A biotechnology company focused on rapidly bringing to market precisely designed DNA medicines to protect and treat people from infectious diseases and cancer, today announced positive interim clinical data of INO-4800, its vaccine candidate against novel coronavirus (SARS-CoV-2), from the first two Phase 1 clinical trial cohorts. In addition, INO-4800 has been selected to participate in a non-human primate (NHP) challenge study as part of the U.S. government's Operation Warp Speed, a new national program aiming to provide substantial quantities of safe, effective vaccine for Americans by January 2021. Furthermore, INOVIO has expanded its Phase 1 trial to add older participants in additional cohorts and plans to initiate a Phase 2/3 efficacy trial this summer upon regulatory concurrence.
Dr. J. Joseph Kim, President and CEO of INOVIO, said, "INOVIO would like to thank all of the trial participants and the investigator staff who have made this trial possible. We are very encouraged by the positive interim safety and preliminary cellular and humoral immune response results to date as well as the inclusion of INO-4800 in Operation Warp Speed. We are also pleased that INO-4800 vaccination abrogated viral replication in the lungs of mice challenged with SARS-CoV-2. We look forward to urgently advancing INO-4800, as it is the only nucleic-acid based vaccine that is stable at room temperature for more than a year and does not require to be frozen in transport or for years of storage, which are important factors when implementing mass immunizations to battle the current pandemic."
The Phase 1 clinical trial of INO-4800 initially enrolled 40 healthy adult volunteers 18 to 50 years of age at two U.S. sites with funding from the Coalition for Epidemic Preparedness Innovations (CEPI). The participants were enrolled into 1.0 mg and 2.0 mg dose cohorts; each participant received two doses of INO-4800 four weeks apart. Each dose was administered by intradermal injection using INOVIO's CELLECTRA 2000 device. An independent Data Safety Monitoring Board reviewed the safety data. INO-4800 was generally safe and well-tolerated in all participants in both cohorts through week 8; all ten reported adverse events (AEs) were grade 1 in severity, and most were local injection site redness. There were no reported serious adverse events (SAEs).
Multiple immunology assays including those for humoral and cellular immune responses are being conducted for both 1.0 mg and 2.0 mg dose cohorts after two doses at week 6. Analyses to date have shown that 94% (34 out of 36 total trial participants) demonstrated overall immunological response rates based on preliminary data assessing humoral (binding and neutralizing) and T cell immune responses. One participant in the 1.0 mg dose cohort and two participants in the 2.0 mg dose cohort were excluded in the immune analyses as they tested positive for COVID-19 immune responses at study entry, indicating prior infection. One participant in the 2.0 mg dose cohort discontinued the study for reasons unrelated to safety or tolerability. INOVIO plans to publish the full data set in a peer-reviewed medical journal.
One key feature of INOVIO's DNA vaccines is the ability to generate balanced antibody and T cell immune responses, which in the case of SARS-CoV-2 infection could be important in the development of potential COVID-19 vaccines. In this regard, recent scientific reports have highlighted that SARS-CoV-2-specific T cells found in convalescent patients have been positively implicated in controlling the severity of their COVID-19 disease (Grifoni et al, 2020) while other studies have shown that a significant proportion (33% to 40%) of convalescent individuals in their reports had neutralizing antibody below detectable levels (Robbiani et al, 2020 and Payne et al, 2020).
In addition to positive interim Phase 1 data, INO-4800 has been shown to protect mice in SARS-CoV-2 viral challenge studies, where vaccination with INO-4800 prevented viral replication in the lungs of animals challenged with SARS-CoV-2. Moreover, INO-4800 is currently being tested in a ferret challenge model as well as in NHP challenge studies as part of Operation Warp Speed.
"While the pathophysiologic profile of SARS-CoV-2 is not completely understood, research and clinical studies suggest that both T cell and antibody immune responses will be important for protection in both mild and serious infections. Leveraging our previous expertise in MERS with INO-4700, where we demonstrated significant antibody and cellular responses, the breadth and profile of the responses observed to date with INO-4800 targeting SARS-CoV-2 provide a promising read towards further development and addressing the existing public health threat," said Dr. Kate Broderick, Senior Vice President of R&D at INOVIO.
As previously announced, INOVIO received $71 million funding from the U.S. Department of Defense to support the large-scale manufacture of the company's proprietary CELLECTRA 3PSP smart device and the procurement of CELLECTRA 2000 devices. INO-4800 development has also been supported by generous funding from CEPI and the Bill & Melinda Gates Foundation.
INO-4800 is INOVIO's DNA vaccine candidate being developed to protect against the novel coronavirus SARS-CoV-2, which causes COVID-19. INO-4800 was designed rapidly using INOVIO's proprietary DNA medicine platform after the publication of the genetic sequence of the coronavirus that causes COVID-19. INOVIO has extensive experience working with coronaviruses and is the only company with a Phase 2 vaccine for a related coronavirus that causes Middle East Respiratory Syndrome (MERS).
INO-4800 is the only nucleic-acid based vaccine that is stable at room temperature for more than a year and does not require to be frozen in transport or storage, which are important factors when implementing mass immunizations.