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

INOVIO Pharmaceuticals, Inc.

2020/7/31 16:46

PR84972

 

PLYMOUTH MEETING, Pa., July 30, 2020 /PRNewswire=KYODO JBN/ --

 

- 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

 

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 (

https://c212.net/c/link/?t=0&l=en&o=2872107-1&h=3520401550&u=https%3A%2F%2Fwww.biorxiv.org%2Fcontent%2F10.1101%2F2020.07.28.225649v1&a=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.

 

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

U.S. Department of Defense. 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

intramuscularly or intradermally using INOVIO's proprietary hand-held smart

device called CELLECTRA(R). 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 ensures 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.

 

About INOVIO

 

INOVIO is a biotechnology company focused on rapidly bringing to market

precisely designed DNA medicines to treat and protect people from infectious

diseases, cancer, and diseases associated with HPV. INOVIO is the first and

only company to have clinically demonstrated that a DNA medicine can be

delivered directly into cells in the body via a proprietary smart device to

produce a robust and tolerable immune response. Specifically, INOVIO's lead

candidate VGX-3100, currently in Phase 3 trials for precancerous cervical

dysplasia, destroyed and cleared high-risk HPV 16 and 18 in a Phase 2b clinical

trial. High-risk HPV is responsible for 70% of cervical cancer, 91% of anal

cancer, and 69% of vulvar cancer. Also in development are programs targeting

HPV-related cancers and a rare HPV-related disease, recurrent respiratory

papillomatosis (RRP); non-HPV-related cancers glioblastoma multiforme (GBM) and

prostate cancer; as well as externally funded infectious disease DNA vaccine

development programs in Zika, Lassa fever, Ebola, HIV, and coronaviruses

associated with MERS and COVID-19 diseases. Partners and collaborators include

Advaccine, ApolloBio Corporation, AstraZeneca, The Bill & Melinda Gates

Foundation, Coalition for Epidemic Preparedness Innovations (CEPI), Defense

Advanced Research Projects Agency (DARPA)/Joint Program Executive Office for

Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND)/Department

of Defense (DOD), GeneOne Life Science/VGXI, HIV Vaccines Trial Network,

International Vaccine Institute (IVI), Medical CBRN Defense Consortium (MCDC),

National Cancer Institute, National Institutes of Health, National Institute of

Allergy and Infectious Diseases, Ology Bioservices, the Parker Institute for

Cancer Immunotherapy, Plumbline Life Sciences, Regeneron, Richter-Helm

BioLogics, Roche/Genentech, University of Pennsylvania, Walter Reed Army

Institute of Research, and The Wistar Institute. INOVIO also is a proud

recipient of 2020 Women on Boards "W" designation recognizing companies with

more than 20% women on their board of directors. For more information, visit

www.inovio.com.

 

CONTACTS:

Media: Jeff Richardson, 267-440-4211, jrichardson@inovio.com

Investors: Ben Matone, 484-362-0076, ben.matone@inovio.com

 

This press release contains certain forward-looking statements relating to our

business, including our plans to develop DNA medicines, our expectations

regarding our research and development programs, including the planned

initiation and conduct of preclinical studies and clinical trials, and the

availability and timing of data from those studies and trials. Actual events or

results may differ from the expectations set forth herein as a result of a

number of factors, including uncertainties inherent in pre-clinical studies,

clinical trials, product development programs and commercialization activities

and outcomes, the availability of funding to support continuing research and

studies in an effort to prove safety and efficacy of electroporation technology

as a delivery mechanism or develop viable DNA medicines, our ability to support

our pipeline of DNA medicine products, the ability of our collaborators to

attain development and commercial milestones for products we license and

product sales that will enable us to receive future payments and royalties, the

adequacy of our capital resources, the availability or potential availability

of alternative therapies or treatments for the conditions targeted by us or our

collaborators, including alternatives that may be more efficacious or cost

effective than any therapy or treatment that we and our collaborators hope to

develop, issues involving product liability, issues involving patents and

whether they or licenses to them will provide us with meaningful protection

from others using the covered technologies, whether such proprietary rights are

enforceable or defensible or infringe or allegedly infringe on rights of others

or can withstand claims of invalidity and whether we can finance or devote

other significant resources that may be necessary to prosecute, protect or

defend them, the level of corporate expenditures, assessments of our technology

by potential corporate or other partners or collaborators, capital market

conditions, the impact of government healthcare proposals and other factors set

forth in our Annual Report on Form 10-K for the year ended December 31, 2019,

our Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 and other

filings we make from time to time with the Securities and Exchange Commission.

There can be no assurance that any product candidate in our pipeline will be

successfully developed, manufactured or commercialized, that final results of

clinical trials will be supportive of regulatory approvals required to market

products, or that any of the forward-looking information provided herein will

be proven accurate. Forward-looking statements speak only as of the date of

this release, and we undertake no obligation to update or revise these

statements, except as may be required by law.

 

SOURCE INOVIO Pharmaceuticals, Inc.

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