PLYMOUTH MEETING, Pa.,
Jan. 15, 2019 /PRNewswire/
-- Inovio Pharmaceuticals, Inc. (NASDAQ: INO) announced today
the successful development of optimized DNA-encoded monoclonal
antibodies (dMAbs™) targeting the immune checkpoint molecule PD-1.
The breakthrough preclinical data demonstrated that a single
injection of synthetic designer dMAb versions of pembrolizumab
(KEYTRUDA®) or nivolumab (OPDIVO®) sequences
targeting PD-1 protein can be robustly redeveloped to be expressed
directly in vivo in mice for up to several months.
Furthermore, Inovio's proprietary sequence optimization of the
molecular design of these therapeutics resulted in significantly
improved expression compared to the original KEYTRUDA and OPDIVO
native sequences while maintaining identical binding
capabilities.
These published dMAb results demonstrate the potential of
advancing of a new generation of checkpoint inhibitors with
multiple benefits including: 1) simplifying the patient regimen for
checkpoint blockade therapy - converting 90-minute intravenous
infusions administered every three weeks with currently marketed
protein-based mAbs into a single local injection of dMAbs, 2)
possibly resulting in more consistency of expression in vivo
providing improved benefits for the patient, and 3) through simple
additional modifications and simplified dMAb combination
formulations, engender further improved functions rapidly providing
additional clinical benefit. The PD-1 dMAb results were published
in the recent edition of Oncotarget in an article entitled,
"Simplifying checkpoint inhibitor delivery through in vivo
generation of synthetic DNA-encoded monoclonal antibodies (dMAbs),"
by Inovio's collaborators at The Wistar Institute.
Dr. J. Joseph Kim, Inovio's
President and CEO, said, "We are rapidly pioneering a potentially
breakthrough class of medicines – dMAbs – produced directly in the
human body. PD-1/PD-L1 targeting checkpoint inhibitor mAb products
represent some of the most important advancements in
immuno-oncology today. We look forward to advancing our PD-1
targeting dMAb products as potentially better versions of
blockbusters KEYTRUDA and OPDIVO – with whole new sets of IP behind
them – through corporate partnerships, external funding and
collaborations."
Inovio recently initiated the first human study of its dMAb
technology. In addition to demonstrating safety and tolerability,
the Phase 1 dose-escalation study of INO-A002 (for preventing or
treating Zika virus infection) will assess initially the level of
the body's production of the Zika dMAb over several doses. Using
direct delivery into the body, the genetic instructions provided by
the designed synthetic dMAbs delivered locally by the
CELLECTRA® platform, instruct the body's cells to become
a customized patient specific factory which manufactures their own
therapeutic antibody products, enabling a major leap in antibody
technology.
Traditional monoclonal antibodies represent the largest segment
of pharmaceutical markets today, accounting for more than
$100 billion in pharmaceutical sales
each year, with treatments spanning cancer, infectious diseases,
inflammation and cardiovascular diseases. With its synthetic design
and in-patient production, dMAb products represent a disruptive
entrant to this important class of pharmaceuticals. Inovio and its
collaborators have already received over $60
million in non-dilutive grant funding to advance its dMAb
platform in the last few years. There is a significant interest in
dMAb's as a disruptive entrant to a highly profitable overall mAb
market as well as its unique applicability for rapid responses
against emerging global infectious disease threats and for
addressing critical vaccine limitations.
In the past few years Inovio and collaborators have published
multiple impactful papers consistently demonstrating potent
preclinical data from the dMAb platform, with therapeutic displays
spanning protection against deadly infections to eliminating
cancers and lowering life-threatening levels of cholesterol. In
this regard dMAbs offer unique features for rapid production,
deployment and advancement of new mAb-like biologics, with much
increased efficiency. In addition, the dMAb's constructed
in vivo likely have additional advantages such as expression
profiles, as well as patient specific glycosylation, and unlike
traditional mAb approaches, there is no reliance on in vivo tissue
culture and costly or time consuming production systems.
Inovio has previously published successful animal testing of dMAbs
targeting the immune checkpoint molecule CTLA-4 (Duperret et al.
Cancer Res. 2018). The preclinical study demonstrated that
highly optimized dMAbs targeting mouse CTLA-4 protein can be
robustly expressed in vivo, and can drive therapeutic
anti-tumor immune responses in established disease models.
Importantly, Inovio's dMAb constructs for anti-human CTLA-4
antibodies ipilimumab and tremelimumab, achieved high levels and
prolonged expression for months from a single delivery. Inovio has
multiple patents awarded in this space including the first two
patents from the U.S. patent office covering this specific dMAb
technology granted last quarter.
KEYTRUDA® is a registered trademark of Merck & Co. (MRK);
OPDIVO® is a registered trademark of Bristol-Myers Squibb Company
(BMY).
About Inovio's DNA-based Monoclonal Antibody
Platform
Traditional monoclonal antibodies are manufactured outside the
body in bioreactors, typically requiring costly large-scale
manufacturing facility development and laborious production.
Inovio's disruptive dMAb technology has the potential to overcome
these limitations by virtue of their simplified design using novel
plasmid vectors and unique formulations allowing for rapidity of
development, product stability, ease of manufacturing and
deployability, ultimately all resulting in increases in cost
effectiveness, providing potential new avenues for treating a range
of diseases. These dMAbs are delivered directly into cells of the
body using CELLECTRA® and the encoded monoclonal antibody is then
produced by the locally transfected cells. Previously published
studies show that a single administration of a highly optimized
DNA-encoded monoclonal antibody targeting Ebola virus produced a
high level of expression of the antibody in the bloodstream of mice
that was protective against lethal animal challenge; Additional
studies similarly reported data showing that dMAb products against
flu, chikungunya and dengue protected animals against lethal
challenge. In addition the team has reported delivery of dMAbs that
impact prostate as well as breast and ovarian cancers in
animals.
About Inovio Pharmaceuticals, Inc.
Inovio is a late-stage biotechnology company focused on the
discovery, development, and commercialization of DNA
immunotherapies that transform the treatment of cancer and
infectious diseases. Inovio's proprietary platform technology
applies next-generation antigen sequencing and DNA delivery to
activate potent immune responses to targeted diseases. The
technology functions exclusively in vivo, and has been demonstrated
to consistently activate robust and fully functional T cell and
antibody responses against targeted cancers and pathogens.
Inovio is the only immunotherapy company that has reported
generating T cells whose killing capacity correlates with relevant
clinical outcomes. Inovio's most advanced clinical program,
VGX-3100, is in Phase 3 for the treatment of HPV-related cervical
pre-cancer. Also in development are Phase 2 immuno-oncology
programs targeting head and neck cancer, bladder cancer, and
glioblastoma, as well as platform development programs for
hepatitis B, Zika, Ebola, MERS, and HIV. Partners and
collaborators include MedImmune, Regeneron, Roche/Genentech,
ApolloBio Corporation, The Bill & Melinda Gates Foundation, The
Wistar Institute, University of
Pennsylvania, Parker Institute for Cancer Immunotherapy,
CEPI, DARPA, GeneOne Life Science, Plumbline Life Sciences,
Drexel University, NIH, HIV Vaccines
Trial Network, National Cancer Institute, U.S. Military HIV
Research Program, and Laval University.
For more information, visit www.inovio.com.
This press release contains certain forward-looking
statements relating to our business, including our plans to develop
electroporation-based drug and gene delivery technologies and DNA
vaccines, our expectations regarding our research and development
programs, including the planned initiation and conduct of clinical
trials and the availability and timing of data from those 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 and
product development programs, 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 vaccines, our ability to support
our pipeline of SynCon® active immunotherapy and vaccine 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, 2017, our Quarterly Report on Form
10-Q for the quarter ended September 30,
2018 and other regulatory filings we make from time to time.
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 licensed
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.