INO-4800 DNA Coronavirus Vaccine
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INO-4800 DNA 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 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, says INOVIO.
The INO-4800 vaccine contains the plasmid pGX9501, which encodes for the full length of the Spike glycoprotein of SARS-CoV-2.
Inovio's proprietary platform hand-held smart device called CELLECTRA® is leading 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, where it is 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, thereby strengthening the body's own natural response mechanisms.
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.
Inovio is aiming 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 that are 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.'
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 the 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 in the 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 as well as in NHP challenge studies as part of the US government's Operation Warp Speed.
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 DNA 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 vaccine efficacy has been disclosed.
INO-4800 DNA Vaccine Dosage
Participants will receive one ID injection of 1.0 milligram (mg) of INO-4800 followed by EP using the CELLECTRA® 2000 device per dosing visit. INO-4800 will be administered ID on Day 0 and Week #4. EP using the CELLECTRA® 2000 device will be administered following ID delivery of INO-4800 on Day 0 and Week #4.
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 the transport of storage, which is important factors when implementing mass immunizations, says the company.
INO-4800 DNA Vaccine Development News
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 has 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 has notified the company it has additional questions about the company's planned Phase 2/3 trial of its COVID-19 vaccine candidate INO-4800, including its CELLECTRA® 2000 delivery device to be used in the trial. 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 and 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 has 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 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 as previously reported monkey vaccine challenge studies were conducted at the time near their peak immune responses (1-4 weeks from their last vaccination).
July 15, 2020 - Seoul National University Hospital said that it has 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. In addition, 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 has 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 safety, tolerability, and immunogenicity of the candidate vaccine in 40 healthy adults aged 19-50 years, and will further expand 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 initial immunogenicity of a synthetic DNA vaccine for SARS-CoV-2 developed in collaboration with Inovio Pharmaceutical, Inc., and other scientists. Published in Nature Communications, the 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 the 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 entered into an agreement 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 being 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 the development of 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 with all 40 healthy volunteers receiving 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 potentially initiate this summer.
April 16, 2020 - The International Vaccine Institute (IVI) announced that the Coalition for Epidemic Preparedness Innovations has 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 in 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 has accepted the company's 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 has awarded Ology Bioservices with a contract valued at $11.9 million to work with Inovio on DNA technology transfer to rapidly manufacture DNA vaccines such as (INO-4800).
March 12, 2020 - INOVIO Pharmaceuticals, Inc. announced that it has 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 is impacting the 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 dollars will 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 DNA Vaccine Clinical Trial Information
ClinicalTrials.gov Identifier: NCT04336410 - Last Update Posted: September 21, 2020.
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 of 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, theINO-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 full protection against SARS-CoV-2 replication in the lungs in mice challenged with the virus
The Phase 2/3 efficacy trial for INO-4800 'to start this summer upon regulatory approval.'
ClinicalTrials.gov Identifier: NCT04447781 - 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) using the CELLECTRA® 2000 device in healthy adults aged 19 to 64 years in the Republic of Korea.
INO- 4800 contains the plasmid pGX9501, which encodes for the full length of the Spike glycoprotein of SARS-CoV-2.
The primary objective of this trial is to evaluate the tolerability, safety, and immunogenicity of INO-4800 administered by ID injection followed by EP in healthy adults in the Part A and Part B. Enrollment into Part A, and Part B will proceed sequentially.
Updated11/09/2020 - 21:15