Inovio Pharmaceuticals Inc (INO)

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((( INO )))INOVIO's COVID-19 DNA Vaccine INO-4800 Provides Protection with Memory Immune Responses In Non-Human Primates Challenged with SARS-CoV-2 Virus

July 30, 2020

http://ir.inovio.com/news-releases/news-releases-details/2020/INOVIOs-COVID-19-DNA-Vaccine-INO-4800-Provides-Protection-with-Memory-Immune-Responses-In-Non-Human-Primates-Challenged-with-SARS-CoV-2-Virus/default.aspx

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- INO-4800 showed durable antibody and T cell responses in rhesus macaques for 4 months
- INO-4800 is the only vaccine to demonstrate long-term protection in non-human primates challenged with SARS-CoV-2 virus 13 weeks from vaccination
- Memory T and B cell responses resulted in reduced viral loads and faster viral clearance in macaques' lungs and nasal passages
- INO-4800 vaccination generated antibodies neutralizing both the earlier strain of virus as well as the mutant variant (D614G) that has emerged with greater infectivity, and now accounts for >80% of newly circulating virus
- No antibody-dependent enhanced disease events were reported
PLYMOUTH MEETING, Pa., July 30, 2020 /PRNewswire/ -- INOVIO (NASDAQ:INO), a biotechnology company focused on rapidly bringing to market precisely designed DNA medicines to treat and protect people from infectious diseases and cancer, today announced that its COVID-19 DNA vaccine INO-4800 targeting SARS-CoV-2 was effective in protecting non-human primates (NHPs; specifically rhesus macaques) from live virus challenge 13 weeks after the last vaccination. These protective results were mediated by memory T and B cell immune responses from INO-4800 vaccination.

These results, submitted to a peer-reviewed journal and also published today on the non-peer reviewed online preprint site bioRxiv, demonstrate that INO-4800 reduced viral load in both the lower lungs and nasal passages in macaques that received two doses of INO-4800 (1 mg) four weeks apart and then were challenged with live virus 13 weeks after the second dose (study week 17). The reduced viral loads following exposure to SARS-CoV-2 infection at this timeframe demonstrate an important durable impact mediated by INO-4800. This is the first time a vaccine protection in non-human primates was reported from memory immune responses as previously reported monkey vaccine challenge studies were conducted at the time near their peak immune responses (1-4 weeks from their last vaccination).

INO-4800-treated animals demonstrated seroconversion after a single vaccination, with protective neutralizing antibodies and T cells lasting in their blood more than four months after the initial dose. The antibody levels were similar to or greater than those seen in patients who have recovered from COVID-19, the infection caused by SARS-CoV-2, and the T cell responses were significantly higher than those from convalescent patients.

Dr. J. Joseph Kim, President and Chief Executive Officer of INOVIO, said, "All other previously reported NHP vaccine protection studies actually challenged the animals at the peak of their immune response. Our study demonstrates that INO-4800 could provide protection in a more real-world setting, where vaccine-generated memory immune responses protected NHPs for more than 3 months (13 weeks) from the last vaccination. Given the importance of protective antibody and T cell responses, this study gives us more confidence as we continue to advance INO-4800 in the clinic. We believe INO-4800 holds significant potential to help address this global public health crisis."

B cells are responsible for producing the antibodies that recognize SARS-CoV-2, while T cells play a role in killing the virally infected cells as well as supporting the B cell response. The published data support that immunization with INO-4800 limits active viral replication and has the potential to reduce severity of disease, as well as reduced viral shedding in the nasal cavity. In the study, researchers assessed the ability of INO-4800 to induce acute and memory T cell and B cell immune responses, including neutralizing antibody responses against both early virus as well as now-dominant G614 mutant variants. To INOVIO's knowledge, this is the first report of vaccine-induced responses driving immunity against G614 variants. A strong anamnestic or memory T and B cell responses were demonstrated following challenge with the live virus.

"As we eagerly anticipate initiating a Phase 2/3 efficacy trials this summer, an animal challenge is currently the closest thing we have to testing a vaccine's efficacy when confronting a live virus. We are very encouraged with the duration of protection that INO-4800 demonstrated in this NHP study and look forward to reassessing its impact on durability of response at 12 months out from our other ongoing non-human primate and animal challenge studies," said Dr. Kate Broderick, Ph.D., INOVIO's Senior Vice President, Research & Development.

"In addition to safety and efficacy, it is essential that any vaccine targeting SARS-CoV-2 generates a relevant durability of response," Dr. Broderick added. "A vaccine that only provides protection for a very short period of time is not going to realistically solve the problem of this pandemic."

A separate NHP study evaluating the durability of INO-4800 at 12 months after vaccination is currently under way. INO-4800 also has been selected by U.S. Operation Warp Speed for its COVID-19 non-human primate challenge study.

In May, the peer-reviewed journal Nature Communications published an INOVIO study ("Immunogenicity of a DNA vaccine candidate for COVID-19") showing that vaccination with INO-4800 generated robust binding and neutralizing antibody and T cell responses in mice and guinea pigs. The study was funded by a grant from the Coalition for Epidemic Preparedness Innovations (CEPI).

About INO-4800

INO-4800 is INOVIO's DNA vaccine candidate created to protect against the novel coronavirus SARS-CoV-2, which causes COVID-19. INO-4800 is currently in Phase 1 trials in the U.S. and a Phase 2/3 trial is planned for the summer. Interim Phase 1 results showed a favorable safety profile and strong immunogenicity, including antibody and T cell responses. The Phase 1 study recently expanded to include adults over the age of 65 with no age limit given the propensity for COVID-19 to severely impact the health of older people. INO-4800 also is in Phase 1/2 trials for COVID-19 in South Korea and China.

In animal studies, INO-4800 has demonstrated robust and durable T cell and B cell acute and memory responses in a non-human primate challenge study showing protective immune responses in both nasal passages and lungs. INO-4800 also was selected by U.S. Operation Warp Speed for its COVID-19 non-human primate challenge study.

INO-4800 was designed using INOVIO's proprietary DNA medicine platform rapidly after the publication of the genetic sequence of SARS-CoV-2. 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 need to be frozen in transport of storage, which are important factors when implementing mass immunizations.