BLA submission on track for INO-3107 in second half of 2024; if approved under accelerated approval pathway, could be first non-surgical treatment for recurrent respiratory papillomatosis (RRP) Planning initiation of confirmatory trial for INO-3107 based on FDA feedback Advancing plans for Phase 3 trial of INO-3112 in combination with LOQTORZITM (toripalimab-tpzi) as a potential treatment for oropharyngeal squamous cell carcinoma (OPSCC) based on FDA feedback Balance sheet strengthened with underwritten offering of common stock and pre-funded warrants completed in April 2024 Cash runway projected into third quarter of 2025 PLYMOUTH MEETING, Pa., May 13, 2024 /PRNewswire/ -- 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 its financial results for the first quarter of 2024 and provided an update on recent company developments. "In the first quarter of 2024, we continued to deliver on our priorities for the year. Of utmost importance, we remain on track to submit our BLA in the second half of 2024 under the accelerated approval pathway for INO-3107 as a treatment for RRP and are working to initiate our confirmatory trial as soon as possible based on feedback from the FDA on the trial's design. We are energized by the opportunity to potentially deliver the first FDA-approved therapy for this devastating disease and continue to work expeditiously to be prepared to serve RRP patients and the physicians caring for them. If approved, INO-3107 would also be the first DNA medicine on the market in the United States, representing a major milestone for our technology platform," said Dr. Jacqueline Shea, INOVIO's President and Chief Executive Officer. "In parallel, we also made progress with our plans to evaluate INO-3112 in combination with the PD-1 inhibitor, LOQTORZI, in a Phase 3 trial, as we believe the combination could address a substantial unmet need in patients with locoregionally advanced, high-risk, HPV-16/18 positive OPSCC, a type of head and neck cancer commonly known as throat cancer. We believe that we are aligned with the FDA on our proposed Phase 3 trial design, and we now plan to discuss these plans with European regulators. We look forward to sharing our continued progress throughout the year." Recent Business Highlights INO-3107 – Recurrent Respiratory Papillomatosis (RRP) INOVIO remains on target to submit its BLA seeking accelerated approval for INO-3107 in the second half of 2024. INOVIO is preparing trial sites for recruitment based on recent feedback from the FDA that they had no additional comments on INOVIO's proposed design for the confirmatory trial. The trial is being strategically designed to focus on evaluating clinical benefit in reducing surgical intervention to control RRP disease for the majority of RRP patients. Repeat surgical interventions is the current standard of care for RRP. INOVIO's market research to date with patients and healthcare professionals indicates that a reduction of even one surgery matters, because every surgery poses a significant risk of causing permanent damage to the vocal cords. The proposed confirmatory trial will be randomized and placebo-controlled, involving approximately 100 patients with a history of ≥2 surgeries per year, with a treatment option for the placebo arm at trial end. This trial design is intended to target a broader spectrum of RRP disease than other candidates currently in development. If INO-3107 receives full approval from the FDA, INOVIO believes the design of the confirmatory trial could also support expansion into global markets based on feedback received to date from European regulators. Immunological data highlighting INO-3107's mechanism of action are expected to be submitted to peer-reviewed publications and key conferences in the second half of 2024. INOVIO continues preparations to be ready to launch commercially in 2025, should INO-3107 be approved. Efforts are focused on building the infrastructure needed to deliver the product to patients as quickly and easily as possible, from distribution and supply efforts to payer and healthcare provider support. INOVIO believes that INO-3107, if approved, has the potential to be the preferred treatment of choice for all patients with RRP, as well as healthcare professionals and payers based on results from completed clinical trials and the competitive strengths of the DNA medicine platform: Reduction in surgeries: 81.3% (26/32) of patients had a decrease in surgical interventions in the year after INO-3107 administration compared to the year prior to treatment, including 28.1% (9/32) that required no surgical interventions during or after the dosing window. INOVIO's Phase 1/2 trial was designed to show the potential of INO-3107 to reduce surgical intervention in the year following the first dose compared to the year prior. Relative to other Phase 1/2 clinical trials, INOVIO's protocol required that all surgeries conducted during the dosing window (a 54-day period during which four doses were administered) be counted in the overall results. The protocol for INOVIO's trial also did not include prescribed laryngoscopy and surgery at weeks 6 and 12 to maintain minimal residual disease during the treatment window. INOVIO believes that these contrasts with other clinical trial designs are important and could offer competitive advantages for INO-3107 should it be approved. Mechanism of action: INO-3107 generated antigen specific T cells with lytic potential targeting both HPV-6 and HPV-11. Immunology: Administration of INO-3107 induced active immune responses in the airway tissues of those patients who showed clinical response, including the production of cytokines and chemokines, known to be critical mediators of inflammatory responses, and increased activity of dendritic cells, macrophages and T cells. Additional analysis of T cell genes in airway tissues revealed an increase in CD4 and CD8 T cell gene signatures after treatment with INO-3107. Benefits of DNA plasmids plus electroporation: INOVIO's proprietary CELLECTRA® devices are designed to optimally deliver DNA medicines within the body's cells without requiring chemical adjuvants or lipid nanoparticles, and without the risk of pre-existing or anti-vector responses historically seen with viral vector platforms. In late-stage clinical trials involving approximately 5,600 doses administered to approximately 1,600 patients, intramuscular delivery has been well tolerated by patients and observed to be easy to use by healthcare providers. Based on historical data from other programs involving redosing, INOVIO believes it will be able to effectively re-dose INO-3107 if required to maintain or enhance immune responses. INO-3112 – Oropharyngeal Squamous Cell Carcinoma (OPSCC) The FDA provided feedback on the proposed Phase 3 trial design to evaluate the combination of INO-3112 and LOQTORZI as a potential treatment for patients with locoregionally advanced, high-risk, HPV-16/-18 positive throat cancer. INOVIO will discuss the proposed trial design with European regulatory authorities, as INOVIO plans to conduct the trial in both Europe and North America. The combination of INO-3112 with LOQTORZI has the potential to address a substantial unmet need in patients with HPV-16 and -18 related high-risk throat cancer. The proposed multi-center Phase 3 trial will investigate whether LOQTORZI can help boost the tumor-infiltrating abilities of the antigen-specific T cells generated by INO-3112. INO-3112 is a DNA medicine candidate containing a DNA plasmid encoding HPV-16/-18 E6 and E7 antigens combined with another DNA plasmid encoding IL-12 as an immune activator. LOQTORZI is an FDA-approved PD-1 inhibitor approved for the treatment of recurrent locally advanced/metastatic nasopharyngeal carcinoma. General Corporate Strengthened balance sheet with an offering of common stock and pre-funded warrants in April 2024; net proceeds from the offering, after deducting underwriting discounts and commissions and offering expenses, were approximately $33.2 million. First Quarter 2024 Financial Results Cash, Cash Equivalents and Short-term Investments: As of March 31, 2024, cash, cash equivalents and short-term investments were $105.6 million compared to $145.3 million as of December 31, 2023. Research and Development (R&D) Expenses: R&D expenses for the three months ended March 31, 2024, were $20.9 million compared to $30.2 million ...