INO-3107 / Inovio - LARVOL DELTA

Inovio Pharmaceuticals INO is approaching an October 30 PDUFA date for INO-3107, its lead DNA medicine candidate for recurrent respiratory papillomatosis, or RRP, President and CEO Jacky Shea said during a Cantor Fitzgerald fireside chat (TradingView) - "INO-3107’s biologics license application was submitted under the accelerated approval pathway. Shea said the FDA’s file acceptance letter included a preliminary conclusion that the application might not be eligible for review under that pathway."

PDUFA • Rare Diseases • Respiratory Diseases

Zopapogene Imadenovec-Drba for Recurrent Respiratory Papillomatosis. (PubMed, Ann Pharmacother) - P1/2 | "The shift from primarily surgical management of RRP to HPV-directed immunotherapy creates an expanded role for pharmacists in high-cost drug stewardship (including formulary evaluation, manufacturer and payer engagement, and revenue cycle optimization), operational management (including procurement, ultra-cold storage, and biosafety handling), clinical monitoring, and patient education on a mechanistically novel therapy."

Journal • Review • Gene Therapies • Oncology

B cell responses in recurrent respiratory papillomatosis patients treated with DNA immunotherapy INO-3107. (ASCO 2026) - P1/2 | "B cell immunogenicity may play a role in mediating clinical responses to DNA immunotherapy INO-3107 for the treatment of RRP. INO-3107 treatment induced expansion and emergence of B cells in the blood of RRP patients, which trafficked to and infiltrated papilloma tissue by EOS as evidenced by increased B cell enrichment and clone counts. These immune responses were associated with improved clinical outcomes."

Clinical • Infectious Disease

The Efficacy and Safety of Systemic Treatment for Managing Recurrent Respiratory Papillomatosis: A Systematic Review and Meta-analysis. (PubMed, J Voice) - "Systemic bevacizumab remains the most mature systemic option with consistent real-world evidence and published dosing guidance. HPV-specific immunotherapy has recently transformed adult RRP management with an FDA-approved, short-course treatment option; ongoing studies will clarify optimal sequencing with bevacizumab and the role of checkpoint inhibition."

Journal • Retrospective data • Cardiovascular • Hypertension • Oncology • Renal Disease • PD-L1

DNA Immunotherapy INO-3107 Long-Term Continued Clinical Effect is Supported by Improved Immune Response in HPV 6/11 Recurrent Respiratory Papillomatosis (COSM 2026) - No abstract available

Clinical

Treatment of Recurrent Respiratory Papillomatosis with DNA immunotherapy INO-3107 induces activation and enrichment of pro-inflammatory CD4+ T cell responses in blood and airways of patients with clinical response Emma L (AACR-IO 2026) - P1/2 | "Mechanisms of immune escape may play a role in mediating clinical responses in recurrent respiratory papillomatosis (RRP) as evidenced by enrichment of Th2 cells in PBMCs and decreased expression of HLA class II genes in airway tissue of non-responders. However, DNA immunotherapy INO-3107 induced activation and enrichment of pro-inflammatory CD4+ T cell responses, inclusive of Th1 and effector memory signatures, in blood and airways of RRP patients. These immune responses were associated with clinical responses during the 52-week trial."

Clinical • IO biomarker • Infectious Disease • CD4 • CD8

FDA Accepts for Review INOVIO's BLA for INO-3107 for the Treatment of Adults with Recurrent Respiratory Papillomatosis (RRP) (Inovio Press Release) - "The FDA assigned INO-3107 a Prescription Drug User Fee Act (PDUFA) review goal date of October 30, 2026, which is the date by which it intends to take action on the application. The FDA has indicated that it is not currently planning to hold an advisory committee meeting to discuss this application....The BLA is supported by data from a Phase 1/2 trial evaluating INO-3107 in adult patients with RRP who had two or more surgeries in the year prior to treatment....Long-term durability data from a retrospective trial of the original trial participants was also included in the BLA filing..."

FDA filing • PDUFA • Rare Diseases • Respiratory Diseases

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