERNALLY FUNDED Cancer Programs EXTERNALLY FUNDED Cancer Programs GLS-5300 MERS Preventive INO-5401 Cancer Target Therapeutic Zika PreventiveGLS-5700