Papzimeos (zopapogene imadenovec-drba) / Precigen - LARVOL DELTA

Zopapogene Imadenovec-drba, a Novel Adenovector-based Immunotherapy, Induces Complete and Durable Responses in Recurrent Respiratory Papillomatosis (AAO-HNSF 2026) - P1/2 | "Zopa treatment demonstrated significant clinical benefit with the vast majority of CR patients experiencing ongoing durable complete responses for up to 4 years with excellent long-term safety. Updated follow-up results for all patients achieving CR will be available at the time of presentation."

Infectious Disease • Musculoskeletal Pain

Zopapogene Imadenovec-drba, a Novel Adenovector-based Immunotherapy, Induces Complete and Durable Responses in Recurrent Respiratory Papillomatosis (AAO-HNSF 2026) - P1/2 | "Zopa treatment demonstrated significant clinical benefit with the vast majority of CR patients experiencing ongoing durable complete responses for up to 4 years with excellent long-term safety. Updated follow-up results for all patients achieving CR will be available at the time of presentation."

Infectious Disease • Musculoskeletal Pain

Combination Bevacizumab and PRGN-2012 in Adults With Recurrent Respiratory Papillomatosis (RRP) (clinicaltrials.gov) - P2 | N=50 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P2 trial • Infectious Disease • Oncology • Otorhinolaryngology • Respiratory Diseases

Discovery of a library of HPV 6/11-specific T cell receptors potentially useful for cell therapy for adults with RRP refractory to approved treatments (AHNS 2026) - "Importantly, treatment with zopapogene imadenovec or bevacizumab has failed to consistently result in regression of pulmonary RRP lesions. Overall, this work identifies up to 11 TCRs sequences targeting epitopes from multiple separate HPV 6/11 genes that are restricted to numerous separate HLA class I alleles. The safety and efficacy of these TCRs as a TCR-engineered cell therapy will be studied in future clinical trials at the NIH Clinical Center for patients with aggressive, refractory or pulmonary RRP."

Clinical • First-in-human • IO biomarker • Head and Neck Cancer • Pulmonary Disease • Respiratory Diseases • Solid Tumor • ENTPD1 • HAVCR2 • IFNG • ITGAE • LAG3 • PD-1

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

The commercial-stage precision medicines company was just granted orphan drug exclusivity by the FDA for PAPZIMEOS (zopapogene imadenovec-drba), its treatment for RRP (ACCESS Newswire) - "The orphan drug exclusivity means the FDA can't approve any similar drugs to treat RRP for seven years, extending PAPZIMEOS' market exclusivity through August 2032...The orphan drug exclusivity of PAPZIMEOS comes at a time when Precigen released encouraging long-term durability data from its pivotal study at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago....The data showed that 15 out of 18 complete responders, or 83%, demonstrated ongoing complete responses for at least 36 months without any additional treatment for RRP....Five didn't need treatments after four years"

Commercial • P1/2 data • Infectious Disease • Respiratory Diseases

Non-replicating adenoviral vectors for cancer gene therapy. (PubMed, Adv Cancer Res) - "To date, three cancer gene therapy products, Gendicine, Adstiladrin, and Papzimeos, that are based on non-replicating adenovirus have been approved for commercialization. As we will explore here, non-replicating adenoviral vectors continue to be developed for cancer gene therapy."

Journal • Gene Therapies • Oncology

Zopapogene imadenovec-drba, a novel non-replicating adenoviral vector-based immunotherapy: Effects on complete and durable responses in recurrent respiratory papillomatosis pivotal trial. (ASCO 2026) - P1/2 | "Zopa treatment demonstrated significant clinical benefit with the vast majority of CR patients experiencing ongoing durable complete responses for up to 4 years with excellent long-term safety. Updated follow-up results for all patients achieving CR will be available at the time of presentation."

Viral vector • Infectious Disease • Musculoskeletal Pain

Precigen Inc…announced today that the U.S. Food and Drug Administration has granted orphan drug exclusivity for PAPZIMEOS (zopapogene imadenovec-drba) for the treatment of adults with recurrent respiratory papillomatosis. (Investing.com) - "The seven-year market exclusivity period is effective through August 14, 2032."

Orphan drug • 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

2026 REVIEW OF GENE THERAPY ACCESS LANDSCAPE (ISPOR 2026) - "The newest gene therapies include Itvisma and Papzimeos, among others. Ultra-high-cost therapies continue to face additional restrictions compared to lower-priced gene therapies. Therapies on market longer generally face less restrictive management, likely due to contracting strategies. Products offering outcomes-based agreements see less restrictive management."

Gene therapy • Review • Gene Therapies

Therapeutic vaccination for active induction of T cell immunity against cancer, ready for a rich harvest after 40 years. (PubMed, J Immunother Cancer) - "Only two therapeutic vaccines for neoplastic disease were approved by the Food and Drug Administration in the past 40 years: sipuleucel-T, approved in 2010 for hormone-resistant metastatic prostate cancer and targeting prostate acid phosphatase; and zopapogene imadenovec, approved in 2025 for recurrent respiratory papillomatosis, a rare, non-malignant but often invalidating disease caused by human papillomavirus (HPV) type 6 or type 11. In another randomized study, patients with R/M HPV16+ head and neck cancer only benefited from the combination of HPV16-specific SLP vaccine and a PD-1 blocker if they had high pretreatment PD-L1 biomarker expression in cancer tissue. Increasingly, biomarker-guided therapy is recommended."

IO biomarker • Journal • Review • Cervical Cancer • Colonic Polyps • Gastroenterology • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Oncology • Prostate Cancer • Solid Tumor

Zopa Retreatment and Vector Shedding in Adults With RRP (clinicaltrials.gov) - P4 | N=30 | Recruiting | Sponsor: Precigen, Inc | Suspended ➔ Recruiting | Phase classification: P3 ➔ P4 | Trial primary completion date: Mar 2027 ➔ Dec 2027

Enrollment open • Phase classification • Trial primary completion date • Infectious Disease • Oncology

From surgery to immunotherapy: Papzimeos as the first FDA-approved therapy for recurrent respiratory papillomatosis (RRP). (PubMed, Ann Med Surg (Lond)) - No abstract available

FDA event • Journal • Oncology

In Reference to A Clinical Consensus Statement on Pulmonary Recurrent Respiratory Papillomatosis. (PubMed, Laryngoscope) - No abstract available

Journal • Gene Therapies • Oncology

Zopapogene Imadenovec: First Approval. (PubMed, Mol Diagn Ther) - "Treatment with zopapogene imadenovec resulted in complete responses in approximately half of treated patients and was associated with a papillary microenvironment that was conducive to T cells in complete responders. This article summarizes the milestones in the development of zopapogene imadenovec leading to this first approval for the treatment of adult patients with recurrent respiratory papillomatosis."

Journal • Oncology

PRGN-2012, a novel HPV-Targeted Immuno-Activator, induces complete and durable responses in recurrent respiratory papillomatosis patients (AAO-HNSF 2025) - P1/2 | "These data demonstrate that patients treated with PRGN-2012 either maintained consistent CRs for at least 3 years or demonstrated a reduction in the need for clinically indicated interventions following recurrence with excellent long-term safety."

Clinical • Late-breaking abstract • Fatigue • Infectious Disease • Musculoskeletal Pain

Emerging Therapeutic Strategies for HPV-Related Cancers: From Gene Editing to Precision Oncology. (PubMed, Curr Issues Mol Biol) - "Key approaches include immune checkpoint inhibitors, therapeutic vaccines such as VGX-3100 and PRGN-2012, and gene-editing tools like CRISPR/Cas9. We also highlight the role of patient-derived organoid models as powerful platforms for personalized drug screening and functional assessment. By integrating these therapeutic innovations with precision oncology approaches, this review outlines a multidimensional framework aimed at improving clinical outcomes and quality of life for patients with HPV-associated cancers."

Journal • Review • Head and Neck Cancer • Infectious Disease • Oncology • Oropharyngeal Cancer • Solid Tumor

Confirmatory Study of PRGN-2012 in Patients With RRP (clinicaltrials.gov) - P3 | N=42 | Suspended | Sponsor: Precigen, Inc | Recruiting ➔ Suspended

Trial suspension • Infectious Disease • Oncology

Precigen Announces Full FDA Approval of PAPZIMEOS (zopapogene imadenovec-drba), the First and Only Approved Therapy for the Treatment of Adults with Recurrent Respiratory Papillomatosis (Precigen Press Release) - "Precigen completed submission of the rolling Biologics License Application (BLA) in December 2024 under an accelerated approval pathway; however, the FDA has granted PAPZIMEOS full approval, which does not require a confirmatory clinical trial...PAPZIMEOS is delivered via four subcutaneous injections over a 12-week interval."

FDA approval • Infectious Disease

Disease Control and Voice Outcomes Following Treatment With PRGN-2012 in Adults With Recurrent Respiratory Papillomatosis. (PubMed, J Voice) - "These data link greater papilloma disease control with reduced need for clinically indicated procedures and reduced voice handicap after PRGN-2012 treatment independent of short- or long-term measures of disease severity."

Journal • Oncology

Precigen Reports Full Year 2024 Financial Results and Business Updates (PRNewswire) - "Key Program Highlights: PRGN-2012:...The Company continues to rapidly advance its commercial and manufacturing readiness campaign in anticipation of a potential launch in 2025. Based on recently updated internal analysis derived from review of claims data, the market opportunity for PRGN-2012 in RRP is estimated to be approximately 27,000 adult patients in the US and more than 125,000 patients outside of the US."

Commercial • Launch US • Infectious Disease

FDA Grants Priority Review to Precigen's BLA for PRGN-2012 for the Treatment of Adults with Recurrent Respiratory Papillomatosis with PDUFA Target Action Date Set for August 27, 2025 (PRNewswire) - "Precigen...announced the US Food and Drug Administration (FDA) has accepted the company's biologics license application (BLA) for PRGN-2012 (nonproprietary name: zopapogene imadenovec), an investigational AdenoVerse gene therapy for the treatment of adults with recurrent respiratory papillomatosis (RRP). The FDA granted priority review to the BLA and set a Prescription Drug User Fee Act (PDUFA) target action date of August 27, 2025. The FDA has indicated that they are not currently planning to hold an advisory committee meeting to discuss this application....The BLA is supported by data from the pivotal Phase 1/2 clinical study (NCT04724980)..."

FDA filing • PDUFA • Priority review • Infectious Disease

PRGN-2012 gene therapy in adults with recurrent respiratory papillomatosis: a pivotal phase 1/2 clinical trial. (PubMed, Lancet Respir Med) - P1/2 | "PRGN-2012 treatment resulted in complete response in 51% of the patients treated and was safe. Based on these positive pivotal study results, a biologics license application to the US Food and Drug Administration (FDA) is planned, positioning PRGN-2012 to be an FDA-approved medical treatment for adult patients with RRP."

Journal • P1/2 data • Fatigue • Gene Therapies • Infectious Disease • Oncology

Precigen Completes Submission of BLA with Request for Priority Review to the FDA for PRGN-2012 for the Treatment of Adults with Recurrent Respiratory Papillomatosis (PRNewswire) - "Precigen, Inc...announced the completion of the rolling submission for a biologics license application (BLA) to the US Food and Drug Administration (FDA) for PRGN-2012 (INN: zopapogene imadenovec) for the treatment of adult patients with recurrent respiratory papillomatosis (RRP)....The BLA included a request for priority review, which, if granted, would reduce the review timeline from the standard 10-month to a priority 6-month review from the date the submission is accepted by the FDA....The BLA is supported by data from the pivotal Phase 1/2 clinical study of PRGN-2012 for the treatment of RRP (NCT04724980)..."

FDA filing • Infectious Disease