PLYMOUTH MEETING, Pa.,
May 14, 2020 /PRNewswire/ -- INOVIO
(NASDAQ: INO) today announced that 85 percent (44 out of 52) of
patients newly diagnosed with the deadly brain cancer glioblastoma
multiforme (GBM) who received the company's DNA medicine INO-5401,
in combination with INO-9012 and PD-1 inhibitor Libtayo®
(cemiplimab), were alive for at least 12 months or more (overall
survival at 12 months: OS12) following treatment. These data will
be featured at an oral poster presentation at the ASCO 2020 Virtual
Scientific Program, May 29-31,
2020.
GBM is the most common and aggressive type of brain cancer.
Currently, the median overall survival with standard of care
therapy, which includes radiation and chemotherapy (temozolomide:
TMZ), is approximately 15 to 22 months.
The Phase 1/2 clinical trial demonstrated that 84.4% percent (27
of 32) of patients with MGMT promoter unmethylated tumors, and 85%
(17 of 20) of patients with MGMT promoter methylated tumors were
alive at 12 months. This promising clinical result is coupled with
a robust immunological response to all three cancer antigens in
INO-5401, including human telomerase (hTERT), Wilms Tumor-1 (WT-1)
and prostate specific membrane antigen (PSMA). Activated, cytotoxic
T cells directed towards these cancer antigens commonly expressed
on GBM tumors were detected in all patients tested to date and
continue to support the immunogenic potential of INOVIO's DNA
medicines. Importantly, INO-5401 + INO-9012 was safe and
well-tolerated when given not only with radiation and TMZ, but also
with PD-1 inhibition with Libtayo, which is being jointly developed
by Regeneron and Sanofi. These results are being presented in a
virtual format at the 2020 Annual ASCO meeting (Abstract
#2514).
Dr. David Reardon, Clinical
Director, Center for Neuro-Oncology of Dana-Farber Cancer Institute
and coordinating principal investigator of GBM-001 said, "Although
these data are preliminary, and follow-up remains early, this novel
combination of a cancer antigen-specific, T cell generating DNA
medicine with a PD-1 inhibitor is exciting and may overcome more
than 20 years of a standard of care that has proven sub-optimal for
our patients with GBM. A tolerable, new combination of medicines
utilizing a novel mechanism of action, such as that provided by
INO-5401 and INO-9012 with cemiplimab, is very welcome for this
hard-to-treat brain cancer, especially when shown to be tolerable
with standards such as radiation and chemotherapy, and when
demonstrating the immunogenicity seen in the GBM-001 study."
Dr. J. Joseph Kim, INOVIO's
President & CEO, said, "While we recognize these data are
early, we are very excited to see robust immunogenicity and the
potential for extending survival, coupled with a clear ability to
be able to combine not only with the standard of care, but with a
checkpoint inhibitor, Libtayo. Where others have failed with
single-agent checkpoint inhibition in GBM, our DNA medicine
combined with Libtayo and standard of care has demonstrated clear
immunogenicity and the potential to extend overall survival."
In a previous announcement, INOVIO reported key interim data
from the 52-patient clinical trial showed that 80% (16 of 20) of
MGMT gene promoter methylated patients and 75% (24 of 32)
unmethylated patients were progression-free at six months (PFS6)
measured from the time of their first dose, exceeding historical
standard-of-care data.
This immunotherapy combination with a PD-1 checkpoint inhibitor
also exhibited supportive safety, tolerability, and immunogenicity
data and suggested an acceptable safety profile consistent with
that of Libtayo and INOVIO's platform technology. The majority of
patients tested had a T cell immune response to one or more
tumor-associated antigens encoded by INO-5401. Immune responses to
all three tumor-associated antigens were demonstrated in this
study. INOVIO plans to report 18-month overall survival data later
this year.
Study Design
The trial was designed to evaluate safety, immunogenicity and
preliminary efficacy of INO-5401 and INO-9012 in combination with
Libtayo, with radiation and chemotherapy, in subjects with
newly-diagnosed glioblastoma (GBM). This is a Phase 1/2,
open-label, multi-center trial conducted in 52 evaluable patients
with GBM. There are two cohorts in this trial. Cohort A includes 32
participants with a tumor with an unmethylated
O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase
(MGMT) promoter. Cohort B includes 20 participants with a tumor
with a MGMT methylated promoter. Both cohorts received INO-5401 and
INO-9012 and Libtayo at the same doses and on the same dosing
schedule, and both cohorts received radiation and temozolomide
(TMZ). Interim data presented here and at SITC was obtained as of
October 2019 and overall survival
data at 18 months is expected in Q4 2020. For more information of
the clinical study, see www.clinicaltrials.gov, identifier
NCT03491683.
Poster Details
Abstract/Poster 2514
Poster Discussion Session: Central Nervous System Tumors
The ASCO 2020 Virtual Scientific Program runs from May 29 -31.
About Glioblastoma Multiforme (GBM)
GBM is the most common and aggressive type of brain cancer and
remains a devastating disease for both patients and caregivers. Its
prognosis is extremely poor, despite a limited number of new
therapies approved over the last 10 years. The median overall
survival for patients receiving standard of care therapy is
approximately 15 to 22 months and the median progression-free
survival is approximately 7 months. In the U.S., the estimated
annual incidence of GBM is 11,362 cases or 3.21 cases per 100,000
persons and the median age at diagnosis is 65 years.
About INO-5401 and INO-9012
INO-5401 encodes for INOVIO's SynCon® antigens for hTERT, WT1,
and PSMA, and has the potential to be a powerful cancer
immunotherapy in combination with checkpoint inhibitors. The
National Cancer Institute previously highlighted hTERT, WT1, and
PSMA among a list of important cancer antigens, designating them as
high priorities for cancer immunotherapy development. These three
antigens were reported to be over-expressed, and often mutated, in
a variety of human cancers, and targeting these antigens may prove
efficacious in the treatment of patients with cancer. INO-9012
encodes for IL-12, which is a T cell immune activator.
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 diseases being developed under grants from the
Coalition for Epidemic Preparedness Innovations (CEPI). 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 demonstrated in
clinical trials.
With more than 2,000 patients receiving INOVIO investigational
DNA medicines in more than 6,000 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 protect and treat 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)/Department of Defense (DOD), GeneOne Life
Science/VGXI, HIV Vaccines Trial Network, International Vaccine
Institute (IVI), 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, Roche/Genentech, 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
DNA medicines, our expectations regarding our research and
development programs, including the planned initiation and conduct
of preclinical studies and clinical trials,
and the availability and timing of data from those
studies and 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, 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 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 March 31, 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.