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Biocitech
                                                                                            102 avenue Gaston Roussel
                                                                                                     93230 Romainville
                                                                                                                France
                                                                                            Tel : +33 (0)1 48 40 65 35
                                                                                   http://www.pherecydes-pharma.com



                                           CORPORATE PROFILE
Summary                 Pherecydes Pharma SA is specialized in the research and development of lytic
                        bacteriophages (or phages) for both therapeutic and diagnostic applications. The company
                        provides innovative and adaptable solutions to combat multi-resistant bacteria, through
                        developing mixtures of natural phages and their accelerated in vitro evolution. Pherecydes
                        Pharma is the only company currently that have been able to harness this evolution
                        technology, allowing a head start on any given bacterium.

Creation                Established at the end of 2007

Workforce               6 people

Intellectual property 3 patent applications filed

Investment              EUR 1,45 million : Fonds Sécurité and La Financière de Brienne (ACE Management) and
                        Bio-Modeling Systems (founding shareholder and instigator of the 2 first patents)

Collaborations          University hospitals (Robert Debré, etc…); military hospitals (Percy, Bégin and Queen
                        Astrid); CNRS laboratory in Marseilles (joint doctorate tutor); University of Paris-Sud;
                        PHAGESPOIRS association

State aids, subsidies   EUR 500K from OSEO, French public-sector                   institution   dedicated   to   economic
                        development
Networks                Member of Medicen, Adebiotech and LEEM

Technology              Pherecydes Pharma is developing phages against three types of bacteria responsible for
                        the majority of infections in industrialized countries: Escherichia coli, Pseudomonas and
                        Staphylococcus. Among other things, the company possesses one of the world’s largest
                        collections against Escherichia coli.
                        Its method for effecting the rapid evolution of phages to combat a new form of bacterial
                        resistance is protected by three patented technologies:
                             • RIPh halts the replication of phages and makes it possible to engineer their
                                 genomes;
                             • TAPE1 performs the simultaneous and rapid introduction of random mutations in
                                 various selected regions of a protein, while preserving other regions;
                             • Ab-ACCUS makes it possible to integrate this genetic diversity into a phage
                                 genome.
                        1
                         TAPE is a targeted accelerated protein evolution process used in phages at the level of the proteins
                        that recognize the host bacterium. The technique can be used for optimizing any type of protein: its
                        efficacy has been demonstrated on monoclonal antibodies in collaboration with BAC BV Company.

Development             In partnership with several public hospitals, Pherecydes Pharma plans to embark on
strategy                clinical trials of its first two therapeutic products in 2013.
2012 - 2013             The long-term objective is to develop several banks of the most varied bacteriophages
                        possible in order to treat all forms of infections, especially those caused by strains that
                        are multi-resistant to antibiotics, or by biofilms. Pherecydes Pharma aims to establish a
                        standardised and certified industrial-scale phage development platform.
                        The company is in the middle of a funding round. It plans to double its workforce in 2012
                        through the recruitment of a manufacturing team and a company pharmacist.
Areas of application         • Biomedicines
                             • Biodefence and bioterrorism
                             • Vaccines
                             • Nanotechnologies
Scientific summary   Bacteriophages (or phages) are natural predators against bacteria. They are present in
                     the whole biosphere and the environment. A bacteriophage consists of a head containing
                     a nucleic acid (DNA or RNA) and a caudal element that enables it to attach to the
                     bacterium in order to infect it. It penetrates the interior of the germ, where it multiplies
                     and is released, triggering bacterial lysis, which is to say the destruction of the bacterium.
                     It is important to distinguish between lytic phages and tempered phages: the first
                     destroys the targeted bacterium each time, while the second may remain dormant.

                     Phagotherapy entails the use of lytic bacteriophages for treating infectious diseases of
                     bacterial origin. Due to the rapid spread of in-hospital infections and multi-resistant
                     bacteria, and to the lack of effective antibiotics to combat them, renewed interest is being
                     shown in bacteriophages.
Market               It is estimated that 25,000 people die from multi-resistant bacterial infections in Europe
                     each year. These multi-resistant bacteria also accounted for more than 260,000
                     bloodstream infections, and over 370,000 extra days in hospital, at a cost of EUR 62
                     million, according to a recent study1. Resistance to antibiotics has become a major public
                     health problem in Europe.
                     According to the World Health Organization, infectious diseases are the second cause of
                     death in the world. Three of them, Escherichia coli, Staphylococcus aureus et epidermis
                     and Pseudomonas aeruginosa, alone account for over 50% of infections in industrialised
                     countries.

                     A dozen private-sector companies are working on bacteriophages around the world, and
                     Pherecydes Pharma is the only one in France.

                     In the field of multi-resistant infections, there are other innovative approaches, such as
                     antibacterial peptides, therapeutic monoclonal antibodies, small RNAs and small anti-
                     adhesin molecules. But these approaches all have the drawback of being static and not
                     very adaptable to bacteria in perpetual mutation.
                     1
                      De Kraker MEA, Davey PG, Grundmann H. Mortality and hospital stay associated with resistant
                     Staphylococcus aureus and Escherichia coli bacteremia: estimating the burden of antibiotic resistance
                     in Europe. “PLoS Medicine”, 2011, 8(10) e1001104 8.
Assets of                •   Phages can be used to treat bacterial infections that no longer respond to
bacteriophages and           antibiotics.
phagotherapy             • They have a rapid mode of action. They propagate at lightning speed so long as
                             the target bacterium is still present.
                         • They act in a similar fashion to a surgical strike. The phages are selected so as
                             not to harm the useful bacteria found in intestinal flora, mucus and skin, unlike
                             antibiotics.
                         • There are no side effects in the treated organism. Furthermore, phages are only
                             effective against bacteria; they have no effect on human, animal or vegetable
                             cells, insects, algae or fungi.
                         • The prospects for industrial-scale production of phages make them an attractive
                             therapeutic option for developing countries.
Management           Jérôme Gabard, Chairman, has 25 years’ experience in various aspects of the life
                     sciences and human health sector:
                         • Departmental head at The MarkeTech Group (2005-2009): 20 employees, in
                             charge of the development of a business unit and carrying out market research
                         • CEO of Euroclide SA (2001-2004): six employees, drug candidate screening.
                             Managed the merger with Faust Pharmaceuticals in 2004 (which became the
                             Domain Therapeutics)
                         • Business Developer at Qualicon (2000): 100 employees, agro-food diagnostics:
                             PCR detection kit
                         • Head of R&D at DuPont de Nemours (1993-99): 10 staff. Wide international
                             exposure.
                         • Post Doc at DuPont de Nemours Inc., USA (1989-1993): Plant biotechnologies.
                     Jérôme Gabard has extensive experience in the management of start-ups and the
                     creation of value. He has been involved in most stages of the product design,
                     development and marketing process.

                     Flavie Pouillot, Research and Development Director. Before joining Pherecydes
                     Pharma, Flavie Pouillot headed a research program at the Institut Pasteur in Paris
                     focusing on the highly sensitive area of protection against the Yersinia pestis species. This
                     highly pathogenic agent is one of the principal threats associated with bioterrorism.
                     Flavie Pouillot has a PhD in microbiology combined with expertise in molecular biology
                     gained at the Institut Pasteur and Pierre & Marie University in Paris. She has published
                     numerous peer-reviewed papers in various international journals.
Contact              Jérôme Gabard – CEO – jerome.gabard@pherecydes-pharma.com

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Pherecydes Corpprofile En

  • 1. Biocitech 102 avenue Gaston Roussel 93230 Romainville France Tel : +33 (0)1 48 40 65 35 http://www.pherecydes-pharma.com CORPORATE PROFILE Summary Pherecydes Pharma SA is specialized in the research and development of lytic bacteriophages (or phages) for both therapeutic and diagnostic applications. The company provides innovative and adaptable solutions to combat multi-resistant bacteria, through developing mixtures of natural phages and their accelerated in vitro evolution. Pherecydes Pharma is the only company currently that have been able to harness this evolution technology, allowing a head start on any given bacterium. Creation Established at the end of 2007 Workforce 6 people Intellectual property 3 patent applications filed Investment EUR 1,45 million : Fonds Sécurité and La Financière de Brienne (ACE Management) and Bio-Modeling Systems (founding shareholder and instigator of the 2 first patents) Collaborations University hospitals (Robert Debré, etc…); military hospitals (Percy, Bégin and Queen Astrid); CNRS laboratory in Marseilles (joint doctorate tutor); University of Paris-Sud; PHAGESPOIRS association State aids, subsidies EUR 500K from OSEO, French public-sector institution dedicated to economic development Networks Member of Medicen, Adebiotech and LEEM Technology Pherecydes Pharma is developing phages against three types of bacteria responsible for the majority of infections in industrialized countries: Escherichia coli, Pseudomonas and Staphylococcus. Among other things, the company possesses one of the world’s largest collections against Escherichia coli. Its method for effecting the rapid evolution of phages to combat a new form of bacterial resistance is protected by three patented technologies: • RIPh halts the replication of phages and makes it possible to engineer their genomes; • TAPE1 performs the simultaneous and rapid introduction of random mutations in various selected regions of a protein, while preserving other regions; • Ab-ACCUS makes it possible to integrate this genetic diversity into a phage genome. 1 TAPE is a targeted accelerated protein evolution process used in phages at the level of the proteins that recognize the host bacterium. The technique can be used for optimizing any type of protein: its efficacy has been demonstrated on monoclonal antibodies in collaboration with BAC BV Company. Development In partnership with several public hospitals, Pherecydes Pharma plans to embark on strategy clinical trials of its first two therapeutic products in 2013. 2012 - 2013 The long-term objective is to develop several banks of the most varied bacteriophages possible in order to treat all forms of infections, especially those caused by strains that are multi-resistant to antibiotics, or by biofilms. Pherecydes Pharma aims to establish a standardised and certified industrial-scale phage development platform. The company is in the middle of a funding round. It plans to double its workforce in 2012 through the recruitment of a manufacturing team and a company pharmacist. Areas of application • Biomedicines • Biodefence and bioterrorism • Vaccines • Nanotechnologies
  • 2. Scientific summary Bacteriophages (or phages) are natural predators against bacteria. They are present in the whole biosphere and the environment. A bacteriophage consists of a head containing a nucleic acid (DNA or RNA) and a caudal element that enables it to attach to the bacterium in order to infect it. It penetrates the interior of the germ, where it multiplies and is released, triggering bacterial lysis, which is to say the destruction of the bacterium. It is important to distinguish between lytic phages and tempered phages: the first destroys the targeted bacterium each time, while the second may remain dormant. Phagotherapy entails the use of lytic bacteriophages for treating infectious diseases of bacterial origin. Due to the rapid spread of in-hospital infections and multi-resistant bacteria, and to the lack of effective antibiotics to combat them, renewed interest is being shown in bacteriophages. Market It is estimated that 25,000 people die from multi-resistant bacterial infections in Europe each year. These multi-resistant bacteria also accounted for more than 260,000 bloodstream infections, and over 370,000 extra days in hospital, at a cost of EUR 62 million, according to a recent study1. Resistance to antibiotics has become a major public health problem in Europe. According to the World Health Organization, infectious diseases are the second cause of death in the world. Three of them, Escherichia coli, Staphylococcus aureus et epidermis and Pseudomonas aeruginosa, alone account for over 50% of infections in industrialised countries. A dozen private-sector companies are working on bacteriophages around the world, and Pherecydes Pharma is the only one in France. In the field of multi-resistant infections, there are other innovative approaches, such as antibacterial peptides, therapeutic monoclonal antibodies, small RNAs and small anti- adhesin molecules. But these approaches all have the drawback of being static and not very adaptable to bacteria in perpetual mutation. 1 De Kraker MEA, Davey PG, Grundmann H. Mortality and hospital stay associated with resistant Staphylococcus aureus and Escherichia coli bacteremia: estimating the burden of antibiotic resistance in Europe. “PLoS Medicine”, 2011, 8(10) e1001104 8. Assets of • Phages can be used to treat bacterial infections that no longer respond to bacteriophages and antibiotics. phagotherapy • They have a rapid mode of action. They propagate at lightning speed so long as the target bacterium is still present. • They act in a similar fashion to a surgical strike. The phages are selected so as not to harm the useful bacteria found in intestinal flora, mucus and skin, unlike antibiotics. • There are no side effects in the treated organism. Furthermore, phages are only effective against bacteria; they have no effect on human, animal or vegetable cells, insects, algae or fungi. • The prospects for industrial-scale production of phages make them an attractive therapeutic option for developing countries. Management Jérôme Gabard, Chairman, has 25 years’ experience in various aspects of the life sciences and human health sector: • Departmental head at The MarkeTech Group (2005-2009): 20 employees, in charge of the development of a business unit and carrying out market research • CEO of Euroclide SA (2001-2004): six employees, drug candidate screening. Managed the merger with Faust Pharmaceuticals in 2004 (which became the Domain Therapeutics) • Business Developer at Qualicon (2000): 100 employees, agro-food diagnostics: PCR detection kit • Head of R&D at DuPont de Nemours (1993-99): 10 staff. Wide international exposure. • Post Doc at DuPont de Nemours Inc., USA (1989-1993): Plant biotechnologies. Jérôme Gabard has extensive experience in the management of start-ups and the creation of value. He has been involved in most stages of the product design, development and marketing process. Flavie Pouillot, Research and Development Director. Before joining Pherecydes Pharma, Flavie Pouillot headed a research program at the Institut Pasteur in Paris focusing on the highly sensitive area of protection against the Yersinia pestis species. This highly pathogenic agent is one of the principal threats associated with bioterrorism. Flavie Pouillot has a PhD in microbiology combined with expertise in molecular biology gained at the Institut Pasteur and Pierre & Marie University in Paris. She has published numerous peer-reviewed papers in various international journals. Contact Jérôme Gabard – CEO – jerome.gabard@pherecydes-pharma.com