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Inovio Pharmaceuticals, Inc. - Revolutionizing the Fight Against Cancers and Infectious Diseases
- 1. Revolutionizing the FightAgainst Cancers and Infectious Diseases Dr. Joseph Kim President & CEO NASDAQ: INO
- 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, 2013, our Form 10-Q for the quarter ended September 30, 2014, and other regulatory filings from time to time. 2
- 3. 3 Inovio: creatingthe 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
- 4. Human Papillomavirus LowGrade 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) 4 Disease Progression Cervical Cancer
- 5. Phase II: StudyDesign •148 subjects: 19-55 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) 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 5
- 6. 0 10 20 30 40 50 60 Phase II: Efficacy Data Meets Primary and Secondary Endpoints Histopathologic Regression to CIN1 or Normal (n=143) 49.5% (53/107) 30.6% (11/36) Statistically significant difference (p=0.017; strata-adjusted) Percent Histopathologic Regression to CIN1 or Normal AND Virological Clearance (HPV16 or 18) Incidence (n=143) 0 10 20 30 40 50 60 40.2% (43/107) 14.3% (5/35) Percent VGX-3100 Placebo VGX-3100 Placebo Statistically significant difference (p=0.001; strata-adjusted) • 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 6
- 7. VGX-3100: Next Steps EXPANSION OF HPV PROGRAM TO RELATED CANCERS AND PRE-CANCERS • Cervical cancer (Ph I/IIa initiated) • Head & neck (Ph I/IIa initiated) • Anogenital cancers • VIN, PIN ANALYSIS OF PHASE II DATA IN PROGRESS • Immunological analysis to further characterize T cell subsets is also in progress. Phase II data will add to Phase I data which has already been extensively characterized (Bagarazzi, et al. Sci Transl Med 2012) • Manuscripts are in preparation PHASE III DEVELOPMENT UNDERWAY • Clinical and regulatory • Commercial EP device development • Quantitative market research • Supply chain strategy • Pricing & reimbursement 7
- 8. T cell Antigen-specifickiller T cell Target cell 8 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. CIN 2/3 Immuno-oncologyStrategy: CIN 2/3 & Beyond 9
- 10. Broad Medical andMarket 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 Phase III 10 INO-3112 INO-3112 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 Preventive/ Therapeutic Ebola Aerodigestive Cancer Therapeutic INO-3106 INO-4200
- 11. 11 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 OROPHARY- NGEAL CANCER US: 11,726 EU5: 13,932 Incident cases in the US and EU5: HPV-Caused Pre-Cancers & Cancers: VGX-3100
- 12. HPV-Associated Cancer TreatmentsAlready 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 12
- 13. 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 13
- 14. 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 14 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
- 15. 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 15 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
- 16. 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 16 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
- 17. Financial Information Cash,cash equivalents & short-term investments2 $ 100.9 M Debt2 0 M Cash runway 4Q 2017 Shares outstanding2 60.5 M Recent share price1 $9.44 Market cap1 $ 571.1 M NASDAQ: INO 1Nov 19, 2014 2Sep 30, 2014 17 Recent insider buying $2.75M
- 18. INTERNALLY FUNDED EXTERNALLYFUNDED Ino-5150 1H 2015 Initiate phase I Prostate cancer Vgx-3100 2016 Initiate phase III Cervical dysplasia INO-3112 2Q 2014 Initiated phase I/IIa Head & Neck Cancer 18 Value Drivers INO-3112 2Q 2014 Initiated phase I/IIa Cervical Cancer Ino-1400 4Q 2014 Initiate phase I/IIa Breast/lung/ Pancreatic Cancer PennVAX® 1Q 2015 Initiate PENNVAX-GP phase I HIV Ino-8000 2015 Report interim phase I data Hepatitis C Ino-1800 2015 Initiate phase I/IIa Hepatitis B Ebola 1H 2015 Initiate phase I INO-3106 3Q 2014 Initiated phase I Aerodigestive Cancer INO-4200
- 19. Best-in-class T cellsto prevent, treat and cure cancers and infectious diseases Targeting broad range of diseases and numerous billion dollar markets Breakthrough active immune therapy technology with potential to save lives Validating partnership with Roche; working toward more deals Phase II data shows clinically significant efficacy Investor Highlights 19
- 20. 20 Revolutionizing theFight Against Cancers and Infectious Diseases
- 21. Strain 1 StrainX Strain 2 Antigen Y Antigen Y Antigen Y T Cells by Design: Antigen-Specific, Optimized, Best-in-Class 21 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
- 22. Insert SynCon® genesequence for selected antigen into DNA plasmid. SYNCON® DNA Antigen consensus sequence DNA Plasmid Designed to Break Tolerance or Provide Universal Protection 22 SynCon DNA plasmid ready to manufacture.
- 23. Electroporation Delivery Playsa Vital Role 23
- 24. DNA Immunotherapies: Disease-SpecificT Cells by Design It’s all about the T cells! 24
- 25. SynCon®+ Electroporation: SignificantAntigen Expression Ref: Sardesai & Weiner Curr. Opin. Immunol. 2011 • 1000x increase in cellular uptake and antigen production/ expression • >500 patents globally Intramuscular Intradermal 25
- 26. PENNVAX®: Highest CD8+T Cell Responses for HIV Vaccine Ref: Kalams et al JID 2013 26 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)
- 27. Inovio Beats PreviousGold 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 27 Ad5 DNA + EP Ad5 DNA + EP
- 28. Combined Cohorts IndividualDose 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 28 ELISpot Assay 0 1 2 3 4 5 6 7 8 9 Dosing Schedule (Months)
- 29. Bagarazzi, Yan, Morrowet al, Science Trans. Med. (2012) HPV16-, HPV18-Specific IFN-γ Production Multi-parameter flow cytometry: CD4, CD8 activation phenotype 29
- 30. HPV16-, HPV18-Specific CD107a,Granzyme B, Perforin Bagarazzi, Yan, Morrow et al, Science Trans. Med. (2012) CD8 cytolytic phenotype 30
- 31. 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 31
- 32. Surgical Standard ofCare for CIN2/3: LEEP • High-voltage electrical arc at 100oC vaporizes a plane through the cervix, then fulguration using a cautery • Black, particulate “coffee ground” discharge for weeks IARC monograph 2003:Edited by J.W. Sellors and R. Sankaranarayanan 32
- 33. INO-1400: Potential UniversalCancer Therapy Targeting hTERT (overexpressed in 85% of cancers) Yan J et al., Cancer Immunol Res. (2013) 33 Dharmapuri et al., Mol Ther. (2009) T-cell generation: older generation DNA vaccine and electroporation device SynCon® T-cell generation with CELLECTRA® electroporation device