Preclinical and Clinical Data Demonstrate Advanced Deployment of
Precision Medicine Tools to Analyze and Potentially More Effectively
Intervene with Highly Focused Therapeutic Interventions
CULVER CITY, Calif.–(BUSINESS WIRE)–NantKwest (Nasdaq:NK),
a leading clinical-stage, natural killer cell based therapeutics
company, NantCell Inc., a privately held immunotherapy company, and
NantOmics, a privately held molecular diagnostic company, today
announced that preclinical and clinical updates will be provided in four
abstracts as part of the upcoming Annual Meeting of the American Society
of Clinical Oncology (ASCO) in Chicago, IL, which runs from May 31st
– June 4th, 2019.
Dr. Patrick Soon-Shiong, Chairman and CEO of NantKwest, NantCell and
NantOmics, commented, “Through a unique collaboration, combining the
expertise of NantOmics’ multi-omics diagnostic capabilities with
NantKwest’s and NantCell’s therapeutic capabilities, we are pleased to
report for the first time the ability to comprehensively analyze a
patient’s circulating cell-free RNA (cfRNA) and T Cell Receptor (TCR)
repertoire and therapeutically intervene across a range of tumor types.
We believe this type of fully integrated diagnostic and therapeutic
intervention represent the next-generation in cancer care and shows real
promise in improving response rates in comparison to traditionally
single agent approaches. We look forward to transitioning these advances
in medicine to the clinical care setting as quickly as possible.”
Abstract Title: Innate and adaptive immunotherapy: An
orchestration of immunogenic cell death by overcoming immune suppression
and activating NK and T-cell therapy in patients with third line or
greater Triple-Negative Breast Cancer (TNBC).
Sub-category: Triple-Negative
Category: Breast Cancer—Metastatic
Meeting: 2019 ASCO Annual Meeting
Abstract Number: e12566
Citation: J Clin Oncol 37, 2019 (suppl; abstr e12566)
Author(s): Chaitali Singh Nangia, Mira Kistler, Leonard S.
Sender, John H. Lee, Frank R. Jones, Omid Jafari, Patrick Soon-Shiong;
Chan Soon Shiong Institute for Medicine, Laguna Hills, CA; Chan Soon
Shiong Institute of Medicine, El Segundo, CA; Children’s Hospital of
Orange County, Laguna Hills, CA; Sanford Health, Sioux Falls, SD;
Etubics Corporation, Seattle, WA; Medical Imaging Center of Southern
California, Santa Monica, CA; NantKwest, Culver City, CA
Summary: Triple-negative breast cancer (TNBC) is a heterogenous
subtype of breast cancer that is frequently aggressive and has limited
treatment options. We hypothesize that effective and sustained response
against TNBC requires a coordinated approach that: (1) reverses the
immune-suppressive tumor microenvironment, (2) induces immunogenic tumor
cell death and (3) Re-engages NK and T-cell tumor response against a
cascade of tumor antigens. To test this hypothesis, we have developed a
temporospatial approach that combines metronomic low dose chemotherapy,
SBRT, off-the-shelf cryopreserved allogeneic NK cells, yeast and
adenoviral tumor-associated antigen vaccines, an IL-15RαFc superagonist,
and checkpoint inhibition. Methods: A phase 1b trial in patients with
previously-treated metastatic TNBC was initiated. Treatment occurred in
3-week cycles of low-dose chemotherapy (aldoxorubicin, cyclophosphamide,
cisplatin, nab-paclitaxel, 5-FU/L), antiangiogenic therapy
(bevacizumab), SBRT, engineered allogeneic CD16 NK-92 cells (haNK),
IL-15RαFc (N-803), adenoviral vector-based CEA, MUC1, brachyury, and
HER2 vaccines, yeast vector-based Ras, brachyury and CEA vaccines, and
an IgG1 PD-L1 inhibitor, avelumab. The primary endpoint is incidence of
treatment-related adverse events (TRAEs). Secondary endpoints include
ORR, DCR, PFS, and OS. Preliminary results reported on 8 subjects
treated with 3rd-line or greater TNBC that have received at least 3
treatment cycles (mean = 6 cycles). All treatment was administered in an
outpatient setting. All subjects had at least 1 grade ≥3 TRAE, primarily
chemotherapy-related neutropenia. Grade ≥3 haNK-related AEs (fever and
fatigue) were observed in 2 subjects. 2 subjects experienced SAEs. 7
subjects remain alive, with 6 subjects receiving ongoing study
treatment. 1 CR (confirmed) and 2 PRs (one confirmed) have been observed
to date. These preliminary data suggest that low-dose chemo-radiation
combined with innate and adaptive immunotherapy can be administered
safely in an outpatient setting with a manageable safety profile.
Clinical trial information: NCT03387085.
Abstract Title: Innate and adaptive immunotherapy: An
orchestration of immunogenic cell death by overcoming immune suppression
and activating NK and T cell therapy in patients with third line or
greater metastatic pancreatic cancer.
Sub-category: Pancreatic Cancer
Category: Gastrointestinal (Noncolorectal) Cancer
Meeting: 2019 ASCO Annual Meeting
Abstract Number: e15787
Citation: J Clin Oncol 37, 2019 (suppl; abstr e15787)
Author(s): Tara Elisabeth Seery, Mira Kistler, Leonard S. Sender,
John H. Lee, Arvind Manohar Shinde, Anand Annamalai, Patrick
Soon-Shiong; Chan Soon Shiong Institute for Medicine, Laguna Hills, CA;
Chan Soon Shiong Institute of Medicine, El Segundo, CA; Chan Soon Shiong
Institute for Medicine, El Segundo, CA; NantKwest, Culver City, CA; St.
Vincent Medical Center, Los Angeles, CA; St. Vincent’s Medical Center,
Los Angeles, CA
Summary:
Pancreatic cancer has multiple mechanisms to prevent immune recognition
that lead to the creation of an immune suppressive tumor
microenvironment. Our hypothesis is that sustained response against
pancreatic cancer requires a coordinated approach that: (1) reverses the
immune-suppressive tumor microenvironment, 2. induces immunogenic tumor
cell death and (3) re-engages NK and T-cell tumor response against a
cascade of tumor antigens. To test this hypothesis, we have developed a
temporospatial approach that combines metronomic low-dose chemotherapy,
SBRT, cryopreserved allogeneic NK cells, yeast and adenoviral
tumor-associated antigen vaccines, an IL-15RαFc superagonist, and
checkpoint inhibition. These preliminary data suggest that low-dose
chemo-radiation combined with innate and adaptive immunotherapy can be
administered safely in an outpatient setting.
Preliminary results of 12 subjects treated with 3rd-line or greater
metastatic pancreatic cancer. All treatment was administered in an
outpatient setting. AEs were primarily hematologic and managed by
planned chemo dose reduction. Grade ≥3 TRAEs were observed in 9 out of
12 subjects, predominately chemotherapy-related neutropenia. 9 out of 12
subjects (75%) had a best response of stable disease (≥ 8 weeks). Median
PFS is 7.1 months (4.4 – 8.8) and median OS is 8.2 months (5.7 – 9.7)
with 1 subject continuing treatment
Preliminary Overall Survival of 8.2 months is encouraging for this
heavily-pretreated population. Clinical trial information: NCT03586869.
Abstract Title: Correlation between circulating cell-free RNA
biomarkers and response during combination immunotherapy in previously
refractory metastatic TNBC patients.
Sub-category: Circulating Biomarkers
Category: Developmental Immunotherapy and Tumor Immunobiology
Meeting: 2019 ASCO Annual Meeting
Abstract No: e14027
Citation: J Clin Oncol 37, 2019 (suppl; abstr e14027)
Author(s): Chad Garner, Tara Elisabeth Seery, Chaitali Singh
Nangia, John H. Lee, Liyang Huang, Leonard S. Sender, Shahrooz
Rabizadeh, Patrick Soon-Shiong; NantHealth, Culver City, CA; Chan Soon
Shiong Institute for Medicine, Laguna Hills, CA; NantKwest, Culver City,
CA; Chan Soon-Shiong Institute for Medicine, El Segundo, CA; NantOmics,
LLC, Culver City, CA; CSS Institute of Molecular Medicine, Culver City,
CA.
Summary: A commercial liquid biopsy test was included as an
exploratory component of an integrated immunotherapy clinical trial in
previously refractory metastatic TNBC patients, combining innate,
high-affinity natural killer cell (haNK) therapy with adenoviral and
yeast-based vaccines and an IL-15 superagonist (NCT 03387085). The
purpose of the study was to assess the utility of cell-free circulating
RNA (cfRNA) as a predictor of treatment response. The amount and
variability of cfRNA was found to be positively correlated with the
tumor size. As cfRNA quantity and variability increased or decreased, a
corresponding increase or decrease in tumor size was observed,
respectively. Not all 18 genes showed consistent patterns of change
across the six patients, however the average expression and variability
of the 18 genes showed evidence of a correlation with tumor size change
from baseline (p-values = 0.08 and 0.03, respectively). Only trace
levels of PD-L1 expression were observed in all 6 patients at baseline,
prior to the initiation of the combination immunotherapy. Among the 5
patients that showed a reduction in tumor size of at least 10%, 4 also
showed an associated increase in cfRNA PD-L1 expression from nearly 0 to
normalized values between 2.1 and 6.8. In an exploratory analysis in an
ongoing combination immunotherapy clinical trial for TNBC showed that
increasing and decreasing cfRNA levels are correlated with increasing
and decreasing tumor size, respectively. Increased PD-L1 cfRNA levels
are correlated with beneficial treatment response. Liquid biopsy of
cfRNA could provide an effective biomarker of treatment response.
Clinical trial information: NCT03387085.
Abstract Title: TCR repertoire analysis from peripheral blood for
prognostic assessment of patients during treatment
Sub-category: Circulating Biomarkers
Category: Developmental Immunotherapy and Tumor Immunobiology
Meeting: 2019 ASCO Annual Meeting
Abstract Number: e14040
Citation:J Clin Oncol 37, 2019 (suppl; abstr e14040)
Author(s): Sadanand Vodala, Andrew Nguyen, Noe Rodriguez, Peter
Sieling, Charles Joseph Vaske, Jon Van Lew, Kayvan Niazi, John H. Lee,
Patrick Soon-Shiong, Shahrooz Rabizadeh; NantOmics, LLC, Culver City,
CA; NantOmics, LLC, Santa Cruz, CA; NantBio, Inc, Culver City, CA;
Sanford Health, Sioux Falls, SD; NantKwest, Culver City, CA
Summary:
Immune checkpoint inhibitor therapy offers substantial clinical
advantage to a subset of patients but predictive/novel prognostic
indicators are still scarce. T cell receptors (TCRs) play a crucial role
in adaptive immunity and anti-tumor immune responses. Net diversity of
TCR repertoires are altered in patients receiving immune checkpoint
inhibitors. To study the prognostic significance of T cell repertoires
as a biomarker of immune responses in cancer patients, TCR repertoires
were characterized from peripheral blood using high throughput
sequencing. Patients that show positive response had TCR clones that
were stable, which may indicate an existing immune related response
towards their tumor. TCR-targeted therapy potentially allows these
existing T-cells to overcome blockade by tumor cells. Patients showing
poor response show a TCR repertoire that is constantly changing
potentially indicating that the tumor cells are not eliciting a strong T
cell specific response. Further functional studies of T cell populations
are planned to expand our understanding of T cell based immune therapies.
For additional information, please visit www.nantkwest,
www.nantcell.com,
and www.nantomics.
About NantKwest
NantKwest, a member of the NantWorks ecosystem of companies, is an
innovative clinical-stage immunotherapy company focused on harnessing
the power of the innate immune system by using the natural killer cell
to treat cancer and virally induced infectious diseases.
NantKwest is uniquely positioned to implement precision cancer medicine,
with the potential to change the current paradigm of cancer care.
Natural Killer (NK) cells are a safeguard in the human body designed to
recognize and detect cells under stress due to cancer or viral
infection. NantKwest’s “off-the-shelf” activated NK cell platform is
designed to destroy cancer and virally infected cells from the body. The
safety of our NK cells as well as their activity against a broad range
of cancers have 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. In addition to being a universal cell-based therapy that
does not require individualized patient sourcing or matching, our NK
cell products have been largely administered in the outpatient setting
as an “off-the-shelf” living drug.
With the capacity to grow active killer cells as a living cancer
therapy, our NK cells have been designed to induce cell death against
cancers and virally infected cells by several mechanisms, including: (i)
innate killing, whereby all of our NK platforms recognize the stress
proteins typically found on cancer cells, which, upon binding, release
toxic granules to immediately kill their targets; (ii) antibody-mediated
killing with our haNK® platform, which are NK cells engineered to
express antibody receptors that can bind to therapeutic antibody
products, thereby enhancing the cancer cell killing effect of that
antibody; and (iii) Chimeric Antigen Receptor directed killing using the
taNK® platform, which includes NK cells engineered to incorporate
chimeric antigen receptors (CARs) to target tumor-specific antigens
found on the surface of cancer cells. All three modes of killing
(innate, antibody-mediated, and CAR directed killing) are employed by
our t-haNK™ platform, which is an innovative combination of our aNK,
haNK® and taNK® platforms in a single product.
Our haNK®, and t-haNK™ platforms have been designed to address certain
limitations of CAR T-cell therapy including the capability to infuse
cell therapy in an outpatient setting which allows for potential
reduction of risk for serious cytokine storms and protracted serious
adverse events. In Phase I and II clinical trials in patients with late
stage cancer, our NK cells have been administered as an investigational
outpatient infusion safely with greater than 300 infusions to date at a
dose of 2 billion cells per infusion. By leveraging an integrated
and extensive genomics and transcriptomics discovery and development
engine, together with a pipeline of multiple, clinical-stage,
immuno-oncology programs, we believe NantKwest is uniquely positioned to
be the premier immunotherapy company and transform medicine by
delivering living drugs in a bag and bringing novel NK cell-based
therapies to routine clinical care. NK-92, aNK, haNK, taNK, and t-haNK
are trademarks of NantKwest, Inc.
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.
Risks and uncertainties related to this endeavor include, but are not
limited to, obtaining FDA approval of NantKwest’s NK cells as well as
other therapeutics as part of the NANT Cancer Vaccine platform as a
cancer treatment.
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 March
31, 2019. 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 NantCell
NantCell is a privately held immunotherapy company with one of the
broadest portfolios of biological molecules spanning albumin-linked
chemotherapeutic, peptide, fusion protein, cytokine, monoclonal
antibody, adenovirus and yeast vaccine therapies.
This platform of technologies has enabled NantCell to achieve one of the
most comprehensive late stage clinical pipelines addressing both the
innate (activated macrophage and natural killer cell) and the adaptive
immune system (dendritic, CD4 and CD8 killer T cells). The pipeline
constitutes over 40 immunological assets with 13 first in human
immunotherapy molecules in active clinical trials. In 2019, NantCell is
planning the enrollment of patients in late stage trials with 3
molecules across 17 indications in solid and liquid tumors.
In the field of oncology, NantCell’s goal is to employ a broad portfolio
of biological molecules that will enable it to activate endogenous NK
and CD8+ T cells, and develop a T cell memory cancer vaccine to combat
multiple tumor types without the use of high-dose chemotherapy.
In the field of infectious disease, NantCell’s goal is to develop
vaccine therapy to treat and prevent diseases stemming from HIV,
Influenza, Zika, and Ebola infection.
For more information please visit www.nantcell.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 NantCell will be successful in improving the treatment of cancer.
Risks and uncertainties related to this endeavor include, but are not
limited to, obtaining FDA approval of NantCell’s IL-15 based Cytokine
therapy, N-803, and other therapeutics as part of the NantCell portfolio.
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.
About NantOmics
NantOmics, a member of the NantWorks ecosystem of companies, invented
and developed the technologies that drive NantHealth’s GPS Cancer®
platform. GPS Cancer® provides actionable intelligence and
molecularly driven decision support for cancer patients and their
providers at the point of care. NantOmics is the first molecular
analysis company to pioneer an integrated approach to unearthing
molecular variances and profiles that initiate and drive cancer, by
analyzing both normal and tumor cells from the same patient and
following identified variances from DNA to RNA to protein to drug.
Having pioneered tumor-normal DNA sequencing and introduced whole RNA
transcriptomic analysis to better inform clinical treatment decisions,
NantOmics has provided molecular insights for thousands of cancer
patients.
NantOmics has a highly scalable cloud-based infrastructure capable of
storing and processing thousands of genomes a day, computing genomic
variances in near real-time and correlating proteomic pathway analysis
with quantitative gene expression and pharmacogenomic signatures, which
guides the use of immunotherapies, chemotherapies and targeted
therapies. Clinical studies for neoepitope vaccines using NantOmics’
proprietary technologies and novel artificial intelligence platforms are
currently underway. For more information please visit www.nantomics.com.
Contacts
Media Contact:
Jen Hodson,
562-397-3639
Jen@nant.com
Investor
Contact:
David Pyrce
951-551-0949
david.pyrce@nantkwest.com