INO-4800 COVID-19 Vaccine Description
INO-4800 is a DNA vaccine candidate matched to the novel coronavirus SARS-CoV-2, which causes the COVID-19 disease in humans.
INOVIO's INO-4800 is the only nucleic-acid-based vaccine stable at room temperature for more than a year and does not require frozen in transport or for years of storage, which are important factors when implementing mass immunizations to battle the current pandemic, says INOVIO.
The INO-4800 vaccine contains the plasmid pGX9501, which encodes for the entire length of the Spike glycoprotein of SARS-CoV-2.
Inovio's proprietary platform hand-held smart device called CELLECTRA® leads the way forward for activation immunotherapy. CELLECTRA uses a brief electrical pulse to open small pores in the cell reversibly to allow the plasmids to enter.
This one-of-a-kind platform delivers optimized DNA into cells, translated into proteins that activate an individual's immune system to generate a robust, targeted T cell and antibody response.
Once inside the cell, the plasmids begin replicating, strengthening the body's own natural response mechanisms.
INOVIO's DNA medicine platform's advantages are how fast DNA medicines can be designed and manufactured, the stability of the products that do not require freezing in storage and transport, and the robust immune response, safety profile, and tolerability that have been demonstrated in clinical trials.
Inovio aims to significantly expand the therapeutic range of monoclonal antibodies with its DNA-encoded monoclonal antibody technology. With dMAb, Inovio encodes DNA to express a monoclonal antibody. Injection of the DNA plasmid into a patient generates robust in vivo monoclonal antibody production.
This approach has the potential to generate in vivo production of therapeutic antibodies. Inovio's DNA medicines are not interfering with or changing in any way an individual's own DNA.
DNA medicines are composed of optimized DNA plasmids, which are small circles of double-stranded DNA synthesized or reorganized by a computer sequencing technology and designed to produce a specific immune response in the body. INOVIO states, 'DNA medicines do not interfere with or change in any way an individual's own DNA.'
INO-4800 COVID-19 Vaccine History
Published in Nature Communications on May 20, 2020, a new report focuses on immune studies in animals, which show induction of functional antibody responses and T-cell responses following immunization. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.
In addition to positive interim Phase 1 data published on June 30, 2020, INO-4800 has been shown to protect mice in SARS-CoV-2 viral challenge studies, where vaccination with INO-4800 prevented viral replication lungs of animals challenged with SARS-CoV-2.
On July 29, 2020, bioRxiv published a non-peer-reviewed study that showed 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 was challenged with the live virus 13-weeks after the second dose (study week 17).
"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.
On October 8, 2020, npj Vaccines published an article titled "Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein." Researchers at the Commonwealth Scientific and Industrial Research Organization (CSIRO), Australia's national science research agency, and INOVIO reported that INO-4800 vaccination in a preclinical model was able to neutralize SARS-CoV-2 viruses with 'D614G' mutation (Aspartate-to-Glycine change at position 614) of the spike protein, which has become the dominant variant in the global COVID-19 pandemic.
Furthermore, INO-4800 is currently being tested in a ferret challenge model and NHP challenge studies as part of the US government's Operation Warp Speed.
On November 14, 2020, the Company stated the planned Phase 2/3 clinical trial, called INNOVATE, is a randomized, blinded, placebo-controlled safety and efficacy trial of INO-4800 to be conducted in adults in the U.S. The INNOVATE trial will be funded by the U.S. Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense in coordination with the Office of the Assistant Secretary of Defense for Health Affairs and the Defense Health Agency.
INOVIO's President & CEO, Dr. J. Joseph Kim, announced on December 3, 2020, "Our partnership with Kaneka Eurogentec, one of the world's largest and most experienced plasmid manufacturers, provides additional scale to our growing global manufacturing coalition. Kaneka Eurogentec will be a crucial member of INOVIO's global manufacturing consortium, supporting our plans to produce, manufacture, and scale our COVID-19 vaccine candidate, INO-4800."
The Lancet published a paper on December 23, 2020, that concluded 'INO-4800 demonstrated excellent safety and tolerability and was immunogenic in 100% (38/38) of the vaccinated subjects by eliciting either or both humoral or cellular immune responses.'
On December 23, 2020, the paper titled "Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: a preliminary report of an open-label, Phase 1 clinical trial" found that INO-4800 was immunogenic in all vaccinated subjects, effectively generating an immune response of humoral (including neutralizing antibodies) and/or cellular responses (both CD4 and CD8 T cells).
Additionally, Phase 1 clinical data found INO-4800 to have favorable safety and tolerability profile with no serious adverse events reported; only six Grade 1 adverse events (AEs) were observed, primarily minor injection site reactions. Notably, these only occurred on the day of the first or second dosing, and the AEs did not increase in frequency with the second administration.
INOVIO is a biotechnology company focused on rapidly bringing to market precisely designed DNA medicines to protect and treat people from infectious diseases. INOVIO's DNA medicines are transient and 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 consistent immune response, safety profile, and tolerability that have been observed in clinical trials with multiple products.
INO-4800 COVID-19 Vaccine Indication
INO-4800 is a DNA vaccine candidate designed to prevent novel coronavirus SARS-CoV-2 from infecting humans, which causes COVID-19 disease.
No pediatric or pregnancy vaccine efficacy has been disclosed.
INO-4800 COVID-19 Vaccine Dosage
The Phase 2 segment of the trial is designed to evaluate the safety, tolerability, and immunogenicity of INO-4800 in a 2-dose regimen (1.0 mg or 2.0 mg), in 3-to-1 randomization to receive either INO-4800 or placebo for each dose to confirm the more appropriate dose(s) for each of three age groups with high risks of infection (18-50 years, 51-64 years and 65 years and older) for the subsequent Phase 3 efficacy evaluation.
INO-4800 is the only nucleic-acid-based vaccine stable at room temperature for more than a year. It does not need to be frozen in the transport of storage, which is an important factor when implementing mass immunizations company.
INO-4800 COVID-19 Vaccine News
February 2, 2021 - Industry press release: High COVID-19 Vaccine Uptake Proving Critical for Achieving Individual and Population Immunity.
January 26, 2021 - Local media reported in documents filed with the Securities and Exchange Commission, Inovio stated it plans to use the $162 million in net proceeds from the stock sale primarily to advance the development of its clinical pipeline, including clinical development expenses relating to INO-4800, the company's Covid-19 vaccine candidate.
January 20, 2021 - INOVIO Pharmaceuticals, Inc. announced the pricing of an underwritten public offering of 17,700,000 shares of its common stock at a public offering. Gross proceeds to INOVIO from the offering are expected to be approximately $150.5 million, before deducting underwriting discounts and commissions and estimated offering expenses, but excluding any exercise of the underwriters' option.
January 4, 2021 - INOVIO and Advaccine Biopharmaceuticals Suzhou Co., Ltd. announced that they have entered into a collaboration and license agreement for COVID-19 DNA vaccine candidate INO-4800, which has the exclusive right to develop, manufacture and commercialize INO-4800 within Greater China, inclusive of Mainland China, Hong Kong, Macao, and Taiwan. Advaccine will license its plasmid manufacturing process for use with INO-4800 and other INOVIO pipeline product candidates to INOVIO with the right to sublicense to INOVIO's manufacturing partners. Additionally, Advaccine will provide its clinical data to INOVIO to support INOVIO's global INO-4800 regulatory filings. INOVIO will provide its INO-4800 clinical data for Advaccine to incorporate into its marketing applications in Greater China. Advaccine will make to INOVIO an upfront payment of $3.0 million and pay an aggregate of $108.0 million upon the achievement of specified development and sales-based milestones for INO-4800 in Greater China. INOVIO will be entitled to receive a royalty equal to a high single-digit percentage of annual net sales in each region within Greater China.
January 2021 - Inovio's Powering a New Decade of DNA Medicines January 2021' presentation.
December 24, 2020 - INOVIO announced the publication of peer-reviewed Phase 1 clinical data from the first cohort of 40 participants for its COVID-19 DNA vaccine candidate, INO-4800, in EClinicalMedicine, an open-access clinical journal published by The Lancet.
December 10, 2020 - INOVIO and Advaccine Biopharmaceuticals Suzhou Co., Ltd. announced the successful dosing of its first subject in its Phase 2 clinical trial for COVID-19 DNA vaccine candidate, INO-4800, in China. The Phase 2 clinical trial, which is expected to enroll by the end of this month fully, is being conducted in China independent of the INNOVATE Phase 2/3 clinical trial of INO-4800 being advanced in the USA enroll approximately 640 participants who are 18 years or older.
December 7, 2020 - INOVIO announced it had dosed its first subject in Phase 2 clinical trial evaluating DNA medicine INO-4800, as part of its Phase 2/3 clinical trial, called INNOVATE (INovio INO-4800 Vaccine Trial for Efficacy). The Phase 2 segment of the trial will enroll approximately 400 participants who are 18 years or older at up to 17 U.S. sites to evaluate safety and immunogenicity to confirm the dose(s) for the subsequent efficacy evaluation Phase 3 segment of the trial. INOVIO plans to fully enroll in the Phase trial by the end of December.
December 3, 2020 - INOVIO announced the execution of an agreement with Kaneka Eurogentec S.A., an affiliate of Kaneka Corporation, for Eurogentec to manufacture INOVIO's COVID-19 vaccine candidate INO-4800 at their industry-leading GMP plasmid production scales. Kaneka Eurogentec joins existing partners Thermo Fisher Scientific, Richter-Helm BioLogics, and Ology Biosciences in INOVIO's global manufacturing consortium.
November 16, 2020 - INOVIO announced that it had received clearance from the U.S. Food & Drug Administration (FDA) to proceed with the Phase 2 segment of its planned Phase 2/3 clinical trial for INO-4800, its COVID-19 vaccine candidate.
November 9, 2020 - INOVIO confirmed it has responded to the US FDA to address the questions related to the partial clinical hold on INOVIO's Investigational New Drug Application for the Phase 2/3 trial of its COVID-19 vaccine candidate INO-4800.
October 2, 2020 - Local media reported Inovio Pharmaceuticals had dropped its appeal of an injunction ruling in its dispute with a former contract manufacturer. "Inovio has decided to focus its efforts on winning the entire case at trial," said Jeff Richardson, a spokesman for the company.
September 28, 2020 - INOVIO announced that the U.S. FDA had notified the company it has additional questions about its planned Phase 2/3 trial of its COVID-19 vaccine candidate INO-4800, including its CELLECTRA® 2000 delivery device to be used in the study. Until the FDA's questions have been satisfactorily addressed, INOVIO's Investigational New Drug Application for the Phase 2/3 trial is on partial clinical hold. The company is actively working to address the FDA's questions. It plans to respond in October, after which the FDA will have up to 30 days to notify INOVIO of its decision as to whether the trial may proceed.
September 8, 2020 - INOVIO announced that Thermo Fisher Scientific had signed a letter of intent to manufacture INOVIO's DNA COVID-19 vaccine candidate INO-4800. With its consortium of third-party manufacturers, INOVIO plans to have 100 million doses of INO-4800 manufactured in 2021, subject to FDA approval of INO-4800 for use as a COVID-19 vaccine. Thermo Fisher Scientific will join existing partners Richter-Helm BioLogics and Ology Biosciences in INOVIO's global manufacturing consortium.
July 30, 2020 - Published on the non-peer-reviewed online preprint site bioRxiv, 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 the 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 vaccine protection in non-human primates was reported from memory immune responses. Previously reported monkey vaccine challenge studies were conducted near their peak immune responses (1-4 weeks from their last vaccination).
July 15, 2020 - Seoul National University Hospital said that it had administered the first dose of INO-4800, Inovio's Covid-19 vaccine, to a patient in his 40s.
July 10, 2020 - Inovio Pharmaceuticals Inc. could be embroiled in a prolonged legal battle with its Blue Bell, Pennsylvania-headquartered subcontractor VGXI, Inc after the subcontractor, sued the company.
June 30, 2020 - INOVIO announced positive interim clinical data of its vaccine candidate against novel coronavirus (SARS-CoV-2) from the first two Phase 1 clinical trial cohorts. Also, INO-4800 has been selected to participate in a non-human primate challenge study as part of the U.S. government's Operation Warp Speed. 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.
June 23, 2020 - INOVIO announced it had received $71 million funding from the U.S. DoD to support the large-scale manufacture of the company's proprietary CELLECTRA® 3PSP smart device and the procurement of CELLECTRA® 2000 devices, which are used to deliver the INO-4800 vaccine candidate directly into the skin, where the vaccine prompts the body's immune system to drive a robust immune response.
June 4, 2020 - INOVIO and Seoul National University Hospital announced a partnership to start a Phase 1/2 clinical trial of INOVIO's COVID-19 vaccine INO-4800 in South Korea. The 2-stage trial of INO-4800, the first clinical study of the COVID-19 vaccine in Korea, will assess the candidate vaccine's safety, tolerability, and immunogenicity in 40 healthy adults aged 19-50 expands to enroll an additional 120 people aged 19-64 years.
June 3, 2020 - Inovio Pharmaceuticals, Inc. filed a complaint in the Court of Common Pleas of Montgomery County, Pennsylvania, seeking, among other requests for emergency relief, to compel VGXI, Inc. and GeneOne Life Science, Inc. (together, “VGXI”) to facilitate the transfer of manufacturing methods, using VGXI’s technology, under the parties’ existing supply agreement (the “Supply Agreement”).
May 20, 2020 - The Wistar Institute announced a study reporting the initial immunogenicity of a synthetic DNA vaccine for SARS-CoV-2 developed in collaboration with Inovio Pharmaceutical, Inc., and other scientists. The report, published in Nature Communications, focuses on immune studies in animals, which show the induction of functional antibody responses and T-cell responses following immunization. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.
May 11, 2020 - INOVIO's President and Chief Executive Officer Dr. J. Joseph Kim said U.S. Phase 1 clinical trial for COVID-19 vaccine candidate INO-4800 completed enrollment with 40 healthy volunteers; preliminary results expected in late June 2020. The Phase 2/3 efficacy trial for INO-4800 'to start this summer upon regulatory approval.'
April 30, 2020 - INOVIO announced it has agreed to expand its manufacturing partnership with the German contract manufacturer Richter-Helm BioLogics GmbH & Co. KG to support large-scale manufacturing of INOVIO's investigational DNA vaccine INO-4800, which currently is in Phase 1 clinical testing in the U.S. for COVID-19 and could potentially advance to Phase 2/3 efficacy trials this summer. The agreement is partly funded by an initial grant of $1.3 million from the Coalition for Epidemic Preparedness Innovations (CEPI), which brings CEPI's total support to date for developing INO-4800 to $17.2 million.
April 28, 2020 - INOVIO announced that its Phase 1 clinical trial for COVID-19 DNA vaccine INO-4800 is fully enrolled. All 40 healthy volunteers receive their first dose, with interim immune responses and safety results expected in late June 2020. The 40 healthy volunteers now enrolled at sites at the University of Pennsylvania, and a clinic in Kansas City, MO, will receive 2-doses of INO-4800, four weeks apart. The Phase 1 study is designed to assess the safety profile and immunogenicity of INO-4800 in support of advancing rapidly to a Phase 2/3 efficacy trial, which is planned to initiate this summer potentially.
April 16, 2020 - The International Vaccine Institute (IVI) announced that the Coalition for Epidemic Preparedness Innovations had granted $6.9 million funding to INOVIO to work with IVI and the Korea National Institute of Health (KNIH) for a Phase 1/2 clinical trial of INOVIO's COVID-19 vaccine candidate (INO-4800) in South Korea. IVI will conduct the trial parallel to INOVIO's Phase 1 INO-4800 study, currently underway in the US since April 6, 2020, with 40 healthy adults receiving the vaccine candidate and eventually expanding to older adults.
April 6, 2020 - INOVIO Pharmaceuticals, Inc. announced that the U.S. FDA had accepted its Investigational New Drug application for INO-4800, its DNA vaccine candidate designed to prevent COVID-19 infection, paving the way for Phase 1 clinical testing of INO-4800 in healthy volunteers beginning this week. The first dosing is planned for today.
March 24, 2020 - Ology Bioservices Inc. and Inovio Pharmaceuticals Inc. announced today that the US DOD had awarded Ology Bioservices with a contract valued at $11.9 million to manufacturing DNA vaccines such as (INO-4800) rapidly.
March 12, 2020 - INOVIO Pharmaceuticals, Inc. announced that it had received a new $5 million grant from the Bill & Melinda Gates Foundation to accelerate the testing and scale-up of CELLECTRA® 3PSP proprietary smart device for the intradermal delivery of INO-4800, a DNA vaccine for COVID-19 disease. Inovio said its Cellectra 3PSP device is a small, hand-held, and portable device that runs on AA batteries and can be used to inject a vaccine. It was originally developed using $8.1 million in funding from the medical arm of the U.S. Defense Threat Reduction Agency’s Medical CBRN Defense Consortium. Inovio reiterated that it expects to deliver 1 million doses of INO-4800 by year-end 2020.
March 3, 2020 - Inovio Pharmaceuticals, Inc. announced an accelerated timeline for developing its DNA vaccine INO-4800. "We plan to begin human clinical trials in the U.S. in April and soon thereafter in China and South Korea, where the outbreak impacts most people. We plan on delivering one million doses by year-end 2020 with existing resources and capacity."
January 30, 2020, Beijing Advaccine Biotechnology announced a collaboration with Inovio Pharmaceuticals, Inc. to advance the development in China of the INO-4800 vaccine candidate, which is targeted against the novel coronavirus named 2019-nCoV.
January 23, 2020, Inovio Pharmaceuticals, Inc. said in a press release that the Coalition for Epidemic Preparedness Innovations funding of $9 million would support Inovio's preclinical and clinical development through Phase 1 human testing of INO-4800, its new coronavirus vaccine candidate matched to the outbreak strain. Inovio's collaborators for this coronavirus vaccine development include the Wistar Institute, VGXI, a fully owned subsidiary of GeneOne Life Science, and Twist Bioscience.
INO-4800 COVID-19 Vaccine Clinical Trials
INOVIO has assembled a global coalition of collaborators, partners, and funders to rapidly advance the development of INO-4800. R&D collaborators to date include the Wistar Institute, the University of Pennsylvania, the University of Texas, Fudan University, and Laval University.
Clinical Trial NCT04642638: Phase 2/3 Randomized, Blinded, Placebo-Controlled Trial to Evaluate the Safety, Immunogenicity, and Efficacy of INO-4800, a Prophylactic Vaccine Against COVID-19 Disease, Administered Intradermally Followed by Electroporation in Healthy Seronegative Adults at High Risk of SARS-CoV-2 Exposure-Last Update Posted: January 12, 2021
This is a Phase 2/3, randomized, placebo-controlled, multi-center trial to evaluate the safety, immunogenicity, and efficacy of INO-4800 administered by intradermal (ID) injection followed by electroporation (EP) using CELLECTRA® 2000 device to prevent COVID-19 disease in participants at high risk of exposure to SARS-CoV-2.
The Phase 2 segment will evaluate immunogenicity and safety in approximately 400 participants at two dose levels across three age groups. Safety and immunogenicity information from the Phase 2 segment will be used to determine the dose level for the study's Phase 3 efficacy segment involving approximately 6178 participants.
Estimated Primary Completion Date: September 2022.
Clinical Trial ChiCTR2000040146: A Phase II, Randomized, Double-blinded, Placebo-controlled, Dose-finding Clinical trial to Evaluate the Safety and Immunogenicity of Different Doses of COVID-19 DNA vaccine INO-4800 Administered Intradermally Followed by Electroporation in 640 Healthy Adult and Elderly (18-85) Volunteers-- Last Update Posted: January 19, 2021
Clinical Trial NCT04336410: - Phase 1 Open-label Study to Evaluate the Safety, Tolerability, and Immunogenicity of INO-4800, a Prophylactic Vaccine Against SARS-CoV-2, Administered Intradermally Followed by Electroporation in Healthy -- the Last Update Posted: January 15, 2021
April 2020 - Human clinical trials begin with 40 healthy adult volunteers in Philadelphia, PA (University of Pennsylvania) and Kansas City, MO (at the Center for Pharmaceutical Research), where screening potential participants has already begun. This is an open-label trial to evaluate the safety, tolerability, and immunological profile of INO-4800 administered by intradermal injection followed by electroporation using CELLECTRA® 2000 device in healthy adult volunteers.
Each participant will receive 2-doses of INO-4800 four weeks apart, and the initial immune responses and safety data from the study are expected by late summer.
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, the INO-4800 regimen was deemed safe and well-tolerated with no serious adverse events; all reported adverse events were grade 1 in severity.
In a preclinical animal challenge study, INO-4800 provided complete protection against SARS-CoV-2 replication in the lungs in mice challenged with the virus.
Clinical Trial NCT04447781: - A Phase I/IIa, Dose-Ranging Trial to Evaluate Safety, Tolerability, and Immunogenicity of INO-4800, a Prophylactic Vaccine Against SARS-CoV-2, Administered Intradermally Followed by Electroporation in Healthy Volunteers--the Last Update Posted: August 19, 2020.
This is a phase I/IIa trial to evaluate the safety, tolerability, and immunological profile of INO-4800 administered by intradermal (ID) injection followed by electroporation (EP) CELLECTRA® 2000 device in 160 healthy adults aged 19 to 64 years in the Republic of Korea.
INO- 4800 contains the plasmid pGX9501, which encodes the Spike glycoprotein's full length of SARS-CoV-2.
This trial's primary objective is to evaluate the tolerability, safety, and immunogenicity of INO-4800 administered by ID injection followed by EP in healthy adults in Part A and Part B. Enrollment into Part A and Part B will proceed sequentially.