PLYMOUTH MEETING, Pa.,
Dec. 24, 2020 /PRNewswire/
-- INOVIO (NASDAQ:INO), a biotechnology company focused on
bringing to market precisely designed DNA medicines to treat and
protect people from infectious diseases and cancer, today 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.
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 a
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.
INO-4800, beyond being safe and tolerable, is stable at room
temperature for more than a year, at 37o C
(98.6o F) for more than a month, has a five-year
projected shelf life at normal refrigeration temperature [i.e., at
2-8o C / 35.6 – 46.4o F] and does not
need to be frozen during transport or storage – all critical
factors for timely global distribution in the fight against
COVID-19.
Dr. J. Joseph Kim, President and
CEO of INOVIO, said, "We are very pleased to share peer-reviewed
Phase 1 clinical data for INO-4800 published in The Lancet's
EClinicalMedicine, and are grateful for the support of all
participants and investigator staff involved in the clinical
trial."
Dr. Stanley Plotkin, Professor
Emeritus at The Wistar Institute, said, "INOVIO's DNA vaccine
appeared to be quite safe with few significant reactions but yet
induced both antibody and T cell responses to SARS-CoV-2."
Findings from the Phase 1 Clinical Trial
- The Phase 1 clinical trial of INO-4800 initially enrolled 40
healthy adult volunteers, ages 18 to 50, at two U.S. sites with
funding from the Coalition for Epidemic Preparedness Innovations
(CEPI).
- The participants were enrolled into 1.0 mg and 2.0 mg dose
cohorts; each participant received two doses of INO-4800 four weeks
apart. Each dose was administered by intradermal injection using
INOVIO's proprietary smart device CELLECTRA®.
- Thirty-nine subjects completed both doses. One subject in the
2.0 mg group discontinued trial participation prior to receiving
the second dose due to lack of transportation to the clinical site;
discontinuation was unrelated to the study or the dosing. One
subject was deemed to be seropositive at trial entry.
- The 1.0 mg and 2.0 mg dose group both demonstrated
seroconversion in 95% of the subjects, respectively, with 78%
demonstrating neutralizing antibodies in the 1.0 mg dose group and
84% demonstrating neutralizing antibodies in the 2.0 mg dose
group.
- Cellular (T cell) response were observed to multiple regions of
the spike protein including the RBD region. 74% had measurable
cellular responses at the 1.0 mg dose group and 100% of the
subjects in the 2.0 mg dose group demonstrated cellular
responses.
- Through week 8, no serious adverse events were reported. Only 6
related Grade 1 adverse events in 5 subjects were observed,
primarily mild injection site reactions (e.g., redness); none of
these increased in frequency with the second administration.
- All 38 subjects who were evaluable for immunogenicity had
balanced cellular and humoral immune responses following the second
dose of INO-4800.
- ClinicalTrials.gov identifier: NCT04336410.
INOVIO is currently conducting the Phase 2 segment of its
planned Phase 2/3 clinical trial for INO-4800, called INNOVATE
(INOVIO INO-4800 Vaccine Trial for
Efficacy). INNOVATE is a randomized, blinded,
placebo-controlled safety and efficacy trial of INO-4800 to be
conducted in adults in the U.S. It will be funded by the U.S.
Department of Defense (DoD) Joint Program Executive Office for
Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND)
in coordination with the Office of the Assistant Secretary of
Defense for Health Affairs (OASD(HA)) and the Defense Health Agency
(DHA).
The DoD has agreed to provide funding for both the Phase 2 and
Phase 3 segments of the INNOVATE clinical trial, in addition to the
$71 million of funding previously
announced in June 2020 for the
large-scale manufacture of the company's proprietary smart device
CELLECTRA® 3PSP and the procurement of
CELLECTRA® 2000 devices.
INOVIO also recently announced the first dosing of its first
subject in its Phase 2 clinical trial for INO-4800 in China, in collaboration with Advaccine. The
company is currently in Phase 1/2a trials for INO-4800 in
South Korea in partnership with
The International Vaccine Institute and the Korea National
Institute for Health.
About the INO-4800 "INNOVATE" Phase 2/3 Clinical
Trial
The lead Principal Investigator for the INNOVATE trial is Dr.
Pablo Tebas, Professor of Medicine
at the Hospital of the University of
Pennsylvania. The Phase 2 segment of the clinical trial is
designed to evaluate safety, tolerability and immunogenicity of
INO-4800 in a 2-dose regimen (1.0 mg or 2.0 mg), in a three-to-one
randomization to receive either INO-4800 or placebo for each dose,
to confirm the more appropriate dose(s) for each of three age
groups (18-50 years, 51-64 years and 65 years and older) for the
subsequent Phase 3 efficacy evaluation. The company intends to work
diligently to ensure diversity in enrollment, targeting specific
populations that are working or residing in environments with high
infection rates and/or areas where there is greater risk of
exposure to SARS-CoV-2, for whom exposure may be relatively
prolonged or for whom personal protective equipment (PPE) may be
inconsistently used, especially in confined settings.
In the Phase 3 segment of the clinical trial, INOVIO intends to
enroll healthy men and non-pregnant women 18 years and older, to
evaluate the efficacy of the proposed dose(s) based on the data
from the Phase 2 evaluation. Participants will be enrolled in
a one-to-one randomization to receive either INO-4800 or a placebo.
The Phase 3 segment will be case-driven with the final number of
enrollees to be determined by the incidence of COVID-19 during the
Phase 3 segment. The primary endpoint of the Phase 3 segment will
be virologically confirmed COVID-19 disease.
About INOVIO's Global Coalition Advancing INO-4800
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. INOVIO has partnered with Advaccine and the
International Vaccine Institute to conduct clinical trials of
INO-4800 in China and South Korea, respectively. INOVIO is also
assessing nonclinical efficacy of INO-4800 in several animal
challenge models with Public Health England (PHE) and Commonwealth
Scientific and Industrial Research Organization (CSIRO) in
Australia. INOVIO is working with
a team of contract manufacturers including Kaneka Eurogentec,
Thermo Fisher Scientific, Richter-Helm BioLogics, and Ology
Bioservices to manufacture INO-4800 on a commercial scale and is
seeking additional external funding and partnerships to further
scale up manufacturing capacities to satisfy the urgent global
demand for safe and effective vaccines. To date, the Coalition for
Epidemic Preparedness Innovations (CEPI), the Bill & Melinda
Gates Foundation, and the U.S. Department of Defense have
contributed significant funding to the advancement and
manufacturing of INO-4800.
About INO-4800
INO-4800 is INOVIO's DNA vaccine candidate against SARS-CoV-2,
the novel coronavirus that causes COVID-19. INOVIO has extensive
experience working with coronaviruses and was the first company to
initiate a Phase 2a trial for INO-4700, a DNA vaccine candidate for
a related coronavirus that causes Middle East Respiratory Syndrome
(MERS).
Composed of an optimized DNA plasmid, INO-4800 is delivered
directly into cells in the body via a proprietary smart device to
produce a robust, safe and tolerable immune response. INO-4800 is
the only nucleic-acid based vaccine that is stable at room
temperature for more than a year, at 37o C for more than
a month, has a five-year projected shelf life 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, 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®. 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 observed 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), HIV Vaccines Trial
Network, International Vaccine Institute (IVI), Kaneka Eurogentec,
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, Thermo Fisher Scientific, 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
and manufacture DNA medicines, our expectations regarding our
research and development programs, including the conduct of the
Phase 2/3 clinical trial of INO-4800, and our ability to
successfully manufacture and produce large quantities of our
product candidates if they receive regulatory approval. Actual
events or results may differ from the expectations set forth herein
as a result of a number of factors, including uncertainties
inherent in preclinical studies, clinical trials, product
development programs and commercialization activities and outcomes,
our ability to secure sufficient manufacturing capacity to mass
produce our product candidates, 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 September 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.
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SOURCE INOVIO Pharmaceuticals, Inc.