Slide 1: Novel DNA Approaches for Cancer Immunotherapies and Multivalent Infectious Disease Vaccines
Novel DNA Approaches for Cancer Immunotherapies and Multivalent Infectious Disease Vaccines
Slide 2: Celsion's Proprietary Plasmid DNA Technology Platforms
Celsion’s Proprietary Plasmid DNA Technology Platforms TheraPlas PLACCINE • Polymeric Nanoparticle Delivers Plasmid DNA Coding for • Plasmid DNA Vaccine Formulations (no virus or device) Therapeutic Proteins • Designed for multiple antigens • Safely Administered to Over 100 Patients To-Date • Option
Slide 3: Multivalent Infectious Disease Vaccines
Multivalent Infectious Disease Vaccines
Slide 4: Multi-cistronic Formulated pDNA Vaccine Platform
Multi-cistronic Formulated pDNA Vaccine Platform Proprietary PLACCINE Platform Technologies PLACCINE pDNA System PLACCINE Delivery Systems -Synthetic Delivery Systems • Non-viral • Non-device Expression Vector Nanoparticles/Complexes Antigen DNA 1 Antigen DNA 2 PLACCINE Vaccines Optional Immune Pote
Slide 5: Hypothesis: PLACCINE Provides a Best-in-class Nucleic Acid Vaccine Platform
Hypothesis: PLACCINE Provides a Best-in-class Nucleic Acid Vaccine Platform Demonstrating Proof of Concept by Developing a multivalent SARS-CoV-2 Vaccine Multivalent pDNA • Broad-based protection and improved resistance to mutations. Durable antigen exposure • Compared to mRNA/protein vaccines yield
Slide 6: PLACCINE Development Strategy
PLACCINE Development Strategy • Vector Optimization- Single Antigen Vectors o Antigen structure o Transcription elements • Multiple Antigen Vectors o Optimized parameters from single antigen vectors • Formulation Development o Synthetic delivery systems o Gene expression and immune response o Adjuva
Slide 7: Single Antigen Vaccines based on Optimized Vectors & Formulation
Single Antigen Vaccines based on Optimized Vectors & Formulation IgG and nAb Levels • Single antigen vectors pVac-15 (D614G), pVac-16 (Delta) • Formulation F3 • 125 mg DNA • IgG titer and nAb (day 35) PLACCINE IgG Titer Comparable Neutralizing Antibody Titers Against Different to mRNA Vaccine (slide
Slide 8: Single Antigen Vaccines based on Optimized Vectors & Formulation
Single Antigen Vaccines based on Optimized Vectors & Formulation T-cell Response • Vector pVac-15 (D614G), pVac-16 (Delta) • Formulation: F3 • 125 mg DNA • IgG titer (day 35) T-cell Response (IFN-g) placebo pVac-15 pVac-16 D614G Delta Variant 8 01-2022
Slide 9: Multicistronic Vector Expressing Two SARS-CoV-2 Antigen Variants
Multicistronic Vector Expressing Two SARS-CoV-2 Antigen Variants Spike Delta antigen 4 Spike D614G antigen 3 2 Two-Variant Multi-cistronic Vector 1 0 ctrl C2 ctrl C3 Distinguishing between D614G and Delta by sequence-specific qPCR primers 9
Slide 10: A Multicistronic PLACCINE Vaccine Protects Against Multiple Variants
A Multicistronic PLACCINE Vaccine Protects Against Multiple Variants IgG and nAb Titers Comparable to a Commercial mRNA Vaccine • Multicistronic vector pVac-17 • Spike antigen D614G, Delta • Formulation: F3 • 125 mg DNA • IgG titer (day 35) IgG Titer Neutralizing Antibody Titer IgG Titer (day 35 aft
Slide 11: Combined data from Two Separate PLACCINE Studies
Combined data from Two Separate PLACCINE Studies Neutralizing Antibody Response • Vectors pVac-15 (D614G) pVac-16 (Delta) pVac-17 (D614G+Delta) • Formulation: F3 • 125 mg DNA • IgG titer (day 35) D614G Variant Delta Variant pVac-15 pVac-16 pVac-17 mRNA Benchmark pVac-15 pVac-16 pVac-17 mRNA Benchmar
Slide 12: A Broad Vaccine Pipeline Opportunity Following Proof of Concept
A Broad Vaccine Pipeline Opportunity Following Proof of Concept Initial POC/Validation Target Potential Pathogen Targets HSV RSV Chikungunya Mycobacterium tuberculosis HIV Dengue Measles Plasmodium falciparum Hep C Ebola MERS-CoV Toxoplasma gondii Zika Yersinia pestis Future Pipeline Criteria Potent
Slide 13: Ongoing Development
Ongoing Development • Immune response durability studies • Dose response, safety toxicity, and biodistribution • Challenge studies – rodent and NHP • Stability studies at optimal commercial conditions 13
Slide 14: GEN-1 IL-12 Immuno-Oncology Program
GEN-1 IL-12 IMMUNO-ONCOLOGY PROGRAM
Slide 15: IL-12: A Powerful Immune-Modulating Agent
IL-12: A Powerful Immune-Modulating Agent Interleukin-12 Can Induce Anti-cancer Immunity Through Multiple Mechanisms Activation/Proliferation 1 Stimulates the proliferation of CD-8 positive T-cells and natural killer (NK) cells and their cytotoxic activity against the tumor 2 Maturation/Proliferatio
Slide 16: Anti-cancer Activity of rIL-12 Observed in Multiple Cancers
Anti-cancer Activity of rIL-12 Observed in Multiple Cancers Serious Systemic Toxicity Warrants Alternate Delivery Strategies CANCER rIL-12 INDICATIONS Toxic Level Protein Levels •Melanoma Desired Therapy •Renal carcinoma •Lymphoma •GI cancer SERIOUS SYSTEMIC TOXICITY • Therapeutic potential of rIL-1
Slide 17: GEN-1: DNA-based IL-12 Delivery by Intraperitoneal Administration
GEN-1: DNA-based IL-12 Delivery by Intraperitoneal Administration A safe alternative to rIL-12 therapy for peritoneal carcinomatosis of Gyn/GI Origin • GEN-1 Concept o Local increases in IL-12 at tumor site for several months w/o systemic toxicity will be safer and more effective than rIL- 12 • Canc
Slide 18: GEN-1 Composition
GEN-1 Composition PPC - 3 Components: Polyethylene Glycol (PEG), Polyethyleneimine (PEI), Cholesterol + IL-12 Plasmid PEI Condenses DNA strands into nanoparticles PEG Cholesterol Improves stability and protects Facilitates uptake and trafficking plasmid from degradation across cell membranes IL-12 p
Slide 19: Treatment Options in Advanced Ovarian Cancer Are Limited
Treatment Options in Advanced Ovarian Cancer Are Limited Recurrence Rates are High and Survival Rates Low 75% of Incidence: Stage III/IV Treatment Naïve Population 1st Line Platinum/Taxane + Pre and Post Surgery GEN-1 PFS 12 months | OS 36 months Platinum Sensitive Platinum Resistant Platinum Refrac
Slide 20: OVATION I: Phase I Trial of GEN-1 in Newly Diagnosed Ovarian Cancer Patients
OVATION I: Phase I Trial of GEN-1 in Newly Diagnosed Ovarian Cancer Patients • Neoadjuvant patient population • Standard 3+3 design with ~30% dose increments + standard carboplatin (C) and paclitaxel (T) • Eight weekly doses of GEN-1 before debulking surgery Safety Common AEs Attributed to GEN-1 Tot
Slide 21: OVATION I Study: Dose-Dependent Clinical Responses Observed
OVATION I Study: Dose-Dependent Clinical Responses Observed • Standard 3+3 design with ~30% dose increments + standard carboplatin (C) and paclitaxel (T) • Eight weekly doses of GEN-1 before debulking surgery Clinical Responses* GEN-1 Low-Dose Cohorts High-Dose Cohorts 36 mg/mg² & 47 mg/mg² 61 mg/mg
Slide 22: OVATION I Study Translational Data
OVATION I Study Translational Data Sampling Marked Dose-Dependent Increase in Anti-Cancer Cytokine Levels Increase in Dendritic and TEM Cells Interleukin-12 Interferon-g 14.0 30 70 Myeloid Dendritic Cells 12.0 Ascites 60 Effector Memory T Cells (pg/mg protein) Ascites 25 Ascites Blood 10.0 Fold Chan
Slide 23: GEN-1 OVATION 2 Ovarian Cancer Study
GEN-1 OVATION 2 Ovarian Cancer Study To Determine Efficacy and Biological Activity With NAC in Stage III/IV Patients 1 : 1 Randomization Added Control Arm to OVATION 2 Newly Diagnosed Neoadjuvant Chemotherapy (NAC) Interval Debulking Adjuvant Chemotherapy Ovarian Cancer + Surgery + Tissue Collection
Slide 24: GEN-1 OVATION 2 Ovarian Cancer Study
GEN-1 OVATION 2 Ovarian Cancer Study Phase I/II Open Label Controlled Trial Phase I Portion (N=14) Completed 100 mg/m² GEN-1 Dose Confirmed 22 Clinical Sites in U.S. and Canada Enrollment Expected to be Completed in Q3 - 2022 Interim Data (After 35 IDS) NACT ONLY NACT + GEN-1 Interval Debulk
Slide 25: Summary
Summary DNA Vaccines • PLACCINE vaccine technology, independent of virus/device, potentially durable immunity and shelf-life • Flexible design & generic manufacturing process better equipped for a rapid response to pandemic • A multi-cistronic vaccine provides protection against multiple variants of
Slide 26: Pipeline Milestone Events
Pipeline Milestone Events 2022 - 2023 PROGRAM & INDICATION 2020 2021 2022 2023 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Initiate Phase II Enrollment GEN-1 Complete Phase II Enrollment Phase II Trial* ORR & Surgical Data OVATION 2 Study from Phase II Ovarian Cancer Primary PFS Data Endpoint (P
Slide 27: Corporate Information
Corporate Information Celsion Corporation 997 Lenox Drive Suite 100 Lawrenceville, NJ 08648 P 609-896-9100 F 609-896-2200 www.celsion.com Nasdaq: CLSN