Genome Engineering

CORPORATE PROfilE 2008

 TABlE Of COnTEnTS

4 letter from the CEO

7 An introduction to the Cellectis Group

10 Cellectis’ subsidiaries

12 Scientific updates

14 Activity and markets – Business Development Strategy

16 Product portfolio

18 intellectual property in 2008

20 Team and governance

22 Share prices and capital in 2008

23 Key events of 2008

25 financial items

Dr. André Choulika
Chief Executive Officer
4 l Cellectis l Corporate Profile 2008
lETTER fROM THE CEO
2008 was a transforming year for Cellectis, as indeed it was for the entire field
of rational genome engineering. During the year we created two subsidiaries
for the downstream application of our technologies: Cellectis BioResearch,
dedicated to the production of research tools, and Cellectis Genome Surgery,
dedicated to the development of meganucleases for therapeutic purposes.
2008 also marked our achievement of a significant proof of concept: demon-
strating that an artificially manufactured meganuclease could effectively target
and correct an endogenous gene. Major partnership agreements have also
strengthened our balance sheet, with nearly Û 28 million in cash at the end of
the year. As we look ahead, we aim to push beyond the capabilities of current
research and ensure that the power of genome engineering is accessible to a
wide range of industries and markets. Cellectis employees and advisors are uni-
fied in their passion to see meganucleases become products that contribute to
the health and wellbeing of each individual, but also to make Cellectis a world
leader in the biotechnology industry.
Our young company has developed in a remarkably short space of time: and
the potential for our technology is greater than ever. The need for new thera-
peutic products continues to grow, and innovation is at the forefront of solu-
tions for difficult to treat or naturally evasive diseases, such as viral infections.
innovation is also an effective tool for responding to the requirements of
regulatory authorities and contributors to in the healthcare system. Of course,
it is not without risk — at the same time, we must consider the products effec-
tiveness, if it is safe and if it meets the terms of patent protection. However,
it is solely by the development of new approaches “at the frontiers of what is
possible” that ground breaking, high-impact innovations emerge, and our
approach to genome surgery using meganucleases fits precisely into this
strategic vision. The exceptional results obtained this year by Cellectis, both
scientifically and commercially, reinforce the potential of our economic model
for creating long-term added value.
We share the pride with our scientists and staff in their considerable progress in
DnA recombination and meganuclease engineering. Today, at the forefront
of this field, they set the pace for progress and constantly improve standards,
to bring a completely new class of products to therapeutic and industrial
development. Our meganuclease platform continues to demonstrate its ability
to target an ever-increasing number of specific genes, thus giving us the
means to create and sustain a solid portfolio of products over the long term.
We plan to direct our technology and talents toward the development of
therapeutic meganucleases, as well as research tools, agricultural chemistry,
the production of new biologicals and renewable energies.
l letter from the CEO l
Since our beginning at the institut Pasteur, we have led innovation in our field
and we continue to strengthen our position as inventors by generating a strong
intellectual property portfolio which includes basic patents for use in biology
and the pharmaceutical industry. We protect the value of our innovations via a
strategy that is both defensive and aggressive in insuring our intellectual property.
We believe that this offensive is key to maximizing the value of our assets,
and their future potential, creating a high value industry, with the potential to
strengthen our company’s balance sheet in the mid term. Thanks to these efforts
to inform and defend with regard to our intellectual property, the agricultural
chemistry and pharmaceutical sectors are planning on utilizing meganucleases
as a major strategy in their development towards new, high added value products.

The success of Cellectis depends primarily on the people who give us their
commitment. During the course of 2008 we continued our efforts to diversify
and strengthen our skill base. We increased the number of senior level staff
members internally, reinforced our governance bodies: board of directors,
scientific advisory board and executive committee; and we increased the num-
ber of collaborative projects, both on a scientific and commercial level. This
strategy gives Cellectis access to a very large network of expertise for building
a position as world leader.

There is considerable potential in genome engineering, and our confidence in

the ability of our technologies to take a central position is continuing to grow.
This is a fascinating period, in which new economies are being constructed on
a global scale, and in which, i believe, Cellectis can achieve a strong and lasting
impact in many different markets.

finally, i would like to thank all of our shareholders for the interest they have
shown in Cellectis. We are delighted that they share our vision, our passion and
our determination in wishing to create a company that can be instrumental in
changing lives. We would like to thank them for their support and we work to
meet the industrial challenge to revolutionize biotechnology.

André Choulika
Chief Executive Officer

l Cellectis l Corporate Profile 2008 l letter from the CEO l 5

AMBITION.
It‘s in our DNA.
Constantly seek to achieve the
most audacious objective,
even if it seems out of reach.
An inTRODuCTiOn TO THE CEllECTiS GROuP

Genome engineering
Cellectis is a biotechnology company specializing in DnA programming. it discovers and develops
technologies enabling the genetic code of living organisms to be changed in a controlled, effective
and precise way. its mission is to repair DnA and unlock its potential to improve the wellbeing,
health and nutrition of humanity.

The universality of DnA, as well as the principles that govern its repair and recombination, mean that
Cellectis’ technologies are applicable to all living organisms. The value of correcting or changing the
genetic code is at the very heart of modern biotechnology. it gives humanity an understanding of the
workings of genetic determinism, and also of the differences and diversity that can result from it.
These variations can also lead to disorders that are often synonymous with disease. Genome surgery
is Cellectis’ planned approach for the treatment of diseased DnA. it is designed to eliminate the cause
of the disease, rather than merely relieve the symptoms. Diseases resulting from genome disorders
can take diverse forms such as congenital genetic diseases, cancers or viral infections.

Humanity has been manipulating the genome for several generations, through the process of genetic
selection, and it has allowed the development of new species and the progress of civilization. freeing
the potential contained in the genetic heritage, using genome engineering, opens the way for new
therapeutic solutions, and new methods for producing fuel, fibers and seeds. The potential inherent
in genome engineering is considerable, both in terms of its diversity and for the value that it contributes
to the development of humanity and human health.

At the heart of discovery, development and growth

Genome engineering remains the ground breaking economic model of Cellectis, as it has been
from the very beginning. inherent in our mission are several types of challenges:

• The growth challenge: Each of the products created by Cellectis generates value.
The aim of Cellectis is to bring its products as close to the market as possible, to maximize their value,
but also to optimize time-to-market for a better financial return.

• The innovation challenge: The implementation of genome engineering often requires associated
technologies: for example, delivery methods for therapeutic meganucleases, the integration
of innovative solutions in research kits or the search for new expertise, such as in plant biology.

• The leadership challenge: Cellectis has been able to capitalize on its leading position. However,
by opening the way for genome engineering using meganucleases, it is also vital to strengthen this
position by investing in research upstream of the induced DnA recombination.

Thus, upstream research, the combination of meganucleases with other technologies and the subsequent
incorporation of development and marketing activities are a critical axis of growth for Cellectis.

l Cellectis l Corporate Profile 2008 l introduction to the Cellectis Group l 7

 Strategy for a universal technology: applications in select fields
Cellectis’ strategy is to selectively diversify its technology across different applications and markets,
leading to short-, medium- and long-term revenue generation.

• Research and production tools: Research and production tools are products in a mature market that
have the potential to be a source of short-term revenue. in addition, making our technology available
to a large number of players in academic research and the industry, helps increase our visibility.
The aim is to place Cellectis products in the majority of the world’s laboratory benches and enable
researchers, technicians and engineers to become familiar with meganucleases, fuelling multiple
applications for our technology.
• Agricultural biotechnology: This sector is growing rapidly; seed producers are investing in technologies
to generate new plants that adhere to environmental regulation and contribute to development
and growth. Our genome engineering products in this sector have the potential to drive medium-term
profitability and therefore we are investing to grow this valuable part of the business.
• Therapeutics: The development of therapeutic products with very high potential value is one of the
company’s major avenues of growth. However, each of these products requires over ten years’ development
from inception to commercialization. The process also requires a very significant capital expenditure and
traditionally carries a high rate of failure. Therefore, the net present value of these products is still modest.

The Cellectis Group

Everyone at Cellectis is unified by the eagerness to create a major industrial player on a global scale. This
ambition is behind the strategy of structuring the group so that the subsidiaries focus on applications.
This enables the group to incorporate in various lines of businesses and address diverse markets targeted
by the Cellectis economic model. The overall consistency of approach is maintained by the science and
the technology. To achieve this ambition, the company must be able to grow in several directions.

Meganucleases on DnA sequences.
The increase in the production capacity of the meganuclease platform to 20 new products per year was
the company’s key milestone in 2008. As a result of this expanded capacity, Cellectis is now in a position
to produce DnA recombination systems in all the company’s strategic applications. Our first research
and production tools have been sold and have become benchmarks in reverse genetics, both in industrial
biology laboratories and in academic research. The development of therapeutic meganucleases has reached
the preclinical stage. Collaborative projects are currently being built up in the agricultural biochemistry
sector and Cellectis plans to take a pivotal role. lastly, although the diversity of markets for its applications
gives the company a solid organic growth perspective, it also offers a very high potential for external
growth by acquisition of technologies, distribution networks, market share and skills, whilst remaining
steadfastly true to the company’s business model based on genome engineering.

Based on this precept, and following the example of the chemical industry in the middle of the 20th century,
Cellectis has implemented strong specializations within the company, so that the target avenues of
development are strengthened and synergized. The inception of subsidiaries by field of application balances
the distribution of resources.

8 l Cellectis l Corporate Profile 2008 l introduction to the Cellectis Group l

The parent company
Cellectis S.A. is focused on upstream activities. its objective is to remain the technological world leader in
genome engineering. Efforts have consequently been made to strengthen research into DnA recombination,
meganucleases and DnA reprogramming technologies. The parent company also sets the group strategy,
controls subsidiary shareholdings and holds intellectual property rights. it is the parent company alone that
produces meganucleases, the fundamental components of the induction of DnA recombination. it also
provides the subsidiaries with the assets that will be instrumental in their development. The parent company
does not see its long-term role as directly developing and selling the products themselves, but as supplying
its subsidiaries with sophisticated prototypes produced by the R&D for DnA reprogramming, whilst
maintaining its role as holding company over the group while controlling intellectual property rights.

The subsidiaries
Cellectis Genome Surgery S.A.S. and Cellectis BioResearch S.A.S. are wholly owned by Cellectis S.A.
Each subsidiary has a specific business plan and over time will be a group profit center, generating value.
The mission of the subsidiaries is to grow not only organically, but also by acquisition. in line with group
strategy, the order book for the parent company’s new meganuclease production platform is filling up as a
result of the subsidiary business plans. Each is committed to the market logic in which it evolved: Cellectis
Genome Surgery is committed to the development of biopharmaceuticals, whilst Cellectis BioResearch is
committed to the development of laboratory reagents. They benefit from maximum development potential,
each in its market sector, but also as a result of the synergy of the group as a whole. The aim is to establish
subsidiaries according to the maturity of the applications markets or the opportunities, such as agricultural
biotechnology, stem cells, green fuels or biofibers.

Cellectis’ value creation model is based on the concept that genome engineering will become a fundamen-
tal aspect of everyday life. This model harbors considerable potential that goes far beyond the biopharma-
ceutical market alone. The information that comes from genome sequencing or the study of poly-
morphisms, in all living species, is growing exponentially. in addition, technology has made such progress
in this field that, very soon, genome sequencing for any individual will become accessible within practical
lead times and costs, on a very large scale. This colossal source of information finds its natural outlet in
genome engineering. We are currently at the dawn of the era of biology as a new technological resource
for wellbeing and growth. Genome engineering represents the future of these perspectives and will be
present in all aspects of everyday life.

l Cellectis l Corporate Profile 2008 l introduction to the Cellectis Group l 9

 CEllECTiS’ SuBSiDiARiES

Cellectis Genome Surgery is wholly dedicated to the development of innovative therapeutic

approaches using meganucleases to treat genetic diseases and persistent viral infections.
The mission of Cellectis Genome Surgery is to provide patients with an appropriate therapeutic solution.
The intended therapy targets the defective DnA that is responsible for chronic diseases. The presence
genome surgery of this “diseased” DnA can be of congenital origin (genetic disease) or acquired (viral infection, cancer).
Our projects aim to take a strong and lasting position in the treatment of patients suffering from rare,
serious diseases that elude conventional treatment.

Genome surgery constitutes a real technological leap that this subsidiary, as well as its partners (pharma-
ceutical companies, academics, doctors and patients’ groups), aspire to transform into an effective medical
product. Since its creation in June 2008, Cellectis Genome Surgery has been structured in project mode
for an effective transition between what can be called the end of the “discovery” phase and preclinical
and clinical development. The first proofs of concept studies initiated in 2008 were, from the beginning,
conducted on the matrix model.

Cellectis BioResearch is involved in the development and marketing of research kits that make genome
engineering accessible to all researchers in biology, the world over.
in particular, it offers “turnkey” solutions, enabling biologists to personalize their daily tools of work with
control and precision, for example, cell-lines with the features of an organ or a tissue, healthy or diseased.
The kits can be seen as a simple and effective means of facilitating access to the technologies developed
by Cellectis as they all contain meganucleases, either natural or with modified specificity. The kits developed
bioresearch to date enable a gene to be integrated into a very precise and unique area
of a genome. for Cellectis BioResearch, this initially involves products for targeted integration into the three
most studied genetic models to date: humans, mice and hamsters. The long-term objective is to make these
kits universally applicable and usable:

• for the greatest number of cell-lines (mammals, insects, plants, etc.);

• for applied and basic research applications;

• in combination with existing technologies;

• to monitor the expression of a gene (positive and negative regulation, constitutive or inductible,
variable in time).

Cellectis believes that genome engineering based on meganucleases will become a reference standard for
21st century biology. By offering high performance kits that are extremely easy to use and that enable rapid
personalization of the genome of any cell system being studied, Cellectis BioResearch is at the forefront
of this revolution.

10 l Cellectis l Corporate Profile 2008 l Cellectis’ subsidiaries l

CREATIVITY.
It‘s in our DNA.
Get off the beaten track and steer our
minds towards free and original thinking
to create true breakthrough innovations.
 SCiEnTifiC uPDATES
The objective of the technologies developed by
Cellectis is to produce a controlled, effective and
precise modification of DnA in the genetic program
of living species. These technologies are based on
a fundamental principle that is common to all living
species – the activation of endogenous cell main-
tenance and repair systems when DnA is broken.
There are numerous non-specific factors that can
alter the DnA of a cell’s genome, such as X-rays,
chemical products, certain enzymes or even ordinary
processes in the life of any cell (cell division, DnA
replication, etc.). However, the cells of all living
species have a finely tuned mechanism that enables
them to repair these alterations in the genome with
the aim of preserving its integrity. This mechanism
can judiciously be used to introduce targeted modi-
fications, in a precise and rational way.
Cellectis uses meganucleases because their
natural function is precisely to cut DnA at a unique
and exact place in the genome in order to modify
the chromosome. The action of a meganuclease
results in the insertion or the replacement of a
DnA sequence at the point where it is cut. The first
meganucleases were discovered over 20 years ago
in bakers’ yeast.
Cellectis has developed a proprietary technology
for reprogramming meganucleases, in order to
target them at will to new DnA sequences. Thanks
Hightech laboratories at Parc Biocitech.
to its protein engineering platform, which now
provides the capacity to produce 20 new mega-
nucleases per year, Cellectis is targeting very
diverse applications, from research and production
tools to therapeutic molecules such as antivirals.
Similar to previous years in our development as a
company, 2008 was a year rich in discoveries.
12 l Cellectis l Corporate Profile 2008 l Scientific updates l
An automated platform able to produce 20 new
meganucleases per year
new, dedicated laboratories have been installed to
accommodate the new meganuclease production
platform, with its capacity to produce 20 new
products per year. The platform operates as follows:
a DnA sequence of interest is analyzed by a
software package developed by the Cellectis bio-
informatics team. This analysis in silico offers a series
of potential target sequences. At the same time,
this software also identifies the modules that will
be assembled to produce new meganucleases with
the ability to cut these target sequences. A series of
meganucleases potentially able to cut the chosen
target is generated, and each new meganuclease is
individually tested for its ability to cut the chosen
target in a living cell (bakers’ yeast). The whole
process is automated by dedicated robots, in order
to test the greatest possible number of candidates.
The best meganucleases are selected for their
activity and their specificity in relation to their tar-
get. Over several refining cycles the lead candidates
are improved and tested finally in mammalian cells.
Each meganuclease is customized to meet pre-
specified activity and specificity requirements for
its intended application. These parameters are
documented in a performance report that is made
available to collaborators and will ultimately form
the basis of any regulatory filing. The meganucleases
produced in this way are developed by Cellectis, its
subsidiaries or partners.
Second- and third-generation meganucleases
Cellectis researchers are putting significant efforts
into understanding the recognition and cutting
mechanisms of natural and artificial meganucleases.
Their objective is to produce meganuclease proto-
types with increased specificity and stronger activity
that will be easier to manipulate and vectorize. The
first generation of meganucleases with modified
specificity was based on heterodimeric molecules,
in other words proteins consisting of independent
subunits that could form associations. This first
generation required the co-expression of two genes
coding for these two subunits. The advances made
throughout 2008, and subsequent production,
involved directly manufacturing “single chain”
meganucleases encoded by a single gene and
excluding any form of homodimerization. To this
was added modifications known as “portable,”
which improved meganuclease activity as well as
specificity. lastly, new meganucleases based on
new molecular back bones have extended the DnA
sequence space obtainable by Cellectis.
Assessment and measurement of meganuclease
activity and specificity
Cellectis researchers have developed a battery
of simple mammalian cell assays which enable the
properties of each specific meganuclease to be
characterized against standard «control» meganu-
cleases with known specificities. This allows Cellectis
to predict the future performance of each mega-
nuclease, in a host cell of interest, and it constitutes
an essential part of the value path from Cellectis
through to partners and customers. in addition,
these assays form the basis for the development
of next generation high-performance tools.
Competitive analysis of meganuclease performance
Cellectis has carried out a detailed analysis of the
performance of its meganucleases versus competitor
products. This analysis relates not only to specificity,
but also to activity at various product concentrations
in the same genomic context. This analysis was con-
ducted on the highest performing products in terms
of activity and specificity, according to the results
published by competitors. it appears that Cellectis’
meganucleases equal or outstrip the performance
of the best available products based on these two
criteria. in addition, analyses of the physicochemical
properties of meganucleases place them ahead of
the competition in terms of resistance and stability.
in fact, thanks to their characteristics, these
meganucleases are very robust and can be purified,
solubilized and preserved as active proteins.
A glance at the meganuclease portfolio
Cellectis produces meganucleases for a large variety
of target interests. During the course of 2008, the
product portfolio was enhanced with several new
meganucleases, cutting new natural genes. Today,
Cellectis has meganucleases that target the human
genome, and that of the mouse, hamster, plant,
fish and several viruses. in total, Cellectis has new
meganucleases cutting more than 30 natural DnA
sequences of interest.
l Cellectis
π10.3® CHO-K1, the first research kit designed
for academic and industrial research
At the end of December 2008 the teams at Cellectis
BioResearch developed the first research kit based
on meganucleases. This kit is used by academic
researchers and the biotechnology industry to ex-
press genes in a commonly used CHO-K1 hamster
cell line. This kit makes it possible for researchers
to carry out a stable and targeted integration of an
exogenous DnA sequence – for example a GPCR
– into the genome of this cell line. Targeting of the
gene is induced by a meganuclease at a predeter-
mined locus, where the meganuclease recognition
site is inserted. Over 90 percent of the cells selected
show integration at the meganuclease cutting site.
The stability of gene expression at the integration
site has been characterized by Cellectis BioResearch,
using various methods, over multiple cell passages.
The ease of use of this kit and the speed of obtain-
ing a targeted stable cell line (24 days) means that
researchers can generate a large number of stable
cells, all of which show the integration of the trans-
gene in the same genomic position.
Meganuclease toxicity and safety studies
in animals
Research projects have been started in order to
assess meganuclease toxicity in animal systems.
These studies take into account various types of
potential meganuclease toxicity: immunotoxicity
(immune reaction to meganucleases), genotoxicity
(toxicity of meganucleases to the animal genome),
and also other potential effects that could occur.
These studies also aim to measure the lifetime
of a meganuclease injected into the animal before
it is eliminated and distributed to the various
tissues and organs.
Meganuclease vectorization
Meganucleases are small proteins (five times smaller
than an antibody, for example). However, mega-
nucleases do not enter cells easily, and need to be
delivered appropriately to achieve their objective.
Once the cell barrier has been overcome, the mega-
nuclease can easily be directed to the cell nucleus,
where genomic DnA is found. There are several
methods to deliver meganucleases, the principal
ones being viral vectors, lipidic vectors (similar
to cell membranes), nanoparticles and transduction
peptides that can be fused to the meganuclease.
in the first instance, Cellectis is planning viral
vectorization of meganucleases, since this type
of delivery method is the most proven and
the most documented, having been validated in
several clinical trials. However, Cellectis is working
in association with partners who are specialists
in delivery methods in order to investigate other
possibilities, with the ultimate objective of using
the simplest and most reliable delivery means.
l Corporate Profile 2008 l Scientific updates l 13
 ACTiViTY AnD MARKETS – BuSinESS DEVElOPMEnT STRATEGY

Starting from its vision of commercializing its technological platform based on meganucleases and
homologous recombination, Cellectis has structured its business development activity to address the key
markets for living organisms: in direct terms, therapeutic applications for repairing DnA, the development
of innovative research tools, and the targeted modification of genes for agriculture; in a more exploratory
fashion, non-fossil fuels, biomaterials and microorganisms. As such, Cellectis offers opportunities to
access a unique set of programs and technologies.

Therapeutic programs
Via its subsidiary Cellectis Genome Surgery, Cellectis is developing several therapeutic programs for
Health. the treatment of hitherto incurable monogenic diseases and chronic infections caused by DnA viruses.
All these projects are at the preclinical stage.

Cellectis is looking for partners to share its programs relating to:

• Correcting the defective gene that causes sickle cell anemia.

• Viral infections including HiV, hepatitis B and herpes simplex where cutting viral DnA in
infected cells enables the patient’s immune system to eliminate viral particles.

Agronomy.
Aware of the proof of concept that must be established in this field, Cellectis is focusing its approach
on a model in which the potential attrition rate is balanced by the number of potential drug candidates
that can be produced by the meganuclease platform. This number balances the risks and the benefits
associated with the development of therapeutic products throughout preclinical trials and the first stages
of clinical development.

Licensing
Cellectis is expanding its development by establishing licensing agreements for proprietary technologies
and technologies for which it holds the exclusive license:

• Access to its meganuclease engineering platform in the context of collaborative projects to develop
Production of biologicals.
new therapeutic programs, cell lines and agricultural traits. This technology will realize the first
proof of concept in animals in the coming years. it is already being used in the commercial development
of plants and therapeutic proteins.

• Access to patents for homologous recombination, to create and use genetically modified cells and mice.
This technology is achieving a certain maturity, since it is used globally by the pharmaceutical and
biotechnology industries. it is currently used at different stages, from research into targeted therapies
to drug manufacturing. Our intellectual property is providing optimum value for Cellectis, as well as for
institut Pasteur, which owns the parent patents.

Research.
Agricultural biotechnology
Cellectis is developing partnership agreements with the Top 7 firms in agricultural biotechnology
sector, with a view to securing the use and general application within this field of its approach
to genome engineering using meganucleases. The Cellectis partners can thus break free from the random
transgenesis methods conventionally used in these organisms. The applications of meganucleases
primarily involve the targeted insertion of genes and the generation of new traits by correcting, modifying
or regulating the genes of the plant itself. in this way, Cellectis is building a circle of licensed users
around itself, who have access to its technologies and its meganuclease engineering platform for the
development of agricultural biotechnology products.

Products
Research kits are marketed and sold by the subsidiary Cellectis BioResearch. They carry out targeted
integration of a gene into various cell lines using natural or modified meganucleases. Standard
terms and conditions are supplied for use solely in research. for all other applications, for example the
production of therapeutic proteins and antibodies, screening or profiling of active molecules,
a commercial license is required.

14 l Cellectis l Corporate Profile 2008 l Activity and markets l

EXCELLENCE.
It‘s in our DNA.
Always seek to achieve the highest
possible standards of quality through
extremely rigorous scientific research,
governance and management.
 PRODuCT PORTfOliO

CeLLeCTiS GenOMe SurGery THerAPeuTiC deveLOPMenT

Products 2008 2009 2010 2011
Genetic diseases Sickle cell anemia
SCiD
XPC
Retina
Antivirals Hepatitis B
HiV/AiDS
Herpes
Preclinical Clinical trials

MArKeTed TOOLS
Products 2008 2009 2010 2011
Cellectis bioresearch π10
Mouse components
Cellectis bioresearch & bioproduction Hamster components
Mouse components
Human components
Hamster metabolism
Plants Confidential targets (partnerships)
in vitro test Partnerships/commercialization

Cellectis products are designed for genome engineering. Their purpose is to modify DnA in a living cell,
for the benefit of humanity. The aim of this modification is to treat the cause of diseases resulting
from a disruption in genetic programming; to create biological products such as therapeutic proteins or
antibodies; to improve the characteristics of certain species; to manufacture tools for research and
development; or simply to understand how DnA functions.

The product portfolio is weighted according to the projects developed wholly by Cellectis and its sub-
sidiaries, and collaborative projects, particularly in the field of agricultural biotechnology. Projects wholly
conducted by Cellectis comprise 80 percent therapeutic projects and 20 percent research and production
tools. This weighting is based on the potential high level of attrition inherent in pharmaceutical products
and the lower risk inherent in tool development. The potential of therapeutic products to provide very high
added value is made on a long-term. On the other hand, tools have a short development cycle, and can
thus generate short-term revenue as well as offer R&D laboratories worldwide access to and familiarity with
Cellectis technologies. Consequently, the risk associated with the development of drugs with high added
value in the long term is balanced by the relative volume of projects in this field, by collaborative projects
in agricultural biotechnology and lastly by the sale of genome engineering tools.

The π10.3® CHO-K1 Kit.

16 l Cellectis l Corporate Profile 2008 l Product portfolio l

THE PORTfOliO Of THERAPEuTiC PRODuCTS DEVElOPED BY CEllECTiS GEnOME SuRGERY

1- Gene repair products designed to treat monogenic diseases

An example is the product for treating sickle cell anemia or β-thalassemia.
in these patients, the hemoglobin beta gene contains particular characteristics that lead to anemia. There
is currently no available therapy for treating the cause of the disease, but only to relieve the symptoms.
Here the meganuclease is programmed to cut the hemoglobin beta gene and, combined with a DnA matrix,
repair the mutation within the gene. This product is being developed in partnership with the Association
française contre les Myopathies (AfM) – the french Muscular Dystrophy Association.

2- Antivirals
Antivirals based on meganucleases operate on the principle of cutting and destroying the viral DnA inside
infected cells. They can also prevent the cell from infection by restricting the presence of the viral DnA.
Here are two examples:

Human immunodeficiency virus (Hiv)

HiV is a virus in which the genome transforms itself into DnA and integrates into the patient’s chromo-
somes. in order to eliminate the virus, it is necessary either to kill the infected cell (in the same way as in an
immune reaction) or physically destroy the viral DnA of the chromosome in which it is integrated. Current
antiviral therapy inhibits the viral activity but does not cure the cells, or the patient, of their infection. The
anti-HiV meganucleases developed by Cellectis cut the viral DnA that has integrated into the chromosomes
and could reduce the viral load and potentially remove the virus from infected cells.

Human hepatitis B virus (HBv)

HBV is a DnA virus that enters the cells of patients and persist under the form of a circular, non-integrated
DnA, known as cccDnA. in this form, the virus remains latent and inactive. Worldwide, nearly 400 million
patients carry the latent form of hepatitis B. All currently available antivirals act only on the virus in its
active phase – not in its latent phase. Anti-HBV meganucleases developed by Cellectis are targeted to cut
the cccDnA and could remove the infection from the cells, reduce the viral load and change the long-term
infection scenario.

fiRST MRS KiT MARKETED BY CEllECTiS BiORESEARCH

π10.3® CHO-K1: a Meganuclease Recombination System (MRS) designed for

academic and industrial research.

This kit was designed for researchers and industrial companies wishing to carry out the stable insertion
of DnA into CHO-K1 cells (hamster cell lines) by eliminating the uncertainties and variations associated
with random integration. The kit contains the CHO-K1 cell line with a meganuclease recognition site at
a specific genomic position. The kit also contains the meganuclease that will target this site, and a DnA
integration matrix where the gene that is to be expressed can be cloned. in addition to its ease of use and
the speed of obtaining cell lines (24 days), the advantage of this new kit is the predictability of expression
of the gene of interest provided by the gene targeting at a specific locus.

l Cellectis l Corporate Profile 2008 l Product portfolio l 17

 inTEllECTuAl PROPERTY in 2008

Patents Applications under

granted ∆2007 examination ∆2007
Europe 33
= 3 +1
Homologous recombination uSA 3 = 3 =
Japan, Singapore 5 = 0 =
Europe 1* = 11 (35)1 +1
Meganucleases
(natural, method of obtaining uSA 18** = 22 (46)1 +4
variants, variants)
Other 2
3*** +3 70 +13
Europe 43 +2 4 -1
Other
(single-lTR, CpG, tetanus toxin) uSA 2 +1 11 =
Other2 3 +1 6 -1

Total for 36 patent families 42 +7 130 +17

* patent belonging solely to the Company ** including 1 patent belonging solely to the Company *** including 2 patents belonging solely to the Company
1: number including international PCT applications designating in particular Europe and the uSA
2: Patents / patent applications in Canada, Australia, Japan, China, israel and international PCT applications
3: number including french patents from priority french applications
a An international PCT application that can be validated in the 139 countries that have ratified the Patent Cooperation Treaty
b A single European patent that can be validated in the 32 countries that have ratified the European Patent Treaty: AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES,
fi, fR, GB, GR, Hu, iE, iS, iT, li, lT, lu, lV, MC, MT, nl, Pl, PT, RO, SE, Si, SK, TR (plus extension agreements with Al, BA, HR, MK, RS)

At the end of 2008, Cellectis owned rights to 36 patent families, including 42 patents granted (38 of these
belonging to institut Pasteur) and 130 patent applications under examination, particularly in Europe,
the uSA, Japan, China, israel, Canada and Australia. in 2008 Cellectis was granted its second patent in
Australia and has submitted 11 new patent applications that are currently under examination. This constant
increase in new patent families is a result of the innovation of the Cellectis laboratories in protecting both
the manufacturing processes for meganucleases with modified specificity and meganucleases as a product.

in January 2008, following an oral procedure, the Opposition Division of the European Patent Office
upheld patent EP419621 (procedure for gene targeting by homologous recombination) licensed to Cellectis
by institut Pasteur. The opposition procedure was instigated by Cell Genesys, nearly fifteen years ago.
This long procedure affected only slightly the breadth of the claims granted in 1995, the first part of the
procedure having led the Opposition Division to uphold the patent as it had been granted. Cell Genesys is
continuing to demand the total withdrawal of the patent; it is possible that the European Patent Office
will adopt the same position as that which it adopted at the beginning of this procedure. in parallel, several
divisional applications have come from patent EP419621, including one giving rise to a patent that was
granted and remained unopposed.

Cellectis gives a particular importance to respecting and maximizing the value of the intellectual property
entrusted to it by institut Pasteur. Cellectis is also committed to promoting its own intellectual property by
ensuring the defense of its rights, and respecting the rights of others.

18 l Cellectis l Corporate Profile 2008 l intellectual property l

ENTHUSIASM.
It‘s in our DNA.
Consider that the pleasure of working
together and sharing a strong company
culture are key drivers for success
in research, productivity and creativity.
 TEAM AnD GOVERnAnCE

A large number of employees have been working with the company for a long time,
some of them since its creation.

Thanks to their innovation, the sustained level of their work contribution, the enthusiasm of their team
spirit, and their commitment to a common project and vision, Cellectis has succeeded in creating significant
technological advances in biotechnology and in being constantly at the cutting edge of innovation.

The majority of Cellectis employees work in the head office premises, on the Parc Biocitech
in the Paris region. Employees can be seconded to academic laboratories in the context of
certain partnerships.

The CEO, Dr. André Choulika, leads the company’s management structure. He supervises
the sales policy and research and development strategy, and ensures the coordination between
the Group’s various management structures. An executive committee assists him.
This committee is a driving force in the management of operations and current business,
as well as in company strategy.

Cellectis also has a steering committee, a compensation committee and a finance committee.

Executive committee:
(from left to right)
Dr. Dirk Pollet,
Dr. David Sourdive,
Dr. frédéric Pâques,
Dr. André Choulika,
Dr. Marc le Bozec.

20 l Cellectis l Corporate Profile 2008 l Team and governance l

TEAM AnD GOVERnAnCE

• André Choulika, PhD, CEO and founder of the company. He is one of the pioneers in the analysis and
use of meganucleases to modify complex genomes. He obtained his PhD in molecular virology from the
university of Pierre et Marie Curie, Paris iV at institut Pasteur, before undertaking post-doctoral studies in
the Genetics Department of Harvard Medical School. He developed the first approaches to the application
of meganucleases to human therapies whilst working in the Molecular Medicine department at Boston
Children’s Hospital. He has also studied at the HEC School of Management (Challenge + program).

• david Sourdive, PhD, EVP of Corporate Development and co-founder of the company. After a
doctorate in molecular virology at the institut Pasteur, he joined one of the top immunology and antiviral
laboratories at the university of Emory, Atlanta, uSA, where his work focused on immunological memory.
Before founding the company, he was head of the biotechnology laboratory at the Centre d’Études
du Bouchet (french Ministry of Defense), between 1998 and 1999. He studied at the École Polytechnique,
and also at the HEC School of Management (Challenge + program).

• Frédéric Pâques, PhD, joined the company in October 2001 as Research and Development Manager,
and has been Chief Scientific Officer since June 2002. He is a renowned world expert in DnA
recombination mechanisms. A former student of the École normale Supérieure (ulm), he gained his
doctorate at the university of Paris Xi in 1994, before undertaking post-doctoral studies at the
university of Brandeis (Waltham, uSA), where he carried out major projects on recombination in
bakers’ yeast. When he returned to france he worked as a researcher for CRnS.

• Marc Le Bozec, Chief finance Officer, was COO at Alfact innovation (Paris, france) until September 2006.
He has over ten years’ experience as consultant in the biotech sector (Arthur D. little, Paris office),
and then as founder, Chairman and CEO of BioProtein Technologies (france) – a company dedicated
to the production of recombinant proteins in the milk of transgenic animals. He is also a graduate of
the HEC School of Management.

• dirk Pollet, PhD, has been Chief Business Officer, Executive Director of Dircs bvba, and consultant for
Cellectis since november 2008. Before founding Dircs bvba, he was Senior Vice President licensing
and intellectual Property for Galapagos nV in Belgium and member of its Executive Committee. Before
joining Galapagos nV in 2000, Dirk Pollet was Director of Molecular Diagnostics with Glaxo Wellcome,
Stevenage, uK. He also contributed to the start-up and construction of the diagnostic group at
innogenetics nV, where he worked for fourteen years. Dirk Pollet holds a PhD in biochemistry from
the university of Antwerp in Belgium.

BOARD Of DiRECTORS SCiEnTifiC ADViSORY BOARD

Christian Policard, PhD Chairman Prof. françois Jacob, Honorary Chairman, M.D.
André Choulika, PhD Prof. Rodney J. Rothstein, Chairman PhD
David Sourdive, PhD Prof. frederick W. Alt, PhD
Martin Bitsch, M.D. Prof. Bernard Dujon, PhD
Raffy Kazandjian Prof. Alain fischer, M.D.
Richard C. Mulligan, PhD Prof. James E. Haber, PhD
Kaminvest (Roger J. Hajjar, M.D. PhD) Prof. Denis Pompon, PhD
AGf Private Equity (Thierry laugel, Pharm D) Prof. José Alain Sahel, M.D.
institut Pasteur (Alain Guédon), Observer Prof. luis Serrano, PhD

l Cellectis l Corporate Profile 2008 l Team and governance l 21

 SHARE PRiCES AnD CAPiTAl STRuCTuRE in 2008

Share price development

6
60000
50000
5
40000
30000
10
20000
4
10
Jan

feb

Mar

Apr

May

Jun

Jul

Aug

Sep

Oct

nov

Dec
10000
0
volume

8
60 K 8
50 K

40 K

30 K

6
20 K
6
10 K

0
Jan

feb

Mar

Apr

May

Jun

Jul

Aug

Sep

Oct

nov

Dec
4 4
Capital structure as at december 31, 2008

Odyssee Venture 5%

lCf Rothschild 5%
Public 28%
AGf PE 11%

Kaminvest 11%
Regeneron 3%

Bankinvest 15%
founders, Personnel & Management 17%

institut Pasteur 5%

22 l Cellectis l Corporate Profile 2008 l Share prices and capital in 2008 l

KEY EVEnTS Of 2008

Corporate

• The creation of two subsidiaries: Cellectis BioResearch (subsidiary dedicated to the

production of research tools) and Cellectis Genome Surgery (subsidiary dedicated to
the development of meganucleases for therapeutic purposes).

• nomination of Pr. Roger J. Hajjar as permanent representative on the Cellectis management

board for Kaminvest Holding.

• nomination of Dr. Dirk Pollet as Chief Business Officer (CBO).

• An increase from 47 to 64 employees, including an intellectual property manager

and a legal adviser. Cellectis has 22 PhDs.

• Re-establishment of Cellectis Headquarters in a cutting-edge 30,000 square feet

new facility at the Biocitech site in October.

Commercial

• The signing of an agreement worth uS$ 17.5 million with Regeneron Pharmaceuticals
for the development of new therapeutic products (July).

• The signing of a genome surgery program worth Û 7 million with the AfM to treat
genetic diseases (September).

• The launch of the ACTiVE program, a Û 10 million project for the antiviral use
of meganucleases in the treatment of persistent infections including HiV and herpes (October).

• The launch of the first Cellectis BioResearch research kit (December).

• The signing of an agreement in the field of research tools.

• The signing of two agreements with academic teams.

intellectual property portfolio

• The filing of 17 new patent applications.

• The granting of seven new patents.

• The upholding of European patent no. EP419621 relating to the procedure of

gene targeting by homologous recombination.

r&d

• Achievement of a production capacity of 20 meganucleases with modified specificity.

• Obtaining the first third generation meganuclease.

• Extension of the meganuclease database, bringing it to about 14,000 meganucleases.

• Six new scientific publications in refereed journals:

-Publication of an article in nucleic Acid Research (2008 Apr; 36(7):2163-73)
-Publication of an article in Methods in Molecular Biology (2008; 435:31-45)
-Publication of an article in Molecular Therapy (2008 Aug; 16(8):1490-9)
-Publication of an article in Journal of Biological Chemistry (2008; 283(7):4364-74)
-Publication of an article in Proceedings of the national Academy of Sciences
(2008; vol. 105 no. 44 16888-16893)
-Publication of an article in nature (2008; 456, 107-111)

l Cellectis l Corporate Profile 2008 l Key events l 23

TransparencY.
It‘s in our DNA.
Make our work, rules, organization and
ethics understandable and visible.
 finAnCiAl iTEMS

Balance sheet

Amounts in thousands of euros December 31, 2008 December 31, 2007

financial items are
ASSeTS
presented according to ifRS.
net intangible assets 17 9
Gross values 3 169 2 622
Depreciation and loss of value (1 741) (1 607)
net tangible assets 1 428 1 015
Share investments 74 0
Other non-current financial assets 230 68
non-current financial assets 304 68
Deferred tax receivable 7 365 6 550
Total non-current assets 9 115 7 642
inventory 121 119
Receivables and related accounts 722 434
Tax repayable 2 891 2 314
Other current assets 2 273 1 244
Cash and cash equivalents 28 576 25 197
Total current assets 34 583 29 308
TOTAL ASSeTS 43 698 36 950
LiABiLiTieS
Share capital 479 461
Profit for the financial year 133 (2 988)
Share capital and reserves 33 195 29 865
Total share capital and reserves 33 195 29 865
Provisions for commitments to staff 32 26
Other financial liabilities 1 289 1 446
Total non-current liabilities 1 321 1 472
Provisions for risks and charges 88 69
Trade payables and related accounts 5 545 4 558
Other current liabilities 3 548 986
Total current liabilities 9 181 5 613
TOTAL LiABiLiTieS 43 698 36 950

Assets
Cellectis is pursuing its policy of investment and this is reflected both in intangible assets, for which
gross values rose by about Û 500,000 (for the most part corresponding to the expenses associated with
11 submissions of new patent applications), and in tangible assets, which increased in gross value by
more than Û 400,000.
Deferred tax assets grew by more than Û 800,000 thanks to the indefinitely deferrable nature of
cumulative losses. This is a specific presentation requirement according to ifRS.
Cash and cash equivalents rose by more than Û 3 million between January 1 and December 31, 2008.

Liabilities
The company’s own reserves grew by Û 3.3 million between the year end 2007 and that of 2008,
corresponding to the increase in capital reserves for Regeneron Pharmaceuticals, inc.
Trade payables increased by Û 1 million, essentially as a result of royalties due to the institut Pasteur,
in line with the increase in turnover.

l Cellectis l Corporate Profile 2008 l financial items l 25

 Balance sheet

Turnover went up by more than 600 percent between 2007 and 2008, thanks to the signing of two
major agreements, with Regeneron Pharmaceuticals, inc., and with AfM.

Charges relating to staff rose by more than Û 1 million, due to a strong increase in headcount
(from 35 staff at the start of 2007, the company had nearly 64 by the end of 2008), and due to the
withdrawal of the status of Jeune Entreprise innovante (JEi) – a preferential tax status for innovative
start-up companies – which almost doubled the social contributions.

The other operating expenditure grew by almost Û 5 million, for several reasons:
- increased recourse to external advisers;
- success fee payable to advisers upon signing the agreement with Regeneron Pharmaceuticals, inc.;
- strong increase in rental charges for equipment (systematic policy of leasing equipment) and premises
(the company occupied about 5,000 m2 at the end of 2008, against 2,000 m2 at the start of the year;
- lastly, royalties due to the institut Pasteur went up significantly in line with the increase in turnover.

Tax on profit or loss increased due to the application of the new method of calculating R&D tax credit.
2008 2007
Amounts in thousands of euros 12 months 12 months
financial items are
Turnover 10 600 1 448
presented according to ifRS.
Other business revenue 10 1 365
revenue from ordinary activity 10 610 2 813
Purchases consumed (1 108) (1 013)
Personnel expenses (4 097) (2 934)
Other operational expenses (8 344) (3 433)
Taxes (220) (185)
net depreciation (348) (383)
net provisions 60 (202)
Current operating income (3 446) (5 337)
Other non-current operating income and expenditure 5
Operating income (3 446) (5 332)
interest income and equivalents 810 573
interest payable (10) (20)
net interest receivable 800 553
Other financial income and expenditure 0 (2)
Taxes on earnings 2779 1 793
net income 133 (2 988)

26 l Cellectis l Corporate Profile 2008 l financial items l

Evolution.
It‘s in our DNA.
Our goal is to build a blue chip
in life sciences based on genome
engineering.
 Cash flow statement

Amounts in thousands of euros 2008 2007

financial items are
net income 133 (2 988)
presented according to ifRS.
Charges and income without impact on cash flow or linked to business activity 0 0
Depreciation and provisions 288 585
Variation of fair value of financial instruments (6) (11)
income from disposal of fixed assets (319)
- Proportion of subsidies allocated to income
Exchange rate adjustment
Deferred tax adjustment (882) (1 593)
Charges relating to equity-based payments 202 241
Cash flow before adjustment for working capital requirements (266) (4 086)
(increase)/reduction in receivables and related accounts (410) 252
(Reduction)/increase in trade payables and related accounts 987 145
Adjustment of net tax debt on income (577) (182)
net adjustment of other assets and liabilities related to activity 1 543 14
Adjustment of working capital requirement relating to activity 1 543 230
neT CASH FLOW reLATinG TO ACTiviTy 1 277 (3 857)
Acquisition of intangible assets (21) (6)
Acquisition of tangible assets (547) v (95)
Acquisition of investments (236)
neT CASH FLOW reLATinG TO inveSTMenT TrAnSACTiOnS (804) 217
increase in long-term financial liabilities 550
Repayments of long-term financial liabilities (157) (5 410)
Cash income from the issue of equity instruments 3 063 28 724
neT CASH FLOW reLATinG TO FinAnCinG TrAnSACTiOnS 2 906 23 864

CASH FLOW AdJuSTMenT 3 379 20 225

net opening cash balance 25 197 4 971
net closing cash balance 28 576 25 197
inCreASe (reduCTiOn) in CASH 3 379 20 225

The operational activity of Cellectis did not consume cash in 2008. The Û 3.38 million difference
in the opening cash balance and the closing cash balance is explained by the increase in capital reserves
for Regeneron Pharmaceuticals, inc.

28 l Cellectis l Corporate Profile 2008 l financial items l

Future.
It‘s in our DNA.
© Cellectis SA, 2009

The cover illustration represents a meganuclease.

Cover illustration: John Hollander

Photographs: Yan Morvan / Karim Daher / Cedric Porchez / iStockphoto

Cellectis SA, Parc Biocitech,

102 Avenue Gaston Roussel, f-93230 Romainville
Tel. +33 1 41 83 99 00, fax +33 1 41 83 99 03

investors@cellectis.com
www.cellectis.com
www.cellectis.com