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1 :INO Corporate Presentation December 2024
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2 Forward-Looking Statements 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 toidentify 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, 2023 and our Form 10-Q for the quarter ended September 30, 2024, which has been filed with the Securities and Exchange Commission (SEC) and are available on the SEC's website at www.sec.gov. 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.
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3 Company Highlights • Clinical-stage biotech focused on developing and commercializing DNA medicines to treat and protect people from HPV-related diseases, cancer, and infectious diseases • Platform technology that allows the design and delivery of therapeutics and vaccines that enable the patient's body to produce their own disease fighting tools • BLA submission targeted for mid-2025 under FDA accelerated approval program for lead program INO-3107 to treat recurrent respiratory papillomatosis (RRP) (Breakthrough Therapy/Orphan Drug) • Deep clinical pipeline of therapeutic and vaccine candidates providing multiple near- and mid-term catalysts • Established commercial-scale manufacturing for plasmids; device manufacturing in-house • $84.8M in cash, cash equivalents, and short-term investments as of 9/30/24; no debt – $30M public offering completed in December : INO
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4 3-Step Strategy to Unlock the Promise of DNA Medicine Lead ProgramLead Program Diversified Clinical PipelineDiversified Clinical Pipeline NextGen DNA MedicinesNextGen DNA Medicines NEAR TERM • Targeting mid-2025 BLA submission - Accelerated Approval Pathway - Request Rolling Submission & Priority Review • If approved, could be 1st DNA medicine available in U.S. MID TERM • 8 additional clinical-stage candidates(1) - Planning new PD-1 combination Ph3 for INO-3112 to target HPV-related throat cancer - Targeting areas of unmet needs across HPV-related diseases, oncology and infectious diseases LONG TERM • DMAbs: targeting infectious disease • dLNPs: next-gen vaccines targeting COVID-19 and other diseases including HIV • Cancer Vaccines INO-3107 for RRP (1) Wholly-owned and in collaboration with third parties
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5 REGISTRATIONPHASE 3PHASE 2PHASE 1PRECLINICAL INO-4800 *** COVID-19 OUT-LICENSED INOVIO Pipeline HPV-RELATED DISEASES IMMUNO-ONCOLOGY INFECTIOUS DISEASES * Preparing BLA submission under accelerated approval program ** VGX-3100 to ApolloBio for China *** INO-4800 to Advaccine for China DMAb Influenza dLNPs Various targets INO-5401 BRCA 1/2 Mutation INO-4201 Ebola Booster INO-6172 HIV INO-6160 HIV DMAb COVID-19 INO-5401 Glioblastoma VGX-3100 ** Cervical Dysplasia (HSIL) VGX-3100 ** Cervical Dysplasia (HSIL) VGX-3100 Anal Dysplasia VGX-3100 Anal Dysplasia INO-3107 * RRP INO-3107 * RRP INO-3112 Head & Neck Cancer
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6 Lead Candidates Target Significant Unmet Needs Sources: RRP Foundation; Delaware Journal of Public Health; National Brain Tumor Society; Centers for Disease Control; World Health Organization; Gribb JP, Wheelock JH, Park ES. Human Papilloma Virus (HPV) and the Current State of Oropharyngeal Cancer Prevention and Treatment. Dela J Public Health. 2023 Apr 22;9(1):26-28. doi: 10.32481/djph.2023.04.008. PMID: 37122346; PMCID: PMC10132363. Recurrent Respiratory Papillomatosis • ~14k prevalent cases in U.S. • Incidence: ~1.8 per 100,000 adults • Surgery standard of care • Chronic disease caused by HPV-6 & HPV-11 HPV-Related Throat Cancer • ~20k new cases a year in U.S. • Rapid increase in incidence • ~5 times more common in men • Caused by HPV-16 & HPV-18 • Surpassed cervical as most common HPV-related cancer Glioblastoma INO-3107INO-3107 INO-3112INO-3112 INO-5401INO-5401 • ~15k new cases annually in U.S. • >10k deaths annually • 50% of all primary malignant brain tumors • 5 yr survival: 6.9% • One of the most complex, deadly & treatment-resistant cancers
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7 INOVIO’S DNA Medicines
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8 INOVIO's DNA Medicines Platform In Vivo Protein Production: Teaching the body to make its own disease-fighting tools PRECISELY DESIGNED PLASMIDS PROPRIETARY DEVICES MECHANISM OF ACTIONTARGET HPV/Cancer Infectious Disease Protein Replacement Diseases Antigen-specific cytotoxic T cells to treat disease Binding/neutralizing antibodies and T cells to prevent disease Monoclonal antibodies to prevent/treat disease Therapeutic proteins
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9 Key Features of our DNA Medicines Platform Strengths include versatility & immunogenicity Induces antigen/protein-specific immune responses offering therapeutic and prophylactic protection Ability to drive antibody and CD8+ T cell responses against multiple indications Allows rapid plasmid construct design and manufacture Well tolerated in nearly 19,000 administrations (~6k clinical trial participants) No frozen storage or shipping required Ability to be re-dosed and sustain immune responses
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10 CELLECTRA® Delivery Device Enhances Uptake of DNA Medicine Track record of success in the clinic: • Nearly 6,000 subjects & 19,000 doses given by both investigational/commercial-ready CELLECTRA devices • 2 generations: CELLECTRA 2000, followed by CELLECTRA 5PSP & 3PSP developed to support commercial launch • 2000 & 5PSP are CE Marked in the EU • Clinical trials conducted in 36 countries across 6 continents (N.S. America, Europe, Africa, Asia, Australia) • Intramuscular (IM) injection • Utilizes synthetic plasmid via cartridge • Utilized in INOVIO’s therapeutic programs • Intradermal (ID) injection • Primarily used for prophylactic programs with potential to broaden use in pediatrics and other indications CELLECTRA 5PSPCELLECTRA 5PSP CELLECTRA 3PSP CELLECTRA 3PSP CELLECTRA 5PSP CELLECTRA 3PSP
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11 Focus on HPV-Related Diseases
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12 Human Papillomavirus (HPV): A Global Concern • HPV is a group of viruses with approximately 200 types • Nearly everyone will become infected with some HPV type in their lifetime – The good news: ~90% of all infections clear naturally and don't result in disease – The bad news: persistent infection can lead to cancer and other debilitating, life-threatening diseases affecting quality of life • HPV types fall into 2 groups: – Low-risk HPV (e.g., HPV-6 and HPV-11) often lead to benign growths (warts or papillomas) that can develop into conditions such as RRP – High-risk HPV (e.g., HPV-16 and HPV-18) often lead to cell changes and lesions (precancerous dysplasia) that can become malignant, such as cervical HSIL, which can lead to cervical cancer • Preventative HPV vaccines have reduced the prevalence of HPV infections, but have not eliminated them – nor can they clear or treat established infections. • Some HPV related diseases such as HPV related OPSCC are rapidly increasing in high income countries. By Opabinia regalis - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=80562689
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13 INOVIO’s Development Experience Across HPV Spectrum 12 trials, 900+ participants, 2000+ administrations in HPV-related diseases • Studies ranging from Phase 1 to Phase 3 • Involving patients with RRP, HSIL (cervical, anal & vulvar), head and neck cancers
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14 Lead Candidate: INO-3107 for Recurrent Respiratory Papillomatosis (RRP) Potentially transformational therapy under accelerated approval pathway
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15 Current Status & Development Timeline for INO-3107 Targeting BLA Submission Mid-2025 July Orphan Drug Designation (US) August Breakthrough Therapy Designation (US) October \INOVIO informed can submit BLA under FDA Accelerated Approval Pathway February Authorization to begin Ph 1/2 clinical trial (US; RRP-001) 2020 2022 2023 May Orphan Drug Designation (EU) 2024 July Innovation Passport Designation (UK) July ATMP Certification (EU) August Pre-BLA Meeting (US) February Positive results from 2nd cohort of Ph 1/2 trial announced (RRP-001) October Positive results from 1st cohort of Ph 1/2 trial announced (RRP-001) Oct & Nov 2024 Immunology data from RRP- 001 presented December 2024 Durability data from retrospective study (RRP-002) announced August Testing as part of BLA req’s found low- level breakage of plastic molded part of disposable single- use array 2025 Targets Complete mfg adjustments for device array and retesting process Submit IND to initiate confirmatory trial Submit BLA (will request rolling submission & priority review) Prepare for commercial launch
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16 Recurrent Respiratory Papillomatosis (RRP) Image Source: National Institute on Deafness and Other Communication Disorders; Available at www.nidcd.nih.gov/health/recurrent-respiratory-papillomatosis; accessed July 27, 2022; Photographs courtesy Aaron Friedman MD, University of Cincinnati College of Medicine (https://voicesurgeon.net/voice-disorders/recurrent-respiratory-papillomatosis-rrp/). Used with permission. • Rare disease characterized by small, wart-like growths (papillomas) in the respiratory tract • Can form anywhere but primarily affect larynx & vocal cords • Can cause difficulty speaking or complete voice loss, difficulty swallowing, shortness of breath and choking episodes • In rare cases, can spread to lungs or become malignant • Insufficient immune response that fails to prevent and clear HPV-6 and -11 infection leads to RRP ◦ Affects adults & children • Annual estimated U.S. prevalence/incidence • ~14k active cases (juveniles and adults) • ~1.8 per 100,000 adults • Surgery is current standard of care • Papillomas grow back since underlying infection remains • Average 4 surgeries per year • Severe RRP may require 100s of surgeries over a lifetime • Surgery can irreversibly damage vocal cords
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17 The cumulative risk for injury increases with every surgery, but ultimately it only takes 1 surgical misadventure to permanently damage the larynx.” Factors Associated with Iatrogenic Laryngeal Injury in RRP Otolaryngology, 2024 Apr;170(4):1091-1098. doi: 10.1002/ohn.629. Epub 2023 Dec 20 Why every surgery matters to RRP patients:
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18 RRP-001: INO-3107 Phase 1/2 Trial Design Focused on What Matters Most to Patients: Reduction in Surgery • INO-3107: Composed of plasmids encoding for E6 and E7 antigens from HPV-6, HPV-11, & a plasmid encoding for IL-12 • Enrollment criteria: Patients requiring 2 or more surgeries in past year to remove HPV-6/11-related papilloma(s) • Efficacy endpoint: Change in number of surgeries in year prior to Day 0 when compared with year following Day 0 • Surgeries: Up to 14 days before Day 0, patients had RRP tissue surgically removed and any surgery performed after Day 0 during the dosing window was counted against efficacy endpoint • Immunology assessment: – Peripheral blood taken at Day 0, Weeks 6, 9, 11, 26 and 52 – Airway tissue/papilloma obtained at Screening and Week 52 (based on ability to obtain while maintaining patient airway safety). Samples taken from same anatomical site whenever possible. 4 doses of INO-3107 on Day 0, Weeks 3, 6, 9 Phase 1/2 open-label, multi-center clinical trial 32 patients enrolled; two cohorts N=32
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19 Promising Clinical Benefit Observed in RRP Patients INO-3107 Efficacy Results Overall Clinical Response Overall Response Partial Response Complete Response 81% (26/32)72% (23/32)44% (14/32)28% (9/32) Parameter Complete Response (CR): no surgeries during a 52- week treatment phase Partial Response (PR): a ≥ 50% reduction and less than 100% in surgeries compared to previous year Overall Response Rate (ORR)=CR+PR: Patients with complete or partial response to treatment Overall Clinical Response (OCR): reduction of ≥ 1 surgery compared to previous year
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20 Phase 1/2 Trial Results Reduced Number of Surgeries for Patients with Varying Disease Burden Before INO-3107 After INO-3107 HPV-6 - Reduction of 3 surgeries - CR HPV-6 - Reduction of 3 surgeries - PR HPV-11 - Reduction of 6 surgeries - CR Before INO-3107 After INO-3107 Before INO-3107 After INO-3107
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21 New Durability of Response Data Retrospective Study – RRP-002 • Collected data on patients who participated in RRP-001, primarily focusing on number of surgeries that have occurred up to 3 years following initial dosing ◦ All patients were still under the same surgeon's care ◦ Four patients did not consent or could not be contacted, so N is reduced to 28 vs 32 ◦ Data presented is modified intent to treat population (mITT) ◦ Median follow up ~1025 days, or 2.8 years • Following data is presented: ◦ Population as a whole post 001 with respect to outcome classification ◦ Longitudinal outcome of patients who achieved clinical response in 001 • No treatment related SAEs were identified
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22 Increase in Complete Responses Observed Over 3-Year Follow-up Parameter Overall Clinical Response (OCR): reduction of ≥ 1 surgery compared to previous year Overall Response Rate (ORR)=CR+PR: Patients with complete or partial response to treatment Complete Response (CR): no surgeries during a 52-week treatment phase Partial Response (PR): a ≥ 50% reduction and less than 100% in surgeries compared to previous year No Response (NR) Analysis of patients meeting the criteria for each efficacy parameter/definition at the end of each post-treatment year (i.e., efficacy parameters assessed independently at the end of years 1, 2, and 3, respectively) 81% 72% 28% 44% 19% 89% 86% 50% 36% 11% 93% 83% 54% 29% 7% OCR ORR CR PR NR Durability Trends During 3-Year Follow-up Yr 1 (N=32) Yr 2 (N=28) Yr 3 (N=28) mITT Dataset Analysis Per Protocol Analysis of CR Year 2 & 3: 55% & 52% respectively
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23 Maintenance of Clinical Response • INO-3107 had an overall response rate (ORR=CR+PR) of 72% without the requirement for additional surgeries during the administration phase & treatment was well-tolerated with minimal systemic AEs – The treatment response observed with INO-3107 was durable with 95% of these patients meeting ORR criteria two years after the initial dose. % of Patients who maintained response in year 3 % of Patients who maintained response at end of year 2 Response rate at end of year 1ComponentsKey Response Parameter 86% (18/21) 95% (20/21)* 72% (23/32) Overall Response Rate (ORR) = CR + PR: Patients who had either a complete or partial response to treatment 63% (5/8) 88% (7/8) 28% (9/32) Complete Response (CR): no surgeries during a 52-week treatment phase 92% (12/13) 92% (12/13) 44% (14/32) Partial Response (PR): a ≥ 50% and < 100% reduction in surgeries compared to previous year 96% (22/23) 91% (21/23) 81% (26/32) Overall Clinical Response (OCR): reduction of ≥ 1 surgery during 52-week treatment phase compared to previous year * One CR patient in year 1 moved to PR by end of year 2 mITT Dataset Analysis
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24 Patients Treated with INO-3107 Demonstrated Durable Response • Overall response rate (ORR=CR+PR ≥ 50%) of 72% without requirement for additional surgeries during administration phase; treatment well-tolerated with minimal systemic adverse events – Treatment response was durable with 95% of these patients meeting ORR criteria two years after the initial dose • During 3-year assessment period, number of patients who required no surgeries each year increased over time – Average number of surgeries required continued to decrease during 3-year follow-up period • Latest durability data, along with ability of DNA Medicine platform to boost immune responses, supports rationale for redosing patients with goal to maintain or improve clinical benefit
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25 New Immunology Data Presented at AACR (October 19) & IPVC (November 14) • INOVIO conducted an immunology assessment of INO-3107 – 32 patients in Phase 1/2 trial (RRP-001) – Blood samples taken throughout trial. Paired airway tissue biopsies taken prior to treatment and at trial end assessed for immune activity • Goal: evaluate whether INO-3107 can induce HPV antigen specific T cell responses in blood that travel to/infiltrate papilloma, eradicate HPV 6/11 infected cells to reduce or eliminate need for surgery • Immunological testing conducted: – Evaluation of peripheral blood samples to confirm induction, activation and expansion of cytotoxic T cells with antigen specificity to HPV-6 and HPV-11 – Evaluation of airway tissues to assess immunological changes, T cell infiltration/profiling and potential impact of papilloma microenvironment
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26 • Poorly infiltrated papillomas • Low Inflammatory signatures • Low cytokine and chemokine production • Uncontrolled and/or progressive disease • Increased Inflammatory signatures • Increased cytokine and chemokine production • Elimination of HPV-infected cells = Controlled disease, reduction/elimination of surgical interventions Pre-existing T cells in blood Expansion of pre-existing T cells and Induction of novel T cells in blood Low T cell trafficking Mass trafficking by INO-3107 induced T Cells Proposed Mechanism of Action Induce HPV antigen-specific T cell responses in periphery, track to/infiltrate papilloma/airway tissue, eradicate HPV infected cells to control/eliminate disease CIRCULATION PAPILLOMAS Treatment with INO-3107 Immunotherapy
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27 Key Takeaways: Immunological Evaluation of INO-3107 Right kind of immune responses generated to fight HPV in all 32 patients T cells get where they need to go – into the papilloma/airway tissue Creates an immune response in papilloma/airway tissue that reduces or eliminates the need for surgery Immune responses in clinical responders are different than for non- responders Papilloma microenvironment doesn’t appear to restrict clinical benefit (antigen specific cytotoxic T cell response)
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28 Why is the immunology data important for INO-3107? • Supports mechanism of action and is an important component of regulatory filings • Confirms the targeting of HPV-6 and HPV-11, the strains that cause disease • Confirms the expansion of existing populations of T cells and induction of new T cells that travel to the airway tissues to reduce or eliminate the need for surgery • Supports clinical benefit across the spectrum of disease severity We believe these data provide compelling evidence that INO-3107’s MOA could be significant for RRP patients by reducing their need for repeat surgeries to treat their disease
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29 Proposed Resolution of Array Issue • Issue: Low percentage of broken hook and/or catches found in a plastic molded part following extensive conditioning as part of a transportation study required for BLA • High confidence in implemented resolution: – Revised design to strengthen the hook and catches and improve fatigue resistance – Reduced the retraction spring force to decrease stress on areas of breakage – Refined the molding process to improve heating and flow and added automated part ejection • Next Steps: – Finalize testing of the resolutions applied – Conduct OQ/PQ* & Metrology** on 800-1000 array – provides final confirmation of resolution due February 2025 – Repeat required testing prior to IND/BLA submission Catches Hook *Operational Qualification/Performance Qualification **Scientific study of measurement
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30 INO-3107 Offers Compelling Product Profile Significant Clinical BenefitSignificant Clinical Benefit • 81% of patients saw a reduction in surgeries; including 28% with CR after one year - CR increased to 50% in year 2 - 95% of patients maintained or enhanced their original ORR by end of year 2 • Favorable tolerability profile • Clinical benefit observed across disease severity spectrum • Data consistent across 8 US clinical study sites • Immunology data supports MoA and clinical outcomes Potential Commercial AdvantagesPotential Commercial Advantages • Targets/demonstrated similar efficacy against both HPV-6 and HPV-11 • DNA medicine platform with targeted localized delivery (no viral vector) - No concern of pre-existing immunity - Potential for re-dosing • Simple treatment delivered at point of care - Administration well tolerated by patients & CELLECTRA easy to use by HCPs - No scoping/surgeries as part of treatment regimen - Refrigerator stable for up to 3 years • Confirmatory study design (placebo-controlled) suitable for global registration
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31 INO-3107: Advancing Plans to be Launch Ready by YE2025* • Refining go-to-market strategy: focused on patient needs • Conducting additional market research to develop thorough market understanding • Driving key strategic choices: – Pricing and access (rare disease) – Channel strategy – Targeting and segmentation – Product positioning to ensure strong differentiation • Planning further build-out of commercial organization in 2025 – Highly concentrated rare disease market; can be served by small/efficient field force footprint *If regulatory approval received
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32 Late-Stage Pipeline Candidates Designed to address high unmet needs, multiple near- and mid-term catalysts
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33 INO-3112: Building on Experience in HPV-Related Diseases with Novel Combination Therapy Clinical Collaboration & Supply Agreement with Coherus BioSciences INO-3112: DNA medicine candidate targeting HPV-16/18, combined with interleukin-12 (immune activator) LOQTORZI: Proven anti-PD-1 monoclonal antibody Plan to evaluate combination therapy as treatment for locoregionally advanced, high-risk, HPV-16/18+ oropharyngeal squamous cell carcinoma (OPSCC/throat cancer)
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34 What is Oropharyngeal Squamous Cell Carcinoma? • Type of head and neck cancer commonly known as throat cancer • Occurs in the base of the tongue, tonsils and/or soft palate • Usually related to high-risk subtypes of HPV; some cases are carcinogen-driven • HPV+ throat cancer rapidly increasing in incidence among patients in high-income countries ◦ Surpassed cervical cancer as most common HPV- related cancer diagnosed in the U.S. (~ 20,000 new cases/yr) • HPV estimated to cause 70%-80% of all oropharyngeal cancers diagnosed in the U.S. https://www.cancer.gov/types/head-and-neck/patient/adult/oropharyngeal-treatment-pdq
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35 Opportunity to Impact HPV-Related Locoregionally Advanced Throat Cancer • Most throat cancer patients diagnosed with locoregionally advanced (LA) disease • Current treatment is with curative intent through use of multi-modal therapy, including surgery & CRT • Outcomes: – 3-year progression-survival (PFS) is good (70-75%) ◦ When patients progress, clinical outcomes are poor, even with addition of immune- checkpoint blockade therapy, with overall survival under one year on average • Proposed Trial target: high-risk patients with HPV-related LA throat cancer – Estimate 3k - 4k new patients per year in US
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36 Existing trial data highlights strong rationale & potential benefit of combining INO-3112 to generate T cells targeting the HPV E6 & E7 oncogenes with a PD-1 inhibitor in HPV-16/18 related OPSCC INO-3112: Strong Case for Combination Therapy Based on Previously Completed Trials Monotherapy: Phase 1/2a in pre-surgery or post CRT patient Combination Therapy: Phase 1b/2a in recurrent/metastatic patients • Combined with AstraZeneca’s PD-L1 checkpoint inhibitor, durvalumab • ORR: 27.6% (4 CR, 4 PR) in 29 evaluable patients Median OS was 29.2 months (confidence interval: 15.2–not calculable) Peripheral HPV-specific T cells and intratumoral CD8+ cells increased after treatment • Updated results and published in Clinical Cancer Research, 2023 CD8 staining prior to dosing CD8 staining after dosing Published in Clinical Cancer Research, 2019
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37 Opportunity for the PD-1 Collaboration & Next Steps • Novel combination of INO-3112 plus LOQTORZI could significantly reduce rate of disease recurrence compared to standard of care in high-risk, HPV-positive, locoregionally advanced OPSCC patients – Provides further support for INOVIO as a leader in addressing HPV-related diseases through generation of antigen-specific T cells • Moving forward with plans for Phase 3 trial based on FDA feedback – Trial designed to show improvement in event-free survival – Targeting multi-center trial in North America and Europe • Submitted Phase 3 trial design to European regulatory authorities
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38 VGX-3100: Anal HSIL Completed Phase 2 Trial in HIV-Negative Participants • VGX-3100: composed of plasmids encoding for HPV-16 and HPV-18 subtypes; E6 and E7 oncogenes • Open-label trial of VGX-3100 in 24 HIV-negative participants with HPV-16 and/or -18-positive anal HSIL • 50% (11/22 evaluable) of participants showed no evidence of HPV-16/18-positive HSIL at Week 36 • 46% (10/22) of participants showed no evidence of HPV-16/18 virus at Week 36 • Adverse events were predominantly mild or moderate, and were in general associated with injection site reactions The Spontaneous Rate is estimated to be less than 27% Clearance of HPV-16/18+ lesions: 50% of patients Final findings (6 months after start of treatment) Trial initiated in May 2018; Results announced in December 2020 Phase 2 open-label trial Precancerous Anal Dysplasia: N=24 3 or 4 dose regimen at Months 0, 1, 3 and Week 36 (optional)
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39 VGX-3100 Ongoing Phase 2 Trial Anal HSIL in HIV-Positive Participants • Trial initiated in September 2018 • 80-participant, open-label Phase 2 trial • 4 doses at week 0, 4, 12, and 24 • Primary endpoint: overall response rate at 48 weeks – defined as regression of anal HSIL to LSIL or normal • Sponsored by AIDS Malignancy Consortium
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40 INO-5401 + INO-9012 and LIBTAYO® for Newly Diagnosed GBM Partnered with Regeneron • INO-5401 is a DNA medicine composed of plasmids that encode for 3 tumor-associated antigens: human telomerase (hTERT), Wilms tumor-1 (WT-1), and prostate-specific membrane antigen (PSMA) ◦ INO-9012 is a DNA plasmid that encodes for human IL-12 ◦ LIBTAYO® is a high-affinity, highly potent, human, hinge-stabilized IgG4 mAB to the PD-1 receptor • Phase 1/2 trial results: • INO-5401 + INO-9012 with LIBTAYO® and 40 Gy radiation/TMZ were observed to have favorable tolerability and immunogenicity • Next steps: In discussions with Regeneron and KOLs regarding clinical path forward Historical 14.6-16 mo.17.9 mo. (14.5 – 19.8)Median OS; unmethylated (A) Historical 23.2-25 mo.32.5 (18.4 – NR)Median OS; methylated (B) -19.5 (16.9 – 23.3)Median OS; combined (A+B) NR: not reached. Gilbert et al. J Clin Oncol 2013; Gilbert et al. N Eng J Med 2014; Comparison is limited due to differences in trial population; Data was presented at 2022 ASCO Annual Meeting; Libtayo® is owned, developed, and marketed globally by Regeneron
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41 INO-4201: Ebola Booster Vaccine Candidate • Recent progress: – Re-submitted Ph 2 trial design to FDA – Preparing to submit Phase 1b trial data to peer-reviewed journal with collaborators – New FANG assay data: indicates 4201 elicits antibody response comparable to Ervebo primary series vaccination • Phase 1b trial data as booster for Ervebo® – Safety & immunological data presented at ECCMID 2023 – Robust immune response, potential to extend vaccine protection INO-4201 Boosts Binding & Neutralizing Antibodies Against Ebola Binding Antibodies Neutralizing Antibodies
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42 DNA Encoded Monoclonal Antibody (DMAb ) The Next Generation of DNA Medicine • INOVIO developing novel DMAb technology that enables in vivo production of monoclonal antibodies • DMAbs potentially transformative approach for the prevention and treatment of infectious diseases, cancer • Ongoing Wistar Institute-led Phase 1 clinical trial in collaboration with AstraZeneca, the University of Pennsylvania, Indiana University and INOVIO to develop anti-SARS-CoV-2-specific DMAbs – Funded by DARPA – Expect publication of data in 4Q24
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43 Power of Partnerships to Advance DNA Medicines Active Clinical Studies
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44 Upcoming Key Catalysts • INO-3112: Gain alignment with EU on Phase 3 design (1Q25) • INO-4201 (Ebola booster): Submit Phase 2 trial design based on FDA feedback (2H24) • First clinical data from Phase 1 DMAb trial (anti-SARS-CoV-2) (1Q25) • INO-3107: - Submit BLA (mid-2025) Resolve disposable array issue Initiate confirmatory study - Submit a re-dosing study to FDA (2H25) - Present/publish immunology, durability, full efficacy and tolerability data (2025)
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45 INOVIO: Drivers for Success Advancing candidates with scientific and clinical promise, achievable pathways to market and strong commercial potential. Extensive experience bringing innovative products to market to benefit patients; focused on operational excellence and financial discipline History of collaboration in industry, academia & government to help drive innovation and advance promising candidates. Growing body of research and late- stage clinical data clarifying competitive advantages of platform: including generation of T cells, clearing virus and lesions, ability for repeat dosing/boosting Diversified Pipeline Diversified Pipeline Unique Technology Unique Technology Power of Partnerships Power of Partnerships Experienced Leadership Experienced Leadership $84.8M in cash, cash equivalents & short-term investments as of 9/30/24 $30M public offering completed in December
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46 :INO Investors: Peter Vozzo Peter.Vozzo@icrhealthcare.com Media: Jennie Willson jennie.willson@inovio.com