INOVIO Pharmaceuticals announced new immunology data supporting the clinical activity of INO-3107 in a Phase 1/2 trial for recurrent respiratory papillomatosis (RRP) patients. The data, presented at the 36th International Papillomavirus Conference, demonstrates that INO-3107 induces the expansion of new clonal T cells that migrate to papilloma and airway tissues, leading to a reduction in the need for surgeries.
Mechanism of Action
The study revealed that INO-3107 stimulates both existing and new clonal T cells to target HPV-6 and HPV-11, the primary causes of RRP. These newly generated T cells constituted the majority of T cells observed in patient papilloma or airway tissue who showed either a complete or partial response to treatment with INO-3107. This immune response helps control or eliminate RRP by reducing the necessity for surgical intervention.
Dr. Matthew Morrow, INOVIO's Vice President of Translational Sciences, stated, "These new immunology data are consistent with the clinical effect observed in our Phase 1/2 trial of elimination or reduction in the incidence of papilloma in the airway of RRP patients. In a thorough immunological assessment, we observed that T cell infiltration in airway tissues of clinical responders was predominantly comprised of a T cell population detectable only after administration of INO-3107."
Clinical Trial Results
The Phase 1/2 trial involved 32 adult RRP patients and spanned 52 weeks. Key findings include:
- Induction of T cell responses specific for HPV-6 and HPV-11, including cytotoxic CD8+ T cells still present at week 52, indicating an establishment of memory response.
- Expansion of new clonal T cell populations in peripheral blood that travel to papilloma or airway tissues.
- Induction of inflammatory responses in papilloma and airway tissue, including interferon, cytokine and chemokine signaling, adaptive and innate immune cell infiltration, with emphasis on T cells, and cytotoxic signatures of infiltrated T cells.
In the Phase 1/2 clinical trial, 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).
RRP and INO-3107
RRP is a rare disease characterized by the development of papillomas in the respiratory tract, primarily caused by HPV-6 and HPV-11. These papillomas can lead to severe airway obstruction and respiratory complications. INO-3107 is an investigational DNA medicine designed to elicit an antigen-specific T cell response against HPV-6 and HPV-11 proteins, aiming to prevent or slow the growth of new papillomas.
The FDA has granted INO-3107 Orphan Drug designation and Breakthrough Therapy designation, advising INOVIO that it can submit a biologics license application under the FDA's accelerated approval program using data from the completed Phase 1/2 trial. The European Commission has also granted INO-3107 Orphan Drug designation. The United Kingdom awarded INO-3107 the Innovation Passport, facilitating accelerated market access.
