BARDA-sponsored study shows
second-generation hAd5 vaccine candidate in both subcutaneous and
room temperature oral formulations inhibits SARS-CoV-2 virus
replication to undetectable levels and clears infection within days
in 100% of vaccinated non-human primates
- The second-generation human adenovirus vector hAd5, which
delivers both outer spike (S) and inner nucleocapsid (N) antigens,
induced T cells and antibodies leading to reduction of SARS-CoV-2
viruses in both lungs and nasal passages within seven days
- The hAd5-COVID-19 oral capsule vaccine candidate was effective
at room temperature in non-human primates suggesting that it may
not require cold chain logistics that can impede global
distribution
- The hAd5-COVID-19 oral vaccine candidate will enter Phase 1
human trials as a prime and a boost and, pending discussions with
the FDA, will be explored to provide a boost to subcutaneous
vaccinations
- Twenty participants have completed testing in the Phase 1 trial
at Hoag Hospital Newport Beach, Calif., which evaluated both low
and high doses of subcutaneous hAd5, with zero grade 3/4 adverse
events reported. The Phase 2 trial is now actively recruiting.
ImmunityBio, a privately-held immunotherapy company, today
announced its COVID-19 vaccine candidate protected nasal and lung
airways of non-human primates against coronavirus (SARS-CoV-2) in a
challenge study. The study, sponsored by the Biomedical Advanced
Research & Development Authority (BARDA), provides further
evidence supporting the company’s use of a second-generation
adenoviral vector that induces the immune system to both activate T
cells and generate antibodies against multiple viral
targets—blocking virus replication and clearing existing
infection.
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In the study, immunization with the hAd5-COVID-19 vaccine
inhibited SARS-CoV-2 virus replication in 100% (10 of 10) of Rhesus
macaques, with a drop in viral replication starting on the first
day of vaccine administration, and undetectable viral levels as
early as three to five days post-challenge in most of the animals.
The vaccine targeted both the inner nucleocapsid (N) and the outer
spike (S) proteins of the virus to maximize the immune response.
The goal of targeting both S and N was to both activate
virus-specific T cells and generate anti-SARS-CoV-2-neutralizing
antibodies. The study showed this broad immune response led to the
complete clearance of the virus in a matter of days after infection
of previously-vaccinated primates. This blocking of viral
replication was observed in both the lung and nasal passages. By
protecting the nasal passages (the primary point of entry for the
virus), the vaccine has the potential to reduce reinfection.
Clearing replicating viruses from nasal passages is critical for
reducing transmission of the virus from immunized recipients to
others.
The hAd5-COVID-19 candidate is designed to address a potential
problem that may emerge when first-generation adenoviral platforms
are used as vaccine vectors: vaccine inactivation due to
pre-existing immunity to the vector itself. This risk exists for
many vaccine candidates being tested in Europe, China, Russia, and
the United States. Many people who have been exposed to the “common
cold” potentially develop adenovirus immunity: the immune system
often attacks and disables these first-generation vaccines before
they can activate the immune response to attack the SARS-CoV-2
virus. This can significantly limit the effectiveness of
first-generation platforms. ImmunityBio has engineered the vector
to overcome this problem and has shown that its second-generation
adenovirus vector can safely and effectively deliver its cargo even
in patients with pre-existing adenovirus immunity.1
“These results provide compelling evidence of the need for
vaccines to target both S and N proteins and to activate T cells to
produce immune system memory to combat this virus,” said Patrick
Soon-Shiong, MD, Chairman and CEO of ImmunityBio. “The adage that
‘B cells forget but T cells remember’ has never been more
important, and leveraging the S plus N combination has resulted in
a vaccine that is not only showing evidence of being effective but
also one that has the potential to provide long-term T-cell memory.
The exciting finding that the thermally-stable oral formulation
triggers immune responses sufficient to inhibit virus replication
to undetectable levels bodes well for the possibility that this
oral formulation could serve as a universal heterologous booster.
Our oral capsule could be a solution to the enormous challenges
facing cold chain logistics and enable global distribution of the
vaccine.”
The manuscript detailing these preclinical data is available on
a preprint server at
https://biorxiv.org/cgi/content/short/2020.12.08.416297v1 and is
concurrently undergoing scientific peer-review for potential
publication.
In vivo Non-Human Primate (NHP) Challenge Study
Design
This study was designed to test the safety, immunogenicity and
protection from infection and disease provided by ImmunityBio’s
hAd5-COVID-19 vaccine. The vaccine was administered in two separate
regimens. In the first, primates received subcutaneous (SC)
vaccination on Day 0, followed by an SC boost on Day 14 and an oral
boost on Day 28. In the second, the SC prime was followed by two
oral boosts on the same schedule. Placebo controls were used for
comparison for both. Subcutaneous injection of hAd5 and oral
administration of enteric-coated capsules in Rhesus macaques did
not result in any treatment-related toxicities.
Study Highlights:
- ImmunityBio’s hAd5-COVID-19 vaccine was determined to be well
tolerated following both subcutaneous and oral capsule
administration.
- ImmunityBio’s hAd5 vaccine activated T cells to provide
protection, and N was particularly effective in this role. This
feature of the hAd5 vaccine distinguishes it from other
vaccines.
- ImmunityBio’s hAd5 vaccine generated robust neutralizing
antibody activity that was present 14 days post-final vaccination.
Additional safety and neutralizing data are currently being
collected/analyzed.
- Both vaccination regimens resulted in complete protection from
subsequent viral ‘challenge’ as reflected by reductions in viral
RNA levels that were below the level of detection by day seven
post-challenge compared to controls.
hAd5-COVID-19 Oral Formulation
The hAd5-COVID-19 liquid drug substance was dried (lyophilized)
and encapsulated to create the thermally-stable oral version of the
vaccine. The capsules are enterically-coated to allow passage
through the stomach to the small intestine, where the capsule
dissolves to deliver the vaccine. Pending discussions with the FDA,
the oral vaccine will enter Phase I trials as a prime and boost,
and will be explored to provide a boost to subcutaneous
vaccinations.
For more information about ImmunityBio’s COVID-19 vaccine
trials, please contact clinicalresearch@hoag.org.
About ImmunityBio and NantKwest Joint Collaboration
Agreement
Under the terms of a definitive agreement announced on August
24, 2020, ImmunityBio, Inc. and its affiliate NantKwest, Inc.
agreed to share equally the costs of development, manufacturing,
marketing and commercialization of the products each is developing
related to COVID-19, including the hAd5 vaccine candidate. Should a
product be commercialized successfully, the companies have agreed
to a 60-40 percent split of net profits, with the larger share
going to the company that developed the product. The agreement also
details the structure of shared governance of the joint
collaboration.
1. https://pubmed.ncbi.nlm.nih.gov/20361185/ 1.
https://theoncologist.onlinelibrary.wiley.com/doi/full/10.1634/theoncologist.2019-0608
About ImmunityBio
ImmunityBio, Inc. is a late-clinical-stage immunotherapy company
developing next-generation therapies that drive immunogenic
mechanisms for defeating cancers and infectious diseases. The
company’s immunotherapy platform activates both the innate (natural
killer cell and macrophage) and adaptive (T-cell) immune systems to
create long-term “immunological memory.” This novel approach is
designed to eliminate the need for high-dose chemotherapy, improve
upon the outcomes of current CAR T-cell therapies, and extend
beyond checkpoint inhibitors.
ImmunityBio’s platform is based on the foundation of three
separate modalities: antibody cytokine fusion proteins, synthetic
immunomodulators, and second-generation human adenovirus (hAd5)
vaccine technologies.
Anktiva™ (ImmunityBio’s lead cytokine infusion protein) is a
novel interleukin-15 (IL-15) superagonist complex and has received
Breakthrough Therapy and Fast Track Designations from the U.S. Food
and Drug Administration (FDA) for BCG-unresponsive CIS non-muscle
invasive bladder cancer (NMIBC). The company is also in Phase 2 or
3 trials for indications such as first- and second-line lung
cancer, triple-negative breast cancer, metastatic pancreatic
cancer, recurrent glioblastoma, and soft tissue sarcoma in
combination with the company’s synthetic immune modulator
(Aldoxorubicin).
ImmunityBio is also developing therapies, including vaccines,
for the prevention and treatment of HIV, influenza, and the
coronavirus SARS-CoV-2 with its second-generation human adenovirus
(hAd5) vaccine technologies.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Forward-looking statements include statements concerning or
implying that ImmunityBio will be successful in improving the
treatment of the novel coronavirus, the timing and results of the
clinical development of hAd5-COVID-19 oral capsule vaccine, or
whether ImmunityBio will be successful in gaining regulatory
approval of, commercializing or distributing the vaccine. Risks and
uncertainties related to these endeavors include, but are not
limited to the successful completion of the currently contemplated
Phase 1 trials and the currently enrolling Phase 2 trial and
subsequent clinical development and FDA approval of the vaccine on
the currently anticipated timeline, if at all, as well as
manufacturing and distribution challenges. Risks and uncertainties
related to this endeavor include, but are not limited to, the
company’s beliefs regarding the success, cost, and timing of its
development activities and clinical trials.
Forward-looking statements are based on management’s current
expectations and are subject to various risks and uncertainties
that could cause actual results to differ materially and adversely
from those expressed or implied by such forward-looking statements.
Accordingly, these forward-looking statements do not constitute
guarantees of future performance, and you are cautioned not to
place undue reliance on these forward-looking statements. These
forward-looking statements speak only as of the date hereof, and we
disclaim any obligation to update these statements except as may be
required by law.
About NantKwest
NantKwest (NASDAQ: NK) is an innovative, clinical-stage
immunotherapy company focused on harnessing the power of the innate
immune system to treat cancer and infectious diseases. NantKwest is
the leading producer of clinical dose forms of off-the-shelf
natural killer (NK) cell therapies. The activated NK cell platform
is designed to destroy cancer and virally-infected cells. The
safety of these optimized, activated NK cells—as well as their
activity against a broad range of cancers—has been tested in phase
I clinical trials in Canada and Europe, as well as in multiple
phase I and II clinical trials in the United States. By leveraging
an integrated and extensive genomics and transcriptomics discovery
and development engine, together with a pipeline of multiple,
clinical-stage, immuno-oncology programs, NantKwest’s goal is to
transform medicine by bringing novel NK cell-based therapies to
routine clinical care. NantKwest is a member of the NantWorks
ecosystem of companies. For more information, please visit
www.nantkwest.com
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Forward-looking statements include statements concerning or
implying that NantKwest will be successful in improving the
treatment of cancer or other critical illnesses, including
COVID-19. Risks and uncertainties related to these endeavors
include, but are not limited to, obtaining FDA approval of
NantKwest’s NK cells and MSC as well as other therapeutics and
manufacturing challenges.
Forward-looking statements are based on management’s current
expectations and are subject to various risks and uncertainties
that could cause actual results to differ materially and adversely
from those expressed or implied by such forward-looking statements.
Accordingly, these forward-looking statements do not constitute
guarantees of future performance, and you are cautioned not to
place undue reliance on these forward-looking statements.
These and other risks regarding NantKwest’s business are
described in detail in its Securities and Exchange Commission
filings, including in NantKwest’s Quarterly Report on Form 10-Q for
the quarter ended September 30, 2020. These forward-looking
statements speak only as of the date hereof, and we disclaim any
obligation to update these statements except as may be required by
law.
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Jen Hodson NANT Jen@nant.com 562-397-3639
NantKwest (NASDAQ:NK)
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