Inovio Pharmaceuticals, Inc. (NASDAQ:INO) announced today the
successful animal testing of DNA-encoded monoclonal antibodies
targeting the immune checkpoint molecule CTLA-4 as published in
Cancer Research. The breakthrough preclinical study demonstrated
that highly optimized dMAbs targeting mouse CTLA-4 protein can be
robustly expressed in vivo, and shrank tumors in mice. More
importantly, Inovio’s dMAb constructs for anti-human CTLA-4
antibodies ipilimumab (YERVOY®) and tremelimumab, achieved high
expression levels in mice (approximately 85µg/ml and 58µg/ml,
respectively). These dMAbs exhibited long-term expression with
maintenance of serum levels >15µg/ml for over a year.
This research publication is significant because
it is the first to report on the use of Inovio dMAb technology to
develop novel monoclonal antibody-based therapies targeting
checkpoint inhibitors. Inovio is developing additional dMAbs
targeting other checkpoint molecules including PD-1. When delivered
directly into the body, the genetic instructions provided from the
dMAb construct enable the patient’s own cells to become the factory
which manufactures the therapeutic monoclonal antibody products.
Inovio has previously published several papers demonstrating its
dMAb product candidate’s ability to treat multiple virus targets
such as flu, dengue, chikungunya, and HIV.
Laurent Humeau, Ph.D., Inovio's Senior Vice
President, Research & Development, said, "Even though
conventional monoclonal antibodies represent one of the most
successful segments of the biotechnology market, accounting for
over $50 billion in sales today, manufacturing complexity and
repeated dosing may limit a broader use of this technology.
Inovio’s dMAb products may improve upon this class using our
synthetic design and in vivo production. This newly published study
further support that Inovio’s potent dMAb platform can be expanded
to target cancer. We plan on advancing the first clinical dMAb
candidate into the first-in-human study in 2019. Moreover, we
expect to form partnerships to advance several dMAb products
targeting cancers and infectious diseases.”
David B. Weiner, Ph.D., the paper’s senior
author and the W.W. Smith Charitable Trust Professor in Cancer
Research at The Wistar Institute, said, “Our work provides the
first demonstration that we can use synthetic DNA technology to
produce checkpoint inhibitor molecules in vivo to impact tumor
growth in a preclinical setting. We showed that dMAbs may represent
a valuable addition to the cancer immunotherapy toolbox: In our
preclinical studies, dMAbs achieved antitumor activity comparable
to that of traditional monoclonal antibodies, while being delivered
through a simpler formulation that may provide a bridge to expand
target populations for checkpoint inhibitors.”
The study highlights that delivery of a
synthetic, sequence-optimized DNA plasmid designed to encode
anti-mouse CTLA-4 monoclonal antibodies, with the aid of an
electroporation device to enhance uptake, resulted in significant
and prolonged antibody expression with even a single dose.
Importantly, this approach stimulated robust CD8+ T cell
infiltration, achieving tumor clearance across multiple mouse tumor
models. The researchers then went on to develop human checkpoint
inhibitor molecules and demonstrated their production in mice and
their ability to stimulate human T cell responses associated with
antitumor activity. The study clearly demonstrates how optimized
dMAbs encoding the human CPI’s ipilimumab and tremelimumab are
potently expressed in vivo and enhance the activation of human
effector T cells with the potential to destroy tumors. This
strategy provides a novel approach to immune checkpoint therapy,
with the potential to expand patient access to this breakthrough
immunotherapy to treat cancer.
Funded with over $60 million in R&D support
from top agencies like DARPA, NIH, and the Gates Foundation, Inovio
dMAb products could extend the medical benefits that marketed
monoclonal antibodies have already achieved, and even potentially
address diseases that conventional monoclonal antibodies
cannot.
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,
rapidity of development, product stability, ease of manufacturing
and deplorability, and cost effectiveness, thereby providing
potential new avenues for treating a range of diseases. Another
significant advancement seen in Inovio dMAb technologies is that
the optimized genes for a desired monoclonal antibody is encoded in
a DNA plasmid, which is produced using very cost effective and
highly scalable fermentation techniques. These plasmids are
delivered directly into cells of the body using electroporation and
the encoded monoclonal antibody is then directly produced by these
cells. Previously published studies show that a single
administration of a highly optimized DNA-based monoclonal antibody
targeting HIV virus produced a high level of expression of the
antibody in the bloodstream of mice; Inovio similarly reported data
showing that dMAb products against flu, Ebola, chikungunya and
dengue protected animals against lethal challenge. Inovio Ebola
dMAb™ product is being developed under a grant from the Defense
Advanced Research Projects Agency (DARPA).
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 in hepatitis B, Zika, Ebola, MERS,
and HIV. Partners and collaborators include MedImmune, Regeneron,
Roche/Genentech, ApolloBio Corporation, 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, and our plans and expectations regarding
partnerships. 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 June 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.
CONTACTS:Investors:
Ben Matone,
Inovio, 484-362-0076, ben.matone@inovio.comMedia:
Jeff Richardson, Inovio, 267-440-4211, jrichardson@inovio.com
Inovio Pharmaceuticals (NASDAQ:INO)
Historical Stock Chart
From Mar 2024 to Apr 2024
Inovio Pharmaceuticals (NASDAQ:INO)
Historical Stock Chart
From Apr 2023 to Apr 2024