Cellectis Publishes an Article in Cancer Immunology Research Demonstrating Preclinical Evidence of UCART20x22 Product Candidate to Target a Broad Spectrum of Patients with B-cell Malignancies
31 Maio 2023 - 5:50PM
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 publishes an article in Cancer Immunology Research
demonstrating pre-clinical proof-of-concept data of UCART20x22
product candidate, Cellectis’ first allogeneic dual CAR T-cell
targeting the CD20 and CD22 antigens, to overcome current
mechanisms of resistance to CAR T-cell therapies in B-cell
Non-Hodgkin lymphoma (B-NHL), while providing a potential
alternative to CD19 directed therapy.
B-cell Non-Hodgkin lymphoma (B-NHL) remains one
of the most common cancers worldwide, with reports an estimate of
544,000 new cases and 260,000 deaths worldwide in 2020. Despite the
groundbreaking efficacy of current CAR T-cell therapies, studies on
patients treated with autologous CAR T-cells are revealing several
causes for relapses that includes: antigen loss, low antigen
expression or insufficient CAR T-cell potency and persistence,
among others. While several suitable targets to treat B-cells
malignancies have been identified, CD19 has been the focus of
attention leading to a crowded space with limited therapeutic
alternatives for CD19 low or negative relapses.
The limited amount of eligible treatment options
after relapse from autologous CAR T-cell therapy or for patients
not eligible for autologous therapies, underscores the urgent need
to develop novel therapies with the potential to improve patient
outcome.
To address these challenges, Cellectis developed
UCART20x22, its first allogeneic dual CAR T-cell product candidate
targeting two validated antigens commonly expressed in B-cell
malignancies, CD20 and CD22, and whose expression is preserved
after CD19 CAR T-cell treatment. Cellectis provides pre-clinical
proof of concept demonstrating potent and sustained activity of
different designs of allogeneic CD20xCD22 CAR in vitro and in vivo
against various antigen combinations and models recapitulating
antigen escape, a current challenge in the field that can lead to
treatment failure. Moreover, UCART20x22 is developed to be
available off-the-shelf and to offer a solution for patients whose
T-cells are not functional or for which autologous manufacturing
fails.
“In this study, we demonstrate that allogeneic
CD20x22 CAR T-cells exhibit robust, sustained and dose-dependent
activity in vitro and in vivo, while efficiently targeting primary
Non-Hodgkin Lymphoma samples with heterogeneous levels of CD22 and
CD20” said Beatriz Aranda Orgilles, Ph.D., Team Leader at
Cellectis. “We are very excited to share these encouraging
preclinical data that support the transition of UCART20x22 into the
clinic and represent a potential therapeutic alternative to
CD19-directed therapies.”
Preclinical data showed
that:
- The use of a bicistronic vector favors the generation of dual
CAR T-cells co- expressing both CD20 and CD22 CARs
- CAR T-cells efficiently and persistently eradicate double
positive tumor cells over time. More importantly, compared to the
single CAR, the dual CAR displayed similarly strong cytolytic
activity over time against tumor cells expressing a single antigen,
validating the benefit of using a dual CAR approach.
- Both CD20xCD22 CAR versions tested in this study potently
targeted tumor cells in vivo in a dose dependent manner, with both
doses of 3 and 10 million CAR T-cells achieving complete tumor
clearance.
- Xenograft models mimicking antigen escape with an aggressive
lymphoma model demonstrate that the dual CD20xCD22 CAR is capable
to eliminate all tumors despite of losing one antigen, thus
providing a potential solution for this challenge in the
field.
- Bone marrow and spleen analysis of the surviving animals
treated with the dual CAR at the end of the study, revealed that
dual CAR T-cells efficiently eradicated the tumor and are capable
to persist in the bone marrow for longer than one hundred days
- Primary NHL samples with variable levels of CD20 and CD22 can
successfully be eradicated with the dual CD20xCD22 CAR suggesting
that UCART20x22 has the potential to reach a large patient
population.
- Full tumor elimination is achieved in a dose dependent manner
in a Patient-Derived Xenograft (PDX) model recapitulating mantle
cell lymphoma at day 20 with a dose of 3 million CAR T-cells or
higher.
UCART20x22 features TALEN®-mediated disruptions
of the TRAC gene (to minimize the risk of graft-versus-host
disease) and of the CD52 gene (to permit use of a CD52-directed
monoclonal antibody in patients’ lymphodepletion regimen) to
enhance CAR T engraftment, expansion and persistence. UCART20x22 is
Cellectis’ first product candidate fully designed, developed and
manufactured in-house at Cellectis.
UCART20x22 is evaluated in the NATHALI-01 Phase
1/2a clinical study in patients with r/r B-NHL (NCT05607420).
This article is available on Cancer Immunology Research website
by clicking on this
link: https://aacrjournals.org/cancerimmunolres/article/doi/10.1158/2326-6066.CIR-22-0910
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 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.comAshley
R. Robinson, LifeSci Advisors, +1 617 430 7577
- UCART20x22 article PR.pdf
Cellectis Nom Eo 05 (EU:ALCLS)
Gráfico Histórico do Ativo
De Abr 2024 até Mai 2024
Cellectis Nom Eo 05 (EU:ALCLS)
Gráfico Histórico do Ativo
De Mai 2023 até Mai 2024