PLYMOUTH MEETING, Pa.,
April 2, 2019 /PRNewswire/
-- Inovio Pharmaceuticals, Inc. (NASDAQ: INO) announced today
the company's novel DNA-Encoded Bi-specific T Cell Engagers
(dBiTEs™) generated potent anti-tumor activities in a
preclinical study. Results were presented as a poster at the
American Association for Cancer Research (AACR) Annual Meeting in
Atlanta. For this study, Inovio,
with its collaborators at The Wistar Institute, developed a novel
dBiTE targeting the HER2 molecule which was tested in therapeutic
models for the treatment of ovarian and breast cancers.
Importantly, just a single dose of Inovio's HER2 dBiTE resulted in
high levels of corresponding BiTE in mice for four months, far
exceeding what is typically displayed with conventional BiTE's
short half-life of only a few hours. The HER2 dBiTE effectively
generated T cell cytotoxicity against HER2-expressing tumor cells
resulting in a near-complete tumor clearance. Also presented
was Inovio's CD19 dBiTE which can kill B cell cancers by targeting
B cell specific marker CD19.
Dr. J. Joseph Kim, Inovio's
President and CEO, said, "In layman's terms, dBiTEs are like a
double-sided tape that binds to a tumor and to a cancer-killing T
cell. By allowing the products be expressed directly and
efficiently in the patient, our dBiTEs could finally fulfill the
therapeutic promise of BiTEs. Based on these promising preclinical
results, we are rapidly preparing for the clinical development of
our dBiTE candidates, as well as constructing more cancer tumor
targeting dBiTE candidates using our transformative dBiTE
platform."
Dr. Kim added, "Leveraging Inovio's in vivo synthetic
nucleic expression platform, we have shown that just one dose of
Inovio's dBiTE could generate corresponding BiTEs at high levels in
mice for several months, demonstrating a dramatic advantage over
conventional BiTEs. Our CD19 dBiTE has the potential to treat
multiple B cell cancers and to compete favorably with CD19 CAR-T
products with potentially improved tolerability and safety
profiles. Similarly, the HER2 dBiTE could be used to treat multiple
solid tumors which express HER2 such as breast, ovarian, and
gastric cancers."
BiTEs are a class of artificial bi-specific monoclonal
antibodies that has the potential to transform the immunotherapy
landscape for cancer. They direct a host's immune system, more
specifically the T cells' cytotoxic activity, against cancer cells.
BiTEs have two binding domains. One domain binds to the targeted
tumor (like HER2 or CD19 expressing cells) while the other engages
the immune system by binding directly to CD3 molecules on T cells.
This double-binding activity drives T cell activation directly at
the tumor resulting in a killing function and tumor
destruction.
The biggest drawback of conventional protein-based BiTEs is the
delivery and expression. The BiTEs have a half-life of only about
two hours, which requires patients to undergo continuous
intravenous infusion for several weeks to maintain therapeutic
levels, making treatment adherence more difficult and resulting in
high levels of infusion-associated adverse events. In addition,
just like other traditional monoclonal antibodies, conventional
BiTEs are also manufactured in bioreactors, typically requiring
costly large-scale manufacturing facility development and laborious
production as well as having to deal with improper product folding
and stability. They must also be kept and distributed frozen at all
times. These difficulties collectively have limited the development
and commercialization of conventional BiTEs as only one licensed
product is currently on the market (BLINCYTO®
(blinatumomab)).
Inovio's dBiTE is a new transformative application of Inovio's
dMAb™ platform. The dBiTEs share many advantages of Inovio's dMAbs
as they both are composed of engineered DNA sequences which encode
two antibody fragments. When administered by Inovio's
CELLECTRA® delivery device, the patient's own cells
become the factory to manufacture functional BiTES encoded by the
delivered dBiTE sequences.
Inovio's dBiTEs provide major potential advantages over a
conventional protein-based BiTE therapy because of dBiTEs' better
product expression and availability as well as simplicity in
administration and manufacturing. Inovio has demonstrated
that a single dose of dBiTE construct delivered with
CELLECTRA® expressed the product at high levels in mice
for four months. Inovio's dBiTEs are developed with simplified
design using novel plasmid vectors and unique formulations allowing
for rapidity of development, long-term product stability at
refrigeration, ease of validated and scalable manufacturing and
deployability.
Earlier this year, Inovio initiated the first clinical trial for
a dMAb. Funded fully by the Bill & Melinda Gates Foundation,
this trial's focus is on evaluating the dMAb's (INO-A002) ability
to prevent or treat Zika virus infection. The clinical results will
help to broadly advance Inovio's dMAb and dBiTE programs in
infectious diseases and cancer.
About Inovio's dBiTE program
Inovio's dBiTEs are able to target the cytotoxic T cells to
tumors by engaging proteins expressed in the tumor surface. The
current preclinical models have shown proof that DNA technologies
are in an advantageous position to launch a more ambitious BiTE
program. The tumor-binding domain can be modified to engage
multiple targets, of which preclinical data targeting HER2 and CD19
will be presented. Of these, the CD19dBiTE can be used to target B
cell cancers and the HER2dBiTE can be used to treat advanced
breast, ovarian, gastric, esophageal and endometrioid cancers.
About Inovio Pharmaceuticals, Inc.
Inovio is a late-stage biotechnology company focused on the
discovery, development, and commercialization of DNA-based
immunotherapies and vaccines that transform the treatment and
prevention of cancer and infectious disease. Inovio's
proprietary technology platform applies 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'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 HPV-related cancers, bladder cancer, and
glioblastoma, as well as platform development programs in hepatitis
B, Zika, Ebola, MERS, and HIV. Partners and collaborators
include AstraZeneca, Regeneron, Roche/Genentech, ApolloBio
Corporation, The Wistar Institute, The Bill & Melinda Gates
Foundation, the University of
Pennsylvania, Parker Institute for Cancer Immunotherapy,
CEPI, DARPA, GeneOne Life Science, Plumbline Life Sciences, NIH,
HIV Vaccines Trial Network, National Cancer Institute, Walter Reed
Army Institute of Research, Drexel
University, 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, 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,
484-362-0076, ben.matone@inovio.com
|
Media:
|
Jeff Richardson,
267-440-4211, jrichardson@inovio.com
|
View original
content:http://www.prnewswire.com/news-releases/inovio-presents-cancer-killing-data-of-its-transformative-dna-encoded-bi-specific-t-cell-engagers-dbites-at-aacr-300822176.html
SOURCE Inovio Pharmaceuticals, Inc.