INO-3112 / Inovio - LARVOL DELTA

Latest generation therapies for the management of HPV infections (FIGO 2025) - "Vvax001 (University Medical Centre Groningen): In a Phase II trial, this therapeutic vaccine targeting HPV type 16 induced regression in high-grade precancerous cervical lesions (CIN3), presenting a potential alternative to standard surgical treatments...INO-3112 (Inovio Pharmaceuticals): A DNA vaccine combining HPV16/18 E6 and E7 antigens with IL-12, studied in combination with durvalumab for recurrent or metastatic HPV-positive head and neck squamous cell carcinoma (HNSCC)...Immunotherapies: Immunotherapy approaches are being explored to treat HPV-related cancers: - Combination therapies. - Oncolytic viruses: Transgene's TG4001 is a therapeutic vaccine expressing HPV-16 E6/E7 antigens, currently under evaluation for recurrent or metastatic HPV16-positive cancers."

IO biomarker • Cervical Cancer • Head and Neck Cancer • Human Papillomavirus Infection • Infectious Disease • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IL12A

INOVIO Reports Fourth Quarter and Full Year 2024 Financial Results and Operational Highlights (PRNewswire) - "INO-3112 - Oropharyngeal Squamous Cell Carcinoma (OPSCC):...Next Steps: (i) Finalize protocol of the Phase 3 trial in consultation with the FDA. INOVIO anticipates it will conduct the trial in North America and Europe in patients with locoregionally advanced, high-risk, HPV16/18-positive OPSCC; (ii) Complete ongoing manufacture of drug supply for trial."

Commercial • New P3 trial • Oropharyngeal Cancer • Squamous Cell Carcinoma

INOVIO Highlights Anticipated 2025 Milestones and 2024 Key Accomplishments (PRNewswire) - "Gain alignment on planned Phase 3 trial design with European Union regulators: Trial to be conducted in North America and Europe through a clinical collaboration and supply agreement signed in 2024 with Coherus BioSciences, Inc., evaluating the combination of INO-3112 and LOQTORZI (toripalimab-tpzi) in patients with locoregionally advanced, high-risk, HPV16/18-positive oropharyngeal squamous cell carcinoma (OPSCC)...Gained alignment with FDA on the planned Phase 3 trial design in 2024..."

Clinical protocol • New P3 trial • Oropharyngeal Cancer • Squamous Cell Carcinoma

INOVIO Reports Second Quarter 2024 Financial Results and Recent Business Highlights (PRNewswire) - "INOVIO submitted its Phase 3 trial design for INO-3112 to European regulatory authorities. The proposed multi-center Phase 3 trial will investigate INO-3112 in combination with LOQTORZI as a potential treatment for oropharyngeal squamous cell carcinoma (OPSCC). INOVIO plans to conduct the trial in Europe and North America. INOVIO received positive feedback on this study protocol from the FDA in the first quarter of 2024. The manufacturing issue with the single use disposable administration component of the device that is impacting INO-3107 will also need to be resolved before we can commence the Phase 3 trial with INO-3112....The Phase 3 study will investigate whether LOQTORZI can help amplify the tumor-infiltrating abilities of the antigen-specific T cells generated by INO-3112."

FDA event • New P3 trial • Oropharyngeal Cancer • Squamous Cell Carcinoma of Head and Neck

DNA Plasmid-encoding Interleukin-12/HPV DNA Plasmids Therapeutic Vaccine INO-3112 and Durvalumab in Treating Patients With Recurrent or Metastatic Human Papillomavirus Associated Cancers (clinicaltrials.gov) - P2 | N=41 | Terminated | Sponsor: M.D. Anderson Cancer Center | N=77 ➔ 41 | Active, not recruiting ➔ Terminated; Project delays

Enrollment change • Metastases • Trial termination • Anal Carcinoma • Cervical Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Penile Cancer • Solid Tumor • Vaginal Cancer • Vulvar Cancer • CD4

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

INOVIO Reports First Quarter 2024 Financial Results and Recent Business Highlights (PRNewswire) - "The FDA provided feedback on the proposed Phase 3 trial design to evaluate the combination of INO-3112 and LOQTORZI as a potential treatment for patients with locoregionally advanced, high-risk, HPV-16/-18 positive throat cancer. INOVIO will discuss the proposed trial design with European regulatory authorities, as INOVIO plans to conduct the trial in both Europe and North America....The proposed multi-center Phase 3 trial will investigate whether LOQTORZI can help boost the tumor-infiltrating abilities of the antigen-specific T cells generated by INO-3112."

European regulatory • FDA event • Oropharyngeal Cancer

INOVIO Reports Fourth Quarter and Full Year 2023 Financial Results and Operational Highlights (PRNewswire) - "INOVIO has submitted the proposed design of a Phase 3 trial to the FDA with the intent to evaluate the clinical benefit of INO-3112 in combination with a PD-1 inhibitor. Feedback on the clinical development plan is expected in the second quarter of 2024. If cleared to proceed by the FDA, the trial will investigate if LOQTORZI can help boost the tumor-infiltrating abilities of the antigen-specific T cells generated by INO-3112."

Clinical protocol • FDA event • Oropharyngeal Cancer • Squamous Cell Carcinoma

INOVIO and Coherus Announce Clinical Collaboration to Advance Development of INO-3112 in Combination with LOQTORZI (toripalimab-tpzi) (PRNewswire) - "INOVIO...today announced a clinical collaboration and supply agreement with Coherus BioSciences, Inc...to evaluate the combination of INO-3112 and LOQTORZI™ (toripalimab-tpzi) as a potential treatment for patients with locoregionally advanced, high-risk, HPV16/18 positive oropharyngeal squamous cell carcinoma (OPSCC), a type of head and neck cancer commonly known as throat cancer....Under the terms of the supply agreement, Coherus will provide LOQTORZI™ (toripalimab-tpzi), for a Phase 3 clinical trial to be conducted by INOVIO, pending alignment with the U.S. Food and Drug Administration (FDA) on study design."

Licensing / partnership • Head and Neck Cancer • Oncology • Solid Tumor

MEDI0457 Plus Durvalumab in HPV-associated HNSCC-Letter. (PubMed, Clin Cancer Res) - No abstract available

Journal • Head and Neck Cancer • Squamous Cell Carcinoma of Head and Neck

MEDI0457 Plus Durvalumab in HPV-associated HNSCC-Response. (PubMed, Clin Cancer Res) - No abstract available

Journal • Head and Neck Cancer • Squamous Cell Carcinoma of Head and Neck

Phase II Trial of MEDI0457 and Durvalumab for Patients With Recurrent/Metastatic Human Papillomavirus-Associated Cancers. (PubMed, Oncologist) - "The combination of MEDI0457 and durvalumab demonstrated acceptable safety and tolerability in patients with advanced HPV-16/18 cancers. The low ORR among patients with cervical cancer led to study discontinuation despite a clinically meaningful disease control rate."

Journal • Metastases • P2 data • Cervical Cancer • Genito-urinary Cancer • Immune Modulation • Oncology • Penile Cancer • Solid Tumor • IL12A

Survival benefit to immunotherapy according to site of organ involvement in metastatic anal cancer. (ASCO-GI 2023) - "58 (71%) received anti-PD-(L)1 immunotherapy, either alone (N=51) or in combination with bevacizumab or with MEDI-0457 on a clinical trial (N=7). In this single-institution retrospective study at a large academic referral center, both chemotherapy and immune checkpoint blockade were effective treatment options for patients with metastatic anal cancer. These data provide historical context in estimating median PFS necessary for future trial design in patients with metastatic anal cancer. Lymph node-only distribution of distant metastatic disease was predictive for improved survival with immunotherapy."

IO biomarker • Metastases • Anal Carcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Safety and Efficacy of MEDI0457 plus Durvalumab in Patients with Human Papillomavirus–Associated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (Clin Cancer Res) - P1/2 | N=35 | NCT03162224 | Sponsor: MedImmune LLC | "We assessed whether...MEDI0457 combined with the PD-L1 inhibitor durvalumab could enhance HPV-specific T-cell response and improve outcomes in recurrent/metastatic HPV-16/18–associated HNSCC....Of 35 treated patients, 29 were response evaluable (confirmed HPV-associated disease; received both agents). ORR was 27.6% [95% confidence interval (CI), 12.7–47.2; four complete responses, four partial responses]; responses were independent of PD-L1 tumor-cell expression (≥25% vs. <25%). DCR-16 was 44.8% (95% CI, 26.5–64.3). Median PFS was 3.5 months (95% CI, 1.9–9.0); median OS was 29.2 months (15.2–not calculable)."

P1/2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Safety and Efficacy of MEDI0457 Plus Durvalumab in Patients With Human Papillomavirus-associated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma. (PubMed, Clin Cancer Res) - "MEDI0457 plus durvalumab was well tolerated. While the primary efficacy endpoint was not reached, clinical benefit was encouraging."

IO biomarker • Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IL12A

Safety and Efficacy of MEDI0457 Plus Durvalumab in Patients With Human Papillomavirus-associated Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (Clin Cancer Res) - P1b/2a | N=35 | NCT03162224 | Sponsor: MedImmune LLC | "We assessed if a DNA vaccine targeting HPV-16/18 E6/E7 with interleukin-12 adjuvant (MEDI0457) combined with the PD-L1 inhibitor durvalumab could enhance HPV-specific T-cell response and improve outcomes in recurrent/metastatic HPV-16/18-associated HNSCC....Of 35 treated patients, 29 were response-evaluable (confirmed HPV-associated disease; received both agents). ORR was 27.6% (95% CI, 12.7-47.2; 4 complete responses, 4 partial responses); responses were independent of PD-L1 tumor-cell expression (≥25% vs <25%). DCR-16 was 44.8% (95% CI, 26.5-64.3). Median PFS was 3.5 months (95% CI, 1.9-9.0); median OS was 29.2 months (15.2-not calculable). Twenty-eight (80.0%) patients had treatment-related adverse events (grade 3: 5 [14.3%]; no grade 4/5), resulting in discontinuation in 2 (5.7%) patients."

P1/2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

DNA Plasmid-encoding Interleukin-12/HPV DNA Plasmids Therapeutic Vaccine INO-3112 and Durvalumab in Treating Patients With Recurrent or Metastatic Human Papillomavirus Associated Cancers (clinicaltrials.gov) - P2 | N=77 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2021 ➔ Dec 2022

Enrollment closed • Trial primary completion date • Anal Carcinoma • Cervical Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Penile Cancer • Solid Tumor • Vaginal Cancer • Vulvar Cancer • CD4

The Efficacy of Therapeutic DNA Vaccines Expressing the Human Papillomavirus E6 and E7 Oncoproteins for Treatment of Cervical Cancer: Systematic Review. (PubMed, Vaccines (Basel)) - "Five different DNA therapeutic vaccines (GX-188E, VGX-3100, pNGVL4a-CRT/E7(detox), pNGVL4a-Sig/E7(detox)/HSP70, MEDI0457) were well-tolerated and clinically effective. Clinical implementation of DNA therapeutic vaccines into treatment regimen as a sole approach or in combination with conservative treatment holds great potential for effective cancer treatment."

Journal • Review • Cervical Cancer • Gene Therapies • Gynecology • Oncology • Solid Tumor

Inovio, AstraZeneca terminate cancer vaccine partnership (Biz Journal) - “MedImmune Ltd…arm of AstraZeneca…is terminating a cancer therapy partnership it has with Inovio Pharmaceuticals….Inovio disclosed MedImmune's decision to terminate the agreement in a document the Plymouth Meeting-based company filed last week with the Securities and Exchange Commission….Inovio (NASDAQ: INO) will reacquire the rights to INO-3112 and will no longer be entitled to receive potential future milestone payments or royalties from MedImmune. Inovio said it will also cease any development activities for which it would be entitled to seek reimbursement from MedImmune. The two companies will continue to have rights to jointly publish work relating to the product candidate….MedImmune, according to Inovio's SEC filing, is conducting a phase 2 clinical trial of MED10457 in patients with head and neck squamous cell carcinomas. MedImmune has completed the final data cutoff for the trial and plans to complete the clinical study report by the end of 2022.”

Licensing / partnership • Trial completion date • Oncology

A phase 1/2A trial of synthetic DNA vaccine immunotherapy targeting HPV-16 and -18 after chemoradiation for cervical cancer. (ASCO 2018) - P1/2; "Adjuvant MEDI0457 is feasible after chemoradiation for locally advanced and/or recurrent cervical cancer. More than half of the patients developed detectable immune responses to HPV antigens after treatment. These results support further study into the efficacy of adding DNA therapy with CELLECTRA EP to chemoradiation for HPV-related cancers."

P1/2 data • Cervical Cancer

[VIRTUAL] Phase II trial of MEDI0457 and durvalumab for patients with recurrent/metastatic HPV-associated cancers. (ASCO 2021) - P2 | "The combination of MEDI0457 and durvalumab demonstrated acceptable safety/tolerability in pts with advanced HPV-16/18 cancers . Despite a clinically meaningful DCR, the low ORR among pts with cervical cancer led to study discontinuation for futility . Correlative studies are ongoing to characterize pts with prolonged disease control with study treatment."

Clinical • P2 data • Anal Carcinoma • Cardiovascular • Cervical Cancer • Genito-urinary Cancer • Heart Failure • Hematological Disorders • Infectious Disease • Neutropenia • Oncology • Penile Cancer • Solid Tumor • Squamous Cell Carcinoma • IL12A

A phase 1b/2a, multi-center, open-label study to evaluate the safety and efficacy of combination treatment with MEDI0457 (INO-3112) and durvalumab (MEDI4736) in patients with recurrent/metastatic human papilloma virusassociated head and neck squamous cell cancer. (ASCO 2018) - P1b/2a; "Primary objectives are safety and objective response rate. Secondary objectives are disease control rate at 16 weeks, overall survival, progression-free survival, and pharmacokinetics and immunogenicity of durvalumab."

Clinical • Head and Neck Cancer

[VIRTUAL] Safety and efficacy of MEDI0457 plus durvalumab in patients (pts) with human papillomavirus-associated recurrent/metastatic head and neck squamous cell carcinoma (HPV+ R/M HNSCC) (ESMO 2020) - P1b/2a | "Funding: AstraZeneca. Clinical trial identification: NCT03162224."

Clinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IL12A • PD-1

Safety and Efficacy of MEDI0457 and Durvalumab in Patients With HPV Associated Recurrent/Metastatic Head and Neck Cancer (clinicaltrials.gov) - P1b/2a; N=35; Completed; Sponsor: MedImmune LLC; Active, not recruiting ➔ Completed

Clinical • Trial completion • Head and Neck Cancer • Immune Modulation • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Therapy for High-Risk HPV 16-Positive Oropharynx Cancer Patients (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; N=66 ➔ 0; Trial completion date: Sep 2027 ➔ Mar 2021; Recruiting ➔ Withdrawn; Trial primary completion date: Sep 2024 ➔ Mar 2021

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Head and Neck Cancer • Immune Modulation • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PCR