rocakinogene sifuplasmid (INO-9012) / Inovio - LARVOL DELTA

Phase Ib study of a plasmid DNA–based immunotherapy encoding the hTERT, PSMA, and WT1 (INO-5401) +/- IL12 (INO-9012) followed by electroporation in cancer patients and healthy individuals with BRCA1/2 mutations. (ASCO 2025) - P1 | "Administration of a recombinant plasmid-derived DNA based immunotherapy encoding hTERT, PSMA and WT1, +/- IL12, followed by electroporation is feasible and safe in individuals with BRCA1/2, including healthy individuals with no prior cancer. The most common AEs are injection site reactions, all of which were Grade 1/2."

Clinical • IO biomarker • P1 data • Dermatology • Genito-urinary Cancer • Hypertension • Immunology • Nephrology • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Urticaria • Wilms Tumor • BRCA1 • BRCA2 • IL12A • TERT • WT1

IMPACT 31: Personalized Neoantigen Vaccine Plus IL-12 (INO-9012) Versus Active Surveillance in Subjects With High-Risk HCC (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Geneos Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Oncology

IMPACT 31: Personalized Neoantigen Vaccine Plus IL-12 (INO-9012) Versus Active Surveillance in Subjects With High-Risk HCC (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: Geneos Therapeutics

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

DNA Vaccine Therapy in Treating Patients With Chronic Hepatitis C Virus Infection (clinicaltrials.gov) - P1 | N=33 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Hepatitis C • Hepatocellular Cancer • Infectious Disease • Inflammation • Oncology • Solid Tumor

INO 5401 Vaccination in BRCA1/2 Mutation Carriers (clinicaltrials.gov) - P1 | N=44 | Active, not recruiting | Sponsor: Abramson Cancer Center at Penn Medicine | Trial completion date: Dec 2025 ➔ Mar 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • BRCA1 • BRCA2

Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2025 ➔ Sep 2027

Trial completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • IDH1 • IDH2 • MGMT

INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) (clinicaltrials.gov) - P1/2 | N=52 | Active, not recruiting | Sponsor: Inovio Pharmaceuticals | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

INO-5401 + INO-9012 in Combination With Atezolizumab in Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma (clinicaltrials.gov) - P1/2 | N=35 | Completed | Sponsor: Inovio Pharmaceuticals | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ May 2025 | Trial primary completion date: Dec 2025 ➔ May 2025

Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Urothelial Cancer

INO 5401 Vaccination in BRCA1/2 Mutation Carriers (clinicaltrials.gov) - P1 | N=44 | Active, not recruiting | Sponsor: University of Pennsylvania | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • BRCA1 • BRCA2

DNA Vaccine Therapy in Treating Patients With Chronic Hepatitis C Virus Infection (clinicaltrials.gov) - P1 | N=33 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Hepatitis C • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Oncology • Solid Tumor • CD4 • CD8 • IFNG

GT-30: GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects with Advanced HCC (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: Geneos Therapeutics | Completed ➔ Active, not recruiting | Trial completion date: Nov 2024 ➔ Nov 2028

Enrollment closed • Trial completion date • Hepatocellular Cancer • Oncology • Solid Tumor • IFNG

GT-30: GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects with Advanced HCC (clinicaltrials.gov) - P1/2 | N=36 | Completed | Sponsor: Geneos Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Jun 2025 ➔ Nov 2024 | Trial primary completion date: Aug 2023 ➔ Nov 2024

Trial completion • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor • IFNG

Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IDH1 • IDH2 • MGMT

INO-5401 + INO-9012 in Combination With Atezolizumab in Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma (clinicaltrials.gov) - P1/2 | N=35 | Active, not recruiting | Sponsor: Inovio Pharmaceuticals | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Urothelial Cancer

INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) (clinicaltrials.gov) - P1/2 | N=52 | Active, not recruiting | Sponsor: Inovio Pharmaceuticals | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Combination therapy • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

INO 5401 Vaccination in BRCA1/2 Mutation Carriers (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: University of Pennsylvania | Phase classification: P1b ➔ P1

Phase classification • Oncology • BRCA1 • BRCA2

INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM) (clinicaltrials.gov) - P1/2 | N=52 | Active, not recruiting | Sponsor: Inovio Pharmaceuticals | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Combination therapy • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

INO-5401 + INO-9012 in Combination With Atezolizumab in Locally Advanced Unresectable or Metastatic/Recurrent Urothelial Carcinoma (clinicaltrials.gov) - P1/2 | N=35 | Active, not recruiting | Sponsor: Inovio Pharmaceuticals | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Urothelial Cancer

Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • IDH1 • IDH2 • MGMT

DNA Vaccine Therapy in Treating Patients With Chronic Hepatitis C Virus Infection (clinicaltrials.gov) - P1 | N=33 | Active, not recruiting | Sponsor: National Cancer Institute (NCI)

Trial completion date • Hepatitis C • Hepatology • Infectious Disease • Inflammation • CD4 • CD8 • IFNG

GT-30: GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects With Advanced HCC (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: Geneos Therapeutics | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2023 ➔ Jun 2025

Combination therapy • Enrollment closed • Metastases • Trial completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Personalized DNA neoantigen vaccine (GNOS-PV02) in combination with plasmid IL-12 and pembrolizumab as second-line (2L) treatment for advanced hepatocellular carcinoma (HCC) (SITC 2022) - P1/2 | "Methods Patients with unresectable or metastatic HCC and progression or intolerance on first-line therapy with tyrosine kinase inhibitors (sorafenib or lenvatinib) are enrolled...Conclusions GNOS-PV02 + INO-9012 combined with pembrolizumab in the 2L setting was well tolerated and induced tumor-neoantigen-directed CD8+ T cells and TILs...Trial Registration NCT04251117 Ethics Approval For GT-30 trial, the protocols were approved by Johns Hopkins Medicine Review Boards (CR00039002/IRB00227771), Icahn School of Medicine-Program for the Protection of Human Subjects (20-00076 GCO#1), and Northern A Health and Disability Ethics committee (Ethics ref: 20/NTA), respectively. Written informed consent was obtained from each patient prior to the patient participating in the trial."

Clinical • Combination therapy • IO biomarker • Tumor-specific neoantigens • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • IL12A • TMB

Neoantigen-based Personalized DNA Vaccine in Patients With Newly Diagnosed, Unmethylated Glioblastoma (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Apr 2023 ➔ Dec 2023

Trial completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CD8 • IDH1 • IDH2 • MGMT

INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12) immunotherapy in biochemically relapsed prostate cancer (ESMO-IO 2017) - P1; "Data demonstrated both PSA and PSMA are immunogenic and INO-5150 induced cellular immune responses. Additional analyses and follow-up are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit that has been initially observed."

Adverse events • Clinical • Prostate Cancer

Synthetic DNA Immunotherapy in Biochemically Relapsed Prostate Cancer (ESMO 2018) - P1; "INO-5150 +/- INO-9012 was safe, well tolerated and immunogenic. Clinical efficacy was observed in the patients with D0 PSADT≤ 12 mos as evidenced by a significant dampening of log2PSA change over time and increased PSADT up to 72 weeks FU. Additional genomic analyses are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit."

Prostate Cancer