INO-5401 / Inovio - LARVOL DELTA

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

Shared epitopes create safety and efficacy concerns in several cancer vaccines. (PubMed, J Immunother Cancer) - "Altogether, our analysis indicates a suboptimal design of several cancer vaccines currently in clinical development: ATP128, BNT111, BNT112, BNT116, INO-5401. We recommend that next-generation cancer vaccines should integrate rigorous epitope filtering strategies to eliminate shared sequences in TAAs."

Journal • Immunology • Oncology • ASCL2 • CLDN6 • KLK2

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

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

INOVIO Reports Fourth Quarter and Full Year 2024 Financial Results and Operational Highlights (PRNewswire) - "Other Pipeline Updates:...Continued efforts to move INO-5401 into its next stage of development for glioblastoma (GBM), which the company believes will be a controlled Phase 2 trial. INOVIO plans on completing manufacture of drug supply for the next trial during 2025."

Commercial • Glioblastoma

INOVIO Highlights Anticipated 2025 Milestones and 2024 Key Accomplishments (PRNewswire) - "INO-5401: Continue to dose patients in the GBM-001 Phase 1 trial in newly diagnosed glioblastoma that combines INO-5401 with Regeneron's PD-1 checkpoint inhibitor Libtayo. Next development step is to conduct a controlled Phase 2 trial; The Basser Center at the University of Pennsylvania is evaluating the tolerability and immunogenicity of INO-5401 in a Phase 1 study exploring the potential to prevent cancer in people with BRCA1 or BRCA2 mutations."

Trial status • Glioblastoma

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

INOVIO Added to Russell 2000 Index Effective July 1, 2024 (PRNewswire) - "INOVIO...announced its inclusion in the Russell 2000 Index as part of the annual reconstitution of the Russell stock indexes....'Being readded to the Russell 2000 signifies the value of the progress we have made recently and our commitment to the next level of our strategy, which includes our plans to submit a BLA for INO-3107 under the FDA's accelerated approval pathway in the second half of 2024 and preparing to be commercial launch-ready in 2025, should INO-3107 be approved. We also continue to work to advance other product candidates, including the next steps for INO-3112 in head and neck cancer, INO-5401 in GBM'..."

FDA filing • Financing • Launch US • Brain Cancer • CNS Tumor • Glioblastoma • Head and Neck Cancer • Oncology • Solid Tumor

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

[VIRTUAL] INO-5401 and INO-9012 delivered intramuscularly (IM) with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma (SNO 2020) - P1/2 | "INO-5401 + INO-9012, a novel DNA plasmid immunotherapy, demonstrates acceptable risk/benefit and generates robust systemic immune responses to encoded tumor antigens when administered with cemiplimab and RT/TMZ in newly diagnosed GBM patients. Overall survival is encouraging. Clinical trial information: NCT03491683."

Combination therapy • IO biomarker • Late-breaking abstract • Glioblastoma • Immune Modulation • Inflammation • Oncology • Solid Tumor • CD8 • IFNG • IL12A

Intramuscular (IM) INO-5401 + INO-9012 with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma. (ASCO 2022) - P1/2 | "INO-5401 + INO-9012 has an acceptable risk/benefit profile and elicits robust immune responses that correlate with enhanced survival when administered with cemiplimab and RT/TMZ to newly diagnosed GBM patients. Pre-treatment gene expression signatures in MGMT-unmethylated patients were statistically associated with OS18. Overall, INO-5401 elicits antigen-specific T cells that can infiltrate GBM tumors."

Combination therapy • IO biomarker • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CD4 • CD69 • CD8 • GZMA • IFNG • IL12A • MGMT • WT1

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 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

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

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 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

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

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: Jun 2022 ➔ Dec 2022 | Trial primary completion date: Jun 2022 ➔ Dec 2022

Combination therapy • 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: Jun 2022 ➔ Dec 2022 | Trial primary completion date: Jun 2022 ➔ Dec 2022

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

"ダナファーバー #ASCO22 発表（1）：【1】膠芽腫に対する免疫療法薬（INO-5401とセミプリマブ）併用は安全かつ有望【2】患者記入型のスクリーニングツールが遺伝性がん（リンチ症候群）リスクの検出率を高める可能性 https://t.co/aT0kam8beq #脳腫瘍　#リンチ症候群" (@cancer_ref)

Targeted Therapy for Adrenocortical Carcinoma: A Genomic-Based Search for Available and Emerging Options. (PubMed, Cancers (Basel)) - "We identified TP53-modulating drugs to be possibly effective in 20-26% of patients, followed by the Wnt signaling pathway inhibitors (15%), Telomelysin and INO5401 (13%), FHD-609 (13%), etc. According to our data, 67% of ACC patients exhibited genomic alterations that might be targeted by FDA-approved drugs or drugs being tested in current clinical trials. Although there are not many current therapy options directly targeting reported ACC alterations, this study identifies emerging options that could be tested in clinical trials."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Rare Diseases • Solid Tumor • CDK4 • CTNNB1 • FLT4 • TP53

INOVIO Announces Survival Results for INO-5401 + INO-9012 in Combination with Libtayo (cemiplimab) in Patients with Newly Diagnosed GBM at ASCO Annual Meeting 2022 (PRNewswire) - P1/2 | N=52 | NCT03491683 | Sponsor: Inovio Pharmaceuticals | "Overall, INO-5401 + INO-9012 is demonstrated to be tolerable and immunogenic when administered with Libtayo and RT/TMZ (radiation and temozolomide) to newly diagnosed GBM patients. Notably, INO-5401 elicited antigen-specific T cells that may infiltrate GBM tumors....The adverse event profile was consistent with known single-agent (INO-5401, INO-9012, EP or Libtayo) events; most events were ≤Grade 2 and no related events were Grade ≥4. Median OS durations in Cohorts A and B were 17.9 months (95% CI 14.5-19.8) and 32.5 months (95% CI 18.4-not reached), respectively. Flow cytometry revealed activated, antigen specific CD4+CD69+PD1+ and CD8+CD69+PD1+ T cells, the latter with lytic potential as defined by presence of perforin and granzyme A. Both subsets exhibited HR < 1.0 and p < 0.05 when accounting for a 0.1% T cell frequency change, translating to a 23% and 28% reduced risk of death at 18 months, respectively."

P1/2 data • Glioblastoma • Oncology

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 2021 ➔ Jun 2022; Trial primary completion date: Dec 2021 ➔ Jun 2022

Clinical • Combination therapy • 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 2021 ➔ Jun 2022; Trial primary completion date: Dec 2021 ➔ Jun 2022

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • IFNG • MRI

INO-5401 and INO-9012 Delivered Intramuscularly (IM) with Electroporation (EP) in Combination with Cemiplimab (REGN2810) in Newly Diagnosed Glioblastoma (SITC 2021) - No abstract available

Combination therapy • Brain Cancer • Glioblastoma • Oncology • Solid Tumor