Forward Looking Statement

Transcription

1 1 February 2019

2 Forward Looking Statement This presentation includes statements that are, or may be deemed, forward-looking statements, within the meaning of Section 27A of the Securities Act of 1933, as amended. All statements, other than statements of historical facts, included in this presentation regarding our strategy, future operations, future financial position, future revenue, projected costs, prospects, plans and objectives of management are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as may, might, will, objective, intend, should, could, can, would, expect, believe, anticipate, project, target, design, estimate, predict, opportunity, proposition, strategy, potential, plan or the negative of these terms and similar expressions intended to identify forward-looking statements. You should not place undue reliance on these forward-looking statements. Forward-looking statements include, but are not limited to, statements about: the timing and success of preclinical studies and clinical trials; the ability to obtain and maintain regulatory approval of our product candidates; the scope, progress, expansion and costs of developing and commercializing our product candidates; our expectations regarding the amount and timing of our expenses and revenue; the sufficiency of our cash resources, plans for the use of our cash resources and needs for additional financing; our ability to adequately manufacture our product candidates; our ability to obtain and maintain intellectual property protection for our product candidates; our expectations regarding competition; the size and growth of the potential markets for our product candidates and the ability to serve those markets; the rate and degree of market acceptance of any of our product candidates; our anticipated growth strategies; the anticipated trends and challenges in our business and the market in which we operate; our ability to establish and maintain development partnerships; our ability to attract or retain key personnel; our expectations regarding federal, state and foreign regulatory requirements; regulatory developments in the United States and foreign countries and other factors that are described in the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of our Annual Report on Form 10-K for the year ended December 31, 2017 and our quarterly report on Form 10- Q for the quarter ended September 30, 2018, each of which has been filed with the Securities and Exchange Commission (SEC) and is available on the SEC's website at In addition, the forward-looking statements included in this presentation represent Inovio's views as of the date hereof. Inovio anticipates that subsequent events and developments may cause its views to change. However, while Inovio may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so, except as may be required by law. These forward-looking statements should not be relied upon as representing Inovio's views as of any date subsequent to the date of this presentation. Third-party industry and market information included herein has been obtained from sources believed to be reliable, but the accuracy or completeness of such information has not been independently verified by, and should not be construed as a representation by, Inovio. The information contained in this presentation is accurate only as of the date hereof. Inovio and the Inovio logo are trademarks and service marks of Inovio. All other trademarks, service marks, trade names, logos and brand names identified in this presentation are the property of their respective owners. 2

3 Inovio Value Proposition Validated Immunotherapy Platform Powerful platform based on optimized DNA constructs, demonstrating Phase 2b clinical efficacy of lead product VGX Well-protected with over 1,000 issued and pending patents Over 1,800 patient safety data and demonstration of high levels of T cell and antibody immune responses Over $160M in non-dilutive funding since 2009: Multiple Near-term Pipeline Catalysts Phase 3 for our lead asset (VGX-3100) treating High-Grade Cervical Dysplasia; ~500k new cases annually across U.S. & Europe Phase 2 programs (5); 3 are combination therapies in the areas of HNCSCC, Bladder Cancer, and Glioblastoma interim data to be reported in 2019/2020 Multiple Funded Vaccine Programs Partnerships with major Pharma and Biotech Companies: Initiated first-in-human study for the development of optimized DNA-encoded monoclonal antibodies (dmabs ) 3

4 Inovio Immunotherapy Technology Platform Inovio s technology platform is designed to work in vivo to activate an individual s immune system, generating robust T cell (CD8+) and antibody responses to fight cancer and infectious disease. CELLECTRA 5PSP Delivery Device 4 SynCon Immunotherapy SynCon : Synthetic consensus full-length DNA plasmid Select appropriate tumor or viral associated antigens as disease targets Create a synthetic consensus DNA sequence for the disease target using sequences from multiple species for cancer or primary isolates of the pathogen Modify the sequence to increase antigen production Insert the proprietary sequence into a platform-validated DNA plasmid CELLECTRA : Delivery device that enhances immune responses SynCon immunotherapy delivered into muscle or skin cells Uses an advanced transfection technology to dramatically increase immunotherapy cellular uptake and generate up to a 1000-fold increase in antigen expression

5 Inovio Immunotherapy Pipeline Product Indication Preclinical Phase 1 Phase 2 Phase 3 Status VGX-3100 Cervical Dysplasia Vulvar/Anal Dysplasia Ongoing Phase 3; BLA target submission 2021 Interim efficacy data 2019 INO-5401 Bladder Cancer Glioblastoma Dosed first subject Aug 2018; interim readouts 2019 Dosed first subject Jun 2018; interim readouts 2019 INO-1800 Hepatitis B Completed Phase 1; Candidate for Out-licensing MEDI0457 Head & Neck Cancer HPV-16/18 Cervical Cancer & Rare Tumors Advanced to P2 stage PD-L1 combo study 1Q18 Dosed first subject Dec INTERNALLY FUNDED PARTNER FUNDED

6 2019 Anticipated Milestones 1/9/19: First clinical trial involving DNA-Encoded Monoclonal Antibody (dmab ) 1H 2019: Complete enrollment REVEAL 1 (primary); initiate for REVEAL 2 (confirmatory) 1H 2019: Publication of MERS, Ebola, Zika-Puerto Rico Phase 1 studies 1H 2019: Design of a novel, cancer combination trial through the Parker Institute agreement 2019: Phase 2 interim data on MEDI0457 H&N study (MedImmune-sponsored study) 2H 2019: Phase 1/2 interim data from Bladder INO-5401 study 2H 2019: Phase 1/2 interim data from GBM INO-5401 study 2H 2019: Report on Phase 1/2 MERS study in Korea/Prepare for Phase 2 field trial 2H 2019: Interim efficacy data for Phase 2 VIN/AIN studies 6

7 HPV-Associated Diseases 7

8 HPV-Related Cancers: Rates & Global Threat Cancers linked to the HPV rose dramatically in a 15-year period within the U.S., despite an increase in vaccination rates 1 CDC reported 43,371 new cases of HPV-associated cancers within the U.S. in % spike since ,000 cases and 311,000 deaths associated with HPV-associated cervical cancer in 2018 worldwide 2 Cervical cancer is the most commonly diagnosed cancer in 28 countries and the leading cause of cancer death in 42 countries 8 1 Van Dyne EA, Henley SJ, Saraiya M, Thomas CC, Markowitz LE, Benard VB. Trends in Human Papillomavirus Associated Cancers United States, MMWR Morb Mortal Wkly Rep 2018;67: Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12-19.

9 Unmet Treatment Needs of HPV-Related Precancers VGX-3100 in Phase 3 study for the treatment of the following precancerous diseases caused by HPV types 16 and 18: High-grade Cervical Dysplasia High-grade Vulvar Dysplasia High-grade Anal Dysplasia First-in-class HPV-specific immunotherapy Targets a major underlying cause of anogenital cancer Treats precancer without invasive surgery Annual Incidence (HPV 16/18+ Precancers) US: 195,000 Cervical EU: 233,000 US: 23,000 Vulvar EU: 15,000 US: 13,400 Anal EU: 2,514 9

10 Vulvar Vulvar Vulvar Anal Anal Anal Cervical Cervical Cervical HPV Caused Precancers: Limitations of Surgery Loss of of of Reproductive Health 10% % 1 Massad LS, et al. Obstet Gynecol. 2013;121: Xi LF, et al. J Infect Dis. 2007;195: Nobbenhuis MA, et al. Br J Cancer. 2001;84: Wright TC, et al. Obstet Gynecol. 1992;79: IARC.Colposcopy and Treatmetn of Cervical Intraepithelial Neoplasia: A Beginner s Manual Kyrgiou M, et al. Cochrane Database Syst Rev. 2015;CD Nobbenhuis MA, et al. Lancet. 2001;358: Pain Recurrence of of of CIN2/3 3,4 3,4 3,4 after LEEP Surgical Complications 23.5% >50% 40-50% Negative Psychosocial Impact HPV-16 DNA detected in in in patients after LEEP Recurrence post-surgery with with clean margins Recurrence post-surgery 10

11 Phase 3 Program: VGX

12 Previously Published Phase 2b Achieved All Primary and Secondary Endpoints Week 0 Week 36 Placebo VGX-3100 Phase 3 Primary Endpoint: Regression to CIN1/Normal AND Virological Clearance (HPV16 or 18) Staining for HPV Trimble et al. Lancet 2015 Primary & Secondary Pre-Specified Endpoints Regression to CIN 1 or Normal Regression to Normal 49.5% P= % P>0.01

13 VGX-3100 Generates T Cells that Infiltrate Pre-cancerous Dysplastic Tissue, and Clears HPV and Dysplasia Week 0 Week 36 Regression of CIN3 & HPV to normal Increase and persistent presence of CD8+ cells (24 weeks post-last dose) Pre Post IHC Staining: Lesion/HPV IHC Staining: CD8 + Active Phase 3 REVEAL Study

14 Phase 3 Program: HPV-Related Cervical HSIL VGX-3100 has the potential to be: 1) the first treatment for HPV infection of the cervix and; 2) the first non-surgical treatment for precancerous cervical lesions VGX-3100: targets HPV 16/18 subtypes; E6/E7 oncogenes Treats high-grade squamous intraepithelial lesions (HSIL) Consists of two studies in parallel: REVEAL I (primary) n=198 REVEAL II (confirmatory) n=198 Randomized (2:1), double-blind, placebo-controlled Dosing: month 0, 1, 3 (as in P2b) Primary endpoint: month 9 (as in P2b) REVEAL 1: Study follow-up through week 88 (as in P2b) REVEAL 2: Study follow-up through week 40 Target BLA submission 2021 Primary Endpoint Regression of HSIL (CIN2/3) AND clearance of HPV 16/18 in the cervix Secondary Endpoints Safety/tolerability Regression of HSIL Virologic clearance of HPV-16 and/or HPV-18 Non-progression to cancer Clearance of HPV from non-cervical anatomic locations 14

15 Immuno-Oncology Programs 15

16 Immuno-Oncology Studies with Efficacy Endpoints MEDI0457 (licensed out to MedImmune) Metastatic HPV-related squamous cell carcinoma of the head & neck (SCCHN) with persistent or recurrent disease after chemotherapy treatment Combination with durvalumab (IMFINZI ) PD-L1 checkpoint inhibitor Phase 1/2 open label study: safety, immunological impact, objective response rate, progression-free survival and overall survival ~50 subjects. Enrolling. INO-5401 (combination of 3 tumor-associated antigens: htert, PSMA, WT1) Advanced unresectable or metastatic urothelial carcinoma (bladder cancer) Combination with atezolizumab (TECENTRIQ ) PD-L1 checkpoint inhibitor Phase 1b/2 open-label trial: safety, immune response and clinical efficacy ~80 subjects; ~60 will be PD-1/PD-L1 refractory patients 1st patient dosed Aug INO-5401 (combination of 3 tumor-associated antigens: htert, PSMA, WT1) Newly diagnosed glioblastoma multiforme (GBM) Combination with REGN2810 PD-1 checkpoint inhibitor Phase 1b/2a open label trial: safety, tolerability, immunological impact, progression-free survival and overall survival. ~50 subjects 1 st patient dosed June

17 Rationale for Checkpoint Combinations with Inovio Products Checkpoint Inhibitor Therapies Combined with Inovio Cancer Products Checkpoint inhibitors are only effective in ~20% of treated patients in most cancer indications Potential to improve response rates, without adding toxicity Tumor infiltration of antigen-specific, functional CD8+ T cells may prime patients for treatment with checkpoint inhibitors and increase response rates Preclinical mouse model 17 Combination studies initiated in MEDI0457 with MedImmune - INO-5401 with Regeneron and Roche/Genentech Paper published in Molecular Therapy 2017

18 MEDI0457: Turning Cold Tumors to Hot Tumors in Phase 1 CD8+ T Cells in H&N Tumor Phase 1 study of MEDI0457 in 22 HPV+ H&N Cancer Patients Before treatment with MEDI0457 After treatment with MEDI0457 Cold Hot Robust antigen-specific CD8+ killer T cell responses observed in 20/ % of patients (both tumor tissue and peripheral blood) Of 22 patients in Phase 1 18 show no progression to date 4 progressed over several year period exhibiting recurrence with metastatic disease; treated with PD-1 2/4 (50%) show complete response to PD-1 therapy and remain tumor free 50% CR rate compares well in metastatic HPV + H&N: o 4% CR rate (8/192) by KEYTRUDA alone o 3% CR rate (6/240) by OPDIVO alone MEDI conducting phase 2 studies combining MEDI0457 and durvalumab (PD-L1 inhibitor) 18 Published in Clinical Cancer Research (CCR) 2018

19 CT and PET Scan of HNSCC Patient with Complete Remission A B One patient remains cancer free for over 24 months and counting The other patient remains cancer free for over 12 months and counting (A) CT neck with IV contrast demonstrating partial response pre- and 6 weeks post-nivolumab. (B) PET scan images pre- and 6 weeks post-nivolumab. 19 Published in Clinical Cancer Research (CCR) 2018

20 Platform Development Programs 20

21 Rapid Clinical Translation of Inovio Vaccine Programs Ebola 15 Months to clinic: 95% response rate post dose 2 (publication submitted) MERS 9 Months to clinic: 95% responses post 2 dose, 98% overall response rate Zika 6.5 Months to clinic (including animal preclinical work): 100% response rate- passive transfer protection (Tebas et al NEJM 2017) 15 months Ebola 9 months MERS 7 months: Can be shortened to weeks Zika!

22 Positive Clinical Data & Partnering Opportunities Product Indication Data Reported (to date) Partner/s Next Milestone PENNVAX-GP HIV Phase 1: 93% (71 of 76) evaluable vaccinated participants showed a CD4+ or CD8+ cellular immune response to at least one of the vaccine antigens 94% (62 of 66) demonstrated an env specific antibody response (NIAID/HVTN) Expect results from P1/2 HIV trial study 2H19 (UCSF; Deeks) INO-4201 Ebola Phase 1: High levels of binding antibodies measured (ELISA) in 95% (170 of 179) of evaluated subjects Publish Phase 1 data 2019 GLS-5300 (INO-4301) MERS Phase 1: High levels of binding antibodies measured (ELISA) in 92% (57 of 62) of evaluated subjects 98% (61 of 62) generated an antibody and/or T cell response against MERS Publish Ph1 data/initiate CEPI funded P2 trial in 2019 GLS-5700 Zika Phase 1: High levels of binding antibodies measured (ELISA) in 100% (39 of 39) of evaluated subjects Publication in NEJM Safety and Immunogenicity of Anti-Zika Virus DNA Vaccine ; Oct. 4, 2017 Report on Puerto Rico study 1H19 22

23 Inovio s Key Differentiators Potent, in vivo generation of antigen-specific CD8+ killer T cells Combining T cell-generating technology with checkpoint inhibitors First and only entity to demonstrate clinical efficacy of an enhanced delivery DNA vaccine Favorable safety profile 6,000+ administrations across 1,800+ patients Zero anti-vector response allows for effective boosting Checkpoint inhibitors are only effective in ~20% of treated patients in most cancer indications Combining CD8+ killer T cells could potentially unlock the full capabilities of checkpoint inhibitors Speed and versatility of platform From concept to human testing in 7 months, fastest in vaccine history (e.g. Inovio Zika vaccine) Thermal stability and distribution (room temp storage >1 yr.) Rapid and scalable manufacturing 23

24 Click to edit Master title style Financials and Management 24

25 Financial Information Market cap 1 Shares outstanding 2 Cash & short-term investments 2 $473.5 M 94.5 M $85.5 M 1 January 31, September 30,

26 Senior Management J. Joseph Kim, PhD President & CEO Peter Kies CFO Niranjan Y. Sardesai, PhD COO Mark L. Bagarazzi, MD CMO Laurent Humeau, PhD CSO Decades of biotechnology/pharma management Merck: hepatitis A and B vaccines manufacturing; HIV vaccine (Ad5) R&D Ernst & Young Experience with growth companies Extensive biotech management and product development experience Led diagnostics development for mesothelioma, bladder cancer, and ovarian cancer for Fujirebio Diagnostics Clinical research experience incl. Merck Led clinical/regulatory for shingles and rotavirus vaccines; DNA vaccine expert Extensive R&D leadership experience in vaccine, cell and gene therapy developments in private biotech and mid-cap companies Led Translational Research, Human Therapeutics Division for Intrexon 26

27 Board of Directors Simon X. Benito Chairman, BOD Former Senior Vice President, Merck Vaccine Division Angel Cabrera, PhD President, George Mason University Morton Collins, PhD General Partner, DSV Ventures, Battelle Ventures and Innovations Val. Partners J. Joseph Kim, PhD President & CEO, Inovio David B. Weiner, PhD Executive VP, The Wistar Institute; Director, Vaccine Center Wendy Yarno Former Chief Marketing Officer, Merck & Co. Lota Zoth, CPA Former MedImmune CFO 27

28 Scientific Advisory Board David B. Weiner, PhD Chairman Father of DNA vaccines Executive VP, The Wistar Institute; Director, Vaccine Center 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 Rafi Ahmed, PhD Professor, Department of Microbiology and Immunology Emory University School of Medicine 28

29 Summary Bringing IMMUNO-INGENUITY to life Powerful T cell-activating immunotherapy platform, with multiple cancer and infectious disease targets Checkpoint inhibitor combination programs leading with big pharma INO: NASDAQ Transforming treatment of HPV-associated diseases Validation: partnerships, publishing, grants, and global expansion 29