Cellectis Presents Clinical Data on AMELI-01 and Preclinical Data
on Multiplex Engineering for Superior Generation of CAR T-cells at
ASGCT 2023
Cellectis (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 presents clinical data on its Phase 1 AMELI-01
clinical trial (evaluating UCART123) that were unveiled in an oral
presentation at the 64th American Society of Hematology (ASH)
annual meeting, as well as preclinical data on multiplex
engineering for superior generation of CAR T-cells, at the American
Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting.
Oral presentation:
AMELI-01, a study evaluating UCART123,
an allogeneic CAR T-cell product candidate, in relapsed/refractory
acute myeloid leukemia (r/r AML)
The oral presentation highlights the
following clinical data:
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 (Cmax) 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
vs. FCA 34.9).
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.
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 in the 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.
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.
Patient Enrollment in a 2-Dose Regimen
Arm
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, a
second dose of UCART123 is given after 10-14 days to allow for
additional UCART123 expansion and clinical activity without the use
of additional lymphodepletion. The UCART123 cell expansion from the
second dose of UCART123, in the setting of reduced disease burden,
is expected to be safe and allow for clearance of residual
disease.
“These clinically meaningful preliminary data
from the AMELI-01 study are very encouraging for patients and for
the future of allogeneic CART-cell therapy. AML is a disease with
an urgent need for alternative treatment options for patients, and
we are excited to be moving the study forward,” said Dr. Mark
Frattini, M.D., Ph.D., Chief Medical Officer at Cellectis. “We have
now implemented a two-dose regimen arm for our AMELI-01 trial and
we look forward to sharing future updates as they become
available.”
Title: AMELI-01: A
Phase I Trial of UCART123v1.2, an Anti-CD123 Allogeneic CAR-T Cell
Product, in Adult Patients with Relapsed or Refractory (R/R) CD123+
Acute Myeloid Leukemia (AML)
Presenter: Daniel Lee, M.D.,
Director, Clinical Sciences at Cellectis
Session Date/Time: 5/17/2023 -
3:45 PM – 5:30PM PDTSession Title: CAR Engineering
and Production Advances for Targeting Hematologic and Solid Tumor
MalignanciesSession Room: 502 AB
Final Abstract Number: 94
A copy of the ASGCT oral presentation will be
available on Cellectis’ website after the presentation:
https://www.cellectis.com/en/investors/scientific-presentations/
Poster Presentation:
Expanding the scope of multiplex
engineering for superior generation of efficient CAR
T-cells
In recent years, advances in genomic-based
cellular engineering are bringing us a step closer to conquering
solid tumors. This glimpse of success also demonstrated that we
need to be able to creatively customize and equip CAR T-cells to
target these tumors.
In this presentation, Cellectis shows that we
can use the state-of-the-art TALEN® technology to precisely edit up
to four loci simultaneously while delivering several additional
payloads to increase the efficacy and persistence of CAR
T-cells.
The preclinical data demonstrate that
multiplexed engineering does not compromise CAR T-cell function,
which can even be enhanced and display improved anti-tumor
activity. Thus, multiplexed engineering at superior efficiency
rates while preserving genomic integrity has the potential to
generate highly functional CAR T-cells to advance in the fight
against solid tumors.
Cellectis takes it a step further and uses a
curated combination of genome engineering technologies including
TALE base editors (TALE-BE) to increase the efficiency of
multiplexed gene editing while protecting genomic integrity.
“The immunosuppressive barriers of the tumor
microenvironment antagonize CAR T-cells and have limited our
ability to target solid tumors. These preclinical data show that we
can precisely select and combine an array of gene and cell
engineering approaches to produce armored CAR T-cells with high
efficiency rates. With this strategy, we can focus on unmeet
clinical needs and equip CAR T-cells with enhanced activity to help
us in our quest to defeat solid tumors,” said Beatriz Aranda
Orgilles, Ph.D., Team Leader at Cellectis.
The poster presentation at ASGCT
highlights the following preclinical data:
- Optimization of delivery timings
and selection of compatible TALEN® pairs provides high editing
efficiency while attenuating potential TALEN® crosstalk.
- TALEN® and TALE-BE technologies can
be integrated in the generation of CAR T-cells to provide high gene
editing rates while preserving genomic safety.
- CAR T-cells can be engineered to
carry multiple edits and simultaneously exhibit several key
features to combat solid tumors: immuno-evasive properties,
secretion of the pro-inflammatory cytokine IL-12, resistance to the
immunosuppressive pathways PD-1 and TGFB1.
- Multi-equipped CAR T-cells can
efficiently target in vivo and in vitro models of triple negative
breast cancer, an aggressive tumor that to date has limited
therapeutic possibilities.
Title: Expanding the Scope of Multiplex
Engineering for Superior Generation of Efficient CAR
T-cells
Presenter: Beatriz Aranda Orgilles, Ph.D., Team
Leader at Cellectis
Session Date/Time: 5/17/2023 12:00 PM
PDTSession Title: Wednesday Poster
SessionPoster Board Number: 604
Final Abstract Number: 604
Poster of the presentation will be available on
Cellectis’ website after the presentation:
https://www.cellectis.com/en/investors/scientific-presentations/
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
23 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).
Forward-looking Statements
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,” “intend”, “expect,” “plan,” “scheduled,”
“could” 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 advancements, timing and
progress of clinical trials, the adequacy and continuity of supply
of clinical supply and alemtuzumab, the ability of an anti-CD52 as
alemtuzumab to improve any efficacy and the potential benefit of
UCART product candidates, the potential of our innovation and
preclinical programs.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
numerous risks associated with biopharmaceutical product candidate
development. With respect to our cash runway, our operating plans,
including product development plans, may change as a result of
various factors, including factors currently unknown to us.
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, 2022 and subsequent filings Cellectis makes with the
Securities Exchange Commission from time to time, 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 on Cellectis, please
contact:
Media
contact: Pascalyne
Wilson, Director, Communications, +33 (0)7 76 99 14
33, media@cellectis.com
Investor Relations
contacts: 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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