Cellectis Studies Safety in New CAR Architecture Controlling CAR T-Cell Functions

NEW YORK–(BUSINESS WIRE)– Regulatory News:

Cellectis
(Paris:ALCLS) (NASDAQ:CLLS), a biopharmaceutical company focused on
developing immunotherapies based on gene edited CAR T-cells (UCART),
today announced the publication of a study in Scientific
Reports, a Nature Publishing Group journal, describing a novel
approach to a CAR design with an integrated environmental signal
utilizing oxygen concentration to manipulate the CAR T-cell response.

In this report, Alexandre Juillerat, Ph.D. and his collaborators from
the Cellectis innovation team designed a new CAR architecture that
contains an integrated microenvironment sensor. Low oxygen concentration
is recognized as a hallmark of the microenvironment of certain solid
tumors. The implementation of the novel oxygen sensitive CAR
architecture empowers CAR T-cells with the possibility to auto-regulate
(switch on or tune-up) their functions in low oxygen (hypoxic)
environments.

With the primary purpose of implementing additional levels of safety to
the CAR T-cell technologies, in particular to minimize « on-target /
off-tumor” effects, this study demonstrated the possibility to use
peculiarities of the tumor microenvironment to create self-decision
making CAR T-cells with impaired functions at high oxygen concentration.
The results showed that this system also possessed the key feature to be
prone to quickly return to its off state in the absence of the inducing
signal (hypoxia), a characteristic that is of prime interest to protect
healthy tissues distant from the tumor site. Beyond this first in
vitro proof of concept, additional studies are expected to fully
assess the therapeutic potential of this approach.

Alexandre Juillerat, Ph.D. Innovation Senior Scientist

Dr. Alexandre Juillerat, Ph.D., graduated in Chemistry from the
University of Lausanne, Switzerland. After receiving in 2006 his Ph.D.
in protein engineering from the École Polytechnique Fédérale de Lausanne
(EPFL, Switzerland), he moved to the laboratory of Structural Immunology
at the Institut Pasteur in Paris, France, performing structure-function
studies on a major adhesin of plasmodium falciparum. In 2010, he joined
the R&D department of Cellectis in Paris, France, working on the
development and implementation of sequence specific designer nucleases
including the transcription activator-like effector nucleases TALEN®. He
then joined the Cellectis facility based in New York, NY, USA, leading
projects associated with the development of the T-cell chimeric antigen
receptor (CAR) technology.

An oxygen sensitive self-decision making engineered CAR T-cell

Alexandre Juillerat, Alan Marechal, Jean Marie Filhol, Yannick Valogne,
Julien Valton, Aymeric Duclert, Philippe Duchateau and Laurent Poirot

http://www.nature.com/articles/srep39833

About Cellectis

Cellectis is a biopharmaceutical company focused on developing
immunotherapies based on gene edited CAR T-cells (UCART). The company’s
mission is to develop a new generation of cancer therapies based on
engineered T-cells. Cellectis capitalizes on its 17 years of expertise
in genome engineering – based on its flagship TALEN® products and
meganucleases and pioneering electroporation PulseAgile technology – to
create a new generation of immunotherapies. CAR technologies are
designed to target surface antigens expressed on cells. Using its
life-science-focused, pioneering genome-engineering technologies,
Cellectis’ goal is to create innovative products in multiple fields and
with various target markets. Cellectis is listed on the Nasdaq market
(ticker: CLLS) and on the NYSE Alternext market (ticker: ALCLS). To find
out more about us, visit our website: www.cellectis.com

Talking about gene editing? We do it. TALEN® is a registered trademark
owned by the Cellectis Group.

Disclaimer

This press release contains “forward-looking” statements that are based
on our management’s current expectations and assumptions and on
information currently available to management. Forward-looking
statements involve known and unknown risks, uncertainties and other
factors that may cause our actual results, performance or achievements
to be materially different from any future results, performance or
achievements expressed or implied by the forward-looking statements. The
risks and uncertainties include, but are not limited to, the risk that
the preliminary results from our product candidates will not continue or
be repeated, the risk of not obtaining regulatory approval to commence
clinical trials on the UCART product candidates, the risk that any one
or more of our product candidates will not be successfully developed and
commercialized. Further information on the risks factors that may affect
company business and financial performance, is included in filings
Cellectis makes with the Security Exchange Commission from time to time
and its financial reports. Except as required by law, we assume no
obligation to update these forward-looking statements publicly, or to
update the reasons actual results could differ materially from those
anticipated in the forward-looking statements, even if new information
becomes available in the future.

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