Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage
CRISPR genome-editing biopharmaceutical company, today announced
that it received clearance of its Investigational New Drug (IND)
application from the U.S. Food and Drug Administration (FDA) for
CB-010, an allogeneic anti-CD19 CAR-T cell therapy with a PD-1
knockout (KO), for the treatment of lupus nephritis (LN) and
extrarenal lupus (ERL). The Phase 1, multicenter, open label GALLOP
clinical trial of CB-010 in patients with LN and ERL is expected to
initiate by year-end 2024.
“CB-010 has demonstrated encouraging initial safety and efficacy
in patients with relapsed or refractory B cell non-Hodgkin
lymphoma, and we are excited to expand CB-010’s clinical
development to include autoimmune diseases,” said Rachel Haurwitz,
PhD, Caribou’s president and chief executive officer. “By targeting
CD19-positive B cells involved in the production of autoantibodies
and the perpetuation of the autoimmune response, our off-the-shelf
CAR-T cell therapy CB-010 has the potential to greatly improve the
standard of care for patients with lupus, a prevalent and severe
autoimmune disease.”
CB-010 is the lead clinical-stage product candidate from
Caribou’s allogeneic CAR-T cell therapy platform. As previously
reported, CB-010 has demonstrated encouraging initial safety and
efficacy from the dose escalation portion of the ongoing ANTLER
Phase 1 trial in patients with relapsed or refractory B cell
non-Hodgkin lymphoma (r/r B-NHL). Caribou continues to enroll
patients with large B cell lymphoma (LBCL) in the second-line
setting, and initial dose expansion data from ANTLER will be
presented at a medical congress in Q2 2024.
“Despite treatment advancements, fatigue, organ damage, and low
health-related quality of life often remain life-long
characteristics of lupus,” said Richard Lafayette, MD, professor of
medicine, Stanford Medicine Health Care. “An allogeneic anti-CD19
CAR-T cell therapy from healthy donor T cells has the potential to
revolutionize lupus treatment, offering a readily available
treatment for patients who need new therapeutic options.”
Lupus is an autoimmune disease characterized by widespread
inflammation that damages tissues and organs throughout the body. B
cells, which normally produce antibodies that protect from
infection, can play a devastating role in lupus by producing
autoantibodies that cause the immune system to attack healthy
tissues. CB-010 targets CD19, a protein on the surface of B cells,
and has a PD-1 knockout (KO) that reduces CAR-T cell exhaustion.
CB-010 holds the potential for deep depletion of disease-causing B
cells which could reset the immune system, leading to sustained
drug-free remission. In the ongoing ANTLER trial, depletion and
recovery of patients’ B cells is on par with the duration of B cell
aplasia recently reported by Müller et al.1 Unlike many
autologous and allogeneic CAR-T cell therapies, the manufacture of
CB-010 does not rely on lentiviral or other retroviral vectors,
which the FDA has recently identified may lead to risk of secondary
malignancy potentially due to random integration of the chimeric
antigen receptor (CAR) construct. Instead, the chRDNA technology
allows for precise insertion of the CAR at an intended location
within the T cell genome. The GALLOP trial will include partial HLA
matching between donor sources and patients, which may lead to
improved clinical outcomes based on data from the ongoing ANTLER
trial.
“The human leukocyte antigen, or HLA, system acts as our body’s
identity card to know one’s ‘self’ from ‘not self.’ In stem cell
transplants, it has been shown that a close HLA match between
patients and donors significantly reduces the rejection of the
therapy. This same logic can be applied to allogeneic CAR-T cells
as well, so that the activity of the therapy persists long enough
to target and destroy the diseased cells,” said Mehdi
Hamadani, MD, professor of medicine, section chief of hematologic
malignancies at Medical College of Wisconsin and investigator for
the ongoing ANTLER Phase 1 trial. “Intriguing data from the ongoing
ANTLER trial support incorporating an HLA matching strategy into
Caribou’s CB-010 trials, an innovative clinical approach that can
potentially improve outcomes for patients. I am pleased to be part
of the ANTLER trial to advance the development of CB-010 as an
off-the-shelf CAR-T cell therapy that aims to address the
limitations of currently approved treatment options.”
Caribou continues to expect the $372.4 million cash, cash
equivalents, and marketable securities, as of December 31, 2023, to
fund the current operating plan into Q1 2026.
About the GALLOP trialThe GALLOP Phase 1 trial
is an open-label, multicenter clinical trial designed to evaluate a
single infusion of CB-010 in adult patients with LN and ERL. The
GALLOP trial will evaluate the safety, pharmacokinetic (PK)
profile, and initial clinical activity of a single dose level of
CB-010 following a lymphodepletion regimen of cyclophosphamide at
20mg/kg/day for 2 days followed by fludarabine at 25mg/m2/day for 3
days. Patients will be screened for donor-specific antibodies and
administered CB-010 manufactured from a donor with partial HLA
matching. The primary endpoint is safety.
Webcast conference call today at 5:00 pm
ETCaribou will host a live conference call and webcast
today at 5:00 pm ET to discuss the expansion of the clinical
development of CB-010 to include an autoimmune program for lupus
and the GALLOP Phase 1 clinical trial plans. The webcast presenters
will include:
- Richard Lafayette, MD, professor of medicine, Stanford Medicine
Health Care
- Mehdi Hamadani, MD, professor of medicine, section chief of
hematologic malignancies at Medical College of Wisconsin and
investigator for the ongoing ANTLER Phase 1 trial
- Rachel Haurwitz, PhD, president and chief executive officer,
Caribou Biosciences
Additional webcast participants include:
- Steve Kanner, PhD, chief scientific officer, Caribou
Biosciences
- Jason O’Byrne, chief financial officer, Caribou
Biosciences
- Tonia Nesheiwat, PharmD, vice president of medical affairs and
project leadership, Caribou Biosciences
If you would like the option to ask a question on the live
conference call, please use this link to register to receive a
personal PIN to access the conference call and to ask a
question.
The listen-only webcast will be accessible under Events in the
Investors section of Caribou’s website. The archived audio webcast
will be available on the company’s website following the call and
will be available for 30 days.
About CB-010CB-010 is the lead clinical-stage
product candidate from Caribou’s allogeneic CAR-T cell therapy
platform, and it is being evaluated in patients with relapsed or
refractory B cell non-Hodgkin lymphoma (r/r B-NHL) and will be
evaluated in patients with LN and ERL. In the ongoing ANTLER Phase
1 trial, Caribou is enrolling second-line patients with large B
cell lymphoma (LBCL) comprised of different subtypes of aggressive
r/r B-NHL (DLBCL NOS, PMBCL, HGBL, tFL, and tMZL). In the GALLOP
Phase 1 trial, CB-010 will be evaluated in patients with LN and
ERL.
CB-010 is an allogeneic anti-CD19 CAR-T cell therapy engineered
using Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology. To Caribou’s
knowledge, CB-010 is the first allogeneic CAR-T cell therapy in the
clinic with a PD-1 knockout, a genome-editing strategy designed to
improve activity against diseases by limiting premature CAR-T cell
exhaustion. To Caribou’s knowledge, CB-010 is also the first
anti-CD19 allogeneic CAR-T cell therapy to be evaluated in the
second-line LBCL setting and, for r/r B-NHL, CB-010 has been
granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track,
and Orphan Drug designations by the FDA. Additional information on
the ANTLER trial (NCT04637763) can be found at
clinicaltrials.gov.
About lupus nephritis and extrarenal lupus
Lupus nephritis (LN) and extrarenal lupus (ERL) are sub-categories
of systemic lupus erythematosus (SLE), the most common form of
lupus. Lupus is a chronic autoimmune disease characterized by B
cell dysfunction in which the immune system attacks its own
tissues, causing widespread inflammation and organ damage.2 There
are approximately 320,000 patients with SLE in the US.3 It has been
estimated about 50% of patients with SLE will develop lupus
nephritis, and of those, roughly 10-30% of patients will progress
to end-stage renal disease, which requires dialysis or kidney
transplant.4
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 chRDNA
technology to carry out high efficiency multiple edits, 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 Cas12a chRDNA technology,
enables superior precision to develop cell therapies that are
armored to potentially improve antitumor activity. Caribou is
advancing a pipeline of clinical-stage off-the-shelf cell therapies
from its CAR-T platform as readily available treatments for
patients with hematologic malignancies and autoimmune disease.
Follow us @CaribouBio and visit www.cariboubio.com.
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 expectations relating to the timing of
initiating patient enrollment in the GALLOP Phase 1 clinical trial
for CB-010. These forward-looking statements also include
statements regarding the timing for, and likelihood of, reporting
progress on and additional clinical data from the ongoing ANTLER
Phase 1 clinical trial for Caribou’s CB-010 product candidate and
the sufficiency of the company’s cash to fund its current operating
plan. 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 the development of
cell therapy products; uncertainties related to the initiation,
cost, timing, progress, and results of Caribou’s current and future
research and development programs, preclinical studies, and
clinical trials; and the risk that initial, preliminary, 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 patient enrollment continues and as more
patient data becomes available; the risk that preclinical study
results observed will not be borne out in human patients or
different conclusions or considerations are reached once additional
data have been received and fully evaluated; 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, 2023 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.
Caution should be exercised when interpreting results from
separate trials involving separate product candidates. Results of
other CAR-T cell therapies referenced in this press release have
been derived from publicly available reports of clinical trials run
independently of Caribou, and Caribou has not performed any
head-to-head trials comparing any of these other CAR-T cell
therapies with CB-010. As such, the results of these clinical
trials may not be comparable to clinical results for CB-010 and
cross-trial comparisons may have no interpretative value on
Caribou's existing or future results.
Caribou Biosciences, Inc. contacts:
Investors:Amy Figueroa,
CFAinvestor.relations@cariboubio.com
Media:Peggy Vorwald,
PhDmedia@cariboubio.com
1 Müller F, Taubmann J, Bucci L, et al. CD19 CAR T-Cell Therapy
in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med.
2024 Feb 22;390(8):687-700. 2 Karrar S, Cunninghame Graham DS.
Abnormal B Cell Development in Systemic Lupus Erythematosus: What
the Genetics Tell Us. Arthritis Rheumatol. 2018 Apr;70(4):496-507.
3 Li D, Yoshida K, Feldman CH, Speyer C, Barbhaiya M, Guan H,
Solomon DH, Everett BM, Costenbader KH. Initial disease severity,
cardiovascular events and all-cause mortality among patients with
systemic lupus erythematosus. Rheumatology (Oxford). 2020 Mar
1;59(3):495-504.4 Bechler KK, Stolyar L, Steinberg E, Posada J,
Minty E, Shah NH. Predicting patients who are likely to develop
Lupus Nephritis of those newly diagnosed with Systemic Lupus
Erythematosus. AMIA Annu Symp Proc. 2023 Apr 29;2022:221-230.
Caribou Biosciences (NASDAQ:CRBU)
過去 株価チャート
から 9 2024 まで 10 2024
Caribou Biosciences (NASDAQ:CRBU)
過去 株価チャート
から 10 2023 まで 10 2024