Caribou Biosciences Selects ROR1 as the Target for CB-020, an iPSC-derived Allogeneic CAR-NK Cell Therapy
December 12 2022 - 8:00AM
Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage
CRISPR genome-editing biopharmaceutical company, today announced
target selection for CB-020, an induced pluripotent stem cell
(iPSC)-derived allogeneic anti-ROR 1 (receptor tyrosine kinase like
orphan receptor 1) CAR-NK cell therapy. Preclinical data on the
selection of the CB-020 CAR construct and armoring strategies for
Caribou’s CAR-NK cell platform will be presented today at the 12th
American Association for Cancer Research and Japanese Cancer
Association (AACR-JCA) Joint Conference.
“ROR1 has been selected as the target for CB-020, Caribou’s
first off-the-shelf iPSC-derived CAR-NK cell therapy, and the
preclinical data presented at AACR-JCA shows that ROR1 may be a
promising target for several solid tumor indications,” said Steve
Kanner, Ph.D., Caribou’s chief scientific officer. “We are
leveraging our chRDNA genome-editing technology across our
allogeneic CAR-T and CAR-NK cell programs to address
disease-specific challenges. For solid tumors, we are exploring
several armoring strategies for our allogeneic CAR-NK cell therapy
platform, including a CBLB knockout, a B2M knockout with a
B2M–HLA-E fusion protein insertion, and a membrane-bound IL-15
insertion/IL-15RA fusion protein to help overcome the complex tumor
microenvironment that has challenged previous cell therapies.”
iPSC-derived NK cells innately exhibit potent antitumor activity
against solid tumors. CB-020 is being engineered using Caribou’s
Cas12a chRDNA genome-editing technology to express a ROR1-specific
CAR, which can enhance the innate NK cell antitumor activity by
increasing specificity and function. ROR1 is a cell signaling
receptor that is overexpressed on the surface of several solid
tumor types and has been shown to drive tumor cell growth,
survival, and metastasis. Preclinical data to be presented at
AACR-JCA show that a single dose of iPSC-derived anti-ROR1 CAR-NK
cells, administered in a tumor xenograft model, significantly
reduced tumor burden compared to iPSC-derived NK cells without an
anti-ROR1 CAR.
Multiple armoring strategies are being developed for Caribou’s
CAR-NK cell platform to enhance tumor targeting, allogeneic CAR-NK
cell survival, and persistence of antitumor activity. Results from
the company’s preclinical studies suggest iPSC-derived NK cells
with a knockout of CBLB (Casitas B-Lineage lymphoma
proto-oncogene-B), a ubiquitin ligase that negatively regulates NK
cell function, results in reduced tumor burden and increased
overall survival in an in vivo solid tumor xenograft model,
compared to unedited iPSC-derived NK cells. Additionally, results
show that iPSC-derived NK cells were not killed by donor-derived T
cells and NK cells when harboring a knockout of B2M and an
insertion of a BM2–HLA-E fusion protein. This strategy may induce
more potent NK activity and help prevent CAR-NK cells from killing
each other, which is a common problem with NK cell therapies. In
addition, results from iPSC-derived NK cells with an insertion of
membrane-bound IL-15/IL-15RA fusion protein, which is shown to
enhance NK cell antitumor activity, demonstrated high cytotoxicity
against tumor cells compared to unedited iPSC-derived NK cells.
Together, these preclinical data demonstrate Caribou’s
genome-editing technology has the potential to be used to implement
a variety of armoring strategies in iPSC-derived CAR-NK cells to
address many of the challenges associated with treating solid
tumors.
Details of the poster presentation at the AACR-JCA Joint
Conference are as follows:
Title: CB-020, an iPSC-derived allogeneic
CAR-NK cell therapySpeaker: Rudy Gonzalez, Ph.D.,
executive director of stem cell therapeutics, Caribou Biosciences,
Berkeley, CADate and time: Monday, December 12 at
5:30 pm HSTAbstract number:
B06Location: Hyatt Regency Maui, Monarchy
Ballroom
The full poster is available on Caribou’s Scientific
Publications webpage.
About Caribou’s Novel Next-Generation CRISPR
PlatformCRISPR genome editing uses easily designed,
modular biological tools to make DNA changes in living cells. There
are two basic components of Class 2 CRISPR systems: the nuclease
protein that cuts DNA and the RNA molecule(s) that guide the
nuclease to generate a site-specific, double-stranded break,
leading to an edit at the targeted genomic site. CRISPR systems are
capable of editing unintended genomic sites, known as off-target
editing, which may lead to harmful effects on cellular function and
phenotype. In response to this challenge, Caribou has developed
CRISPR hybrid RNA-DNA guides (chRDNAs; pronounced “chardonnays”)
that direct substantially more precise genome editing compared to
all-RNA guides. Caribou is deploying the power of its Cas12a chRDNA
technology to carry out high efficiency multiple edits, including
multiplex gene insertions, to develop CRISPR-edited therapies.
About Caribou Biosciences, Inc.Caribou
Biosciences is a clinical-stage CRISPR genome-editing
biopharmaceutical company dedicated to developing transformative
therapies for patients with devastating diseases. The company’s
genome-editing platform, including its proprietary Cas12a chRDNA
technology, enables superior precision to develop cell therapies
that are specifically engineered for enhanced persistence. Caribou
is advancing a pipeline of off-the-shelf CAR-T and CAR-NK cell
therapies for the treatment of patients with hematologic
malignancies and solid tumors.
For more information about Caribou, visit www.cariboubio.com and
follow the company @CaribouBio.
“Caribou Biosciences” and the Caribou logo are registered
trademarks of Caribou Biosciences, Inc.
Forward-Looking Statements This press release
contains forward-looking statements, within the meaning of the
Private Securities Litigation Reform Act of 1995. These
forward-looking statements include, without limitation, statements
related to Caribou’s strategy, plans, and objectives, and
expectations regarding its clinical and preclinical development
programs, including its timing and expectations relating to the
target selection for CB-020 and armoring strategies for the
company’s CAR-NK cell platform. Management believes that these
forward-looking statements are reasonable as and when made.
However, such forward-looking statements are subject to risks and
uncertainties, and actual results may differ materially from any
future results expressed or implied by the forward-looking
statements. Risks and uncertainties include, without limitation,
risks inherent in development of cell therapy products;
uncertainties related to the initiation, cost, timing, progress,
and results of current and future research and development
programs, preclinical studies, and clinical trials; and the risk
that initial or interim clinical trial data will not ultimately be
predictive of the safety and efficacy of Caribou’s product
candidates or that clinical outcomes may differ as more patient
data becomes available; as well as other risk factors described
from time to time in Caribou’s filings with the Securities and
Exchange Commission, including its Annual Report on Form 10-K for
the year ended December 31, 2021, and subsequent filings. In light
of the significant uncertainties in these forward-looking
statements, you should not rely upon forward-looking statements as
predictions of future events. Except as required by law, Caribou
undertakes no obligation to update publicly any forward-looking
statements for any reason.
Caribou Biosciences, Inc. Contacts:
Investors:Amy Figueroa,
CFAafigueroa@cariboubio.com
Media:Peggy Vorwald,
Ph.D.pvorwald@cariboubio.com
Investors and Media: Elizabeth Wolffe, Ph.D.,
and Sylvia WheelerWheelhouse LSA
lwolffe@wheelhouselsa.comswheeler@wheelhouselsa.com
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