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Cellectis - Activity Report 2010
Cellectis - Activity Report 2010
ACTIVITY REPORT
CONTENTS
6 2010 Highlights
10 CELLECTIS IN BRIEF
16 CELLECTIS IN 2010
18 Our science
22 Business development
24 Corporate development
30 SUBSIDIARIES
31 Cellectis bioresearch
36 Ectycell
38 Cellectis therapeutics
41 FINANCIAL STATEMENTS
47 APPENDICES
CONTENTS
6 2010 Highlights
10 CELLECTIS IN BRIEF
16 CELLECTIS IN 2010
18 Our science
22 Business development
24 Corporate development
30 SUBSIDIARIES
31 Cellectis bioresearch
36 Ectycell
38 Cellectis therapeutics
41 FINANCIAL STATEMENTS
47 APPENDICES
NOTE FROM THE CEO
Cellectis and the French National Institute Cellectis receives INPI National Cellectis launches Cellectis plant New journal publication details in vivo Cellectis bioresearch and Lonza New study shows meganuclease-driven
January
January
March
April
June
July
for Agricultural Research (INRA) sign Innovation Award 2009 sciences, a subsidiary dedicated to activity of Cellectis’ meganucleases in enter development and commercial targeted integration using Cellectis
cooperation agreement Cellectis won a National Innovation plant applications muscle fibres manufacturing agreement bioresearch’s cGPS® CHO-K1 kit to be
Cellectis and INRA wished to collaborate Award from the French National Institute The main aims of this subsidiary are to Researchers at the Laval University Cellectis bioresearch and Lonza, a world highly efficient for drug discovery
in the fields of cell biology and plant for Industrial Property (INPI). Cellectis’ increase and accelerate usage of Cellectis’ Hospital Center in Quebec, Canada, leader in biotechnology manufacture Scientific research based on a unique
and animal biotechnologies. They IP Manager Michèle Paquier received proprietary technology in agricultural used meganucleases engineered by have entered into a contract for the method for generating stable cell lines
decided to pool their expertise, where the award from the President of the biology, broaden the company’s skills Cellectis to restore the expression of development and marketing of bioengi- compatible with high throughput
possible, to acquire new scientific INPI Board, Thierry Morin. The awards, base to attract new and expanded microdystrophin in human myoblasts neered cell lines. Cellectis bioresearch screening (HTS) was published in the
knowledge, to create technological organized annually by the INPI since licensing opportunities and explore the in vitro and in muscle fibers in vivo. will use its meganucleases to inactivate Journal of Biomolecular Screening.
innovations, and to share these 1991, honor small and medium-sized development of proprietary traits for (“knock-out”) the glutamine synthetase
results, knowledge, and transfer enterprises whose growth can be attri- selected applications. Cellectis plant They were therefore able to show the (GS) in CHOK1SV, Lonza’s proprietary This research showed that the techno-
technology to businesses, particularly buted to their outstanding innovation sciences is located in Minneapolis, potential of using meganucleases to host cell line. John Birch, CSO of logy developed by Cellectis bioresearch,
to small and medium-sized enterprises policies and which use a comprehensive Minnesota, USA, with laboratory space treat Duchenne muscular dystrophy, a Lonza Biopharmaceuticals, said, “Lonza based on meganuclease-driven targeted
in the agrofood, agriculture and intellectual property strategy to leverage close to the University of Minnesota hereditary disease that is characterized is delighted to work with Cellectis integration, is faster, more practical
environment sectors. business growth. “Cellectis represents a and its greenhouse facilities. Its Chief by rapid degeneration of the muscle bioresearch. This collaboration makes and more efficient than traditional
fine balance between research activities Scientific Officer, Professor Daniel Voytas, tissue, eventually leading to loss of sense and will enhance our long- methods in deriving cell-based assays
and a healthy management strategy,” currently Director of the University mobility and death. The results of this standing and successful GS technology.” for HTS studies.
said Thierry Morin. of Minnesota Center for Genome research were published in the scientific
Engineering, is an internationally journal Gene Therapy.
renowned scientist and established
expert in plant genome engineering.
Stylized meganuclease.
Cellectis and the French National Institute Cellectis receives INPI National Cellectis launches Cellectis plant New journal publication details in vivo Cellectis bioresearch and Lonza New study shows meganuclease-driven
January
January
March
April
June
July
for Agricultural Research (INRA) sign Innovation Award 2009 sciences, a subsidiary dedicated to activity of Cellectis’ meganucleases in enter development and commercial targeted integration using Cellectis
cooperation agreement Cellectis won a National Innovation plant applications muscle fibres manufacturing agreement bioresearch’s cGPS® CHO-K1 kit to be
Cellectis and INRA wished to collaborate Award from the French National Institute The main aims of this subsidiary are to Researchers at the Laval University Cellectis bioresearch and Lonza, a world highly efficient for drug discovery
in the fields of cell biology and plant for Industrial Property (INPI). Cellectis’ increase and accelerate usage of Cellectis’ Hospital Center in Quebec, Canada, leader in biotechnology manufacture Scientific research based on a unique
and animal biotechnologies. They IP Manager Michèle Paquier received proprietary technology in agricultural used meganucleases engineered by have entered into a contract for the method for generating stable cell lines
decided to pool their expertise, where the award from the President of the biology, broaden the company’s skills Cellectis to restore the expression of development and marketing of bioengi- compatible with high throughput
possible, to acquire new scientific INPI Board, Thierry Morin. The awards, base to attract new and expanded microdystrophin in human myoblasts neered cell lines. Cellectis bioresearch screening (HTS) was published in the
knowledge, to create technological organized annually by the INPI since licensing opportunities and explore the in vitro and in muscle fibers in vivo. will use its meganucleases to inactivate Journal of Biomolecular Screening.
innovations, and to share these 1991, honor small and medium-sized development of proprietary traits for (“knock-out”) the glutamine synthetase
results, knowledge, and transfer enterprises whose growth can be attri- selected applications. Cellectis plant They were therefore able to show the (GS) in CHOK1SV, Lonza’s proprietary This research showed that the techno-
technology to businesses, particularly buted to their outstanding innovation sciences is located in Minneapolis, potential of using meganucleases to host cell line. John Birch, CSO of logy developed by Cellectis bioresearch,
to small and medium-sized enterprises policies and which use a comprehensive Minnesota, USA, with laboratory space treat Duchenne muscular dystrophy, a Lonza Biopharmaceuticals, said, “Lonza based on meganuclease-driven targeted
in the agrofood, agriculture and intellectual property strategy to leverage close to the University of Minnesota hereditary disease that is characterized is delighted to work with Cellectis integration, is faster, more practical
environment sectors. business growth. “Cellectis represents a and its greenhouse facilities. Its Chief by rapid degeneration of the muscle bioresearch. This collaboration makes and more efficient than traditional
fine balance between research activities Scientific Officer, Professor Daniel Voytas, tissue, eventually leading to loss of sense and will enhance our long- methods in deriving cell-based assays
and a healthy management strategy,” currently Director of the University mobility and death. The results of this standing and successful GS technology.” for HTS studies.
said Thierry Morin. of Minnesota Center for Genome research were published in the scientific
Engineering, is an internationally journal Gene Therapy.
renowned scientist and established
expert in plant genome engineering.
Stylized meganuclease.
September
September
October
October
December
CytoPulse Sciences Inc. availability of research kits through new website - Information sharing, interactivity establishment of subsidiary in the US stem cell technology from iPS a license to CytoPulse electroporation
CytoPulse specializes in the development, online online-store, provides enhanced and new media space Located at the Cambridge Innovation Academia Japan – First patent license instruments
manufacture and marketing of electro- accessibility to meganuclease technology Visitors to the new website are ensured Center in Cambridge, Massachusetts, in the therapeutic field Cellectis and Harvard Apparatus, a division
poration technology and equipment. Cellectis bioresearch announced the enhanced usability and information Cellectis bioresearch Inc. will be responsible Cellectis entered into two separate non- of Harvard Bioscience Inc. which develops,
Electroporation is a highly efficient way launch of its e-store, with approximately sharing, including more streamlined for the US-wide promotion of Cellectis exclusive license agreements granting manufactures and markets a broad
for molecules such as meganucleases one hundred ready-to-use products access to information about Cellectis’ bioresearch products and services. the company worldwide access to the range of tools to advance life science
to be introduced into any type of cell, available for sale online via a new func- technology and products. induced Pluripotent Stem (iPS) cell patent research and regenerative medicine
with applications ranging from research tional and intuitive website to meet the portfolio arising from the work of worldwide, signed a license agreement
and biomanufacturing to agriculture needs of both academic and industry The new Cellectis website focuses on Professor Shinya Yamanaka at the Center that grants Harvard Apparatus the
and therapeutics. “CytoPulse’s assets research. “The launch of a website with three central themes: research and for iPS Cell Research and Application worldwide exclusive right to manu-
are a great strategic acquisition for online purchasing capability was a vital technology, business development and (CiRA) at the University of Kyoto, Japan. facture and market, for research use,
Cellectis,” said Cellectis Chief Executive step in improving researchers’ access investor relations. the full line of electroporation-based
Officer André Choulika. to our meganuclease technology,” Cellectis is the first company in the world instruments acquired by Cellectis
explained Luc Selig, VP Sales and to be licensed by iPS Academia Japan to from CytoPulse in September 2010.
“As we announced in 2009, part of Marketing at Cellectis bioresearch. use this patent portfolio for applications
our development strategy is to acquire “Our product offering has expanded in human therapeutics and prophylactics. Cellectis, however, retains all rights to
technologies that complement our rapidly, and we now market over In the research tool field, this is the the use of these instruments for its own
existing meganuclease platform and can one hundred different products on first agreement with a French company, research and development programs as
be leveraged across all aspects of our three target markets.” following agreements with US and well as in clinical trials and prophylactic
business, from research to therapeutics. German companies. or therapeutic procedures, for both
We saw such an opportunity in the humans and animals.
technologies at CytoPulse Sciences
Inc. and look forward to unlocking the
value of these assets.”
September
September
October
October
December
CytoPulse Sciences Inc. availability of research kits through new website - Information sharing, interactivity establishment of subsidiary in the US stem cell technology from iPS a license to CytoPulse electroporation
CytoPulse specializes in the development, online online-store, provides enhanced and new media space Located at the Cambridge Innovation Academia Japan – First patent license instruments
manufacture and marketing of electro- accessibility to meganuclease technology Visitors to the new website are ensured Center in Cambridge, Massachusetts, in the therapeutic field Cellectis and Harvard Apparatus, a division
poration technology and equipment. Cellectis bioresearch announced the enhanced usability and information Cellectis bioresearch Inc. will be responsible Cellectis entered into two separate non- of Harvard Bioscience Inc. which develops,
Electroporation is a highly efficient way launch of its e-store, with approximately sharing, including more streamlined for the US-wide promotion of Cellectis exclusive license agreements granting manufactures and markets a broad
for molecules such as meganucleases one hundred ready-to-use products access to information about Cellectis’ bioresearch products and services. the company worldwide access to the range of tools to advance life science
to be introduced into any type of cell, available for sale online via a new func- technology and products. induced Pluripotent Stem (iPS) cell patent research and regenerative medicine
with applications ranging from research tional and intuitive website to meet the portfolio arising from the work of worldwide, signed a license agreement
and biomanufacturing to agriculture needs of both academic and industry The new Cellectis website focuses on Professor Shinya Yamanaka at the Center that grants Harvard Apparatus the
and therapeutics. “CytoPulse’s assets research. “The launch of a website with three central themes: research and for iPS Cell Research and Application worldwide exclusive right to manu-
are a great strategic acquisition for online purchasing capability was a vital technology, business development and (CiRA) at the University of Kyoto, Japan. facture and market, for research use,
Cellectis,” said Cellectis Chief Executive step in improving researchers’ access investor relations. the full line of electroporation-based
Officer André Choulika. to our meganuclease technology,” Cellectis is the first company in the world instruments acquired by Cellectis
explained Luc Selig, VP Sales and to be licensed by iPS Academia Japan to from CytoPulse in September 2010.
“As we announced in 2009, part of Marketing at Cellectis bioresearch. use this patent portfolio for applications
our development strategy is to acquire “Our product offering has expanded in human therapeutics and prophylactics. Cellectis, however, retains all rights to
technologies that complement our rapidly, and we now market over In the research tool field, this is the the use of these instruments for its own
existing meganuclease platform and can one hundred different products on first agreement with a French company, research and development programs as
be leveraged across all aspects of our three target markets.” following agreements with US and well as in clinical trials and prophylactic
business, from research to therapeutics. German companies. or therapeutic procedures, for both
We saw such an opportunity in the humans and animals.
technologies at CytoPulse Sciences
Inc. and look forward to unlocking the
value of these assets.”
CELLECTIS IN BRIEF
CELLECTIS IN BRIEF
The principle of genome engineering is simple: it involves Meganucleases are natural proteins found in many single-celled organisms. They are highly
specific “DNA scissors”. They are able to recognize their binding site by identifying a nucleic
modifying the genome of an individual or species for the acid sequence (nucleic acids are the constituents of DNA), which contains between 12 and
purposes of understanding the way it works, producing useful over 30 base pairs. This site is statistically unique in a genome. Once the DNA break has been
proteins or treating a disease. made, the cell activates its maintenance and repair system (for example, homologous recom-
bination). This system corrects the DNA molecule by using, for example, its twin copy (gene
Genetics has demonstrated the link between the physical attributes of species and their correction) or a similar fragment specifically introduced into the cell as a model (insertion or
genes, and thereby shown how particular genes are implicated in certain diseases or attri- “knock-in”). It is the same principle as the “copy and paste” function in word processing.
butes. Genome engineering enables species’ genes to be modified in order to change certain When a gene just needs to be inactivated rather than replaced, the broken DNA is bound and
attributes, to rectify an error, or to add a new trait of physiological or economic interest. loses information, therefore the targeted gene is inactivated (known as “knock-out”).
This approach is not new: cross-breeding different plants or selecting the best animals for
reproduction is based on the same principle. The aim is to improve species by giving them Cellectis manufactures meganucleases that can cut precise new sequences, and are thus tailor-
the best possible attributes – drought tolerance or pest resistance for crops, for example. made for genes of interest. The feasibility of meganuclease engineering allows the creation
of a wide range of specific tools to modify the targeted genes. It is the technological vision
The targeted approach of genome engineering is predictable, more reliable and more effective upon which Cellectis was founded 11 years ago. This was achieved when the meganuclease
than earlier techniques, and can even be applied to humans. The genomes of over 1,000 platform was able to produce custom meganuclease specific of any new gene of interest,
organisms have now been decoded. Knowledge of the sequence and location of the genes of with the same characteristics as the wild type ones (efficacy, specificity, …). This expertise in
living beings is therefore constantly improving, even though the workings of these genes are genome engineering tools production has allowed Cellectis to evolve from a tool producer to
still not fully known. Our understanding in this field allows us to manipulate genes directly. a product-delivering company.
The principle of genome engineering is simple: it involves Meganucleases are natural proteins found in many single-celled organisms. They are highly
specific “DNA scissors”. They are able to recognize their binding site by identifying a nucleic
modifying the genome of an individual or species for the acid sequence (nucleic acids are the constituents of DNA), which contains between 12 and
purposes of understanding the way it works, producing useful over 30 base pairs. This site is statistically unique in a genome. Once the DNA break has been
proteins or treating a disease. made, the cell activates its maintenance and repair system (for example, homologous recom-
bination). This system corrects the DNA molecule by using, for example, its twin copy (gene
Genetics has demonstrated the link between the physical attributes of species and their correction) or a similar fragment specifically introduced into the cell as a model (insertion or
genes, and thereby shown how particular genes are implicated in certain diseases or attri- “knock-in”). It is the same principle as the “copy and paste” function in word processing.
butes. Genome engineering enables species’ genes to be modified in order to change certain When a gene just needs to be inactivated rather than replaced, the broken DNA is bound and
attributes, to rectify an error, or to add a new trait of physiological or economic interest. loses information, therefore the targeted gene is inactivated (known as “knock-out”).
This approach is not new: cross-breeding different plants or selecting the best animals for
reproduction is based on the same principle. The aim is to improve species by giving them Cellectis manufactures meganucleases that can cut precise new sequences, and are thus tailor-
the best possible attributes – drought tolerance or pest resistance for crops, for example. made for genes of interest. The feasibility of meganuclease engineering allows the creation
of a wide range of specific tools to modify the targeted genes. It is the technological vision
The targeted approach of genome engineering is predictable, more reliable and more effective upon which Cellectis was founded 11 years ago. This was achieved when the meganuclease
than earlier techniques, and can even be applied to humans. The genomes of over 1,000 platform was able to produce custom meganuclease specific of any new gene of interest,
organisms have now been decoded. Knowledge of the sequence and location of the genes of with the same characteristics as the wild type ones (efficacy, specificity, …). This expertise in
living beings is therefore constantly improving, even though the workings of these genes are genome engineering tools production has allowed Cellectis to evolve from a tool producer to
still not fully known. Our understanding in this field allows us to manipulate genes directly. a product-delivering company.
Qpix robot, meganucleases tested on targets Colored test for mutant selection FX robot, DNA production in plates
Qpix robot, meganucleases tested on targets Colored test for mutant selection FX robot, DNA production in plates
Four subsidiaries of Cellectis were created between 2008 and 2010. Their aim is to fully develop
the applications of our technology within their given market sectors. The parent company centralizes
the financial department of the group, the intellectual property, the legal department and other
support functions, as well as the research and development around genome engineering technologies.
The “DNA scissors” platform production will remain the strategic center of the company as a whole
as well as the driving force of the group activity.
Four subsidiaries of Cellectis were created between 2008 and 2010. Their aim is to fully develop
the applications of our technology within their given market sectors. The parent company centralizes
the financial department of the group, the intellectual property, the legal department and other
support functions, as well as the research and development around genome engineering technologies.
The “DNA scissors” platform production will remain the strategic center of the company as a whole
as well as the driving force of the group activity.
This achievement resulted from a proper In 2010 we used dozens of meganucleases The core activity of Cellectis In the labs at Cellectis, upstream research
industrialization of our processes, which in immortalized cells, plants, animal models is split into two areas. One team of
illustrates the overall maturity and adapta- and stem cells. This broad applicability is
internal R&D team is to researchers focuses on the engineering of
bility of the organization. This enhanced a key feature of the potential of Cellectis engineer meganucleases that proteins – meganucleases in particular –
production capacity means that Cellectis technology. The amount of data gathered are specific to a chosen DNA in order to improve their activity and speci-
can position itself as a supplier of tools by different teams, both at Cellectis and ficity, and to increase the sequence space
for a very broad spectrum of applications elsewhere, is indicative of the robustness
target, i.e. to create “custom” that can be targeted by these “tailor-made”
and products. of this technology. Many of these results will meganucleases for each gene meganucleases. The other team focuses
be published throughout 2011. of interest. on the activity of meganucleases in cells,
But the progress that has been made in and particularly on improving the efficiency
our manufacturing processes should not Finally, our research has enabled us to assess The teams at Cellectis can identify the of gene targeting and its recombination.
Dr. Frédéric Pâques, Chief Scientific Officer overshadow the advances made in the the challenges that lie ahead, particularly areas responsible for the “DNA scissor” This team is also working on new appli-
application of our products. One of the in 2011 and and it is the therapeutic sector function within the meganuclease structure, cations for meganucleases.
2010 was a particularly most significant achievements is the use of which holds some of the biggest challenges as well as the areas that correspond to
our products in genome surgery, which is for us. Among them, the ability to get our the recognition of specific DNA sites. Our In 2010, the R&D group made important
productive year in terms of now happening on an unprecedented scale, molecules in sufficient numbers into the progress, including the identification of
researchers are therefore able to modify
the research and advancement with over 15 collaborations with academic target cells will be a major priority for our the recognition and DNA fixation area so new protein structures with the capability
research labs all over the world (HSR-TIGET research. Another key priority is ensuring to be engineered more quickly and
of our core technology. One as to generate new variants that target new
in Milan, VIB in Leuven, Children Hospital the safety of this approach, which is directly sites in a genome. As a result of this research, offering new properties. This led to new
of our main achievements in Boston, …) producing both in vitro and linked to the specificity of the meganucleases. Cellectis now has a large bank of proteins meganucleases with optimized usage.
was the consolidation of in vivo data. This represents a greater The specificity criteria are the most strictly with over 40,000 motifs that can be
number of meganucleases used as well as applied in therapeutic applications,
our production platform in combined to obtain chimeric proteins
a broader variety of application methods, and safety most stringently assessed. capable of binding to different sequence A very complete publication, which
order to produce a record particularly the cell types that can be combinations of the DNA. describes the different tools used in
number of meganucleases successfully targeted. Both aspects are Safety and vectorization (or the method genome engineering and compares their
directly linked to the increase in our used to insert a meganuclease into a target properties, was published in Current Gene
(271 in 2010). Therapy by the Cellectis research team at
manufacturing capacity, which is meeting cell) are therefore the two key words
the growing needs of our customers, for 2011, as we spend the year focusing the end of 2010.
our partners and our in-house research wholeheartedly on the applications of
Meganucleases and other Tools for
and development activities. genome engineering – across research Targeted Genome Engineering: Perspectives
tools, agriculture or medicine. and Challenges for Gene Therapy
Silva G, Poirot L, Galetto R, Smith J,
Dr. Frédéric Pâques Montoya G, Duchateau P, Pâques F.
Curr Gene Ther. 2010, Dec 24
This achievement resulted from a proper In 2010 we used dozens of meganucleases The core activity of Cellectis In the labs at Cellectis, upstream research
industrialization of our processes, which in immortalized cells, plants, animal models is split into two areas. One team of
illustrates the overall maturity and adapta- and stem cells. This broad applicability is
internal R&D team is to researchers focuses on the engineering of
bility of the organization. This enhanced a key feature of the potential of Cellectis engineer meganucleases that proteins – meganucleases in particular –
production capacity means that Cellectis technology. The amount of data gathered are specific to a chosen DNA in order to improve their activity and speci-
can position itself as a supplier of tools by different teams, both at Cellectis and ficity, and to increase the sequence space
for a very broad spectrum of applications elsewhere, is indicative of the robustness
target, i.e. to create “custom” that can be targeted by these “tailor-made”
and products. of this technology. Many of these results will meganucleases for each gene meganucleases. The other team focuses
be published throughout 2011. of interest. on the activity of meganucleases in cells,
But the progress that has been made in and particularly on improving the efficiency
our manufacturing processes should not Finally, our research has enabled us to assess The teams at Cellectis can identify the of gene targeting and its recombination.
Dr. Frédéric Pâques, Chief Scientific Officer overshadow the advances made in the the challenges that lie ahead, particularly areas responsible for the “DNA scissor” This team is also working on new appli-
application of our products. One of the in 2011 and and it is the therapeutic sector function within the meganuclease structure, cations for meganucleases.
2010 was a particularly most significant achievements is the use of which holds some of the biggest challenges as well as the areas that correspond to
our products in genome surgery, which is for us. Among them, the ability to get our the recognition of specific DNA sites. Our In 2010, the R&D group made important
productive year in terms of now happening on an unprecedented scale, molecules in sufficient numbers into the progress, including the identification of
researchers are therefore able to modify
the research and advancement with over 15 collaborations with academic target cells will be a major priority for our the recognition and DNA fixation area so new protein structures with the capability
research labs all over the world (HSR-TIGET research. Another key priority is ensuring to be engineered more quickly and
of our core technology. One as to generate new variants that target new
in Milan, VIB in Leuven, Children Hospital the safety of this approach, which is directly sites in a genome. As a result of this research, offering new properties. This led to new
of our main achievements in Boston, …) producing both in vitro and linked to the specificity of the meganucleases. Cellectis now has a large bank of proteins meganucleases with optimized usage.
was the consolidation of in vivo data. This represents a greater The specificity criteria are the most strictly with over 40,000 motifs that can be
number of meganucleases used as well as applied in therapeutic applications,
our production platform in combined to obtain chimeric proteins
a broader variety of application methods, and safety most stringently assessed. capable of binding to different sequence A very complete publication, which
order to produce a record particularly the cell types that can be combinations of the DNA. describes the different tools used in
number of meganucleases successfully targeted. Both aspects are Safety and vectorization (or the method genome engineering and compares their
directly linked to the increase in our used to insert a meganuclease into a target properties, was published in Current Gene
(271 in 2010). Therapy by the Cellectis research team at
manufacturing capacity, which is meeting cell) are therefore the two key words
the growing needs of our customers, for 2011, as we spend the year focusing the end of 2010.
our partners and our in-house research wholeheartedly on the applications of
Meganucleases and other Tools for
and development activities. genome engineering – across research Targeted Genome Engineering: Perspectives
tools, agriculture or medicine. and Challenges for Gene Therapy
Silva G, Poirot L, Galetto R, Smith J,
Dr. Frédéric Pâques Montoya G, Duchateau P, Pâques F.
Curr Gene Ther. 2010, Dec 24
The scientists identify the protein modules By carrying out its research work, the At Cellectis, the mission of the Computational design involves using
whose DNA targets match with fragments Platform team is able to expand the software based on energy level calculations
from the targeted genome site. Then they database, enhancing Cellectis’ knowledge
computational biology team in a protein, and completely relies on the
combine the modules to create a new and scientific expertise. 2010 was marked is to produce engineered availability of structural data (i.e. tridimen-
meganuclease with recognition specificity by a reduction and stabilization in meganucleases using a rational sional structures of meganucleases bound
for the required gene target. The activity manufacturing times within the Platform. to their DNA target). Cellectis established in
of each newly created meganuclease is This resulted in a significant increase in
approach. 2009-2010 a dedicated computational
then tested in a series of functional trials our production output, with 271 mega- New meganucleases are today essentially biology group, in parallel with the set up
developed by Cellectis. nucleases manufactured in 2010 compared produced by a so-called semi-rational of a major structural biology program.
with 99 in 2009. approach: collections of meganuclease The program is held at the CNIO (Madrid)
All the creation and analysis work is carried variants are built by randomly modifying in collaboration with Dr Guillermo Montoya.
out by the production Platform team, who specific areas of the protein, and these Exclusive access to a significant amount of Dr. George Silva, head of the computational biology
create from start to finish all the enzymes structural data has been a key factor in the
When a project requires a An article describing the work of Cellectis collections are tested by the platform to department
used and sold by Cellectis. The Platform on meganucleases and the techniques identify the mutants with the expected computational biology group gaining a better
different site in the genome to team creates high quality meganucleases used to create and produce new proteins properties. Striving for a rational approach understanding of the mechanisms governing
be modified, Cellectis’ teams compliant with the precise specifications of that can cut new targets was published in
aims at determining, with more precision, meganuclease/DNA interactions, and
each Cellectis partner or customer, internal November in the journal Protein Engineering optimizing the molecular modeling process
create a new meganuclease Design and Selections. This article also
which variants are more likely to be
and external. The Platform team can functional in order to generate and test a and gradually replacing the experimental
from the Omegabase, validate and secure orders by supplying each
describes the broad range of applications
smaller number of these variants. high-throughput screening method.
of meganucleases: development of cell
a bank of meganucleases customer with a solution that best meets its lines enabling protein expression, modified
needs. Using its array of robots, the Platform
with modified characteristics, plants and animals, therapeutics applications The Cellectis computational biology program
team is able to measure the activity of a like gene therapy, or creation of a new aims to improve Platform performance in An article was published in the scientific
property of Cellectis. vast number of meganucleases. It is actually class of antiviral drugs. terms of delivery, cost, capacity, sequencing journal Nucleic Acids Research, resulting
able to run up to 1 million tests per week. area and product quality. There has been from a collaboration between Cellectis and
The I-CreI meganuclease and its Dr. Guillermo Montoya’s laboratory at the
regular progress in the last few years and
engineered derivatives: applications from CNIO of Madrid. It describes the structure of
These data are then processed, analyzed with the use of innovative new techniques
cell modification to gene therapy a meganuclease bound to its DNA target.
and used to design meganucleases that are recently implemented at Cellectis, we can
Arnould S, Delenda C, Grizot S,
appropriate for each project. The Platform Desseaux C, Pâques F, Silva GH, Smith J. better address the core performance Molecular basis of engineered mega-
team enables the research departments to Protein Eng Des Sel. 2010, Nov 3 improvement aim of computational biology. nuclease targeting of the endogenous
assess their theories in standard production Print: 2011 Jan. 24(1-2) pp27-31 human RAG1 locus.
conditions while following strict procedures Muñoz IG, Prieto J, Subramanian S,
that guarantee full sample traceability and Coloma J, Redondo P, Villate M, Merino N,
quality. This work is supported by a bio- Marenchino M, D’Abramo M, Gervasio FL,
informatics team that supplies essential data Grizot S, Daboussi F, Smith J, Chion-Sotinel I,
to the research teams, enabling them to Pâques F, Duchateau P, Alibés A, Stricher F,
Serrano L, Blanco FJ, Montoya G.
predict the correct structures for developing
Nucleic Acids Res. 2010, Sep 16
effective meganucleases in the shortest
Print: 2011; 39;729-743
possible time.
The scientists identify the protein modules By carrying out its research work, the At Cellectis, the mission of the Computational design involves using
whose DNA targets match with fragments Platform team is able to expand the software based on energy level calculations
from the targeted genome site. Then they database, enhancing Cellectis’ knowledge
computational biology team in a protein, and completely relies on the
combine the modules to create a new and scientific expertise. 2010 was marked is to produce engineered availability of structural data (i.e. tridimen-
meganuclease with recognition specificity by a reduction and stabilization in meganucleases using a rational sional structures of meganucleases bound
for the required gene target. The activity manufacturing times within the Platform. to their DNA target). Cellectis established in
of each newly created meganuclease is This resulted in a significant increase in
approach. 2009-2010 a dedicated computational
then tested in a series of functional trials our production output, with 271 mega- New meganucleases are today essentially biology group, in parallel with the set up
developed by Cellectis. nucleases manufactured in 2010 compared produced by a so-called semi-rational of a major structural biology program.
with 99 in 2009. approach: collections of meganuclease The program is held at the CNIO (Madrid)
All the creation and analysis work is carried variants are built by randomly modifying in collaboration with Dr Guillermo Montoya.
out by the production Platform team, who specific areas of the protein, and these Exclusive access to a significant amount of Dr. George Silva, head of the computational biology
create from start to finish all the enzymes structural data has been a key factor in the
When a project requires a An article describing the work of Cellectis collections are tested by the platform to department
used and sold by Cellectis. The Platform on meganucleases and the techniques identify the mutants with the expected computational biology group gaining a better
different site in the genome to team creates high quality meganucleases used to create and produce new proteins properties. Striving for a rational approach understanding of the mechanisms governing
be modified, Cellectis’ teams compliant with the precise specifications of that can cut new targets was published in
aims at determining, with more precision, meganuclease/DNA interactions, and
each Cellectis partner or customer, internal November in the journal Protein Engineering optimizing the molecular modeling process
create a new meganuclease Design and Selections. This article also
which variants are more likely to be
and external. The Platform team can functional in order to generate and test a and gradually replacing the experimental
from the Omegabase, validate and secure orders by supplying each
describes the broad range of applications
smaller number of these variants. high-throughput screening method.
of meganucleases: development of cell
a bank of meganucleases customer with a solution that best meets its lines enabling protein expression, modified
needs. Using its array of robots, the Platform
with modified characteristics, plants and animals, therapeutics applications The Cellectis computational biology program
team is able to measure the activity of a like gene therapy, or creation of a new aims to improve Platform performance in An article was published in the scientific
property of Cellectis. vast number of meganucleases. It is actually class of antiviral drugs. terms of delivery, cost, capacity, sequencing journal Nucleic Acids Research, resulting
able to run up to 1 million tests per week. area and product quality. There has been from a collaboration between Cellectis and
The I-CreI meganuclease and its Dr. Guillermo Montoya’s laboratory at the
regular progress in the last few years and
engineered derivatives: applications from CNIO of Madrid. It describes the structure of
These data are then processed, analyzed with the use of innovative new techniques
cell modification to gene therapy a meganuclease bound to its DNA target.
and used to design meganucleases that are recently implemented at Cellectis, we can
Arnould S, Delenda C, Grizot S,
appropriate for each project. The Platform Desseaux C, Pâques F, Silva GH, Smith J. better address the core performance Molecular basis of engineered mega-
team enables the research departments to Protein Eng Des Sel. 2010, Nov 3 improvement aim of computational biology. nuclease targeting of the endogenous
assess their theories in standard production Print: 2011 Jan. 24(1-2) pp27-31 human RAG1 locus.
conditions while following strict procedures Muñoz IG, Prieto J, Subramanian S,
that guarantee full sample traceability and Coloma J, Redondo P, Villate M, Merino N,
quality. This work is supported by a bio- Marenchino M, D’Abramo M, Gervasio FL,
informatics team that supplies essential data Grizot S, Daboussi F, Smith J, Chion-Sotinel I,
to the research teams, enabling them to Pâques F, Duchateau P, Alibés A, Stricher F,
Serrano L, Blanco FJ, Montoya G.
predict the correct structures for developing
Nucleic Acids Res. 2010, Sep 16
effective meganucleases in the shortest
Print: 2011; 39;729-743
possible time.
The Business Development strategy In 2010, Cellectis entered Harvard Apparatus granted license Agreement with Lonza for modification
comprises five main areas, which will From a Business Development perspective, agreement of bioengineered cell line
help Cellectis advance its leadership 2010 initiated a shift in focus from
into a license agreement with This agreement granted Harvard Apparatus Cellectis bioresearch will use its mega-
in genome engineering. outlicensing of intellectual property Boehringer Ingelheim to obtain, the worldwide exclusive right to manufacture nucleases to inactivate (“knock-out”) the
towards generating income from products
developed using such intellectual property.
breed and utilize animal models and market, for research use, the full line of glutamine synthetase (GS) gene in CHOK1SV,
These are: electroporation-based instruments that Lonza’s proprietary host cell line. Lonza is
Whereas the main source of revenue for pharmaceutical research Cellectis acquired from CytoPulse. world leader in therapeutic proteins produc-
remained licenses to homologous recom-
• To give priority to meganucleases for
bination patents, the incorporation and
throughout Europe, as well as tion. Its ability to control production of the
therapeutic applications in order to treat expansion of Cellectis plant sciences, with Bayer HealthCare to use Cellectis retains all rights to use these instru- highest quality cell lines makes the company
rare genetic diseases and viral infections, the expansion of the stem cell activities ments for its own research and development a perfect partner for the application of
and to develop new products to fight cancer in Ectycell thanks to the Shinya Yamanaka
its homologous recombination programs as well as in clinical trials and pro- Cellectis technology and its meganucleases.
Dr. Dirk Pollet, Chief Business Officer or to improve allogeneic transplantation iPS license, and the acquisition of patents. BASF plant sciences phylactic or therapeutic procedures, for both
the CytoPulse electroporation technology
(transplant between two genetically
will form the cornerstones of products
has also broadened its collabo- humans and animals. Under the agreement, “We are delighted to be work-
The aim of the Business different persons).
based on Cellectis genome engineering ration with Cellectis to utilize Cellectis will receive a payment of $1.3 M
ing with Cellectis bioresearch.
from Harvard Apparatus. Cellectis will also
Development team is • To pro-actively transfer its technology to
technologies. This trend will continue
its custom meganucleases. continue to receive annual licensing fees This collaboration makes sense
through 2011 where Cellectis expects
to commercialize Cellectis’ major academic and industrial laboratories significant income from licensing of from some of its customers. and will enhance our long-
intellectual property and for research purposes. its intellectual property portfolio, but also Acquisition of assets from CytoPulse Inc.
expects to sign an increasing number Electroporation is a very efficient way of License to use Evrogen fluorescent standing and successful GS
to acquire other companies’ • To enter into business agreements in its of partnerships to develop innovative inserting molecules such as meganucleases proteins technology.”
IP that would support the four main fields of application: healthcare, products in multiple fields. into any type of cell and has applications This non-exclusive agreement with Evrogen
John Birch, CSO of Lonza Biopharmaceuticals
development of new biotechnology, agricultural biotechnology, ranging from research and biomanufacturing (Moscow, Russia) has allowed Cellectis
Dr. Dirk Pollet, Chief Business Officer to agriculture and therapeutics.
and stem cells. bioresearch to incorporate these proteins
technologies or products. into its own products and thus expand its
License agreement with Midwest
Cellectis’ innovative intellectual Through this transaction, Cellectis acquired Oilseeds for plant transformation
• To strengthen privileged partnerships range of genome engineering tools.
three other technologies based on elec- This agreement enables Cellectis plant
property has a broad range established with some of the major players
sciences to use Midwest Oilseeds’ Aerosol
in agricultural biotechnology. troporation and developed by CytoPulse: The integration matrix is one of the key com-
of applications such as Dermavax for transdermal DNA vaccination, ponents of the Cellectis bioresearch kits. It
Beam Injector (ABI) technology for the
health, agriculture or research Oncovet for veterinary vaccination appli- targeted modification of plant genomes.
• And to sustain Cellectis’ competitive is this matrix that allows the user to express
regarding stem cells and advantage by continuing to enhance its cations, and Hybrimmune to manufacture a gene of interest. By extending the choice
hybridomas for monoclonal antibodies The Midwest Oilseeds ABI technology
patent portfolio and by increasing its of promoters and tags in these matrices,
alternative energies. The technological lead and expertise in order production. The transaction was finalized Cellectis bioresearch can offer its customers
enables functional meganucleases to be
Business Development team is on September 2, 2010, for $2.2 M. delivered directly into plant cells, thus avoid-
to bring value to the portfolio. a full range of methods to achieve single-
ing the need for DNA vectors. This approach
also in charge of the business phase developments, thus saving valuable
will allow Cellectis plant sciences to modify
time during experiments.
contracts with our partners. plant genomes without integrating DNA in
the plant.
The Business Development strategy In 2010, Cellectis entered Harvard Apparatus granted license Agreement with Lonza for modification
comprises five main areas, which will From a Business Development perspective, agreement of bioengineered cell line
help Cellectis advance its leadership 2010 initiated a shift in focus from
into a license agreement with This agreement granted Harvard Apparatus Cellectis bioresearch will use its mega-
in genome engineering. outlicensing of intellectual property Boehringer Ingelheim to obtain, the worldwide exclusive right to manufacture nucleases to inactivate (“knock-out”) the
towards generating income from products
developed using such intellectual property.
breed and utilize animal models and market, for research use, the full line of glutamine synthetase (GS) gene in CHOK1SV,
These are: electroporation-based instruments that Lonza’s proprietary host cell line. Lonza is
Whereas the main source of revenue for pharmaceutical research Cellectis acquired from CytoPulse. world leader in therapeutic proteins produc-
remained licenses to homologous recom-
• To give priority to meganucleases for
bination patents, the incorporation and
throughout Europe, as well as tion. Its ability to control production of the
therapeutic applications in order to treat expansion of Cellectis plant sciences, with Bayer HealthCare to use Cellectis retains all rights to use these instru- highest quality cell lines makes the company
rare genetic diseases and viral infections, the expansion of the stem cell activities ments for its own research and development a perfect partner for the application of
and to develop new products to fight cancer in Ectycell thanks to the Shinya Yamanaka
its homologous recombination programs as well as in clinical trials and pro- Cellectis technology and its meganucleases.
Dr. Dirk Pollet, Chief Business Officer or to improve allogeneic transplantation iPS license, and the acquisition of patents. BASF plant sciences phylactic or therapeutic procedures, for both
the CytoPulse electroporation technology
(transplant between two genetically
will form the cornerstones of products
has also broadened its collabo- humans and animals. Under the agreement, “We are delighted to be work-
The aim of the Business different persons).
based on Cellectis genome engineering ration with Cellectis to utilize Cellectis will receive a payment of $1.3 M
ing with Cellectis bioresearch.
from Harvard Apparatus. Cellectis will also
Development team is • To pro-actively transfer its technology to
technologies. This trend will continue
its custom meganucleases. continue to receive annual licensing fees This collaboration makes sense
through 2011 where Cellectis expects
to commercialize Cellectis’ major academic and industrial laboratories significant income from licensing of from some of its customers. and will enhance our long-
intellectual property and for research purposes. its intellectual property portfolio, but also Acquisition of assets from CytoPulse Inc.
expects to sign an increasing number Electroporation is a very efficient way of License to use Evrogen fluorescent standing and successful GS
to acquire other companies’ • To enter into business agreements in its of partnerships to develop innovative inserting molecules such as meganucleases proteins technology.”
IP that would support the four main fields of application: healthcare, products in multiple fields. into any type of cell and has applications This non-exclusive agreement with Evrogen
John Birch, CSO of Lonza Biopharmaceuticals
development of new biotechnology, agricultural biotechnology, ranging from research and biomanufacturing (Moscow, Russia) has allowed Cellectis
Dr. Dirk Pollet, Chief Business Officer to agriculture and therapeutics.
and stem cells. bioresearch to incorporate these proteins
technologies or products. into its own products and thus expand its
License agreement with Midwest
Cellectis’ innovative intellectual Through this transaction, Cellectis acquired Oilseeds for plant transformation
• To strengthen privileged partnerships range of genome engineering tools.
three other technologies based on elec- This agreement enables Cellectis plant
property has a broad range established with some of the major players
sciences to use Midwest Oilseeds’ Aerosol
in agricultural biotechnology. troporation and developed by CytoPulse: The integration matrix is one of the key com-
of applications such as Dermavax for transdermal DNA vaccination, ponents of the Cellectis bioresearch kits. It
Beam Injector (ABI) technology for the
health, agriculture or research Oncovet for veterinary vaccination appli- targeted modification of plant genomes.
• And to sustain Cellectis’ competitive is this matrix that allows the user to express
regarding stem cells and advantage by continuing to enhance its cations, and Hybrimmune to manufacture a gene of interest. By extending the choice
hybridomas for monoclonal antibodies The Midwest Oilseeds ABI technology
patent portfolio and by increasing its of promoters and tags in these matrices,
alternative energies. The technological lead and expertise in order production. The transaction was finalized Cellectis bioresearch can offer its customers
enables functional meganucleases to be
Business Development team is on September 2, 2010, for $2.2 M. delivered directly into plant cells, thus avoid-
to bring value to the portfolio. a full range of methods to achieve single-
ing the need for DNA vectors. This approach
also in charge of the business phase developments, thus saving valuable
will allow Cellectis plant sciences to modify
time during experiments.
contracts with our partners. plant genomes without integrating DNA in
the plant.
The aim is to organize a collection of cells Cellectis has also entered into a collabora- Meganucleases offer new Focus on oil substitute
that represent the physiology, pathology tion with CiRA to combine Cellectis’ genome Our meganuclease technology would be
and diversity of a population so that we can engineering technologies with CiRA’s iPS cell
possibilities for establishing well suited to help optimize these traits and
understand this diversity in vitro. The initial technology to improve the natural character- a viable alternative to oil. enable an industrialization of the processes.
purpose is to utilize stem cells to improve istics of iPS cells for use as cellular tools. Microalgae are actually As a natural source, algae alone are currently
understanding of diseases and their mecha- thought to be able to meet the demand
nisms. If we can collect cell samples from
thought to be a very promising
“We are starting 2011 with for fuel effectively without competing with
donors who have these diseases, and have source of alternative to another need, such as food supply. Algae
the essential keys for success.
access to their medical files, it will then be oil derivative: fuel, chemical also use the process of photosynthesis and
possible to study the disease via the induced It is now up to us to ensure therefore need light, water and CO2, making
Pluripotent Stem (iPS) cells generated from
molecules or materials.
that our projects reach their them an environmentally friendly fuel.
the patient’s cells. This is partly due to their
Dr. David Sourdive, EVP Corporate Development full potential.” Dr. Alberto Amato, project leader, genome engineering
strong ability to produce It was for these reasons that, in 2010, on algae
The CellMill platform project was therefore Cellectis set up a research team to focus on
The aim of the Corporate set up primarily to industrialize iPS cells and Dr. David Sourdive oils and their growth and micro-algae, and diatoms in particular, as a
Development team for 2010 make them both robust and safe. 2010 effective yield rate. possible substitute for oil. Diatoms already
enabled us to ensure that all our projects play an important role in the environment
was to set into action the materialized by giving them the necessary because they produce one-fifth of all oxygen
opportunities available to us resources. The CellMill project received produced on earth every year. Diatoms
in the field of stem cells by a funding commitment from the regional are unicellular algae found in most humid
authorities, the Caisse des dépôts et environments and offer huge diversity, with
establishing a cell platform consignations (Bank for Official Deposits) 100,000 species already identified.
for population leading to and OSEO, a public enterprise whose
two different applications: aim is to fund and support innovation and A preliminary program was therefore set
company growth. up at Cellectis in order to provide proof of
research tools and cell therapy principle as soon as possible, particularly
Different kinds of diatoms
(transplants). In addition, two non-exclusive license agree- regarding the potential of meganuclease
ments have given Cellectis worldwide access efficiency in these algae.
to the induced Pluripotent Stem (iPS) cell
patent portfolio arising from the work of
Professor Shinya Yamanaka at the Center for
iPS Cell Research and Application (CiRA) at
the University of Kyoto (Japan). Cellectis is
the first company in the world to be licensed
by iPS Academia Japan under this iPS cell
patent portfolio for human therapeutics and
prophylactics.
The aim is to organize a collection of cells Cellectis has also entered into a collabora- Meganucleases offer new Focus on oil substitute
that represent the physiology, pathology tion with CiRA to combine Cellectis’ genome Our meganuclease technology would be
and diversity of a population so that we can engineering technologies with CiRA’s iPS cell
possibilities for establishing well suited to help optimize these traits and
understand this diversity in vitro. The initial technology to improve the natural character- a viable alternative to oil. enable an industrialization of the processes.
purpose is to utilize stem cells to improve istics of iPS cells for use as cellular tools. Microalgae are actually As a natural source, algae alone are currently
understanding of diseases and their mecha- thought to be able to meet the demand
nisms. If we can collect cell samples from
thought to be a very promising
“We are starting 2011 with for fuel effectively without competing with
donors who have these diseases, and have source of alternative to another need, such as food supply. Algae
the essential keys for success.
access to their medical files, it will then be oil derivative: fuel, chemical also use the process of photosynthesis and
possible to study the disease via the induced It is now up to us to ensure therefore need light, water and CO2, making
Pluripotent Stem (iPS) cells generated from
molecules or materials.
that our projects reach their them an environmentally friendly fuel.
the patient’s cells. This is partly due to their
Dr. David Sourdive, EVP Corporate Development full potential.” Dr. Alberto Amato, project leader, genome engineering
strong ability to produce It was for these reasons that, in 2010, on algae
The CellMill platform project was therefore Cellectis set up a research team to focus on
The aim of the Corporate set up primarily to industrialize iPS cells and Dr. David Sourdive oils and their growth and micro-algae, and diatoms in particular, as a
Development team for 2010 make them both robust and safe. 2010 effective yield rate. possible substitute for oil. Diatoms already
enabled us to ensure that all our projects play an important role in the environment
was to set into action the materialized by giving them the necessary because they produce one-fifth of all oxygen
opportunities available to us resources. The CellMill project received produced on earth every year. Diatoms
in the field of stem cells by a funding commitment from the regional are unicellular algae found in most humid
authorities, the Caisse des dépôts et environments and offer huge diversity, with
establishing a cell platform consignations (Bank for Official Deposits) 100,000 species already identified.
for population leading to and OSEO, a public enterprise whose
two different applications: aim is to fund and support innovation and A preliminary program was therefore set
company growth. up at Cellectis in order to provide proof of
research tools and cell therapy principle as soon as possible, particularly
Different kinds of diatoms
(transplants). In addition, two non-exclusive license agree- regarding the potential of meganuclease
ments have given Cellectis worldwide access efficiency in these algae.
to the induced Pluripotent Stem (iPS) cell
patent portfolio arising from the work of
Professor Shinya Yamanaka at the Center for
iPS Cell Research and Application (CiRA) at
the University of Kyoto (Japan). Cellectis is
the first company in the world to be licensed
by iPS Academia Japan under this iPS cell
patent portfolio for human therapeutics and
prophylactics.
We have since developed a strong propri- With a headcount that has The policy at Cellectis involves enabling our The new Cellectis website focuses on three
etary portfolio, with patents across three Evolution of Cellectis’ IP portfolio staff to evolve as the company does so. central themes:
broad categories – general principles,
grown from 5 in 2000 to 129 Reflective of their passion and determination
Number of patents granted to Cellectis, per year
meganucleases and their specific appli- and geographic area at the end of 2010, the key to see Cellectis become a major player in • Research and technology
cations, and manufacturing processes of word in our company is clearly biotechnology, some of the previous project • Business development
modified meganucleases. Our strategy leaders are now at the head of a department • Investor relations
involves expanding the intellectual property
100
“development,” in terms and some laboratory technicians have taken
portfolio to further protect our products, 80 of our employees and their up engineering assistant functions. In addition to these focus areas, the website
their applications, and the corresponding talents, as well as our core offers new features and fresh content including:
body of technological knowledge. 60 Moreover, Cellectis provides support for
technology. those individuals who would like to further • Several specific RSS feeds, so that
40
The Intellectual Property Team
At the end of 2010, Cellectis owned the their education in engineering. subscribers can monitor the Company’s
rights to 83 patents worldwide, including 35 business in real time, choosing only the
20
in the United States and Canada. This means These dynamics help us attract new talent subjects that interest them.
One of Cellectis’ foremost that 25 new patents were obtained over the 0 to Cellectis, unify current staff and establish
assets is its intellectual property course of the year. Cellectis currently has a genuine company identity in the midst • Information sharing via social networks
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
more than 260 patent applications pending. of continuous growth and development. (particularly Facebook and Twitter).
portfolio. The Institut Pasteur In 2010, Cellectis bought all the assets of US/CA Europe Asia Australia Cellectis is proud of its team spirit and intends
patent families covering the use CytoPulse Inc., a company that specializes to expand all its energy to maintain it. • Downloadable documents that explain
of homologous recombination in electroporation systems, and through this Cellectis’ technology.
operation obtained 16 new patents to add Team building is also achieved through
and meganuclease-type to its intellectual property portfolio. Thanks seminars and other regular in-house events • Illustrative videos and regular features on
endonucleases for inducing to these new patents, Cellectis will receive a that are organized by the Communications various aspects of Cellectis’ technology
DNA recombination formed regular income (>$600,000 in 2009), derived Department. The department is also respon- to help improve the public’s understanding
from the granting of exploitation licenses sible for promoting Cellectis’ technology of our scientific progress.
the platform upon which for CytoPulse’s HybrimuneTM electrofusion and expertise. One of the main tools set up
Cellectis was initially founded. technology. by the Communications Department in
2010 was the new corporate website with
The company strives to optimize and uphold several key features: information sharing,
the intellectual property it licensed from the interactivity and a dedicated media area.
Institut Pasteur. Cellectis also endeavors to
promote its intellectual property by defend- In light of its expansion, Cellectis chose to
ing its own rights, while respecting the rights provide visitors to the website with clearer
of others. and more accessible insight into its work,
products and achievements. Visitors to the
new website are ensured enhanced usability
and information sharing, including more
streamlined access to information about
Cellectis’ technologies and products.
We have since developed a strong propri- With a headcount that has The policy at Cellectis involves enabling our The new Cellectis website focuses on three
etary portfolio, with patents across three Evolution of Cellectis’ IP portfolio staff to evolve as the company does so. central themes:
broad categories – general principles,
grown from 5 in 2000 to 129 Reflective of their passion and determination
Number of patents granted to Cellectis, per year
meganucleases and their specific appli- and geographic area at the end of 2010, the key to see Cellectis become a major player in • Research and technology
cations, and manufacturing processes of word in our company is clearly biotechnology, some of the previous project • Business development
modified meganucleases. Our strategy leaders are now at the head of a department • Investor relations
involves expanding the intellectual property
100
“development,” in terms and some laboratory technicians have taken
portfolio to further protect our products, 80 of our employees and their up engineering assistant functions. In addition to these focus areas, the website
their applications, and the corresponding talents, as well as our core offers new features and fresh content including:
body of technological knowledge. 60 Moreover, Cellectis provides support for
technology. those individuals who would like to further • Several specific RSS feeds, so that
40
The Intellectual Property Team
At the end of 2010, Cellectis owned the their education in engineering. subscribers can monitor the Company’s
rights to 83 patents worldwide, including 35 business in real time, choosing only the
20
in the United States and Canada. This means These dynamics help us attract new talent subjects that interest them.
One of Cellectis’ foremost that 25 new patents were obtained over the 0 to Cellectis, unify current staff and establish
assets is its intellectual property course of the year. Cellectis currently has a genuine company identity in the midst • Information sharing via social networks
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
more than 260 patent applications pending. of continuous growth and development. (particularly Facebook and Twitter).
portfolio. The Institut Pasteur In 2010, Cellectis bought all the assets of US/CA Europe Asia Australia Cellectis is proud of its team spirit and intends
patent families covering the use CytoPulse Inc., a company that specializes to expand all its energy to maintain it. • Downloadable documents that explain
of homologous recombination in electroporation systems, and through this Cellectis’ technology.
operation obtained 16 new patents to add Team building is also achieved through
and meganuclease-type to its intellectual property portfolio. Thanks seminars and other regular in-house events • Illustrative videos and regular features on
endonucleases for inducing to these new patents, Cellectis will receive a that are organized by the Communications various aspects of Cellectis’ technology
DNA recombination formed regular income (>$600,000 in 2009), derived Department. The department is also respon- to help improve the public’s understanding
from the granting of exploitation licenses sible for promoting Cellectis’ technology of our scientific progress.
the platform upon which for CytoPulse’s HybrimuneTM electrofusion and expertise. One of the main tools set up
Cellectis was initially founded. technology. by the Communications Department in
2010 was the new corporate website with
The company strives to optimize and uphold several key features: information sharing,
the intellectual property it licensed from the interactivity and a dedicated media area.
Institut Pasteur. Cellectis also endeavors to
promote its intellectual property by defend- In light of its expansion, Cellectis chose to
ing its own rights, while respecting the rights provide visitors to the website with clearer
of others. and more accessible insight into its work,
products and achievements. Visitors to the
new website are ensured enhanced usability
and information sharing, including more
streamlined access to information about
Cellectis’ technologies and products.
2010 Highlights
2010 was for Cellectis bioresearch a year of consolidation in terms of research and develop-
ment, such that we are now able to market over 150 products. We are particularly pleased
with this growth, given that we only launched our first kit in December 2008 following the
creation of Cellectis bioresearch in June of that year. We are able to supply a large number
of new products, illustrating a very diverse offering. In 2010, we have adapted our products to
a variety of cell lines, evidence of the efficiency by which we bring new products to market.
We also adopted a new marketing strategy to increase our visibility and rapidly come to
competition with the main global players in research. This involved both traditional advertising
in the press and on the web, as well as attendance at some 20 trade shows, but also more
original marketing methods: an interactive web platform aimed at the scientific community
engaged in using new genomics-related techniques1 and a competition to provide financing
for a post-doctoral position involving a project including genome customization. From a
business perspective, the results were very encouraging since we more than doubled our
operating revenues. We also integrated the market share of CytoPulse, an American company
SUBSIDIARIES whose assets we acquired. This included a complete range of electroporation instruments
already commercialized, as well as the related intellectual property. Cellectis bioresearch’s 2010
operating revenues met the targets and expectations set. In the current economic climate,
this is something we can be very proud of. Our success is due to our talented team,
which now includes 20 employees, two-thirds in R&D and one-third in sales and marketing. Marc Le Bozec, Chief Financial Officer of Cellectis and
Chief Executive Officer of Cellectis bioresearch
2010 Highlights
2010 was for Cellectis bioresearch a year of consolidation in terms of research and develop-
ment, such that we are now able to market over 150 products. We are particularly pleased
with this growth, given that we only launched our first kit in December 2008 following the
creation of Cellectis bioresearch in June of that year. We are able to supply a large number
of new products, illustrating a very diverse offering. In 2010, we have adapted our products to
a variety of cell lines, evidence of the efficiency by which we bring new products to market.
We also adopted a new marketing strategy to increase our visibility and rapidly come to
competition with the main global players in research. This involved both traditional advertising
in the press and on the web, as well as attendance at some 20 trade shows, but also more
original marketing methods: an interactive web platform aimed at the scientific community
engaged in using new genomics-related techniques1 and a competition to provide financing
for a post-doctoral position involving a project including genome customization. From a
business perspective, the results were very encouraging since we more than doubled our
operating revenues. We also integrated the market share of CytoPulse, an American company
SUBSIDIARIES whose assets we acquired. This included a complete range of electroporation instruments
already commercialized, as well as the related intellectual property. Cellectis bioresearch’s 2010
operating revenues met the targets and expectations set. In the current economic climate,
this is something we can be very proud of. Our success is due to our talented team,
which now includes 20 employees, two-thirds in R&D and one-third in sales and marketing. Marc Le Bozec, Chief Financial Officer of Cellectis and
Chief Executive Officer of Cellectis bioresearch
These kits are an easy and efficient way of using Cellectis’ meganuclease technologies.
With the kits, a gene can be integrated into an extremely precise site in the genome.
“The challenge is to replace At the end of 2010, Cellectis bioresearch was supplying over 150 products via its online
traditional cell engineering shop and international distribution network (India and Canada). The company Cellectis
methods based on random bioresearch Inc. was recently set up in Cambridge, Massachusetts (United States) to
promote the company’s products and cell line engineering services throughout America.
modification with targeted Wild type
DNA Repair
Engineered
DNA Repair
Meganuclease Meganuclease
integration.” The genome customization kits contain reagents and protocols that enable precise and
Marc Le Bozec targeted modification of DNA sequences in the genome of interest, of whether a cell line,
a primary cell, a stem cell or an entire organism.
These kits are an easy and efficient way of using Cellectis’ meganuclease technologies.
With the kits, a gene can be integrated into an extremely precise site in the genome.
“The challenge is to replace At the end of 2010, Cellectis bioresearch was supplying over 150 products via its online
traditional cell engineering shop and international distribution network (India and Canada). The company Cellectis
methods based on random bioresearch Inc. was recently set up in Cambridge, Massachusetts (United States) to
promote the company’s products and cell line engineering services throughout America.
modification with targeted Wild type
DNA Repair
Engineered
DNA Repair
Meganuclease Meganuclease
integration.” The genome customization kits contain reagents and protocols that enable precise and
Marc Le Bozec targeted modification of DNA sequences in the genome of interest, of whether a cell line,
a primary cell, a stem cell or an entire organism.
Between now and the year 2050, the world’s population will The near-term goal of Cellectis plant sciences is to move away from model plants (Arabi-
dopsis and tobacco) and to apply its technology to commercial plant species. The Cellectis
grow from approximately 6 billion to more than 9 billion people. plant sciences team already has expertise in transforming corn, rice and soybean, and these
This increase in population size, coupled with a changing skills will be essential in deploying the next phase of the company.
climate and increasingly limited resources for agriculture, will
It has to be taken into account that the regulatory process required to release genetically
place enormous strains on our planet’s collective ability to provide modified plants into the environment is very expensive. As Cellectis plant sciences scientific
the food, fuel and fiber necessary to sustain humankind. team implements its genome engineering strategies, they ensure that only minimal
changes are made to the plant’s genome. It is hoped that plant genomes modified with
One bright spot on this otherwise troublesome scenario is the promise of new technologies. this kind of precision will be better accepted in the marketplace.
Genome engineering, in particular, will provide new crop plants with traits that can meet
the demands placed on agriculture in the coming decades. Pr. Daniel Voytas, Chief Scientific Officer of
Professor Voytas has been with Cellectis plant sciences as Chief Scientific Officer since Cellectis plant sciences
Created in March 2010, Cellectis plant sciences is a subsidiary dedicated to applying the company was set up. He is a professor in the Department of Genetics, Cell Biology
sequence-specific nucleases for plants to develop new species with traits of value. The and Development, and Director of the Center for Genome Engineering at the University “This is a very exciting time in
company’s main goals are to increase and accelerate use of Cellectis’ proprietary techno- of Minnesota in Minneapolis. Specializing in molecular biology and genetics, Pr. Voytas’ plant biology, and our recent
logy in agricultural biotechnology, to broaden the company’s expertise to attract new and research focuses on plant genome modification using nucleases that can recognize
expanded licensing opportunities, and to explore the development of proprietary traits.
advances in genome engineering
specific DNA sequences.
mark a new era. It is stimulating
Cellectis plant sciences is directed by a world-class scientific team. The company’s scientists He is an elected Fellow of the American Association for the Advancement of Science. to be involved in a company
were the first to implement genome engineering in plants. Among the team members is He is an Associate Editor for the journal Genetics and Editor-in-Chief for the journal
the subsidiary Chief Scientific Officer, Daniel Voytas, who is internationally renowned for
that can have such a direct
Mobile DNA. He is the co-founder of the Zinc Finger Consortium, a group of scientists
his work on plant genome engineering. Dr. Voytas is also a professor at the University of dedicated to promoting applications of zinc finger proteins for genome modification. impact on human lives and the
Minnesota where he heads the Center for Genome Engineering. Dr. Feng Zhang serves He has authored or co-authored dozens of scientific papers in the field of genome well-being of the planet.”
as the subsidiary Director of Research, and he has extensive experience in maize, rice and engineering in plant species. Pr. Daniel Voytas
Arabidopsis genome modification. In addition, the company is staffed by two PhD-level
scientists and two research associates.
In its first year of operation, Cellectis plant sciences demonstrated efficient modification
of plant genes by engineered meganucleases. Luc Mathis, Programs and Business Deve-
lopment Director, highlighted that within months of its inception, Cellectis plant sciences
obtained proof-of-concept data. These results demonstrate that meganucleases have similar
capacities in plant cells as previously shown in human cells. From this strong data, Cellectis
plant sciences is now focusing on its commercial aims: to deliver products, services and
licenses for the agriculture industry as well as to build a portfolio of agricultural traits in its
field of expertise – targeted mutagenesis in selected plant species.
Between now and the year 2050, the world’s population will The near-term goal of Cellectis plant sciences is to move away from model plants (Arabi-
dopsis and tobacco) and to apply its technology to commercial plant species. The Cellectis
grow from approximately 6 billion to more than 9 billion people. plant sciences team already has expertise in transforming corn, rice and soybean, and these
This increase in population size, coupled with a changing skills will be essential in deploying the next phase of the company.
climate and increasingly limited resources for agriculture, will
It has to be taken into account that the regulatory process required to release genetically
place enormous strains on our planet’s collective ability to provide modified plants into the environment is very expensive. As Cellectis plant sciences scientific
the food, fuel and fiber necessary to sustain humankind. team implements its genome engineering strategies, they ensure that only minimal
changes are made to the plant’s genome. It is hoped that plant genomes modified with
One bright spot on this otherwise troublesome scenario is the promise of new technologies. this kind of precision will be better accepted in the marketplace.
Genome engineering, in particular, will provide new crop plants with traits that can meet
the demands placed on agriculture in the coming decades. Pr. Daniel Voytas, Chief Scientific Officer of
Professor Voytas has been with Cellectis plant sciences as Chief Scientific Officer since Cellectis plant sciences
Created in March 2010, Cellectis plant sciences is a subsidiary dedicated to applying the company was set up. He is a professor in the Department of Genetics, Cell Biology
sequence-specific nucleases for plants to develop new species with traits of value. The and Development, and Director of the Center for Genome Engineering at the University “This is a very exciting time in
company’s main goals are to increase and accelerate use of Cellectis’ proprietary techno- of Minnesota in Minneapolis. Specializing in molecular biology and genetics, Pr. Voytas’ plant biology, and our recent
logy in agricultural biotechnology, to broaden the company’s expertise to attract new and research focuses on plant genome modification using nucleases that can recognize
expanded licensing opportunities, and to explore the development of proprietary traits.
advances in genome engineering
specific DNA sequences.
mark a new era. It is stimulating
Cellectis plant sciences is directed by a world-class scientific team. The company’s scientists He is an elected Fellow of the American Association for the Advancement of Science. to be involved in a company
were the first to implement genome engineering in plants. Among the team members is He is an Associate Editor for the journal Genetics and Editor-in-Chief for the journal
the subsidiary Chief Scientific Officer, Daniel Voytas, who is internationally renowned for
that can have such a direct
Mobile DNA. He is the co-founder of the Zinc Finger Consortium, a group of scientists
his work on plant genome engineering. Dr. Voytas is also a professor at the University of dedicated to promoting applications of zinc finger proteins for genome modification. impact on human lives and the
Minnesota where he heads the Center for Genome Engineering. Dr. Feng Zhang serves He has authored or co-authored dozens of scientific papers in the field of genome well-being of the planet.”
as the subsidiary Director of Research, and he has extensive experience in maize, rice and engineering in plant species. Pr. Daniel Voytas
Arabidopsis genome modification. In addition, the company is staffed by two PhD-level
scientists and two research associates.
In its first year of operation, Cellectis plant sciences demonstrated efficient modification
of plant genes by engineered meganucleases. Luc Mathis, Programs and Business Deve-
lopment Director, highlighted that within months of its inception, Cellectis plant sciences
obtained proof-of-concept data. These results demonstrate that meganucleases have similar
capacities in plant cells as previously shown in human cells. From this strong data, Cellectis
plant sciences is now focusing on its commercial aims: to deliver products, services and
licenses for the agriculture industry as well as to build a portfolio of agricultural traits in its
field of expertise – targeted mutagenesis in selected plant species.
Ectycell was established in September 2009 to apply the Ectycell was founded on the fact that developing early-stage high throughput screening
assays that better predict a molecule’s effect on the organism as a whole or on a geneti-
benefits of Cellectis’ core technologies to developments cally diverse population could significantly reduce the high attrition rate currently observed
within the field of stem cells, especially induced pluripotent during drug development. Advances under development at Ectycell may also open new
stem (iPS) cells. opportunities in therapeutics, including regenerative medicine.
This subsidiary will utilize these technologies to transform stem cells into true develop- What is an induced Pluripotent Stem cell?
ment and manufacturing tools that will be novel, robust, reproducible and usable in high An induced pluripotent Stem cell (or iPS cell) is an adult cell that has been reprogrammed
throughput experiments. to behave like an embryonic Stem cell (or ES cell).
Ectycell has a number of research initiatives underway that take advantage of the benefits When an ovum is fertilized, the egg divides, and within a short space of time cells are
of meganucleases for genomic engineering. These programs include: formed that have the potential to develop into all the tissues of the body. These cells are
called embryonic stem cells and are known as pluripotent cells. Pluripotency is the ability
• Development of ‘Clean iPS Cells’ by generating iPS cells from adult cells using targeted to generate all different cell types. How to make an iPS
integration and excision of reprogramming factors, which will circumvent the necessity to 4 genes
use random viral integration methods for iPS cell production. As they mature, ES cells gradually lose their differentiation potential and develop a
functional specialization. For example, a lymphocyte will tackle infections, whereas a
• Development of novel and reproducible methods for cellular differentiation from iPS cells pancreatic cell will be capable of producing insulin – for the rest of its life.
using targeted genome engineering technologies.
Until recently, it was believed to be impossible for a cell to return to a state of immaturity
“Ectycell is responsible for • Development of robust methodologies and processes for large scale production of iPS and recover its differentiation potential. In 2006, the team of Professor Shinya Yamanaka
and differentiated cells at Kyoto University demonstrated that it is possible to reprogram a mature adult cell to give
spreading Cellectis’ genome it back the properties of an embryonic stem cell. In order for this adult cell to return to a
Adult cell
engineering technologies onto • Creation of iPS based cell libraries that will be ideally suited to high throughput drug state of immaturity and be able to differentiate into all cell types, you just need it to express
the stem cell field in order to screening applications. four genes (not normally expressed in adult cells). These cells are termed induced pluripo-
tent stem cells, or iPS cells.
transform these cells into true
In October, Cellectis in-licensed induced Pluripotent Stem Cell Technology from iPS Academia Pluripotent stem cells
manufacturing tools that Japan. The two separate non-exclusive agreements grant Cellectis worldwide access
are robust, reproducible and to the induced Pluripotent Stem (iPS) cells patent portfolio arising from the work of
Professor Shinya Yamanaka at the Center for iPS Cell Research and Application (CiRA)
usable in high throughput
of the University of Kyoto, Japan.
experiments.”
David Sourdive, CEO of Ectycell Professor Yamanaka and his colleagues pioneered this groundbreaking work and Cellectis
precisely required cell types like ...
is the first company worldwide to be licensed by iPS Academia Japan under this iPS cell
patent portfolio for human therapeutics and prophylactics.
Ectycell was established in September 2009 to apply the Ectycell was founded on the fact that developing early-stage high throughput screening
assays that better predict a molecule’s effect on the organism as a whole or on a geneti-
benefits of Cellectis’ core technologies to developments cally diverse population could significantly reduce the high attrition rate currently observed
within the field of stem cells, especially induced pluripotent during drug development. Advances under development at Ectycell may also open new
stem (iPS) cells. opportunities in therapeutics, including regenerative medicine.
This subsidiary will utilize these technologies to transform stem cells into true develop- What is an induced Pluripotent Stem cell?
ment and manufacturing tools that will be novel, robust, reproducible and usable in high An induced pluripotent Stem cell (or iPS cell) is an adult cell that has been reprogrammed
throughput experiments. to behave like an embryonic Stem cell (or ES cell).
Ectycell has a number of research initiatives underway that take advantage of the benefits When an ovum is fertilized, the egg divides, and within a short space of time cells are
of meganucleases for genomic engineering. These programs include: formed that have the potential to develop into all the tissues of the body. These cells are
called embryonic stem cells and are known as pluripotent cells. Pluripotency is the ability
• Development of ‘Clean iPS Cells’ by generating iPS cells from adult cells using targeted to generate all different cell types. How to make an iPS
integration and excision of reprogramming factors, which will circumvent the necessity to 4 genes
use random viral integration methods for iPS cell production. As they mature, ES cells gradually lose their differentiation potential and develop a
functional specialization. For example, a lymphocyte will tackle infections, whereas a
• Development of novel and reproducible methods for cellular differentiation from iPS cells pancreatic cell will be capable of producing insulin – for the rest of its life.
using targeted genome engineering technologies.
Until recently, it was believed to be impossible for a cell to return to a state of immaturity
“Ectycell is responsible for • Development of robust methodologies and processes for large scale production of iPS and recover its differentiation potential. In 2006, the team of Professor Shinya Yamanaka
and differentiated cells at Kyoto University demonstrated that it is possible to reprogram a mature adult cell to give
spreading Cellectis’ genome it back the properties of an embryonic stem cell. In order for this adult cell to return to a
Adult cell
engineering technologies onto • Creation of iPS based cell libraries that will be ideally suited to high throughput drug state of immaturity and be able to differentiate into all cell types, you just need it to express
the stem cell field in order to screening applications. four genes (not normally expressed in adult cells). These cells are termed induced pluripo-
tent stem cells, or iPS cells.
transform these cells into true
In October, Cellectis in-licensed induced Pluripotent Stem Cell Technology from iPS Academia Pluripotent stem cells
manufacturing tools that Japan. The two separate non-exclusive agreements grant Cellectis worldwide access
are robust, reproducible and to the induced Pluripotent Stem (iPS) cells patent portfolio arising from the work of
Professor Shinya Yamanaka at the Center for iPS Cell Research and Application (CiRA)
usable in high throughput
of the University of Kyoto, Japan.
experiments.”
David Sourdive, CEO of Ectycell Professor Yamanaka and his colleagues pioneered this groundbreaking work and Cellectis
precisely required cell types like ...
is the first company worldwide to be licensed by iPS Academia Japan under this iPS cell
patent portfolio for human therapeutics and prophylactics.
Cellectis therapeutics, launched in 2008 under the name Cellectis 2010 was a turning point for Cellectis therapeutics, which
genome surgery, focuses on the development of innovative obtained very promising results, particularly in terms of proof of
therapeutic approaches that use meganucleases to treat genetic concept on the antiviral activity of meganucleases*.
diseases (such as muscular dystrophies and hemophilias…), cancers During the year, we also made significant progress in our cell
and persistent viral infections (herpes keratitis, AIDS). therapy programs.
This subsidiary has a team of 19, including 10 PhDs, and endeavors to find innovative Indeed, our team has been able to identify good targets for the so-called “Safe Harbor”
treatments to treat patients with serious conditions that are resistant to conventional approach. This approach consists in defining a site in a genome that allows the insertion of
therapy. Cellectis therapeutics’ aim is to fulfill unmet medical needs. The treatment a new gene, which might be expressed without interfering with the cell functions.
Dr. Carole Desseaux, Director of operations at
paradigm involves targeting the DNA sequence that causes the disease, which may be Cellectis therapeutics
innate (genetic disease) or acquired (viral infection, cancers). We also implemented an effective non-viral vectorization approach using the electro-
poration system obtained from the takeover of CytoPulse’s assets. In addition, we
The genome surgery approach aims to fight the cause of a particular disease and cure obtained very good preliminary results in homologous recombination in primary cells,
“Meganucleases can
the patient, rather than merely treat symptoms. Since its inception, Cellectis therapeutics which prepare the ground for our cell therapy development.
has worked together with its partners – academic research groups and clinicians all over resolve the issue of random
the world (including Children Hospital Boston, Institut de la Vision, Genomic Vision, CNRS, In gene therapy, the results obtained by our Canadian partners on Duchenne muscular integration. The precision
INSERM, and many others) – to transform its research into effective medical treatments. dystrophy* offers a good example of the energy put in our therapeutic research on
of the Cellectis technology
meganucleases by our academic partners.
Current clinical trials means that the new
“2010 was a year of intensive After Cellectis’ buyout of the assets of CytoPulse in September 2010, the company decided In conclusion, our work in 2010 enabled us to obtain proofs of concept and confirm gene can be delivered at
learning for both the Cellectis to pursue the partnership program that had been set up by CytoPulse for the use of electro- our scientific and regulatory strategy. We start 2011 with the aim of obtaining proofs of
a predetermined and safe
porators for vaccination. CytoPulse’s electroporation technology is particularly effective for principle for these results on key pathologies such as hemophilia*.
therapeutics teams and the location. We have high
integrating molecules such as meganucleases into any kind of cell.
partners and organizations in Dr. Carole Desseaux hopes that one day this
the medical biotechnology field Cellectis supplies the Dermavax intradermal electroporation equipment to laboratories research will lead to
carrying out clinical trials requiring this kind of equipment. Dermavax is a system that
with whom we collaborated. effective and life-enhancing
applies an electric field to facilitate the integration of small fragments of DNA into cells,
Alongside the first proofs of thereby potentializing the effect of DNA vaccines by stimulating the immune response. therapies for hemophilia
concept, we often pioneered patients.”
Although Dermavax was originally developed for cancer vaccine treatments, it is also
technology use, production and Dr. Thierry VandenDriessche and Dr. Marinee
being tested today as a prophylactic approach on HIV infections. Three clinical trials are
validation.” being conducted at the Karolinska Institute and at the Cancer Center in Stockholm,
Chuah, VIB Vesalius Research Center at the
Catholic University of Leuven (Belgium)
Sylvain Arnould, PhD, preclinical project leader in the laboratories headed by Professors Britta Wahren and Eric Sandström, as well as at
at Cellectis therapeutics
Uppsala University by Professor Totterman and Doctor Yachnin.
Cellectis therapeutics, launched in 2008 under the name Cellectis 2010 was a turning point for Cellectis therapeutics, which
genome surgery, focuses on the development of innovative obtained very promising results, particularly in terms of proof of
therapeutic approaches that use meganucleases to treat genetic concept on the antiviral activity of meganucleases*.
diseases (such as muscular dystrophies and hemophilias…), cancers During the year, we also made significant progress in our cell
and persistent viral infections (herpes keratitis, AIDS). therapy programs.
This subsidiary has a team of 19, including 10 PhDs, and endeavors to find innovative Indeed, our team has been able to identify good targets for the so-called “Safe Harbor”
treatments to treat patients with serious conditions that are resistant to conventional approach. This approach consists in defining a site in a genome that allows the insertion of
therapy. Cellectis therapeutics’ aim is to fulfill unmet medical needs. The treatment a new gene, which might be expressed without interfering with the cell functions.
Dr. Carole Desseaux, Director of operations at
paradigm involves targeting the DNA sequence that causes the disease, which may be Cellectis therapeutics
innate (genetic disease) or acquired (viral infection, cancers). We also implemented an effective non-viral vectorization approach using the electro-
poration system obtained from the takeover of CytoPulse’s assets. In addition, we
The genome surgery approach aims to fight the cause of a particular disease and cure obtained very good preliminary results in homologous recombination in primary cells,
“Meganucleases can
the patient, rather than merely treat symptoms. Since its inception, Cellectis therapeutics which prepare the ground for our cell therapy development.
has worked together with its partners – academic research groups and clinicians all over resolve the issue of random
the world (including Children Hospital Boston, Institut de la Vision, Genomic Vision, CNRS, In gene therapy, the results obtained by our Canadian partners on Duchenne muscular integration. The precision
INSERM, and many others) – to transform its research into effective medical treatments. dystrophy* offers a good example of the energy put in our therapeutic research on
of the Cellectis technology
meganucleases by our academic partners.
Current clinical trials means that the new
“2010 was a year of intensive After Cellectis’ buyout of the assets of CytoPulse in September 2010, the company decided In conclusion, our work in 2010 enabled us to obtain proofs of concept and confirm gene can be delivered at
learning for both the Cellectis to pursue the partnership program that had been set up by CytoPulse for the use of electro- our scientific and regulatory strategy. We start 2011 with the aim of obtaining proofs of
a predetermined and safe
porators for vaccination. CytoPulse’s electroporation technology is particularly effective for principle for these results on key pathologies such as hemophilia*.
therapeutics teams and the location. We have high
integrating molecules such as meganucleases into any kind of cell.
partners and organizations in Dr. Carole Desseaux hopes that one day this
the medical biotechnology field Cellectis supplies the Dermavax intradermal electroporation equipment to laboratories research will lead to
carrying out clinical trials requiring this kind of equipment. Dermavax is a system that
with whom we collaborated. effective and life-enhancing
applies an electric field to facilitate the integration of small fragments of DNA into cells,
Alongside the first proofs of thereby potentializing the effect of DNA vaccines by stimulating the immune response. therapies for hemophilia
concept, we often pioneered patients.”
Although Dermavax was originally developed for cancer vaccine treatments, it is also
technology use, production and Dr. Thierry VandenDriessche and Dr. Marinee
being tested today as a prophylactic approach on HIV infections. Three clinical trials are
validation.” being conducted at the Karolinska Institute and at the Cancer Center in Stockholm,
Chuah, VIB Vesalius Research Center at the
Catholic University of Leuven (Belgium)
Sylvain Arnould, PhD, preclinical project leader in the laboratories headed by Professors Britta Wahren and Eric Sandström, as well as at
at Cellectis therapeutics
Uppsala University by Professor Totterman and Doctor Yachnin.
Subsequent analysis of the treated cells by sequencing showed that the viral DNA had
successfully been clipped by the meganuclease, and therefore lost its capacity to replicate
and spread.
Publications
Herpes virus
Duchenne muscular dystrophy
Meganuclease-mediated Inhibition of Researchers at the Laval University Hospital Center in Quebec (Canada) used mega-
HSV1 Infection in Cultured Cells nucleases engineered by Cellectis to restore the expression of microdystrophin in human
Grosse S, Huot N, Mahiet C, Arnould S,
Barradeau S, Clerre DL, Chion-Sotinel I, myoblasts in vitro and in human cells in vivo. They were therefore able to show the
Jacqmarcq C, Chapellier B, Ergani A, potential of using meganucleases to treat Duchenne muscular dystrophy. These new
Desseaux C, Cédrone F, Conseiller E,
Pâques F, Labetoulle M, Smith J.
findings were published in the scientific journal Gene Therapy.
Molecular Therapy. 2011 Jan 11.
Gene therapy for treating hemophilia
Duchenne muscular dystrophy
Meganucleases can restore the reading The life sciences research institute VIB and Cellectis are collaborating on research into new
frame of a mutated dystrophin approaches to treat hemophilia. They are using meganucleases to replace faulty blood
Chapdelaine P, Pichavant C, Rousseau J,
Pâques F and Tremblay J.P
clotting factor genes with functional copies. Hemophilia is a group of hereditary, recessive,
Gene Therapy (2010) 17, 846–858; X-linked genetic disorders that impair the body’s ability to control blood clotting or
coagulation. Hemophilia patients suffer to various degrees from uncontrolled internal or
external bleeding if a blood vessel is broken. In areas such as the brain or inside joints,
this bleeding can be fatal or permanently debilitating. FINANCIAL STATEMENTS
Subsequent analysis of the treated cells by sequencing showed that the viral DNA had
successfully been clipped by the meganuclease, and therefore lost its capacity to replicate
and spread.
Publications
Herpes virus
Duchenne muscular dystrophy
Meganuclease-mediated Inhibition of Researchers at the Laval University Hospital Center in Quebec (Canada) used mega-
HSV1 Infection in Cultured Cells nucleases engineered by Cellectis to restore the expression of microdystrophin in human
Grosse S, Huot N, Mahiet C, Arnould S,
Barradeau S, Clerre DL, Chion-Sotinel I, myoblasts in vitro and in human cells in vivo. They were therefore able to show the
Jacqmarcq C, Chapellier B, Ergani A, potential of using meganucleases to treat Duchenne muscular dystrophy. These new
Desseaux C, Cédrone F, Conseiller E,
Pâques F, Labetoulle M, Smith J.
findings were published in the scientific journal Gene Therapy.
Molecular Therapy. 2011 Jan 11.
Gene therapy for treating hemophilia
Duchenne muscular dystrophy
Meganucleases can restore the reading The life sciences research institute VIB and Cellectis are collaborating on research into new
frame of a mutated dystrophin approaches to treat hemophilia. They are using meganucleases to replace faulty blood
Chapdelaine P, Pichavant C, Rousseau J,
Pâques F and Tremblay J.P
clotting factor genes with functional copies. Hemophilia is a group of hereditary, recessive,
Gene Therapy (2010) 17, 846–858; X-linked genetic disorders that impair the body’s ability to control blood clotting or
coagulation. Hemophilia patients suffer to various degrees from uncontrolled internal or
external bleeding if a blood vessel is broken. In areas such as the brain or inside joints,
this bleeding can be fatal or permanently debilitating. FINANCIAL STATEMENTS
Figures in thousands of euros December 31 2010 December 31 2009 Figures in thousands of euros December 31 2010 December 31 2009
Note:
Net intangible assets 3 976 903 Share capital 584 582
Since 2010, the company has endeavored to
improve the quality of its financial reporting by Net tangible assets 3 913 2 893 Share premium and reserves 45 170 52 404
publishing complete accounts in line with IFRS
standards. Non-current financial assets 231 231 Net income/loss (8 063) (7 768)
This process is an ongoing one, requiring further Deferred tax assets 8 169 5 133 Equity 37 691 45 218
restatements, particularly those concerning
revenue recognition, leasing contracts, deferred Total non-current assets 16 289 9 160 Retirement benefit obligation 120 42
tax assets and the capitalization of certain
development expenses. The figures presented
Inventories 153 118 Borrowings 809 491
here therefore include all the restatements
Trade receivables 2 491 1 768 Other financial liabilities 588 795
required by IFRS standards, but at the time of
publishing this report, the consolidated accounts
Research tax credit and subsidies 6 588 1 570 Provisions 50 71
were still being reviewed by the statutory auditors.
Other current assets 2 486 2 465 Total non current liabilities 1 567 1 399
Total current assets 35 766 51 001 Other financial liabilities 257 107
The (current and non-current) “Borrowings” item mainly corresponded to the restatement of
leasing contracts for laboratory equipment.
The other financial liabilities consisted of refundable advances granted to the group for
various research programs. In summary, the company financial debt is negligible while equity
capital reached 38 M at the end of 2010.
Figures in thousands of euros December 31 2010 December 31 2009 Figures in thousands of euros December 31 2010 December 31 2009
Note:
Net intangible assets 3 976 903 Share capital 584 582
Since 2010, the company has endeavored to
improve the quality of its financial reporting by Net tangible assets 3 913 2 893 Share premium and reserves 45 170 52 404
publishing complete accounts in line with IFRS
standards. Non-current financial assets 231 231 Net income/loss (8 063) (7 768)
This process is an ongoing one, requiring further Deferred tax assets 8 169 5 133 Equity 37 691 45 218
restatements, particularly those concerning
revenue recognition, leasing contracts, deferred Total non-current assets 16 289 9 160 Retirement benefit obligation 120 42
tax assets and the capitalization of certain
development expenses. The figures presented
Inventories 153 118 Borrowings 809 491
here therefore include all the restatements
Trade receivables 2 491 1 768 Other financial liabilities 588 795
required by IFRS standards, but at the time of
publishing this report, the consolidated accounts
Research tax credit and subsidies 6 588 1 570 Provisions 50 71
were still being reviewed by the statutory auditors.
Other current assets 2 486 2 465 Total non current liabilities 1 567 1 399
Total current assets 35 766 51 001 Other financial liabilities 257 107
The (current and non-current) “Borrowings” item mainly corresponded to the restatement of
leasing contracts for laboratory equipment.
The other financial liabilities consisted of refundable advances granted to the group for
various research programs. In summary, the company financial debt is negligible while equity
capital reached 38 M at the end of 2010.
The R&D tax credit increased significantly in 2010 ( 6.1 M compared with 1.3 M in 2009), Opening cash and cash equivalents 45 080 27 928
mainly due to the increase in R&D expenditure (+54%) and the reduction in grants received Closing cash and cash equivalents 24 048 45 080
in 2010. A background study was conducted by Cellectis with the help of consultants in order INCREASE (DECREASE) IN CASH AND CASH EQUIVALENTS (21 032) 17 152
to estimate the R&D tax credit.
The increase in the R&D tax credit in 2010 resulted in a considerable increase in this receivable
The increase in operating expenses in 2010 is due to the implementation of a major growth
at December 31. Intangible investments in 2010 consisted of 1.9 M capitalized development
strategy outlined in 2009, the consolidation of upstream research teams for Cellectis, and
expenses, along with patent acquisitions. Approximately one third of the year’s cash burn
application platform development for each of the subsidiaries. Research and development
was affected by a temporary unfavorable variation in working capital requirements. In 2011,
expenses increased by approximately 50%, which remains consistent with the staff increase
the change in cash (and cash equivalents) is expected to be near the level of net income.
(+50% from the end of 2009 to the end of 2010).
The R&D tax credit increased significantly in 2010 ( 6.1 M compared with 1.3 M in 2009), Opening cash and cash equivalents 45 080 27 928
mainly due to the increase in R&D expenditure (+54%) and the reduction in grants received Closing cash and cash equivalents 24 048 45 080
in 2010. A background study was conducted by Cellectis with the help of consultants in order INCREASE (DECREASE) IN CASH AND CASH EQUIVALENTS (21 032) 17 152
to estimate the R&D tax credit.
The increase in the R&D tax credit in 2010 resulted in a considerable increase in this receivable
The increase in operating expenses in 2010 is due to the implementation of a major growth
at December 31. Intangible investments in 2010 consisted of 1.9 M capitalized development
strategy outlined in 2009, the consolidation of upstream research teams for Cellectis, and
expenses, along with patent acquisitions. Approximately one third of the year’s cash burn
application platform development for each of the subsidiaries. Research and development
was affected by a temporary unfavorable variation in working capital requirements. In 2011,
expenses increased by approximately 50%, which remains consistent with the staff increase
the change in cash (and cash equivalents) is expected to be near the level of net income.
(+50% from the end of 2009 to the end of 2010).
Cellectis’ share price saw a downturn during the 2010 financial year. In fact, the first
Share Price Evolution trading day of 2010 finished at a price of 10.95 per share and the last day (December
31st) finished at a price of 7.40 per share, thus showing a net fall of 32.4%. Several
Share Price in € !!!!!!!Share Volume in thousands of shares
12
factors explain this downturn: the continued exit of venture capitalists as historical
100
11 shareholders, low daily trade volumes and market volatility linked to significant macro-
80
10 economic uncertainty.
60
9
40
8 The capital structure has continued to evolve by the exit of venture capital shareholders
7 20 and changes resulting from the capital increase at the end of 2009. The free float
6 0 has now reached more than 60% but the “hard core” holding, centered around the two
Apr Jul Oct
2010
2009
founders, the Institut Pasteur, the business angel present in the capital since 2000
€ 100 million market capitalization. About 10,000 share and the industrial companies that entered in 2008 (Regeneron) and 2009 (Monsanto),
average volume.
NYSE-Euronext ACLS.PA
remains unchanged.
APPENDICES
Shareholders Breakdown as of December 31, 2010
2. Corporate Partners 4% 3
6. Institut Pasteur 4%
5
6
Cellectis’ share price saw a downturn during the 2010 financial year. In fact, the first
Share Price Evolution trading day of 2010 finished at a price of 10.95 per share and the last day (December
31st) finished at a price of 7.40 per share, thus showing a net fall of 32.4%. Several
Share Price in € !!!!!!!Share Volume in thousands of shares
12
factors explain this downturn: the continued exit of venture capitalists as historical
100
11 shareholders, low daily trade volumes and market volatility linked to significant macro-
80
10 economic uncertainty.
60
9
40
8 The capital structure has continued to evolve by the exit of venture capital shareholders
7 20 and changes resulting from the capital increase at the end of 2009. The free float
6 0 has now reached more than 60% but the “hard core” holding, centered around the two
Apr Jul Oct
2010
2009
founders, the Institut Pasteur, the business angel present in the capital since 2000
€ 100 million market capitalization. About 10,000 share and the industrial companies that entered in 2008 (Regeneron) and 2009 (Monsanto),
average volume.
NYSE-Euronext ACLS.PA
remains unchanged.
APPENDICES
Shareholders Breakdown as of December 31, 2010
2. Corporate Partners 4% 3
6. Institut Pasteur 4%
5
6
Contact:
Cellectis
102 avenue Gaston Roussel
93230 Romainville
France
Tel: +33 (0)1 41 83 99 00
investors@cellectis.com
www.cellectis.com
Photos:
Ramon Martinez
Franck Beloncle
Cellectis
Tim Rummelhoff
Eric Merle
INRA Christophe Maitre
Cédric Porchez
iStockphoto
Graphic Design:
Valentina Herrmann
Printing:
GraphiCentre
Disclaimer
This publication and the information contained
herein do not constitute an offer to sell or subscribe,
or a solicitation of an offer to buy or subscribe,
for shares in Cellectis in any country. This
publication contains forward-looking statements
that relate to the Company’s objectives based
on the current expectations and assumptions of
the Company’s management only and involve
unforeseeable risk and uncertainties that could
cause the Company to fail to achieve the objectives
expressed by the forward-looking statements bove.
®
Cellectis
Contact:
Cellectis
102 avenue Gaston Roussel
93230 Romainville
France
Tel: +33 (0)1 41 83 99 00
investors@cellectis.com
www.cellectis.com
Photos:
Ramon Martinez
Franck Beloncle
Cellectis
Tim Rummelhoff
Eric Merle
INRA Christophe Maitre
Cédric Porchez
iStockphoto
Graphic Design:
Valentina Herrmann
Printing:
GraphiCentre
Disclaimer
This publication and the information contained
herein do not constitute an offer to sell or subscribe,
or a solicitation of an offer to buy or subscribe,
for shares in Cellectis in any country. This
publication contains forward-looking statements
that relate to the Company’s objectives based
on the current expectations and assumptions of
the Company’s management only and involve
unforeseeable risk and uncertainties that could
cause the Company to fail to achieve the objectives
expressed by the forward-looking statements bove.
MADE BY CELLECTIS