- Long-lasting in vivo antibody production: DMAb levels
remained stable for 72 weeks in all participants (n=24) who have
reached that timepoint
- No anti-drug antibodies (ADA): no immune rejection of
the DMAbs was detected across ~1,000 blood samples, unlike
other gene-based antibody delivery approaches where ADA formation
has been a challenge
- Well-tolerated: most common side effects were mild,
temporary injection site reactions such as pain and redness; no
serious adverse events (SAEs) related to study drug
- Effective target binding: expressed DMAbs successfully
bound to the SARS-CoV-2 Spike protein receptor-binding domain
(RBD), confirming functional activity through week 72
PLYMOUTH
MEETING, Pa., March 13,
2025 /PRNewswire/ -- INOVIO (NASDAQ: INO), a
biotechnology company focused on developing and commercializing DNA
medicines to help treat and protect people from HPV-related
diseases, cancer, and infectious diseases, today announced
promising interim results from an ongoing Phase 1 proof-of-concept
trial evaluating DMAbs for COVID-19. In the trial, 100% (24/24) of
participants who have reached week 72 maintained biologically
relevant levels of DMAbs, confirming the durability of in
vivo antibody production. Notably, no participant developed
anti-drug antibodies (ADA), a common challenge observed in other
gene-based delivery platforms, such as adeno-associated virus (AAV)
mediated antibody expression. Additionally, the DMAbs were well
tolerated, with the most common side effects being mild, temporary
injection site reactions, such as pain and redness. The trial is
being led by The Wistar Institute in collaboration with INOVIO,
AstraZeneca, and clinical investigators at the Perelman School of
Medicine at the University of
Pennsylvania.
"This study provides the first clinical proof-of-concept that
DNA-encoded monoclonal antibodies can be durably and tolerably
expressed in humans," said David B.
Weiner, Ph.D, Executive Vice President of The Wistar
Institute and lead investigator for the study. "These findings
could represent a breakthrough as they demonstrate the potential of
DMAb technology to overcome traditional monoclonal antibody
production challenges, such as short half-life and anti-drug immune
responses, making it a promising platform for a broad range of
diseases. This technology has the potential to transform treatments
for infectious diseases, as well as cancer and metabolic disorders
by enabling long-term expression of therapeutic antibodies and
other proteins."
"One of the biggest hurdles for gene-based antibody delivery has
been the immune system's response to the vector or the antibody
itself, leading to anti-drug antibodies that can limit how long a
treatment will be effective," said Pablo
Tebas, M.D., a professor of Infectious Diseases at
Penn. "Our DNA-based approach has
demonstrated sustained antibody expression without generating ADA.
And because antibodies are remaining active for longer, our
approach may be a potentially promising long-term solution for
conditions requiring continuous therapeutic protein delivery."
INOVIO's Chief Scientific Officer, Laurent Humeau, Ph.D. added: "We believe these
data highlight the potential to apply our DNA Medicines technology
to deliver a broad spectrum of therapeutic proteins that could be
used to treat diseases with missing or defective proteins. We'd
like to thank our partners in advancing this important new
technology and we look forward to working with them to complete
this trial and on future research where we anticipate exploring
broader applications of our technology for long-term therapeutic
protein delivery."
A manuscript describing interim results from the trial has been
uploaded to Research Square for early dissemination and is under
peer review by a leading scientific journal for publication. The
consortium plans to present interim results from the trial at
upcoming scientific conferences in 2025.
About the Phase 1 Trial
The Phase 1 trial is the first
clinical study to report using synthetic DNA technology to enable
in vivo production of monoclonal antibodies directly from
muscle cells. Participants received an intramuscular (IM) injection
of synthetic DNA plasmids encoding AZD5396 and AZD8076 (derived
from AstraZeneca's cilgavimab and tixagevimab) delivered via
INOVIO's proprietary CELLECTRA 2000 electroporation (EP) device.
This delivery method temporarily increases cell permeability, which
is intended to facilitate efficient DNA uptake and enable sustained
antibody production.
The study is an open-label, single center, dose-escalation
trial. Enrollment began in May 2022
and was completed in March 2024. The
most common side effects observed were temporary local injection
site reactions, such as pain and erythema, associated with the
administration of the study product. There were three SAEs all of
which were considered unrelated to the study product.
Now in its third year, the trial is led by The Wistar Institute
in collaboration with INOVIO, AstraZeneca, and clinical
investigators at the University of
Pennsylvania. It is funded by the Coronavirus Aid, Relief,
and Economic Security Act (CARES Act) and the Defense Advanced
Research Projects Agency (DARPA).
About INOVIO's DNA Medicines Platform
INOVIO's DNA
medicines platform has two innovative components: precisely
designed DNA plasmids, delivered by INOVIO's proprietary
investigational medical device, CELLECTRA®. INOVIO uses proprietary
technology to design its DNA plasmids, which are small circular DNA
molecules that work like software that the body's cells can
download to produce specific proteins to target and fight disease.
INOVIO's proprietary CELLECTRA® delivery devices are designed to
optimally deliver its DNA medicines to the body's cells without
requiring chemical adjuvants or lipid nanoparticles and without the
risk of the anti-vector response historically seen with viral
vector platforms.
About INOVIO
INOVIO is a biotechnology company focused
on developing and commercializing DNA medicines to help treat and
protect people from HPV-related diseases, cancer, and infectious
diseases. INOVIO's technology optimizes the design and delivery of
innovative DNA medicines that teach the body to manufacture its own
disease-fighting tools. For more information, visit
www.inovio.com.
Forward-Looking Statements
This press release contains
certain forward-looking statements relating to INOVIO's business,
including the planned publication of data from clinical trials and
the potential benefits of INOVIO's DMAb technology platform. 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 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, 2023, our Quarterly
Report on Form 10-Q for the quarter ended September 30, 2024, 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 the 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.
This project was supported by the Joint Program Executive Office
for Chemical, Biological, Radiological and Nuclear Defense
(JPEO-CBRND) Joint Project Lead for Enabling Biotechnologies (JPL
CBRND EB) in collaboration with the Defense Health Agency (DHA)
COVID funding initiative for (Phase 1, dose-escalation trial of the
safety and pharmacokinetics of SARS-CoV-2 DNA-encoded monoclonal
antibodies (DMAb) in healthy adults, The Wistar Institute, Inovio
Pharmaceuticals, AstraZeneca, University of
Pennsylvania, HR0011-21-9-0001) for this effort.
The views expressed in this press release reflect the views of
the authors and do not necessarily reflect the position of the
Department of the Army, Department of Defense, nor the United
States Government. References to non-federal entities do not
constitute or imply Department of Defense or Army endorsement of
any company or organization.
Penn and Dr. Weiner have either
received, or may receive in the future, financial consideration
related to the licensing of certain Penn intellectual property to INOVIO. Dr. Weiner is
a member of the Scientific Advisory Board and Board of Directors
for INOVIO.
Contacts
Media: Jennie
Willson, (267) 429-8567, communications@inovio.com
Investors: Peter Vozzo - ICR
Healthcare, 443-213-0505, investor.relations@inovio.com
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