INOVIO's DNA medicines immunotherapy in
combination with Libtayo® elicits
vaccine-associated immune responses when administered with RT/TMZ
to newly diagnosed GBM patients
INO-5401 + INO-9012 +
Libtayo® elicits cancer antigen-specific T
cells
55% of MGMT methylated subjects remain alive
at a median of 32.5 months
Dr. David
Reardon, Principal Investigator, to present on June 6, 2022 at ASCO
PLYMOUTH
MEETING, Pa., May 27, 2022
/PRNewswire/ -- INOVIO (NASDAQ: INO) announced results from the
company's novel Phase 1/2 trial of INO-5401 and INO-9012 in
combination with PD-1 inhibitor Libtayo® (cemiplimab) in
the treatment of newly diagnosed glioblastoma (GBM), including
encouraging median overall survival (OS) data from fifty-two
subjects. Median OS duration in unmethylated MGMT (Cohort A) was
17.9 months. Median OS data in MGMT Methylated patients (Cohort B)
are being presented for the first time, at a median of 32.5 months,
which compares favorably to historical comparisons (23.2-25
months).
Overall, INO-5401 + INO-9012 is demonstrated to be tolerable and
immunogenic when administered with Libtayo and RT/TMZ (radiation
and temozolomide) to newly diagnosed GBM patients. Notably,
INO-5401 elicited antigen-specific T cells that may infiltrate GBM
tumors. The data from this study was selected to be presented in an
oral presentation by Dr. David
Reardon on Monday, June 6,
2022, at the 2022 American Society of Clinical Oncology
(ASCO) at the McCormick Place Convention Center in Chicago, Illinois.
Presentation Details: June 6,
2022, 12:42 – 12:54 p.m. CDT
Presenting Author: David A.
Reardon
Central Nervous System Tumors Session
Abstract #2004: Intramuscular (IM)
INO-5401 + INO-9012 with electroporation (EP) in combination
with cemiplimab (REGN2810) in newly diagnosed glioblastoma
Fifty-two subjects were enrolled: 32 in Cohort A; 20 in Cohort B
(35% women; median age 60 years [range 19-78 years]). The adverse
event profile was consistent with known single-agent (INO-5401,
INO-9012, EP or Libtayo) events; most events were ≤Grade 2 and no
related events were Grade ≥4. Median OS durations in Cohorts A and
B were 17.9 months (95% CI 14.5-19.8) and 32.5 months (95% CI
18.4-not reached), respectively. Flow cytometry revealed activated,
antigen specific CD4+CD69+PD1+ and CD8+CD69+PD1+ T cells, the
latter with lytic potential as defined by presence of perforin and
granzyme A. Both subsets exhibited HR < 1.0 and
p < 0.05 when accounting for a 0.1% T cell frequency
change, translating to a 23% and 28% reduced risk of death at 18
months, respectively.
A post-hoc exploratory analysis showed that gene expression
levels of INO-5401 antigens and immune cell markers from
pre-treatment tumor tissues were similar between alive and deceased
groups; however, the alive group displayed significant differential
expression of genes regulating apoptosis, proliferation, and immune
responses. Post-treatment tumor tissue displayed altered gene
expression for immune-related markers versus pre-treatment tissue,
including markers of T cell infiltration, activation, and lytic
potential.
Dr. David Reardon, Clinical
Director, Center for Neuro-Oncology of Dana-Farber Cancer Institute
and coordinating principal investigator of the study said, "GBM
remains one of the most aggressive and hard-to-treat cancers. The
fact that we have seen this novel combination trial of a T cell
generating DNA medicine combined with a PD-1 checkpoint benefit a
large percent of trial participants past 32 months is very
encouraging. These latest results and continued development are
welcoming as it continues to improve upon a standard of care which
was defined 17 years ago and remains sub-optimal for our patients
with GBM."
Dr. Jeffrey Skolnik, INOVIO's
Senior Vice President, Clinical Development, said, "We, along with
our collaborative partner Regeneron, remain encouraged with the
progress to date from this novel combination therapy study. As
concluded in the abstract, INO-5401 + INO-9012 has an acceptable
risk/benefit profile and elicits robust immune responses that may
correlate with a potentially enhanced survival when administered
with Libtayo and RT/TMZ to newly diagnosed GBM patients. Our goal
is to build upon INO-5401's ability to elicit antigen-specific T
cells that can infiltrate GBM tumors and complement the
clinically-active profile of Libtayo to a potentially larger study
in the future."
INO-5401, INO-9012, Libtayo, and the combination of these
products have not been approved or evaluated by any Regulatory
Authority worldwide for the treatment of newly diagnosed GBM.
Study Design
The trial was designed to evaluate safety, immunogenicity and
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 TMZ. For more information of the clinical study, see
www.clinicaltrials.gov, identifier NCT03491683.
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 including glioblastoma, 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 Glioblastoma (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, with very few 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 7-10
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 INOVIO
INOVIO is a biotechnology company focused
on developing and commercializing DNA medicines to help protect
people from infectious diseases and help treat people with cancer
and HPV-associated diseases. Our DNA medicines are delivered using
our proprietary smart device to produce a robust and tolerable
immune response against targeted pathogens and cancers.
Partners and collaborators include Advaccine, ApolloBio
Corporation, AstraZeneca, The Bill & Melinda Gates Foundation,
Coalition for Epidemic Preparedness Innovations, Defense Advanced
Research Projects Agency/Joint Program Executive Office for
Chemical, Biological, Radiological and Nuclear Defense/Department
of Defense, HIV Vaccines Trial Network, International Vaccine
Institute, Kaneka Eurogentec, Medical CBRN Defense Consortium,
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, Thermo Fisher
Scientific, University of Pennsylvania,
Walter Reed Army Institute of Research, and The Wistar Institute.
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, and our ability to
successfully manufacture and produce large quantities of our
product candidates if they receive regulatory approval. 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,
our ability to secure sufficient manufacturing capacity to mass
produce our product candidates, 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, 2021, our
Quarterly Report on Form 10-Q for the quarter ended March 31, 2022 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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