- First human adenovirus (hAd5) vector vaccine candidate to
deliver both outer spike (S) and inner nucleocapsid (N) antigens
from SARS-CoV-2, offering potential long-term T cell and antibody
immunity to the SARS-CoV-2 virus
- Second-generation adenoviral vector platform designed to
generate immune response even in patients with pre-existing
adenovirus immunity
- Ongoing development proceeding for oral, inhalational and
intranasal administration of hAd5
- Phase I trial recruitment to begin at Hoag Hospital Irvine in
Orange County, Calif. this month
ImmunityBio, Inc., a privately-held immunotherapy company, today
announced it has received authorization from the U.S. Food and Drug
Administration (FDA) to begin a Phase I clinical trial of
hAd5-COVID-19, the company’s novel COVID-19 vaccine candidate that
targets both the inner nucleocapsid (N), engineered to activate T
cells, and outer spike (S) protein, engineered to activate
antibodies against the coronavirus (SARS-CoV-2). These dual
constructs (bivalent sequences) of SARS-CoV-2 offer the potential
for the hAd5 vaccine to provide recipients with durable, long-term
cell-mediated immunity with potent antibody stimulation against
both the S and N proteins.
The company anticipates launching a Phase I trial at Irvine,
Calif. based Hoag Hospital this month with adult subjects up to age
55.
“While there are a number of vaccine candidates in development,
we believe most are limited by their sole focus on antibody
responses to the monovalent spike protein, which may be
insufficient to activate the full potential of the immune system to
fight the coronavirus,” said Dr. Patrick Soon-Shiong, Chairman and
CEO of ImmunityBio. “By targeting the nucleocapsid protein on the
interior of the virus particle as well as the spike protein on the
virus’s surface, we believe this vaccine can stimulate both
T-cell-mediated and antibody-mediated immunity to SARS-CoV-2.”
hAd5 Vaccine Seeks to Develop Immune Memory The
hAd5-COVID-19 vaccine candidate is a novel, engineered,
second-generation human adenovirus serotype 5 vaccine. Because it
delivers both the S and N proteins, the vaccine has the potential
to enable recipients to develop immune “memory”, promoting
long-lasting immunity to SARS-CoV-2. The N protein has been
engineered with a novel signaling domain to enhance T cell
activation. The hAd5 vaccine with this Enhanced T cell Signaling
Domain (ETSD) has generated potent CD4+ and CD8+ COVID specific T
cell activation recognizing S and N following hAd5 vaccination in
pre-clinical studies.
ImmunityBio’s approach differs from first-generation adenoviral
platforms, including one based on the chimpanzee adenovirus and the
first-generation human adenovirus vaccines being tested in Europe,
China, Russia and the United States. All first-generation COVID-19
vaccines in late-stage clinical trials deliver only the monovalent
spike protein on the surface of the virus and therefore focus
primarily on antibody protection as their primary endpoints.
“Based on our studies in cancer, we recognized that potent
T-cell activation can kill the affected cells and requires multiple
antigen targets to be maximally activated,” Soon-Shiong said. “Our
preclinical studies showed that the N protein was highly
immunogenic and generated potent CD4+ and CD8+ T cells.
Furthermore, studies have shown that patients with SARS-CoV
infection have long-term T cell memory to the N protein.”
“On the basis of these findings,” continued Soon-Shiong, “we are
targeting both the N and S proteins in order to drive T cell
response, with the goal of generating B and T cell memory to the
COVID-19 antigens, and long-term immunity to the virus.”
hAd5 Vaccine Circumvents Pre-Existing Adenoviral Immunity
Current first-generation adenovirus platforms suffer from the
disadvantage of generating neutralizing antibodies which occur
after repeated administration, resulting in the attack of the
adenovirus vector itself and reduce the effectiveness of the
vaccine. ImmunityBio’s hAd5 second generation adenovirus platform
has four deletions which overcome pre-existing adenoviral immunity
allowing for multiple administrations. This ability to circumvent
pre-existing adenoviral immunity has been demonstrated in multiple
Phase I / II clinical trials of hAd5 showing tumor specific CD4+
and CD8+ T cells following repeated administrations in the presence
of pre-existing adenovirus immunity.i,ii,iii,iv
ImmunityBio plans to administer the hAd5-COVID-19 vaccine both
as a prime and boost to sustain protection against SARS-CoV-2 since
multiple re-immunizations using the same vector platform are now
possible with the novel hAd5 platform. The company is also pursuing
preclinical development for oral, inhalational and intranasal
administration to provide mucosal immunity in addition to durable
humoral and cell-mediated immunity against COVID-19.
“Given the need for global distribution in both developing and
developed countries, the enormous challenge of cold-chain
requirements could be mitigated by a room temperature stable
formulation of hAd5 that can be administered without the need for
needles,” Soon-Shiong said.
COVID-19 Vaccine Program Status:
- IND Clearance for Phase I Clinical Trial Evaluating Oral
COVID-19 Vaccine The Phase I, open-label, dose-ranging study
will be conducted in healthy adults aged 18 to 55 years old. The
study’s primary objective is to examine the safety and
reactogenicity of two-doses of the vaccine. Additionally,
immunogenicity, duration of immune response and occurrence of
symptomatic COVID-19 will be measured.
- Phase I Trial Design 35 patients to begin enrollment in
October at the following doses of hAd5 S+N:
- Cohort 1 (n = 10): Prime (Day 1) + Boost (Day 22) at 5 × 1010
VP per dose
- Cohort 2 (n = 10): Prime (Day 1) + Boost (Day 22) at 1 × 1011
VP per dose
- Cohort 3 (n = 15): Prime (Day 1) + Boost (Day 22) at 1 × 1011
VP or 5 x 1010 VP per dose based on Cohort 1 & 2 results.
- GMP Manufacturing Doses GMP dosage formulations have
been manufactured in the United States with a drug substance
capacity of >100 million doses annually under a joint
development agreement with NantKwest, Inc.
- Data from Non-Human Primate (NHP) Study Initial results
from a non-human primate (NHP) study that is being conducted in
collaboration with the Biomedical Advanced Research and Development
Authority (BARDA) are encouraging. This NHP study utilizes our GMP
final dosage form of hAd5 vaccine in both subcutaneous and oral
formulations. Final data relating to seroconversion and generation
of neutralizing antibodies together with T cell generation are
being compiled for a final study report.
- Data from SARS-CoV-2 Convalescent Serum and T Cells
Demonstrating Immune Recall to hAd5-COVID-19 Vaccine
ImmunityBio is in the process of publishing the study demonstrating
that COVID-19 convalescent antibodies and T cells recognize human
cell-expressed hAd5 S+N vaccine antigens, with rapid immune
T cell recall.
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
percentage 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.
In addition to the vaccine candidate, the agreement currently
covers a mesenchymal stem cell therapeutic from NantKwest, whose
goal is to reduce the time a critically ill patient spends on a
ventilator.
“By working together and combining the novel technologies of the
two companies, as well as their resources, we believe we have been
able to more rapidly develop products that will address the needs
of COVID-19 patients,” said Soon-Shiong, who also serves as
Chairman and CEO of NantKwest. “We also will be better able to
contribute to the global fight being waged against this deadly
pandemic.”
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 various diseases, including, but not limited to the
novel coronavirus and cancer. 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 June 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.
iGatti‐Mays, et al. A Phase I Trial Using a Multitargeted
Recombinant Adenovirus 5 (CEA/MUC1/Brachyury)‐Based Immunotherapy
Vaccine Regimen in Patients with Advanced Cancer. The Oncol,
25: 479-e899. doi:10.1634/theoncologist.2019-0608
iiGabitzsch ES, et al. Anti-tumor immunotherapy despite
immunity to adenovirus using a novel adenoviral vector Ad5 [E1-,
E2b-]-CEA. Cancer Immunol Immunother. 2010 Jul;59(7):1131-5.
doi: 10.1007/s00262-010-0847-8. Epub 2010 Apr 2. PMID:
20361185.
iiiMorse MA, et al. Novel adenoviral vector induces T-cell
responses despite anti-adenoviral neutralizing antibodies in
colorectal cancer patients. Cancer Immunol Immunother. 2013
Aug;62(8):1293-301. doi: 10.1007/s00262-013-1400-3. Epub 2013 Apr
30. PMID: 23624851; PMCID: PMC3732790.
ivOsada T, et al. Optimization of vaccine responses with an
E1, E2b and E3-deleted Ad5 vector circumvents pre-existing
anti-vector immunity. Cancer Gene Ther. 2009 Sep;16(9):673-82.
doi: 10.1038/cgt.2009.17. Epub 2009 Feb 20. PMID: 19229288; PMCID:
PMC3800002.
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Jen Hodson NANT 562-397-3639 Jen@nant.com
NantKwest (NASDAQ:NK)
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