INOVIO (NASDAQ: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, today announced new immunology data that supports the clinical activity of its lead product candidate, INO-3107, that was previously observed in a Phase 1/2 trial of RRP patients. In that prior trial, patients experienced a reduction in surgeries needed to control their RRP caused by HPV-6 and HPV-11. In the recent immunology study, INO-3107 induced the expansion of both existing and new clonal T cells that travel from the blood to the papilloma and airway tissues. The new clonal T cells accounted for 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. These new data build upon previously reported evidence that INO-3107 elicits an antigen-specific immune response targeting HPV-6 and HPV-11, to help eliminate or control RRP by reducing the need for surgery.

"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," said Dr. Matthew Morrow, INOVIO's Vice President of Translational Sciences. "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. This evidence supports the mechanism of action of INO-3107 and its ability to induce antigen-specific cytotoxic T cells targeting HPV-6 and HPV-11. Furthermore, this data adds to the body of evidence indicating that DNA medicines are an effective CD8 T cell generating platform."

Bettie M. Steinberg, Interim Dean and Professor, Elmezzi Graduate School of Molecular Medicine, Northwell Health, said, "This is very encouraging data. Not only did most patients improve clinically with INO 3107 treatment, but the induction of a systemic inflammatory T-cell response and new T-cell clones that travel to the papilloma tissue to contribute to a cytotoxic response shows that it is possible to effectively address the immune dysregulation against HPV that is a hallmark of RRP."

Summary of Immunology Data
The new immunology data is to be presented at the 36^th International Papillomavirus Conference (November 12-15). It builds on data presented at the American Association for Cancer Research (AACR) Special Conference on October 19. Collectively, these immunology data provide further support of INO-3107's ability to induce antigen-specific T cell responses against HPV-6 and HPV-11 and drive recruitment of T cells into papilloma and airway tissues of RRP patients, which could potentially slow or eliminate papilloma regrowth.

INOVIO conducted a number of immunological assessments on blood samples taken throughout the trial and tissue samples taken at the beginning and end of its 52-week Phase 1/2 trial involving 32 adult RRP patients. The immunological testing showed INO-3107 produced:

• 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
• Cytotoxic signatures of infiltrated T cells in papilloma/airway tissue, and direct evidence of increased overall T cell infiltration compared to pre-treatment
• Clinical activity not impacted by immunosuppressive papilloma microenvironment