Everything that you should know about human trials of the COVID-19 vaccine INO-4800 by Inovio Pharmaceuticals (NASDAQ: INO).

Inovio Pharmaceuticals (NASDAQ: INO), an American biotechnology company from Plymouth Meeting, Pennsylvania, has initiated human trials of its DNA-based coronavirus vaccine INO-4800. The company announced the administration of the first dose in a phase 1 US-based clinical trial on April 6th 2020 and the completion of enrollment in the phase 1 trial on April 28th 2020 with all patients dosed .

The vaccine is intended to reduce morbidity and mortality associated with the pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes the coronavirus disease 2019 (COVID-19).

COVID-19 Vaccine Progress and Timeline January 2020: Inovio Partners with CEPI and Beijing Advaccine Biotechnology Co. February 2020: Inovio Demonstrated Immune Responses in Animal Models, Began to Design Human Trials March 2020: Bill and Melinda Gates Foundation and Department of Defense Funding April 2020: Inovio Initiated Human Trials of their Vaccine and Completed Enrollment in a US-Based Phase 1 Study May 2020: INO-4800 Demonstrates “Robust” Immunogenicity in Preclinical Animal Models

Inovio’s DNA-Based Vaccine Platform Results of a Phase 1 Study Evaluating the Safety and Efficacy of their MERS Vaccine



COVID-19 Vaccine Progress and Timeline

January 2020: Inovio Partners with CEPI and Beijing Advaccine Biotechnology Co.

During a meeting with the US Coronavirus Task Force on Tuesday March 2nd at the White House, Inovio President and CEO Dr. J. Joseph Kim stated, “Inovio is the leader in coronavirus vaccine development and the only company with a Phase 2 vaccine for a related coronavirus that causes Middle East Respiratory Syndrome (MERS).”

“Using our modern DNA medicines platform, we designed our DNA vaccine INO-4800 in three hours after the publication of the genetic sequence of the novel coronavirus that causes COVID-19.”

“We immediately began preclinical testing and small-scale manufacture and have already shared robust preclinical data with our public and private partners. We plan to begin human clinical trials in the U.S. in April and soon thereafter in China and South Korea, where the outbreak is impacting the most people.”

“We plan on delivering one million doses by year end with existing resources and capacity. However, we will need additional resources to scale up to make enough doses to help protect Americans from COVID-19 as well as to lead global efforts to curtail this virus,” continued Dr. Kim.

On January 23rd, 2020, the Coalition for Epidemic Preparedness Innovations (CEPI) issued Inovio a grant of up to $9 million to fund preclinical and clinical development of INO-4800.

CEPI CEO Richard Hatchett stated, “Given the rapid global spread of the 2019-nCoV virus the world needs to act quickly and in unity to tackle this disease. Our intention with this work is to leverage our work with Inovio on the MERS coronavirus and rapid response platform to speed up vaccine development.”

Dr. Kim responded, “We’re extremely honored to expand our partnership with CEPI to tackle this new threat to global public health. Our DNA medicine platform represents the best modern day approach to combatting emerging pandemics. We have already demonstrated positive clinical outcomes with our vaccine against MERS-CoV, another coronavirus.”

“Importantly, following the Zika viral infection outbreak, Inovio and our partners developed a vaccine that went from bench to human testing in just seven months – the fastest vaccine development on record in recent decades. We believe we can further improve upon this accelerated timeline to meet the current challenge of the emerging Chinese coronavirus 2019-nCoV.”

On January 30th, 2020, Inovio announced that it would develop INO-4800 in collaboration with China-based Beijing Advaccine Biotechnology Co., with the goal of expediting the testing of INO-4800 and progress towards human trials.

Dr. Kim stated, “Our collaboration with Beijing Advaccine and its Founder, Emeritus Professor Bin Wang from the prestigious Fudan University and China’s premier DNA vaccine expert, will tremendously accelerate our coronavirus vaccine INO-4800 development in China because of its expertise and experience with regulatory authorities and clinical trial management.”

“This collaboration allows us to enter China and deliver our vaccine into the areas where they need it most as soon as possible. Our shared goal is to utilize both company’s expertise in developing vaccines for emerging infectious diseases and hopefully achieve an accelerated regulatory approval for INO-4800.”

February 2020: Inovio Demonstrated Immune Responses in Animal Models, Began to Design Human Trials

In February, Inovio Pharmaceuticals demonstrated immune responses to their vaccine in animal models and began to design human clinical trials of their SARS-CoV-2 vaccine.

March 2020: Bill and Melinda Gates Foundation and Department of Defense Funding

On March 12th, 2020, Inovio announced that it received a $5 million grant from the Bill and Melinda Gates Foundation to support the testing and production of its “CELLECTRA 3PSP” device, which is used during the delivery of its vaccine into the muscles or skin and will be important for the initiation of human trials of the vaccine.

Dr. Kim stated, “INOVIO is grateful to the Bill & Melinda Gates Foundation for their continued investment in INOVIO’s DNA medicines platform and for their support for DNA vaccines to potentially protect those at risk globally given the current COVID-19 outbreak. Our team of vaccine experts are working around the clock to advance INO-4800 and we look forward to attracting additional partnerships to expedite its development to meet this urgent global health need.”

On March 24, 2020 Inovio Pharmaceuticals announced that Florida-based Ology Bioservices Inc. was awarded an $11.9 million contract by the Department of Defense (DoD) to support the rapid and large-scale manufacture of the DNA-based coronavirus vaccine INO-4800.

President and CEO of Ology Bioservices Peter H. Khoury, Ph.D., stated, “We are excited to be working with the Department of Defense and Inovio to rapidly respond to this crisis. The Advanced Development and Manufacturing Facility operated by Ology Bioservices was designed to respond to just such emergencies as we are now experiencing, and we are proud to be part of this effort to protect the U.S. warfighter and the nation.”

Dr. Kim stated, “Along with advancing INO-4800 through clinical studies as rapidly as possible, Inovio’s goal is to scale up the manufacturing of this vaccine for future studies and for potential emergency use, if appropriate. Powered by the U.S. Department of Defense support, Inovio is pleased to partner with Ology to enable rapid response manufacture of INO-4800 especially for the nation’s warfighters and other military personnel.”

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“This DOD-funded partnership is a testament to the importance and strength of public-private partnerships in meeting the challenges the world faces with the COVID-19 outbreak. This partnership increases Inovio’s manufacturing capabilities for our COVID vaccine and establishes an additional DNA vaccine manufacturing facility to protect the U.S. military against current and future disease outbreaks,” Dr. Kim continued.

Joint Program Executive Officer for Chemical, Biological, Radiological and Nuclear Defense Douglas Bryce stated, “Given the current global health crisis, prophylaxis/vaccine development is critical to defend against the coronavirus disease 2019. We need several approaches to ensure we have a quick solution, and the medical countermeasures Advanced Development and Manufacturing Facility is poised to contribute to the race for a vaccine in coordination with our interagency partners like Health and Human Services, along with our partners in industry and academia.”

Joint Project Lead CBRN Defense Enabling Biotechnologies Dr. Matthew Hepburn, M.D., stated, “We are sincerely optimistic about the partnership between Inovio and Ology Bioservices, in order to make doses of a vaccine that could potentially protect our military personnel. It is urgently needed.”

During March, Inovio also finalized the designs of human clinical trials evaluating the safety and efficacy of INO-4800 and prepared necessary doses.

April 2020: Inovio Initiated Human Trials of their Vaccine and Completed Enrollment in a US-Based Phase 1 Study

On April 6th, 2020, Inovio announced the initiation of a phase 1 clinical trial of its SARS-CoV-2 vaccine in healthy volunteers in the United States, with the first dosage planned for administration on the same day. This news follows the acceptance of their Investigational New Drug (IND) Application for INO-4800 by the Food and Drug Administration (FDA).

Up to 40 healthy volunteers at the Perelman School of Medicine in Philadelphia, Pennsylvania, and the Center for Pharmaceutical Research in Kansas City, Missouri, will be enrolled in the phase 1 study. The participants will receive two doses of the vaccine, the second one month after the first. Doses have already been delivered to the study locations.

The results of the trial are anticipated to be available by “late summer” and provide insight into the safety and efficacy of the vaccine. The phase 1 study follows preclinical studies of the vaccine in multiple animal models which demonstrated “promising immune responses.” Additional preclinical trials including challenge studies, which involve the deliberate exposure of vaccine recipients to SARS-CoV-2, will “continue in parallel” with the human trials, according to Inovio.

After receiving data from the phase 1 trial, the company intends to advance their vaccine candidate to phase 2 trials “as rapidly as possible.”

Dr. Kim stated, “This is a significant step forward in the global fight against COVID-19. Without a new safe and effective vaccine, the COVID-19 pandemic is likely to continue to threaten lives and livelihoods. It also demonstrates the power of our DNA medicines platform to rapidly develop and advance a vaccine for COVID-19 into Phase 1 clinical testing.”

“Our dedicated team of staff, partners and funders have been mobilized since the genetic sequence of the virus became available in early January and continues to work around the clock to ensure that we are rapidly advancing INO-4800 through this Phase 1 study towards planned efficacy trials,” Dr. Kim continued.

CEO of the Coalition for Epidemic Preparedness Innovations (CEPI) Richard Hatchett stated, “This development is an important step forward in the world’s search for a COVID-19 vaccine. INOVIO’s DNA vaccine platform was one of the first technologies selected by CEPI to develop a vaccine candidate against COVID-19. We are pleased to see the rapid advancement of their vaccine candidate into clinical safety testing.”

“Producing a COVID-19 vaccine within the next 12 to 18 months is not only a scientific challenge; it will also require new levels of collaboration and investment across industry and government. There is still a long road ahead before we have a safe, effective, and globally accessible vaccine ready for broader use, but today we have reached an important milestone on that journey,” Mr. Hatchett continued.

Senior Vice President of Regulatory Affairs at Inovio Dr. Ami Shah Brown stated, “Development and manufacture of a new vaccine with preclinical data to support a first-in-human trial in ten weeks from funding is a major milestone for INOVIO and our collaborators.”

Infectious disease specialist and professor of Medicine at the Hospital of the University of Pennsylvania and Principal Investigator of the study Dr. Pablo Tebas, MD, stated, “We anticipate rapid enrollment of this initial study. There has been tremendous interest in this vaccine among people who want to do what they can to help protect the greater public from this pandemic as soon as possible.”

Director of the Wistar Institute’s Vaccine and Immunotherapy Center and Executive Vice President of the Institute Dr. David B. Weiner stated, “INOVIO’s leadership and the team’s experience combined with the consistency of this DNA technology for clinical translation continue to be a major asset for the program.”

On April 16th, 2020, Inovio announced that it has received a $6.9 million grant from the CEPI to collaborate with the International Vaccine Institute (IVI) and the Korea National Institute of Health (KNIH) to perform a phase 1/2 clinical trial of INO-4800 in South Korea. The study will be conducted in parallel to the phase 1 clinical trial currently underway in the United States.

Director General of IVI Dr. Jerome H. Kim stated, “Vaccines are the long-term solution to controlling the COVID-19 pandemic. The rapid global response to developing vaccine candidates has been a profound demonstration of governments, industry, and the scientific community coming together to confront a common crisis, and we’re looking forward to accelerating one of those candidates through clinical testing.”

“IVI has achieved promising trial results with INOVIO’s DNA vaccine platform in the past, and we’re pleased to partner again to test the safety and immunogenicity of an urgently needed COVID-19 vaccine,” Dr. Jerome Kim continued.

President and CEO of Inovio Dr. J. Joseph Kim stated, “Developing a safe and effective COVID-19 vaccine is a global imperative, and we’re pleased to partner with IVI and KNIH to test INO-4800 in South Korea. Our DNA vaccine platform was one of the first technologies to receive support from CEPI to accelerate a COVID-19 vaccine, and IVI conducting safety and efficacy trials in South Korea is a crucial step forward in evaluating this vaccine.”

CEO of CEPI Dr. Richard Hatchett stated, “Developing a safe and effective vaccine and ensuring its global supply is our best exit strategy from the COVID-19 pandemic. CEPI is pleased to work with INOVIO and IVI in this critical next stage of testing.”

On April 28th, 2020, Inovio announced the completion of enrollment in the US-based phase 1 study of its coronavirus vaccine INO-4800 with all 40 healthy volunteers in the trial having received their first dose of the vaccine. According to Inovio, data on the safety of the vaccine and “interim immune responses” are expected in late June.

Dr. Kim stated, “We are extremely grateful to the volunteers in Philadelphia and Kansas City who have stepped forward in the midst of this deadly pandemic to help advance our promising DNA vaccine against COVID-19. Without these volunteers, we would not be able to advance the clinical study of INO-4800 at record speed and potentially provide INO-4800 as a viable vaccine against the global COVID-19 pandemic.”

According to the press release, INO-4800 has produced “promising immune responses” against the SARS-CoV-2 virus in multiple animal models, and the company is “on track” to deliver one million doses of the vaccine by the end of 2020.

Dr. Pablo Tebas, M.D., an infectious disease specialist and Professor of Medicine at the Hospital of the University of Pennsylvania, and the Lead Principal Investigator of the phase 1 clinical trial stated, “We anticipated rapid enrollment of this study and the response at both our Philadelphia and Kansas City study sites exceeded all expectations. We are profoundly inspired by this level of volunteerism for the greater good as well as grateful to our dedicated team of health care professionals for their tireless dedication to this worldwide effort.”

On April 30th, 2020, Inovio announced that German contract manufacturer Richter-Helm BioLogics GmbH & Co. KG would support the large-scale production of INO-4800 in an agreement partially funded by the CEPI. Richter-Helm BioLogics has been manufacturing Inovio’s drug candidate VGX-3100 scale since 2014 and is able to support commercial-scale production.

Dr. Kim stated, “We are grateful to CEPI for its continued generous funding and pleased to expand our work with Richter-Helm BioLogics to support large-scale manufacturing capacity for INO-4800. Richter-Helm has deep experience working with our optimized DNA plasmids, which are the building blocks of our DNA vaccines, and have consistently produced DNA medicines of the highest quality under stringent GMP standards.”

Managing Director of Richter-Helm BioLogics Dr. Kai Pohlmeyer stated, “Richter-Helm BioLogics has a strong, long-standing relationship with INOVIO and is a leading manufacturer of DNA plasmids. We will mobilize all our resources to ensure sufficient supply of late-stage clinical and commercial batches of INO-4800 and contribute to the fight against the deadly COVID-19 pandemic.”

Vice President of Biological Manufacturing and Clinical Supply Management at Inovio Dr. Robert Juba stated, “Having a trusted and proven partner with extensive experience manufacturing INOVIO’s DNA medicines is critical as we scale up our INO-4800 production. We look forward to continue to work closely together in our efforts to reduce the worldwide impact of COVID-19.”

May 2020: INO-4800 Demonstrates “Robust” Immunogenicity in Preclinical Animal Models

According to a publication the in journal Nature Communications, INO-4800 induced “robust” neutralizing antibody and T cell responses against the SARS-CoV-2 virus in preclinical animal models including guinea pigs and mice.

The data, published on May 20th, indicate that administration of the vaccine could protect against infection by the coronavirus, importantly promoting an immune response within the lungs that could prevent the development of life-threatening lung pathology.

Inovio’s DNA-Based Vaccine Platform

Inovio’s DNA-based vaccine platform is centered around speed of manufacturing, stability during transport and storage, and efficacy for inducing a robust immune response.

INO-4800 consists of small circles of engineered DNA that can be directly injected into cells through the controlled use of electricity, which creates temporary pores in the membranes of target cells and allows the double-stranded DNA circles contained within the vaccine to enter cells, alter their activity, and eventually lead to an immune response.

Since Inovio’s formulation is composed only of highly purified DNA, water, and salt, it avoids potential toxicity and can be manufactured relatively quickly and stored and transported without freezing.

Results of a Phase 1 Study Evaluating the Safety and Efficacy of their MERS Vaccine

During the epidemic of the Middle East Respiratory Syndrome (MERS), a coronavirus related to the virus that causes COVID-19, Inovio was the first biotechnology company to test a vaccine against the MERS virus (INO-4700) in human trials. The company plans to further evaluate INO-4700 in a Phase 2 clinical trial in the Middle East, where the majority of MERS cases have occurred.

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The results of a Phase 1 clinical trial evaluating the immunogenicity, safety, and tolerability of the MERS coronavirus vaccine GLS-5300 (INO-4700), published in the journal Lancet Infectious Diseases, demonstrated that their DNA-based vaccine technology is well-tolerated and capable of inducing an antiviral immune response.

After two vaccinations, 47 of 66 (71%) study participants showed evidence of a T-cell response. 44 of 58 (76%) participants demonstrated a T-cell response after three vaccinations. Seroconversion was detected by S1-ELISA in 59 of 69 (86%) and 61 of 65 (94%) participants after two and three vaccinations, respectively, and 34 of 68 (50%) individuals were found to bear neutralizing antibodies.

No serious adverse events were associated with the use of the MERS coronavirus vaccine. The authors stated that the antibody and cellular immune responses associated with the vaccine were durable and similar to those of patients that recovered naturally from infection by the MERS coronavirus.

Modjarrad K, Roberts CC, Mills KT, et al. (2019) Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial. Lancet Infectious Diseases, 19(9), P1013-1022. DOI: https://doi.org/10.1016/S1473-3099(19)30266-X











