Slide 1: A Promising Novel Approach to DNA Vaccines
A Promising Novel Approach to DNA Vaccines Kh u r s h e ed A n we r, , P h . D. , M BA Executive Vice President and CSO IVC 2025 October 23-26, 2025 Orlando, Florida, USA © 2022 IMUNON Inc. PAGE 1
Slide 2: DNA Vaccines are Well-Suited to Overcome the Limitations of Current mRNA and Protein Vaccines
DNA Vaccines are Well-Suited to Overcome the Limitations of Current mRNA and Protein Vaccines Current Vaccines & their Limitations Advantages of DNA Vaccines mRNA • Longer duration of antigen expression/ • Short duration of antigen expression & exposure immune responses • Strong T-cell responses (co
Slide 3: DNA Vaccines Require a DNA Delivery System
DNA Vaccines Require a DNA Delivery System Current Delivery Systems Warrant Alternate Approaches Viral Vectors • Biological in nature • High delivery efficiency • Poor repeatability • Safety limitations Electroporation devices • User compliance • Tissue damage • Additional cost Jet devices • Injecti
Slide 4: PlaCCine – A Novel DNA Vaccine Platform Technology
PlaCCine – A Novel DNA Vaccine Platform Technology Relies on Synthetic Vectors for DNA Delivery PlaCCine Vaccines do not Require Virus or Device: A PlaCCine Synthetic Delivery Systems: covalently-functionalized amphiphilic polymer X X Backbone X- functional group: same or different • Dispersion • Ge
Slide 5: DNA Protection & Enhanced Gene Expression by PlaCCine Delivery System
DNA Protection & Enhanced Gene Expression by PlaCCine Delivery System Protection of DNA Degradation Gene Expression: 10-15-fold > Naked DNA Non-functionalized Functionalized 10 8 7 days 24 hours Luciferase (RLU/mg protein) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 10 7 10 6 Degraded DNA Protected DNA 21-025
Slide 6: PlaCCine gives more Durable Antigen Expression Compared to mRNA-LNP
PlaCCine gives more Durable Antigen Expression Compared to mRNA-LNP PBS mRNA(Luc)/Acuitas LNP (1 ug) 10 9 pLuc/CP (100 ug) PBS mRNA-LNP 10 8 PlaCCine Luciferase Expression 10 7 Total Flux [p/s] 10 6 10 5 ~100%- fold 10 4 Day 1 Day 3 Day 6 Day 17 Day 24 Day 30 Day 37 Day 43 1 3 6 17 24 30 37 43 Days
Slide 7: Multivalent Antigen Expression Cassette in an Optimized Backbone
Multivalent Antigen Expression Cassette in an Optimized Backbone Allows for a Broad-based Antigen Targeting- One or More Pathogens • A template backbone cassette with optimized transcriptional elements • Flexible cloning sites for rapid gene incorporation/removal • Up to four gene sequences have bee
Slide 8: Novel Delivery Systems & Antigen Plasmids Constitute the PlaCCine Technology
Novel Delivery Systems & Antigen Plasmids Constitute the PlaCCine Technology PlaCCine pDNA PlaCCine Delivery Construct Systems Synthetic Delivery Systems • Non-viral Expression • Non-device Vector Nanoparticles/Complexes Antigen DNA 1 Antigen DNA 2 PlaCCine Vaccines Optional Immune modifier DNA Pote
Slide 9: PlaCCine Immunogenicity Demonstrated Against Various Pathogens in Multiple Species
PlaCCine Immunogenicity Demonstrated Against Various Pathogens in Multiple Species Pathogens Species • SARS CoV-2 (multiple variants) • Mouse • Influenza • Rabbit • Marburg • Monkey • Lassa • Human • Monkeypox © 2022 IMUNON Inc. PAGE 9
Slide 10: PlaCCine Immunogenicity Against SARS CoV-2 Variants- Mice
PlaCCine Immunogenicity Against SARS CoV-2 Variants- Mice IgG, NAb, and T-cell Responses IgG NAb Delta LV D614G (Euro) LV ns 4 4 ns 3 3 Log IC50 Titer Log IC50 Titer 2 2 1 1 0 0 Placebo pVac-15 pVac-16 pVac-17 pVac-15 pVac15(125) pVac-16 pVac16(125) pVac-17 pVac17(125) pVac-15 pVac15(125) pVac-16 pV
Slide 11: Protection Against SARS-CoV-2- hACE2:K16 Mice
Protection Against SARS-CoV-2- hACE2:K16 Mice >90% Protection • Formulation: PlaCCine including an adjuvant • Dose - 125 g DNA 7 days post challenge 10 7 10 6 D614G Challenge- 2.5 X 106 Delta Challenge - 7 X 104 10 6 > 90% Protection TCID50/gm of lung 10 5 TCID50/gm of lung 10 5 10 4 10 4 Complete
Slide 12: PlaCCine Immunogenicity Against SARS CoV-2 Variants- Cynomolgus Monkeys
PlaCCine Immunogenicity Against SARS CoV-2 Variants- Cynomolgus Monkeys IgG, NAb, and T-cell Responses Day 0 Day 0 NHP Plaque Reduction Neutralization Assay 10 6 IgG 4wkp2 10 5 4wkp2 NAb 7wkp2 7wkp2 3wkp3 3wkp3 4wkp2 3wkp3 10 5 10 4 7d post-challenge Endpoint Titer 10 4 Titer IC50 10 3 10 3 10 2 10
Slide 13: PlaCCine Protection Against Viral Challenge in Cynomolgus Monkeys
5 55 5 5 5 5 5 Log copies/ml Log copies/ml Log copies/ml Log copies/ml Log copies/ml Log copies/ml 4 4 Log copies/ml Log copies/ml Log copies/ml Log copies/ml 4 4 copies/ml Log copies/ml Log copies/ml Logcopies/ml 4 Log copies/ml 4 4 4 4 44 4 4 4 4 4 3 33 PlaCCine Protection Against Viral Challenge
Slide 14: PlaCCine Vaccines for Marburg, Influenza, and Lassa- Mice
PlaCCine Vaccines for Marburg, Influenza, and Lassa- Mice Marburg Influenza Lassa IgG IgG T-cell IFN- MARV GP-binding 1500 IgG Titers c e l ls 6 1000 S F C /10 500 0 PBS pVac-68 pVac-69 pVac-70 *p <0.05 **p <0.01 T-cell ****p<0.001 T-cell T-cell 1.0 0.8 CD4+ T cells TNFa IFN TNFa IFNy IL-2 IL2 CD4
Slide 15: PlaCCine Addresses the Limitations of Current Vaccines
PlaCCine Addresses the Limitations of Current Vaccines © 2022 IMUNON Inc. PAGE 15
Slide 16: Rising Immune Response Kinetic Compared to mRNA-LNP at a Single Dose
Rising Immune Response Kinetic Compared to mRNA-LNP at a Single Dose 10 5 2wkp1 500 Rising response 4wkp1 Higher T-cell response over time 5wkp1 at final timepoint No increase 400 10 4 over time Endpoint Titer SFC/106 cells 300 10 3 200 10 2 100 0 PBS PBS mRNA mRNA pVac-50 pVac50 PBS PBS mRNA mRNA p
Slide 17: Better T Cell Responses Compared to Viral Vector DNA & Protein Vaccines
Better T Cell Responses Compared to Viral Vector DNA & Protein Vaccines PlaCCine Offers Better Commercial Viability due to Safety Advantage 106 PBS Day 35- two doses Day 35- two doses PlaCCine 1500 Adenovirus 105 Protein SFC/106 Cells Endpoint Titer 1000 104 500 103 102 PlaCCine has safety advantage
Slide 18: Comparable Immune Responses to Electroporated DNA Vaccines
Comparable Immune Responses to Electroporated DNA Vaccines PlaCCine Offers Better Commercial Viability due to User Compliance Advantage Day 21 PlaCCine 10 g Day 35 PlaCCine 10 g (pre-boost) EP 10 g (post-boost) EP 10 g (Geometric mean. 99% CI) Ab Titer Day 35 (Geometric mean. 99% CI) PlaCCine 10
Slide 19: Commercial Advantages of PlaCCine over mRNA Vaccines: Stable at 4°C
Commercial Advantages of PlaCCine over mRNA Vaccines Stable at 4o C for at Least 12-Months • Vector: pVac-17 (D614G-Delta) IgG Response • Formulation: PlaCCine 1m 3m 6m 10 5 9m 12m 10 4 Endpoint Titer 10 3 10 2 4⁰C Storage 1 3 6 9 12 10 1 Months 10 0 4C 4C 4C 4C 4C h h h h h es es es es es Fr Fr Fr
Slide 20: Commercial Advantages of PlaCCine over mRNA Vaccines: Stable at 37°C
Commercial Advantages of PlaCCine over mRNA Vaccines Stable at 37o C for at Least 14 Days Sodium Citrate PBS NS = 0.141 NS = 0.06 Day-7 10 5 10 5 Day-14 10 4 10 4 Endpoint Titer 10 3 10 3 10 2 10 2 10 1 10 1 10 0 10 0 4C 37C 4o C 4C37o C 4o C 37C37o C 4o C 37o C 4o C 37o C Day 7 Day 7 Day 14 Day 14
Slide 21: IMNN-101: A Clinical Stage PlaCCine Vaccine
IMNN-101 A C l i n i c a l S t a g e P l a C C i n e Va c c i n e © 2022 IMUNON Inc. PAGE 21
Slide 22: IMNN-101- A COVID-19 Vaccine
IMNN-101- A COVID-19 Vaccine First-in-Human PlaCCine Vaccine IMNN-101 *XBB1.5 Variant PlaCCine delivery system Spike DNA Vaccine Plasmid Delivery System * Variant of Concern (FDA: VRBPAC 2023) Adjuvant Alum PO4 © 2022 IMUNON Inc. PAGE 22
Slide 23: IMNN-101- Single Dose, Placebo Controlled Phase 1 Trial in Healthy Subjects
IMNN-101- Single Dose, Placebo Controlled Phase 1 Trial in Healthy Subjects NCT06283459 Rapid Dose Escalation for Speedy Completion DNA Dose Escalation (mg) 0.5 1.0 2.0 Placebo (n = 8 each) Vaccine -30 Days Day-1 Day-7 Day-28 Day-90 Day-180 Prescreening/ Daily reactogenicity Enrollment assessment fo
Slide 24: Demographic Characteristics of the Study Patients
Demographic Characteristics of the Study Patients Baseline All Participants Dose Group 1 Dose Group 2 Dose Group 3 Characteristics (n = 24) (n = 8) (n = 8) (n = 8) Age (years) Mean 47.7 47.9 44.7 50.5 Sex Male 9 (37.5%) 3 (37.5%) 4 (50%) 2 (25%) Female 15 (62.5%) 5 (62.5%) 4 (50%) 6 (75%) Ethnicity
Slide 25: Safety Profile of IMNN-101
Safety Profile of IMNN-101 Treatment-emergent Adverse Events During 6-Month Follow Up n (%) Body System/Class TEAE Preferred Term Grade 1 Grade 2 Grades 3 – 5 (n = 24) Ear and labyrinth Vertigo 1 (4.2%) 1 (4.2%) 0 (0%) 0 (0%) disorders Bronchitis 1 (4.2%) 0 (0%) 1 (4.2%) 0 (0%) Infections and COVID-
Slide 26: NAb Responses to XBB.1.5/JN.1 Variant following a Single Dose of IMNN-101
NAb Responses to XBB.1.5/JN.1 Variant following a Single Dose of IMNN-101 Subjects Previously Infected/Vaccinated Multiple Times XBB.1.5 JN.1 XBB1.5 JN.1 ✱ ns 10 6 week-0 ✱✱ ✱ week-2 10 5 ✱ ✱ week week00 week-4 week week22 IC50 Titer week-24 10 4 241 326 616 512 361 744 869 636 week week44 10 3 week
Slide 27: Dose-dependence of the Neutralizing Antibody Responses to XBB.1.5 and JN.1 Variant
Dose-dependence of the Neutralizing Antibody Responses to XBB.1.5 and JN.1 Variant 4 XBB1.5 XBB1.5 5 JN.1 0.5 mg 0.5mg JN1 0.5 mg 0.5mg 11mg mg 4 1mg 1 mg 3 Fold change Fold change 22mg mg 2mg 2 mg 3 2 2 1 1 0 0 wk2 wk24 wk2 wk24 weeks weeks Fig. 2: Fold changes in median NAb titers at different vac
Slide 28: Cellular Immune Responses to XBB.1.5 & JN.1 Following IMNN-101
Cellular Immune Responses to XBB.1.5 & JN.1 Following IMNN-101 Subjects Previously Infected/Vaccinated Multiple Times CD4+ T-cells CD8+ T-cells % Responders IFN-g TNF-a IL-2 IFN- g TNF-a IL-2 XBB1.5 53% 47% 68% 63% 63% 32% JN.1 56% 61% 61% 50% 63% 50% Highest Fold-increase from Baseline & Dose XBB1.
Slide 29: T-cell Responses to JN.1 Following a Single Dose of IMNN-101
T-cell Responses to JN.1 Following a Single Dose of IMNN-101 Subjects Previously Infected/Vaccinated Multiple Times CD4+ ns ns Prominent Increases in CD4+ T-cells over Time 10 0 ✱ 10 0 10 0 % TNFα+ / CD4+ T Cells % IFN-γ+ / CD4+ T Cells % IL2 / CD4+ T Cells 0.1 10 -1 10 -1 10 -1 10 -2 10 -2 10 -2 0.
Slide 30: PlaCCine Summary
PlaCCine Summary- • A novel platform for prophylactic vaccines that leverages DNA advantages on: • Durability of antigen expression, temperature stability, flexible manufacturing, rapid development • Safety and immunogenicity demonstrated in healthy human subjects after a single injection. • NAb res