INO-4800 Selected for the U.S. Government's Operation Warp Speed
- 94% of Phase 1 trial participants demonstrated overall immune responses at Week 6 after two doses of INO-4800 in trial with 40 healthy volunteers in preliminary analyses
- Through Week 8 INO-4800 regimen was deemed safe and well-tolerated with no serious adverse events; all reported adverse events were grade 1 in severity
- In preclinical animal challenge study, INO-4800 provided full protection against SARS-CoV-2 replication in the lungs in mice challenged with the virus
- INOVIO to begin U.S. Phase 2/3 efficacy study this summer upon regulatory concurrence
PLYMOUTH MEETING, Pa. -- INOVIO (NASDAQ:INO), 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, Cell 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, Nature 2020 and Payne et al, MMWR 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.
About INO-4800
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.
About INOVIO's DNA Medicines Platform
INOVIO has 15 DNA medicine clinical programs currently in development focused on HPV-associated diseases, cancer, and infectious diseases, including coronaviruses associated with MERS and COVID-19 diseases being developed under grants from the Coalition for Epidemic Preparedness Innovations (CEPI) and the DoD. DNA medicines are composed of optimized DNA plasmids, which are small circles of double-stranded DNA that are synthesized or reorganized by a computer sequencing technology and designed to produce a specific immune response in the body.
INOVIO's DNA medicines deliver optimized plasmids directly into cells intradermally or intramuscularly using INOVIO's proprietary hand-held smart device called CELLECTRA®. The CELLECTRA device uses a brief electrical pulse to reversibly open small pores in the cell to allow the plasmids to enter, overcoming a key limitation of other DNA and other nucleic acid approaches, such as mRNA. Once inside the cell, the DNA plasmids enable the cell to produce the targeted antigen. The antigen is processed naturally in the cell and triggers the desired T cell and antibody-mediated immune responses. Administration with the CELLECTRA device is designed to ensure that the DNA medicine is efficiently delivered directly into the body's cells, where it can go to work to drive an immune response. INOVIO's DNA medicines do not interfere with or change in any way an individual's own DNA. The advantages of INOVIO's DNA medicine platform are how fast DNA medicines can be designed and manufactured, the stability of the products which do not require freezing in storage and transport, and the robust immune response, safety profile, and tolerability that have been demonstrated in clinical trials.
With more than 2,000 patients receiving INOVIO investigational DNA medicines in more than 7,000 applications across a range of clinical trials, INOVIO has a strong track record of rapidly generating DNA medicine candidates with potential to meet urgent global health needs.