On May 10, 2021, Inovio Pharma announced positive safety, tolerability and immunogenicity data from its placebo-controlled and blinded Phase 2 segment of its Phase 2/3 clinical trial in the U.S., called INNOVATE (INOVIO INO-4800 Vaccine Trial for Efficacy), evaluating INO-4800, its DNA vaccine candidate for COVID-19.  Preliminary results showed in a larger population that INO-4800 was generally safe, well-tolerated and immunogenic in all studied age groups. The trial was funded by the Department of Defense.

Findings from the Phase 2 Clinical Trial:

• The Phase 2 segment of the trial enrolled approximately 400 participants, 18 years of age or older, at 16 U.S. sites.
• Participants received either INO-4800 (1.0 mg or 2.0 mg dose) or placebo at 0 and 4 weeks (randomized 3:3:1:1). Each dose was administered by intradermal injection followed by electroporation using INOVIO’s CELLECTRA^®, its proprietary smart device.
• Safety endpoints included systemic and local administration site reactions through 8 weeks post-dose one (or 4 weeks post-dose 2). Immunology endpoints included antigen-specific binding antibody titers, neutralization titers, and antigen-specific interferon-gamma (IFN-γ) cellular immune responses after two doses of the vaccine.
• Vaccine administration was generally safe and well-tolerated. The majority of adverse events (AEs) were Grade 1 and Grade 2 in severity and did not appear to increase in frequency with the second dose. The number of participants experiencing each of the most common AEs did not differ between the two dosing groups.
• The geometric mean fold rise (GMFR) of binding and neutralizing antibody levels were statistically significantly greater in the 2.0 mg dose group versus the 1.0 mg dose group.
• The T cell immune responses measured by the ELISpot assay were also higher in the 2.0 mg dose group compared to the 1.0 mg dose group.

The Phase 2 segment of INNOVATE was designed to evaluate the safety, tolerability and immunogenicity of INO-4800 in a two-dose regimen (1.0 mg or 2.0 mg) in a three-to-one-randomization to receive either INO-4800 or placebo for each dose to identify optimal dose(s) for two age groups (18-50 years and 51 years and older) for the subsequent Phase 3 efficacy evaluation. The preliminary Phase 2 results showed that INO-4800 was safe, well-tolerated and immunogenic in all tested age groups. The trial was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, (JPEO-CBRND) in coordination with the Office of the Assistant Secretary of Defense for Health Affairs (OASD(HA)) and the Defense Health Agency.

INOVIO plans to file preliminary Phase 2 results and device data with the U.S. Food and Drug Administration (FDA). Following the submission and FDA concurrence to proceed, the company plans to conduct a global Phase 3 clinical trial for INO-4800. The company recognizes the growing and unmet global demand for both initial as well as boosting doses of COVID-19 vaccines and looks forward to supporting the rollout of much needed additional vaccines to prevent the spread of COVID-19 – including both current and future variants – around the world.

The Phase 3 segment of the INNOVATE trial in the U.S. remains on partial clinical hold until INOVIO satisfactorily resolves the FDA’s remaining questions related to the CELLECTRA^® 2000 device that will be used to deliver INO-4800 into the cells of the skin. The company plans to satisfy the remaining device questions during the Phase 2 segment and prior to the start of the Phase 3 segment of INNOVATE. In the Phase 3 segment of the trial, INOVIO intends to enroll men and non-pregnant women 18 years and older, to evaluate the efficacy of the proposed dosing level(s) for each age group based on the data from the Phase 2 evaluation. The trial will predominately be conducted globally; participants will be enrolled in a two-to-one randomization to receive either INO-4800 or a placebo. The Phase 3 segment will be case-driven with the final number of enrollees to be determined by the incidence of COVID-19 during the Phase 3 segment. The primary endpoint of the Phase 3 segment will be virologically-confirmed COVID-19 disease.