Inovio Pharmaceuticals SynCon® TERT Cancer Immunotherapy Combined with Checkpoint Inhibitor Synergistically Shrinks Tumor a...
November 27 2017 - 8:00AM
Inovio Pharmaceuticals, Inc. (NASDAQ:INO) demonstrated the
synergistic effect of combining Inovio’s TERT (telomerase reverse
transcriptase) cancer immunotherapy in combination with a
checkpoint inhibitor in preclinical tumor model. The combination
therapies resulted in robust anti-tumor effects and showed
significant improvement in survival compared to either therapy
alone. Preclinical TERT study results were detailed in a paper
published in the most recent edition of Molecular Therapy entitled,
“Synergy of Immune Checkpoint Blockade with a Novel Synthetic
Consensus DNA Vaccine Targeting TERT,” by Inovio and its
collaborators at the Wistar Institute.
Dr. J. Joseph Kim, President and CEO, said, “The
synergistic anti-tumor effect observed in this published
preclinical study provides Inovio with added confidence in the
company’s recently initiated efficacy studies combining checkpoint
inhibitors and INO-5401, Inovio’s cancer immunotherapy which
includes three of Inovio’s top SynCon® cancer antigens – hTERT,
WT1, and PSMA, which are over-expressed in multiple tumor types.
MedImmune, Regeneron and Genentech have all turned to Inovio’s
DNA-based immunotherapy products to evaluate increased response
rates in combination with their checkpoint inhibitors. We
look forward in sharing combination data from these efficacy trials
when they become available.”
Inovio is currently evaluating its human TERT
(hTERT) immunotherapy, INO-1400, as a mono-therapy, in nine
different solid tumors including breast, lung and pancreatic
cancers. A recent poster presentation at the SITC annual conference
demonstrated that INO-1400 generated hTERT-specific T cell immune
responses in patients. Furthermore, hTERT along with WT1 and PSMA
antigens also comprise the new multi-antigen immunotherapy
INO-5401, which is being evaluated in two separate phase 1/2
efficacy trials in combinations PD-L1 (with Genentech) and PD-1
(with Regeneron) checkpoint inhibitors in metastatic bladder cancer
and in newly diagnosed Glioblastoma multiforme (GBM),
respectively.
INO-5401 is being tested in combination with
PD-1/PD-L1 inhibitors to bring about better anti-tumor effects in
metastatic bladder and GBM. Nearly 430,000 new cases of urinary
bladder cancer are diagnosed each year worldwide; it accounts for
about 165,000 deaths worldwide annually. Advanced unresectable or
metastatic UC remains a high unmet medical need as survival remains
poor for most patients. The approval of several checkpoint
inhibitors for advanced unresectable or metastatic UC has improved
response and survival rates for some patients, however, the
majority (~80%) of patients do not experience meaningful clinical
responses to checkpoint inhibitor monotherapy. GBM is the most
aggressive brain cancer and its prognosis is extremely poor. The
median overall survival for patients receiving standard of care
therapy is approximately 15 months and the average five-year
survival rate is less than three percent. Clinical responses
to checkpoint inhibitors in GBM patients have been poor overall
(ORR<10%). Both of these INO-5401 combination studies are
designed to test the synergistic anti-tumor effects of the
combination therapies.
Significant early checkpoint combination effects
were seen in a clinical study of another Inovio T-cell generating
product, INO-3112 (licensed to MedImmune and now called MEDI0457).
In a phase 1 study of MEDI0457 in 22 HPV-positive patients with
squamous cell carcinoma of the head and neck, Inovio has previously
demonstrated that this cancer immunotherapy generated robust
antigen-specific CD8+ killer T cell responses measured in both
tumor tissue and peripheral blood. One patient who initially
displayed a slight increase in T cell immune responses developed
progressive disease at 11 months into the study. The patient
subsequently received nivolumab, a PD-1 checkpoint inhibitor and
sustained complete response after only four doses of
nivolumab. This patient continues on therapy with no evidence
of disease, 16 months after initiation of nivolumab. Medimmune is
currently conducting a separate phase 1/2 efficacy trial combining
its PD-L1 inhibitor (durvalumab) with MEDI0457 in 50 metastatic
HPV-associated head and neck cancer patients to evaluate the
clinical efficacy of the combination treatment. Head and neck
cancer caused by HPV is the fastest growing cancer in men today,
and the checkpoint inhibitor therapies alone have only been
positive in limited percentage (ORR<20%) of treated
patients.
This published paper highlights the potential
benefits of DNA immunotherapy/immune checkpoint blockade
combinations using PD-1 or CTLA4 checkpoint inhibitors in patients
that respond poorly to immune checkpoint blockade alone, and allow
for better rational design of combination therapies. Furthermore,
these results suggest that this synergistic anti-tumor effect is
due to the effect of immune checkpoint blockade on expanding
effector T cells generated from the TERT therapy in the tumor
microenvironment rather than boosting vaccine responses in the
periphery.
About Inovio Pharmaceuticals,
Inc.
Inovio is taking immunotherapy to the next level
in the fight against cancer and infectious diseases. We are the
only immunotherapy company that has reported generating T cells in
vivo in high quantity that are fully functional and whose killing
capacity correlates with relevant clinical outcomes with a
favorable safety profile. With an expanding portfolio of immune
therapies, the company is advancing a growing preclinical and
clinical stage product pipeline. Partners and collaborators include
MedImmune, Regeneron, Genentech, The Wistar Institute, University
of Pennsylvania, DARPA, GeneOne Life Science, Plumbline Life
Sciences, ApolloBio Corporation, 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 the sufficiency of our capital resources. 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
the company or its collaborators, including alternatives that may
be more efficacious or cost effective than any therapy or treatment
that the company and its collaborators hope to develop, issues
involving product liability, issues involving patents and whether
they or licenses to them will provide the company 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 the company can finance or devote other
significant resources that may be necessary to prosecute, protect
or defend them, the level of corporate expenditures, assessments of
the company's 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, 2016,
our Form 10-Q for the period ended September 30, 2017, and
other regulatory filings we make from time to time. There can be no
assurance that any product candidate in Inovio's 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 Inovio undertakes no obligation to update or
revise these statements, except as may be required by law.
CONTACTS:
Investors/Media: Jeff Richardson,
Inovio Pharmaceuticals, 267-440-4211, jrichardson@inovio.com
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