INOVIO Pharmaceuticals announced new data at scientific conferences for its lead candidate, INO-3107, a DNA immunotherapy targeting Recurrent Respiratory Papillomatosis (RRP). The data, presented at the American Association for Cancer Research (AACR) Special Conference and the International Society of Vaccines Conference, highlight the potential of INO-3107 to reduce surgical interventions and stimulate an immune response against HPV-6 and HPV-11, the primary causes of RRP. INOVIO is preparing a Biologics License Application for targeted submission in mid-2025 under the U.S. Food and Drug Administration's Accelerated Approval Pathway Program.
Immunology Data from AACR Conference
At the AACR conference, INOVIO presented new immunology data demonstrating INO-3107's ability to induce antigen-specific T cell responses against HPV-6 and HPV-11. The data showed that INO-3107 drives the recruitment of T cells into airway tissues and papilloma of RRP patients, which could ultimately slow or eliminate papilloma regrowth. According to Dr. Matthew Morrow, INOVIO's Vice President of Translational Science, the data supports the proposed mechanism of action of INO-3107, which is to generate an immune response that can seek out and eliminate HPV-6 and HPV-11 infected cells that are the underlying cause of papilloma growth. The analysis showed that INO-3107 induced significant clonal T cell expansion in the blood, including antigen-specific killer T cells, and investigators also observed T cell infiltration into airway tissue, which is positively associated with clinical response.
Phase 1/2 Trial Data from International Society of Vaccines Conference
INOVIO presented its full safety and efficacy data set for the Phase 1/2 trial for INO-3107 at the International Society of Vaccines Conference. In the trial, INO-3107 was found to be well tolerated and immunogenic. Of the 32 patients in the trial, 26 patients, or 81%, experienced a decrease in the number of surgical interventions in the year after treatment when compared to the year before treatment.
The overall clinical response (OCR) was 81%, with 26 of the 32 enrolled patients experiencing a decrease in the number of surgical interventions in the year after INO-3107 administration compared to the prior year, including 28% (9/32) that required no surgical intervention (i.e., complete response or "CR") during or after the dosing window. Further, 44% (14/32) of patients had a partial response ("PR"), measured by a reduction of at least 50%, but less than 100%, in the number of surgeries when compared to the prior year. The overall response rate (ORR) of patients (CR+PR) was therefore 72% (23/32).
Other key data points presented include:
- INO-3107 was well tolerated and immunogenic in the 32 patients enrolled
- 41% (13/32) of patients reported a treatment-related Adverse Event (AE)
- Most frequent treatment-related AE's reported were injection site pain (31%) and fatigue (9%)
- No treatment-related AEs greater than Grade 2 severity were reported
- Modified Derkay-Pransky severity scores improved from baseline to the end of 52-week trial
- INO-3107 induced durable cellular responses and generated T cells against HPV-6 and HPV-11
INO-3107: A Potential Treatment for RRP
INO-3107 is a DNA immunotherapy designed to elicit an antigen-specific T cell response against both HPV-6 and HPV-11 proteins. These targeted T cells are designed to seek out and kill HPV-6 and HPV-11 infected cells, with the aim of potentially preventing or slowing the growth of new papillomas. In a Phase 1/2 clinical trial conducted with INO-3107, 81.3% (26/32) of patients had a decrease in surgical interventions in the year after INO-3107 administration compared to the prior year, including 28.1% (9/32) that required no surgical intervention during or after the dosing window. Patients in the trial had a median range of 4 surgeries (2-8) in the year prior to dosing. After dosing, there was a median decrease of 3 surgical interventions (95% confidence interval -3, -2). Treatment with INO-3107 generated a strong immune response in the trial, inducing activated CD4 T cells and activated CD8 T cells with lytic potential. T-cell responses were also observed at Week 52, indicating a persistent cellular memory response. INO-3107 was well tolerated by participants in the trial, resulting in mostly low-grade (Grade 1) treatment-emergent adverse effects such as injection site pain and fatigue.
RRP Disease Burden and Current Treatment Landscape
RRP is a debilitating and rare disease caused primarily by HPV-6 and/or HPV-11. RRP is characterized by the development of small, wart-like growths, or papillomas, in the respiratory tract. While papillomas are generally benign, they can cause severe, life-threatening airway obstruction and respiratory complications. RRP can also significantly affect quality of life for patients by affecting the voice box, limiting the ability to speak effectively. Surgery to remove papillomas is the standard of care for RRP; however, the papillomas often grow back. The most widely cited U.S. epidemiology data published in 1995 estimated that there were 14,000 active cases and about 1.8 per 100,000 new cases in adults each year.
Regulatory Designations
The FDA granted INO-3107 Orphan Drug designation and Breakthrough Therapy designation, and advised INOVIO that it could submit its BLA under the accelerated approval program using data from its already completed Phase 1/2 trial. The European Commission granted INO-3107 Orphan Drug designation and assigned INOVIO's delivery device CELLECTRA® a CE marking, a regulatory standard that certifies that a product has met European Union's safety, health, and environmental standards. The United Kingdom awarded INO-3107 the Innovation Passport. This designation serves as the entry point to the Innovative Licensing and Access Pathway (ILAP), which aims to accelerate time to market and facilitate patient access to medicines.
