INO-3107 / Inovio - LARVOL DELTA

DNA IMMUNOTHERAPY (INO-3107) INDUCES PERSISTENT IMMUNE RESPONSES RESULTING IN LONG-TERM EFFICACY THROUGH POST-TREATMENT YEAR 2 FOR HPV-6 & 11 RECURRENT RESPIRATORY PAPILLOMATOSIS (IPVC 2025) - P1/2 | "DNA immunotherapy INO-3107 demonstrates a continued clinical effect with further surgery reduction seen over time supported by generation of a long-lasting antigen-specific T-cell response in recurrent respiratory papillomatosis patients."

Clinical • CD8 • TRB

CLINICAL RESPONSE TO INO-3107 IN RECURRENT RESPIRTORY PAPILLOMATOSIS IS IRRESPECTIVE OF PAPILLOMA MICROENVIRONMENT AND MOLECULAR SUBTYPE (IPVC 2025) - P1/2 | "Reduction in surgical interventions after INO-3107 treatment was not contingent on low viral loads, a pre-inflamed papilloma or reduced expression of VEGFA or PD-L1. A differentiated subtype did not preclude clinical efficacy. These data indicate that INO-3107 effectively reduced surgical burden irrespective of papilloma microenvironment and molecular subtype."

Clinical • IO biomarker • Gene Therapies • Human Papillomavirus Infection • Infectious Disease • CXCL10 • CXCL9 • IL15 • IL18 • IL1B • PD-L1

INOVIO Completes Rolling BLA Submission Seeking Accelerated Approval for INO-3107 as a Treatment for RRP in Adults (GlobeNewswire) - "Expect to receive file acceptance by year end 2025 with potential PDUFA date in mid-2026 if request for priority review granted...INOVIO submitted the BLA under the FDA's Accelerated Approval program and has requested a priority review, which if granted, is expected to be completed within six months following the 60-day filing period...'We look forward to continued communication and collaboration with the FDA during the review process and will be focused on finalizing our preparations for a potential commercial launch in 2026.'"

FDA approval • FDA filing • Launch US • Rare Diseases

DNA Immunotherapy (INO-3107) Demonstrates a Durable Response for Treatment of HPV-6/11 Recurrent Respiratory Papillomatosis (AAO-HNSF 2025) - P1/2 | "INO-3107 for recurrent respiratory papillomatosis demonstrates a durable response through post-treatment Year 2 with 91% of patients continuing to experience clinical effect. Two years post-INO-3107, no response to treatment was limited to only 2 patients. This supports INO-3107's ability to provide long-term immunologic and clinical effects."

INOVIO's BLA for INO-3107 for RRP on track for 2H25 FDA acceptance. (AInvest) - "INOVIO Pharmaceuticals, Inc. (NASDAQ: INO) has received FDA approval to proceed with its rolling submission of the Biologics License Application (BLA) for INO-3107, an investigational DNA medicine designed to treat Recurrent Respiratory Papillomatosis (RRP) in adults....The FDA's accelerated approval program allows INOVIO to submit its BLA using data from its completed Phase 1/2 trial, which demonstrated the drug's safety and efficacy."

FDA filing • Respiratory Diseases

DNA Immunotherapy (INO-3107) Results in Long-Term Surgery Reduction in RRP. (PubMed, Laryngoscope) - "INO-3107 is well tolerated and provides a continued clinical effect against HPV-6 and 11 RRP that results in further reduction of the surgical burden observed in Year 1. These data support the role of INO-3107 immunotherapy for adult patients with RRP."

Journal • Oncology

Successful Treatment of Recurrent Respiratory Papillomatosis with INO-3107 is Irrespective of Papilloma Microenvironment and Molecular Subtype (ASGCT 2025) - P1/2 | "Reduction in surgical interventions for the management of RRP after immunotherapy were not contingent on low viral loads, a pre-inflamed papilloma status or reduced expression of modulators such as VEGFA or PD-L1. Presence of a Differentiated molecular papilloma subtype did not preclude clinical efficacy. Taken together these data indicate that INO-3107 was able to effectively reduce surgical burden in RRP patients irrespective of papilloma microenvironment and molecular subtype."

IO biomarker • Gene Therapies • Human Papillomavirus Infection • Infectious Disease • Oncology • Solid Tumor • CXCL10 • CXCL9 • IL15 • IL18 • IL1B • PD-L1

Operational Highlights (PRNewswire) - "The DV testing for INO-3107 has been initiated and is anticipated to be completed in the first half of 2025. INOVIO plans to begin rolling submission of the BLA in mid-2025 under FDA's accelerated approval program, subject to FDA concurrence, with the goal of completing the submission in the second half of 2025 and receiving FDA acceptance of the submission by the end of the year. FDA has previously awarded breakthrough therapy designation for INO-3107 and INOVIO plans to request priority review of its BLA, which if granted would allow for an FDA approval decision (PDUFA date) in mid-2026."

FDA approval • FDA filing • Respiratory Diseases

INOVIO to Present at Upcoming Scientific and Investor Conferences (Inovio Press Release) - "INOVIO...announced that it will be presenting at several upcoming conferences, including a fireside chat at the Citizens JMP Life Sciences Conference in New York. INOVIO will also present for the first time data on the long-term clinical effect of lead candidate INO-3107 at the American Broncho-Esophagological Association (ABEA) program at the Combined Otolaryngology Spring Meetings (COSM), the largest meeting of otolaryngologists in the U.S."

Clinical data • Respiratory Diseases

DNA Immunotherapy (INO-3107) Durability and Long-Term Clinical Effect in Treatment of Recurrent Respiratory Papillomatosis Caused by HPV 6 & 11 (COSM 2025) - No abstract available

Clinical • Oncology

INOVIO to Present at Upcoming Scientific Conferences (Inovio Press Release) - "INOVIO...announced that it will highlight key data associated with its lead candidate, INO-3107, at several upcoming conferences, including an opportunity to join other leading voices at the inaugural National HPV Conference. INOVIO will also discuss its novel DNA-encoded monoclonal antibody technology at a preconference workshop at the World Vaccine Congress."

Clinical data • Respiratory Diseases

INOVIO Reports Fourth Quarter and Full Year 2024 Financial Results and Operational Highlights (PRNewswire) - "INO-3107 – Recurrent Respiratory Papillomatosis (RRP): Complete FDA-required design-verification testing - anticipated to be complete in first half of 2025. Update IND and initiate confirmatory trial. Submit BLA to the FDA – anticipate beginning rolling submission process mid-2025 and requesting priority review with goal of completing submission in second half of 2025 and receiving FDA acceptance of submission by year end. Submit a long-term study protocol to the FDA following BLA submission."

FDA event • FDA filing • Priority review • Rare Diseases • Respiratory Diseases

Clinical and Immunological Results from Phase 1/2 Study of INO-3107 as a Treatment for Recurrent Respiratory Papillomatosis Published in Nature Communications (Inovio Press Release) - P1/2 | N=32 | NCT04398433 | Sponsor: Inovio Pharmaceuticals | "INOVIO...today announced that peer-reviewed data from its Phase 1/2 clinical trial with INO-3107 as a potential treatment for recurrent respiratory papillomatosis (RRP) were published online in Nature Communications...81.3% (26/32) of patients had a decrease of at least one surgical intervention from the prior year (defined as the Overall Clinical Response Rate) after INO-3107 administration, including 28.1% (9/32) that required no surgical intervention (Complete Response) during or after the dosing window; The Overall Response Rate, which includes those patients who had either a Complete Response or a Partial Response (defined as ≥ 50% reduction in surgeries) was 72%; Patients in this trial were required to have ≥2 RRP surgical interventions in the year prior to initiating treatment...41% (13/32) of patients reported a treatment-related Adverse Event (AE)."

P1/2 data • Rare Diseases • Respiratory Diseases

DNA immunotherapy for recurrent respiratory papillomatosis (RRP): phase 1/2 study assessing efficacy, safety, and immunogenicity of INO-3107. (PubMed, Nat Commun) - P1/2 | "INO-3107 provides clinical benefit to HPV-6 and/or HPV-11-associated RRP adults and is well-tolerated. Importantly, treatment-induced peripheral T-cell responses traffic to airway tissue and are associated with clinical response."

Journal • P1/2 data • Inflammation • Oncology • Respiratory Diseases • CD8

Immune Response Data for INO-3107 to be Presented as a Poster at American Association for Cancer Research Immuno-Oncology (AACR-IO) Conference (PRNewswire) - "Poster will describe loss of detectable HPV-6 in Recurrent Respiratory Papillomatosis patients following treatment with INO-3107...INOVIO...today announced that an abstract describing the immunological activity of INO-3107 will be presented as a poster at the following scientific conference: American Association for Cancer Research – Immuno-Oncology Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy (February 23-26, 2025); Poster entitled: 'Loss of Detectable HPV-6 Following Induction of Emergent T cells in Patients with Durable Complete Clinical Response to Treatment for Recurrent Respiratory Papillomatosis using INO-3107'"

Clinical data • Respiratory Diseases

INOVIO Highlights Anticipated 2025 Milestones and 2024 Key Accomplishments (PRNewswire) - "Anticipated Milestones for 2025: i) Submit BLA to the U.S. Food and Drug Administration (FDA) by mid-2025 and request priority review. INO-3107 could be the preferred non-surgical therapeutic option for recurrent respiratory papillomatosis (RRP) and would be the first DNA medicine approved for any indication in the United States, should it be approved...ii) Initiate confirmatory trial...iii) Submit a redosing study protocol to the FDA...iv) Present and publish recently announced durability data and immunology data, as well as the full efficacy and tolerability data from completed Phase 1/2 clinical trial, in a peer-reviewed scientific journal."

Clinical protocol • FDA filing • New trial • P1/2 data • Respiratory Diseases

CLINICAL RESPONSE TO INO-3107 TREATMENT FOR RECURRENT RESPIRATORY PAPILLOMATOSIS IS ASSOCIATED WITH CD4 AND CD8 T CELL ACTIVITY AND CYTOTOXICITY IN PATIENT AIRWAYS (IPVC 2024) - P1/2 | "Analysis via multiple platforms confirms that administration of INO-3107 in RRP patients increased T cell quantity and activity in patient airways, inclusive of both CD4 and CD8 T cells as well as cytotoxicity. Significant elevation/enrichment of these various T cell pathways was associated with clinical response."

Clinical • Oncology • CD3E • CD4 • CD8 • CXCR3 • GZMA • TRB

TREATMENT OF RECURRENT RESPIRATORY PAPILLOMATOSIS WITH INO-3107 INDUCES SIGNIFICANT ENRICHMENT IN HALLMARK INTERFERON ALPHA, INTERFERON GAMMA AND INFLAMMATORY MOLECULAR SIGNATURES IN PAPILLOMA TISSUE OF RESPONDERS (IPVC 2024) - P1/2 | "Administration of INO-3107 in RRP patients induced new immune responses in papilloma tissue consistent with inflammatory processes inclusive of activation markers, upregulation of cytokines and chemokines known to be critical mediators of an active inflammatory response, increased antigenic presentation through upregulation of HLA expression and induction of dendritic cell and macrophage activity. This activity was associated with clinical response."

IO biomarker • Infectious Disease • Inflammation • Oncology • Rare Diseases • BST2 • CXCL10 • CXCL9 • IFNG • IL15 • IRF1 • IRF4 • TNFRSF9

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

Inovio Receives Advanced Therapy Medicinal Product Certificate from European Medicines Agency for Quality and Non-Clinical Data for Lead Candidate INO-3107 (PRNewswire) - "INOVIO...announced that the European Medicines Agency's Committee for Advanced Therapies (CAT) has certified the quality and non-clinical data for INO-3107, INOVIO's lead candidate for the treatment of Recurrent Respiratory Papillomatosis (RRP). The certification confirms that INOVIO's chemistry, manufacturing and controls (CMC) data and nonclinical results available to date comply with the scientific and technical standards that would be used for evaluating a European Marketing Authorization Application."

European regulatory • Respiratory Diseases

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

Advancing DNA Medicine: INO-3107 for Recurrent Respiratory Papillomatosis (FOB-USA 2024) - No abstract available

Oncology

INO-3107 With Electroporation (EP) in Participants With HPV-6- and/or HPV-11-Associated Recurrent Respiratory Papillomatosis (RRP) (clinicaltrials.gov) - P1/2 | N=32 | Completed | Sponsor: Inovio Pharmaceuticals | Active, not recruiting ➔ Completed | Trial completion date: Jul 2023 ➔ Dec 2022 | Trial primary completion date: Jul 2023 ➔ Dec 2022

Trial completion • Trial completion date • Trial primary completion date • Oncology • IFNG

INOVIO Announces Orphan Drug Designation for INO-3107 for the Treatment of Recurrent Respiratory Papillomatosis from the European Commission (PRNewswire) - "INOVIO...announced that the European Commission (EC) has granted orphan drug designation for INO-3107, the company's product candidate for the treatment of Recurrent Respiratory Papillomatosis (RRP). INO-3107 is an investigational DNA medicine candidate designed to elicit a targeted T cell response against HPV-6 and HPV-11, the HPV types that cause RRP and other HPV-related diseases."

Orphan drug • Rare Diseases • Respiratory Diseases

Interim Results of a Phase 1/2 Open-Label Study of INO-3107 for HPV-6 and/or HPV-11-Associated Recurrent Respiratory Papillomatosis. (PubMed, Laryngoscope) - P1/2 | "The data suggest that INO-3107 administered by IM/EP is tolerable and immunogenic and provides clinical benefit to adults with RRP."

Journal • P1/2 data • Oncology • Pain • CD4 • CD8