Cellectis S.A. (the “Company”) (Euronext Growth: ALCLS -
NASDAQ: CLLS), a clinical-stage biotechnology company using its
pioneering gene-editing platform to develop life-saving cell and
gene therapies, today will host a live webcast reviewing updated
clinical data on its Phase 1/2a BALLI-01 clinical trial (evaluating
UCART22) and on its Phase 1 AMELI-01 clinical trial (evaluating
UCART123) that were presented in an oral session on December 12,
2022 at the 64th Annual Meeting of the American Society of
Hematology (ASH).
Preliminary Data from the BALLI-01
Clinical Study
BALLI-01 is a Phase 1/2a open-label
dose-escalation trial evaluating the safety and clinical activity
of UCART22 given at escalating dose levels after lymphodepletion
(LD) with either fludarabine and cyclophosphamide (FC) or FC with
alemtuzumab (FCA) in patients with relapsed or refractory acute
lymphoblastic leukemia (r/r ALL). Alemtuzumab was added to the LD
regimen to sustain host T-cell and Natural Killer (NK) cell
depletion and to promote UCART22 cell expansion and
persistence.
Compared to the last clinical update on BALLI-01
at ASH 2021, the webcast presented data from five additional
patients who received UCART22 at dose level 3 (DL3) 5x106 cells/kg
after lymphodepletion with FCA. No dose limiting toxicities (DLTs),
Grade 2 or higher cytokine release syndrome (CRS), immune effector
cell-associated neurotoxicity syndrome (ICANS) or adverse events of
special interest (AESI) were observed.
Evidence of UCART22 anti-tumor activity was
observed in 60% (n=3) of the five patients at DL3 after
lymphodepletion with FCA:
- A patient experienced a durable
minimal residual disease (MRD) negative complete response with
incomplete count recovery (CRi) that continues beyond 6
months.
- A patient experienced an MRD
negative complete response (CR) that continues beyond Day 56.
- A patient experienced a morphologic
leukemia-free state (MLFS) that continues beyond Day 84
(MRD-negative until Day 84; MRD-positive at Day 117).
All three of the responders failed multiple
lines of prior therapy including chemotherapy, CD19-directed
autologous CAR T cell therapy, and allogeneic stem cell transplant.
Additionally, the patient with the MRD negative CR also failed both
prior blinatumomab (a CD19-directed bi-specific antibody) and
inotuzumab (a CD22-directed antibody-drug conjugate).
“These treatment responses in combination with the safety data
are very encouraging for patients with r/r B-cell ALL who have
limited, if any, treatment options, especially for those who have
failed prior CD19 directed CAR T-cell therapy and allogeneic stem
cell transplant,” said Nitin Jain, M.D., The University of Texas MD
Anderson Cancer Center, Department of Leukemia, and coordinating
investigator for the BALLI-01 study.
Next Steps
Overall, these preliminary data support the
continued administration of UCART22 after FCA lymphodepletion in
patients with r/r ALL. The Company is now enrolling patients in
BALLI-01 with product candidate manufactured fully in-house at DL2
after FCA lymphodepletion. The first patient has been dosed at dose
level 2 (DL2) 1x106 cells/kg. The next data set is expected to be
released in 2023.
Preliminary Clinical Data from the
AMELI-01 Study Presented at ASH 2022
AMELI-01 is a Phase 1 open-label dose-escalation
trial evaluating the safety, tolerability, expansion and
preliminary activity of UCART123 given at escalating dose levels
after lymphodepletion (LD) with either fludarabine and
cyclophosphamide (FC) or FC with alemtuzumab (FCA) in patients with
relapsed or refractory acute myeloid leukemia (r/r AML).
The oral presentation reviewed preliminary data
from patients who received UCART123 at one of the following dose
levels: dose level 1 (DL1) 2.5x105 cells/kg; dose level 2 (DL2)
6.25x105 cells/kg; intermediate dose level 2 (DL2i) 1.5x106
cells/kg; or dose level 3 (DL3) 3.30x106 cells/kg after
lymphodepletion with FC ([n=8], DL1 – DL3) or FCA ([n=9], DL2 &
DL2i).
Preliminary Safety Data
The FCA LD regimen resulted in robust
lymphodepletion for greater than 28 days in all patients. Seven out
of nine patients demonstrated UCART123 expansion, with maximum
concentration (C max) ranging from 13,177 to 330,530 copies/μg DNA,
an almost nine-fold increase compared with FC LD, and a significant
increase in area under the curve (AUC)(0-28 days) (p=0.04; FC
10.2±15.7 vs. FCA 34.9±28.4).
Cytokine release syndrome (CRS) occurred in
eight patients in the FC arm and nine patients in the FCA arm. In
the FC arm, one patient experienced Grade 3 immune effector
cell-associated neurotoxicity syndrome (ICANS) and two patients
experienced Grade 4 protocol-defined dose limiting toxicities
(DLTs) secondary to CRS. In the FCA arm, two patients experienced
Grade 5 DLTs secondary to CRS. Grade 4 toxicities are potentially
life threatening and Grade 5 toxicities result in death.
Preliminary Efficacy Data
Evidence of UCART123 anti-tumor activity was
observed in four patients out of fifteen at DL2 or above with best
overall responses in the FCA arm. Two out of eight patients (25%)
at DL2 with FCA arm achieved meaningful response:
- A patient who failed five prior
lines of therapy experienced a durable minimal residual disease
(MRD) negative complete response (CR) with full count recovery at
Day 56 that continues beyond one year.
- A patient with stable disease
achieved greater than 90% bone marrow blast reduction (60% to 5%)
at Day 28.
“Exemplary activity was seen in a
64-year-old female with AML who had relapsed after allogeneic stem
cell transplantation (allo-SCT) and has maintained a durable
MRD-negative complete response for over one year without
salvage donor lymphocyte infusion or second allo-SCT,” said David
A. Sallman, M.D., Moffit Cancer Center, Department of Malignant
Hematology, Tampa, FL. “Overall, these encouraging clinical data
are a meaningful step forward for patients and support further
enrollment into the study. This trial addresses a patient
population with severe unmet medical need, where a successful CAR
T-cell product candidate could be a major breakthrough.”
The preliminary data show that adding
alemtuzumab to the FC LD regimen was associated with sustained
lymphodepletion and significantly higher UCART123 cell expansion,
which correlated with improved anti-tumor activity.
Next Steps: 2-Dose Regimen
Overall, these preliminary data support the
continued administration of UCART123 after FCA lymphodepletion in
patients with r/r AML. Based on observed UCART123 expansion
patterns and cytokine profiles, pursuant to an amended protocol (as
described below), a second dose of UCART123 will be given after
10-14 days to allow for additional UCART123 expansion and clinical
activity without the use of additional lymphodepletion. The second
expansion phase in the setting of reduced disease burden is
expected to be safe and allow for clearance of residual
disease.
After a protocol-based pause in patient
recruitment following a Grade 5 event related to CRS, the protocol
treatment strategy has been modified and AMELI-01 has now commenced
enrolling patients in the FCA 2-dose regimen arm at DL2, a dose
that has already been administered and cleared for safety as a
single dose. The arm incorporates the use of prophylactic
tocilizumab, which is associated with reduced incidence of CRS.
A copy of the ASH oral presentation is available
on Cellectis’ website.
“These clinically meaningful preliminary data from both the
BALLI-01 and AMELI-01 studies are very encouraging for patients and
for the future of allogeneic CART-cell therapy. Both ALL and AML
are diseases with an urgent need for alternative treatment options
for patients, and we are excited to be moving each of these studies
forward,” said Dr. Mark Frattini, M.D., Ph.D., Chief Medical
Officer at Cellectis. “We are now implementing a two-dose regimen
arm for our AMELI-01 trial, as well as enrolling patients with
in-house manufactured product for our BALLI-01 trial. We look
forward to sharing future updates as they become available for both
of these clinical studies.”
Pipeline Overview
The following chart highlights our and
our licensee’s key product candidates:
https://www.globenewswire.com/NewsRoom/AttachmentNg/8537f59f-74ad-49d2-a243-9c6af66b6d17
NATHALI-01 Study (evaluating
UCART20x22):
Cellectis is enrolling patients at dose level 1
(50x106 cells) with a fludarabine, cyclophosphamide, and
alemtuzumab lymphodepletion regimen in the NATHALI-01 Phase 1
dose-escalation clinical study of UCART20x22. UCART20x22 is
Cellectis’ first allogeneic dual CAR T-cell product candidate being
developed for patients with relapsed or refractory non-Hodgkin
lymphoma and fully designed, developed and manufactured
in-house.
MELANI-01 Study (evaluating
UCARTCS1):
Cellectis is enrolling patients at dose level 1
(1.0x106 cells/kg) with a fludarabine and cyclophosphamide (FC)
lymphodepletion regimen in the MELANI-01 Phase 1 dose-escalation
clinical study of UCARTCS1 for patients with relapsed or refractory
multiple myeloma (MM).
ASH 2022 Poster Presentation on
UCARTCS1, in Collaboration with Amsterdam UMC
On December 10, 2022, the Amsterdam University
Medical Center (VUmc location), in collaboration with Cellectis,
presented preclinical data in a poster session showcasing
Cellectis’ UCARTCS1 product candidate. These initial preclinical
data demonstrated anti-tumor activity in vitro and in vivo,
supporting the potential benefit of Cellectis’ UCARTCS1 first
in-human study MELANI-01.
Collectively, the preclinical data demonstrated
that UCARTCS1 has potent anti-MM activity against MM cell lines and
primary MM cells, as well as in a MM xenograft model. These
preclinical data support the ongoing Phase 1 clinical trial with
UCARTCS1 in heavily pretreated multiple myeloma patients.
A copy of the poster presentation is available
here on Cellectis’ website.
Webcast Information
The event will feature presentations by the
management team and will be followed by a live Q&A. A replay of
the webcast will be made available under the “Events and Webcasts”
section on the Investor page of the Company’s website:
https://cellectis.com/en/investors/events-and-webcasts/
In this context, the listing of the Company’s
ordinary shares on Euronext Growth will be suspended on December
13, 2022 until the opening of trading of Cellectis’ ADSs on the
Nasdaq Global Market at 3:30 pm (Paris time)/ 9:30 a.m. (New York
time).
About Cellectis
Cellectis is a clinical-stage biotechnology
company using its pioneering gene-editing platform to develop
life-saving cell and gene therapies. Cellectis utilizes an
allogeneic approach for CAR-T immunotherapies in oncology,
pioneering the concept of off-the-shelf and ready-to-use
gene-edited CAR T-cells to treat cancer patients, and a platform to
make therapeutic gene editing in hemopoietic stem cells for various
diseases. As a clinical-stage biopharmaceutical company with over
22 years of experience and expertise in gene editing, Cellectis is
developing life-changing product candidates utilizing TALEN®, its
gene editing technology, and PulseAgile, its pioneering
electroporation system to harness the power of the immune system in
order to treat diseases with unmet medical needs. Cellectis’
headquarters are in Paris, France, with locations in New York, New
York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq
Global Market (ticker: CLLS) and on Euronext Growth (ticker:
ALCLS).
For more information, visit www.cellectis.com.
Follow Cellectis on social media: @cellectis, LinkedIn and
YouTube.
Forward-looking Statements
and Legal Notices
Caution should be exercised when interpreting preliminary
results and results relating to a small number of patients or
individually presented case studies—such results should not be
viewed as predictive of future results.
This press release contains “forward-looking” statements within
the meaning of applicable securities laws, including the Private
Securities Litigation Reform Act of 1995. Forward-looking
statements may be identified by words such as “anticipate,”
“believe,” “can,” “could,” “expect,” “intend,”, “is designed to,”
“may,” “might,” “plan,” “potential,” “predict,” “objective,”
“scheduled,” “should,” and “will,” or the negative of these and
similar expressions. These forward-looking statements, which are
based on our management’s current expectations and assumptions and
on information currently available to management. Forward-looking
statements include statements about the preliminary results for the
AMELI-01 and BALLI-01 trials and the objectives of such trials,
which remain ongoing; the ability to progress our clinical trials
and to present any additional data from these trials; clinical
outcomes from our trials, which may materially change as more
patient data becomes available, potential benefits of our UCART
product candidates; and our manufacturing capabilities. These
forward-looking statements are made in light of information
currently available to us and are subject to numerous risks and
uncertainties, including with respect to the risk that initial,
interim and preliminary data from clinical trials may change as
more data becomes available, and that subsequent data may not
confirm any early result; the risk of disruptions or delays in our
clinical trials as a result of failures by third-parties on whom we
rely or arising out of regulatory inquiries or delays; the risk of
manufacturing delays or problems; the risk associated with
increased competition and/or adequate enrollment to support our
clinical trials; and the numerous other risks associated with
biopharmaceutical product candidate development. Furthermore, many
other important factors, including those described in our Annual
Report on Form 20-F and the financial report (including the
management report) for the year ended December 31, 2021 and
subsequent filings Cellectis makes with the Securities Exchange
Commission from time to time, which are available on the SEC’s
website at www.sec.gov, as well as other known and unknown risks
and uncertainties may adversely affect such forward-looking
statements and cause our actual results, performance or
achievements to be materially different from those expressed or
implied by the forward-looking statements. Except as required by
law, we assume no obligation to update these forward-looking
statements publicly, or to update the reasons why actual results
could differ materially from those anticipated in the
forward-looking statements, even if new information becomes
available in the future.
For further information, please
contact:
Media contacts: Pascalyne
Wilson, Director, Communications, +33 (0)7 76 99 14
33, media@cellectis.com Margaret Gandolfo, Senior Manager,
Communications, +1 (646) 628 0300
Investor Relation contact: Arthur
Stril, Chief Business Officer, +1 (347) 809 5980,
investors@cellectis.com Ashley R. Robinson, LifeSci
Advisors, +1 617 430 7577
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