Viral-based immunotherapies to transform the fight against cancers and infectious diseases. November 2017 Corporate Presentation

Transcription

1 Viral-based immunotherapies to transform the fight against cancers and infectious diseases November 2017 Corporate Presentation

2 Disclaimer This presentation contains forward-looking statements, which are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. There can be no guarantee that (i) the results of pre-clinical work and prior clinical trials will be predictive of the results of the clinical trials currently under way, (ii) regulatory authorities will agree with the Company s further development plans for its therapies, or (iii) the Company will find development and commercialization partners for its therapies in a timely manner and on satisfactory terms and conditions, if at all. The occurrence of any of these risks could have a significant negative outcome for the Company s activities, perspectives, financial situation, results and development. For a discussion of risks and uncertainties which could cause the Company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors ( Facteurs de Risque") section of the Document de Référence, available on the AMF website ( or on Transgene s website ( Forward-looking statements speak only as of the date on which they are made and Transgene undertakes no obligation to update these forwardlooking statements, even if new information becomes available in the future. 2

3 Management Experienced team focused on delivery Philippe Archinard, PhD Chairman & Chief Executive Officer Eric Quéméneur, PhD Executive VP and Chief Scientific Officer E C Christophe Ancel, PharmD VP Quality and Qualified Person Maud Brandely, MD, PhD Chief Medical Officer A B C D E F A B D Jean-Philippe Del VP Finance Thibaut du Fayet, MBA VP Marketing, Alliance, and Project Mgt John Felitti, JD, MBA General Counsel and VP Legal F Hemanshu Shah, PhD, MBA VP Corporate Development & Medical Affairs 3

4 Transgene Poised to play a key role in immunotherapy A pioneer in developing viral vector-based immunotherapies Focus on cancers and infectious diseases: High level of unmet medical need New treatments leave significant opportunities 2 Cutting-edge immunotherapy platforms Therapeutic vaccines Oncolytic viruses 5 Immunotherapy products in clinical trials focus on combinations 4

5 ORR % Anti-PD-1/PD-L1 A new paradigm need for improvement Targeting substantial non-responder populations Transgene s indications of interest 100 Non-responders 50 0 FDA approved agent available ORR = approximate objective response rate % Source: from ASCO Annual meeting 2017, by Gregory L. Beatty, MD PhD *Anti-PD-1 FDA approved in Sept

6 The power of immunotherapy combinations Strong scientific rationale for adding our immunotherapies to ICIs Immune Checkpoints Inhibitors (ICIs) Transgene s immunotherapies Block the signal that prevents activated T-cells from attacking cancer cells Enhance the efficacy of anti-tumor T-cell response Need for increased response rate Therapeutic Vaccines Stimulate the immune response to kill cancer cells Oncolytic Viruses Directly attack tumor cells and boost the immune system Safety - Preserve healthy cells Compelling preclinical and clinical packages Increased response rate, longer duration of response, extended OS Positive effects of the combination of Transgene s immunotherapies with ICIs have been demonstrated in several preclinical tumor models 6

7 Transgene Building momentum in immuno-oncology Clinical collaborations validate the potential of ICI+TG immunotherapy combinations Clinical collaborations made possible by Transgene s compelling clinical and pre-clinical packages Refocused clinical development on combination trials with ICIs Oct 2016 Clinical collaboration for TG4001 Apr 2017 Clinical collaboration for TG4010 (NSCLC 1L) 7 clinical trials initiated in last 18 months Readouts expected on 5 products Dec 2016 Clinical collaboration for TG4010 (NSCLC 2L) Jun 2017 Research collaboration agreement for UCART-19 production Sep 2017 Launch OV platform for a new generation OV 7

8 Diversified portfolio of clinical-stage immunotherapies Product THERAPEUTIC VACCINES Indication Preclinical Clinical Phase Major Expected Milestones Non-small cell lung cancer 1 st line + nivolumab (ICI) + CT FPI YE17 TG4010 Non-small cell lung cancer 2 nd line + nivolumab (ICI) First data 1Q 2018 Non-small cell lung cancer Neo-adjuvant (translational) TG4001 HPV positive cancers + avelumab (ICI) First data in 2H 18 TG1050 Chronic hepatitis B + antiviral Full data in 1H 18 ONCOLYTIC VIRUSES HCC 1 st line (PHOCUS) + sorafenib First data 2019 Pexa-Vec* HCC 1 st line Other solid tumors + nivolumab (ICI) + ipilimumab (ICI) First data in 2H 2018 Sarcoma Breast cancer + cyclophosphamide Solid tumors Neo-adjuvant (translational) TG6002 Glioblastoma First data in 2H 18 Ongoing FPI < 6 months * Transgene has commercial rights to Pexa-Vec in Europe and additional selected countries. SillaJen has a co-promote option in five European countries. 8

9 Therapeutic Vaccines Ideally suited for combination immunotherapy regimens

10 Our Therapeutic Vaccine platform Therapeutic vaccines express tumor/viral antigens To stimulate a safe and specific immune response Antigen (MUC1) expression leading to maturation of Antigen Presenting Cell (APC) Mature APCs present MUC1 antigen to naive T-cells SC injection T-cells get activated, multiply and reach the blood stream Important benefit when combined with CT and ICIs Activated T-cells infiltrate the tumor, recognize and kill MUC1+ tumor cells 10

11 TG4010 targeting 1 st and 2 nd line NSCLC Modified Virus Ankara (MVA) expressing MUC1 antigen & interleukin 2 Clinical collaborations with

12 TG4010 Strong lung cancer clinical data Improved response rate & duration of response TG4010 TG chemotherapy (n=39) [23.9 [ ] 54.1] wks wks Non-squamous (n) ORR Median duration of response (wks) TG CT 98 40% 41 Placebo + CT 98 28% 18 Placebo Chemotherapy + chemotherapy (n=27) 18.1 [ ] wks Improved response rate & duration of response Good safety profile Source: Quoix, E. et al., TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial, The Lancet Oncology, Dec. 2015, (17:212) 12

13 TG4010 Strong lung cancer clinical data Well positioned for further development in NSCLC SUCCESSFUL PHASE 2B TRIAL (RANDOMIZED, PLACEBO-CONTROLLED, 222 PATIENTS) TG4010 in combination with chemotherapy for 1 st line NSCLC Progression-free survival (months) Patients with non sq. tumors (n=196) Overall survival (months) Patients with non sq. tumors (n=196) Significant improvements in PFS and OS in patients in patients with non sq. tumors TG chemotherapy Placebo + chemotherapy 35% 19% TG chemotherapy Placebo + chemotherapy 36% 20% Clinical efficacy in both PD-L1 negative and PD-L1 positive patients Source: Quoix, E. et al., TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial, The Lancet Oncology, Dec. 2015, (17:212) 13

14 TG4010 Proven mechanism of action Efficacy driven by T-cell response (CD8+) Specific CD8+ T cell response to MUC1 epitopes is associated with increased survival OS improvement during TG4010 treatment is driven by the development of a larger CD8+ T cell anti-muc1 repertory Specific CD8+ T cell response to MUC1 after TG4010 administration is associated with responses against other lung tumor antigens Increased CD8+ response without increase in inhibitory T reg frequency Source: Tosch et al., Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC, Journal for ImmunoTherapy of Cancer, 2017 (5:70) 14

15 TG4010 Clinical positioning A very large population in NSCLC, stage IV, non-squamous patients Eligible Population (US, EU, JP), in thousands of patients STAGE IV 710 K NON-SQUAMOUS NON-MUTATED (ALK, EGFR, ) 441 K 532 K 1L - TG4010 positioning 2L - TG4010 positioning LOW PD-L1-1ST LINE 2ND LINE (INDEPENDENT OF PD-L1 STATUS) 265 K 331 K Source: Globocan, Company estimates 15

16 TG4010 Clinical development plan (non sq. NSCLC) 2 PoC trials to demonstrate the efficacy of TG4010 combined with ICIs Position TG4010 in all settings of advanced NSCLC in combination with PD-1 inhibitor NSCLC - 2 nd line TG PD-1 Inhibitor (nivolumab) Multi-center Phase 2 trial in the US PI: Dr. Karen Kelly (UC Davis) BMS to supply nivolumab First data expected 1Q 2018 NSCLC - 1 st line patients with no or low level of PD-L1 expression TG chemotherapy + PD-1 Inhibitor (nivolumab) Multi-center Phase 1/2 trial in US and Europe BMS to supply nivolumab US FDA IND approval granted (Sept. 2017) FPI expected to be enrolled end 2017 First data expected in 2H

17 TG4010 Non-Small Cell Lung Cancer (NSCLC) - 2 nd line Phase 2 in combination with Opdivo (nivolumab) Support of Protocol Up to 33 patients Multi-center, single-arm, open-label study Stage IV non-squamous NSCLC who have progressed after one line of systemic therapy Principal Investigator: Dr. Karen Kelly Collaborative arrangement UC Davis Medical Center, USA (sponsor) Bristol-Myers Squibb (supply of nivolumab) Transgene (supply of TG4010) First patient treated in March 2017 First planned data expected 1Q 2018 (15 patients) Endpoints Primary endpoint: Objective response rate (ORR) Secondary endpoints: progression-free survival (PFS), overall survival (OS), duration of response and safety Participating centers UC Davis UC San Francisco City of Hope UC San Diego 17

18 TG4010 Non-Small Cell Lung Cancer (NSCLC) - 1 st line Phase 1/2 in combination with Opdivo (nivolumab) + chemotherapy Support of Collaborative agreement with BMS (supply of nivolumab) US FDA IND Approval (Sept. 2017) First patient expected to be enrolled by the end of 2017 First data expected in 2H 2018 Study regimen TG PFU weekly for 6 weeks then every 3 weeks by SC route Nivolumab 360 mg every 3 weeks by IV route Pemetrexed-carboplatin (or cisplatin) every 3 weeks for 4 cycles Protocol Up to 39 patients Multi-center, single-arm, open-label study Stage III B-IV or delayed relapse, tumors with low or undetectable PD-L1 expression Endpoints (Phase 2 part) Primary endpoint: Objective response rate (ORR) Secondary endpoints: progression-free survival (PFS), overall survival (OS), duration of response and safety Participating countries USA Belgium Denmark France 18

19 TG4001 targeting HPV-positive head and neck cancer MVA expressing HPV16 E6 & E7 antigens & interleukin 2 Supported by

20 TG4001 No specific treatment regimens for HPV+ head and neck cancer patients ~60% of oropharyngeal SCCHN are HPV+ Increasing incidence in western countries 25,000 patients* Dismal prognosis Much better therapeutic options needed Current treatment options for all head and neck cancer cases First-line therapy For patients with good performance status: historically platinum-based doublet (e.g. Cisplatin/5-FU or carboplatin/paclitaxel) ORR: 30% to 40% Median OS: 6-9 months regardless of specific drug For patient with poor performance status: use single agent CT or cetuximab Second-line therapy Nivolumab, pembrolizumab ORR: 16% to 19% Median OS: 7-8 months Significant opportunity for TG4001 to improve the ORR of ICIs in a large head and neck cancer population * Source: Globocan, Company estimates 20

21 TG4001 Strong rationale for combining a vaccine targeting HPV with an ICI in advanced/metastatic HPV-positive SCCHN TG already demonstrated efficacy in the clinic: Randomized, placebo-controlled Phase 2b (n=206) in HPV+ high grade cervical carcinoma in situ (CIN2/3) Demonstrated immunogenicity Demonstrated efficacy (resolution and viral clearance) Study confirmed safety (injection site reaction most common adverse event) TG4001 was nevertheless not progressed further in CIN 2/3 (LEEP efficacy) Thanks to KOLs and Merck KGaA/Pfizer s commitment, decision to progress rather in advanced HPV positive cancers in combination with avelumab Very strong scientific rationale for combining TG4001 and avelumab to address the high unmet medical in this important HPV-positive cancer population 21

22 TG4001 HPV + Head & Neck Cancers (SCCHN) On-going Phase 1b/2 in combination with avelumab (Bavencio ) Support of Protocol Up to 50 patients (France) Multi-center, single-arm, open-label trial Metastatic or refractory/recurrent HPV-16+ head & neck cancers, after failure of standard therapy Lead investigator: Prof Christophe Le Tourneau, Institut Curie Collaborative agreement with the alliance of Merck KGaA and Pfizer (supply of avelumab) First patient treated in September 2017 Endpoints (Phase 2 part) Primary endpoint: Objective response rate (ORR) Secondary endpoints: progression-free survival (PFS), overall survival (OS), duration of response and safety First data expected in 2H

23 TG1050 targeting chronic hepatitis B Modified Adenovirus 5 that expresses 3 different HBV (Hepatitis B Virus) antigens

24 TG1050 Current therapies focus on disease management, not cure Large unmet medical need as cure rate is extremely low Need to improve clinical outcome: High risk of developing cirrhosis and hepatocellular carcinoma 500,000 eligible patients* Treatment recommendations (EASL 2017 clinical guidelines) Long-term administration of entecavir (Baraclude ), tenofovir disoproxil fumarate (Viread ) or tenofovir alafenamide (Vemlidy ) as monotherapy High level of viral suppression 98 % Low level of functional cure (HBsAg loss) < 3 % per year PegIFN for 48 weeks in highly selected patients Moderate level of viral suppression 50 % Low level of functional cure < 9% per year * Source: Decision Resources, Company estimates Note: Includes patients from the US, EU, and Japan 24

25 HBsAg Fold Change (Mean +/- SEM) HBV DNA Fold Change (Mean +/- SEM) TG1050 Strong pre-clinical data Sustained anti-viral effects in HBV mouse models (AAV) Only viral-based therapeutic vaccine that integrates the 3 relevant HBV antigens (polymerase, core, HBsAg) Demonstrated immunogenicity & functionality Similar to those of spontaneous resolvers i.e. robust and broad CD8 T-cell responses Capacity of HBV-specific T cells induced by TG1050 to recognize epitopes all HBV genotypes Capacity to induce functional T-cells in tolerant HBV mouse models (Novel AAV-based model, other) Antiviral properties Capacity to control HBsAg and induce HBsAg seroconversion with no detectable liver inflammation in tolerant HBV mouse models Ongoing preclinical experiments (direct/indirect antivirals, immunomodulators, ) HBV DNA (viral load) Mean viral load at D28 : 1.4x106 copies/ml Empty Ad TG1050 Days post AAV-HBV injection Circulating HBsAg Mean HBsAg titers at D28 : 20µg/mL Empty Ad TG Days post AAV-HBV injection Martin et al., Gut, 2014 Inschauspé et al., EASL,

26 TG1050 Phase 1/1b trial Principal investigator Prof Fabien Zoulim, Hospices civils, Lyon (France) Protocol Up to 48 patients International, randomized safety and dosefinding study Patients currently being treated with standard-of-care antiviral therapy (tenofovir or entecavir) Initial safety data in 12 patients reported First efficacy data expected 1H 2018 (n=48) Participating countries Canada, France, Germany Primary objectives Evaluate safety and tolerability of TG1050 administered in single and multiple doses (3 injections at one week interval) Determine dose and schedule of administration for further development Secondary endpoints Antiviral activity: HBsAg levels Cellular and humoral immune responses Phase I/Ib enrolment completed Preliminary data (AASLD Liver Meeting 2017): Good safety profile in 12 patients TG1050 induces a robust specific cell-mediated immune response in patients that have received a single dose of TG

27 Oncolytic Viruses Pioneered by Transgene A new highly promising therapeutic class in the fight against cancer

28 Our Oncolytic Virus (OV) platform IT/IV administration to directly attack tumor cells and stimulate immune response OV infect tumor cells where they selectively replicate This replication leads to immunogenic cell death, virus propagation in neighboring cells and in situ vaccination Active payloads are expressed locally and released into the tumor micro-environment Cytotoxic T-cells enter into the tumor, attracted by local inflammation and danger signals Infiltrated T-cells kill tumor cells and boost anti-tumor response by active release of tumor antigens Preclinical models show OV s ability to reduce tumor burden and have an abscopal effect on distant metastasis via induced immunogenic cell death mechanism 28

29 Pexa-Vec in hepatocellular carcinoma (HCC) Replicative Vaccinia Virus expressing GM-CSF

30 Pexa-Vec Collaboration with SillaJen Transgene owns development and commercialization rights in Europe EU rights of Pexa-Vec in-licensed in 2010 Current licensor: SillaJen (KOSDAQ: ) Ongoing pivotal Phase 3 trial in HCC 1L SillaJen responsible for conducting Phase 3 trial Transgene own all rights for its territory Transgene s remaining funding obligation amounts to $1.5 million 4 Phase 2 trials conducted by Transgene 30

31 Pexa-Vec Large unmet medical need in HCC Dismal prognosis Better therapeutic options needed 25,000 eligible patients in Europe* First-line therapy Sorafenib is currently the only approved product - modest activity ORR: 2% ; median OS: 10.7 months Nivolumab could become a new therapeutic option: Promising activity in Phase 2 (still ongoing) Second-line therapy Regorafenib ORR: 10%; median OS: 10.6 months Nivolumab recently approved by FDA ORR: 18%; median OS: 15.6 months * Source: Globocan, Company estimates 31

32 Pexa-Vec Key Phase 2 clinical trial results Clinical activity demonstrated in multiple trials Trials with >300 patients treated with Pexa-Vec in variety of tumor types, including liver, colorectal and kidney Proof of concept for MOA: active immunotherapy 30-patient dose-finding Phase 2 trial in HCC (80% of patients first-line) OS results - high dose versus low dose Median OS: 14.1 (high dose) vs. 6.7 months (low dose) Hazard Ratio = 0.39 p = Nature Medicine, Volume 19, Issue 2, February

33 Pexa-Vec Clinical development plan in HCC - 1 st line Pivotal Phase 3 and combination Phase 2 Position Pexa-Vec with SoC treatment for all PD-L1 status patients Advanced HCC 1 st line Advanced HCC 1 st line Pexa-Vec + sorafenib Pexa-Vec + Opdivo (nivolumab) Multi-center Phase 3 trial in Europe, US, Asia Randomized, two arm trial Ongoing recruitment First data (efficacy vs SoC) expected in 2019 Multi-center Phase 1/2 trial in France, Italy, US Sponsor: Transgene Open-label, single-arm trial 1 st patient dosed in July 2017 Efficacy data expected in 2H

34 Pexa-Vec Ongoing Phase 3 clinical trial (PHOCUS trial) 1 st line advanced hepatocellular carcinoma Phase 3 study in combination with sorafenib (Kinase inhibitor) Design Pexa-Vec + sorafenib versus sorafenib (only approved drug for advanced HCC) N= 600 patients (Europe, North America, and Asia), 140 clinical centers 1:1 randomized trial Conducted by Endpoints Primary: overall survival (OS) Secondary: safety, time to progression, progression-free survival, overall response rate and disease control rate Orphan drug designation granted SPA with FDA SFDA authorization (July 2017) First patient enrolled in January 2016 Recruitment ongoing First efficacy data expected in

35 Pexa-Vec Phase 1/2, combo with nivolumab Advanced stage HCC - 1 st line Principal Investigator: Prof Olivier Rosmorduc, Pitié-Salpêtrière Hospital, Paris (France) First patient treated in July 2017 Study regimen Pexa-Vec: 3 intratumoral injections, 10 9 pfu, q2w +/- boosts Nivolumab: IV, 240mg, q2w until progression, start at D15 Protocol Up to 36 patients Multi-center, open label trial Patients with advanced-stage HCC, treatment naive Participating countries France, Italy, US Endpoints (Phase 2 part) Primary endpoint: Objective response rate (ORR) Secondary endpoints: progression-free survival (PFS), overall survival (OS), duration of response and safety Exploratory endpoints: extended translational program (PDL1 ) including biopsy during treatment Efficacy data expected in 2H

36 Oncolytic viruses Our clear roadmap for success FUTURE GENERATIONS Level of innovation Imlygic/T-Vec, Pexa-Vec Oncolytic activity IT administration Indirect immune stimulation, via non-specific immune modulators (e.g. GM-CSF) NEW GENERATION TG6002 Oncolytic activity Systemic (IV) administration Better tumor selectivity (double gene deletion) Additional functionality - targeted chemotherapy Oncolytic activity Systemic (IV) administration Better tumor selectivity (double gene deletion) Armed targeted immune modulators expressed in tumor microenvironment Time to market 36

37 TG6002 First product incorporating our newest vector Improved virus and advanced therapeutic payload Superior oncolytic properties with local production of chemotherapy Proprietary virus Double gene deletion TK- RR- Viral oncolysis Targeted chemotherapy FCU1 gene Prodrug 5-FC Prodrug activating enzyme Cytotoxic drug 5-FU Cell death Phase 1 trial in glioblastoma, open label, dose escalation, IV administration PI: Prof A. Idbaih, MD, PhD (Pitié Salpêtrière Hospital, France) INCA Grant First data in 2H 18 First-in-human trial 1 st patient treated in Oct Development in GI cancers in active preparation 37

38 Significant anticipated value-creating news flow through 2018 Clinical readouts expected on all 5 products TG4010 Lung cancer (NSCLC) First Phase 2 data 1Q 2018 (2 nd line, TG nivolumab) 5 products in the clinic TG4001 TG1050 Pexa-Vec HPV+ head & neck cancer (SCCHN) Chronic hepatitis B (HBV) Liver cancer (HCC) First Phase 2 data in 2H 2018 (TG avelumab) Full Phase 1b data in 1H 2018 Phase 2 efficacy data in 2H 2018 (Pexa-Vec + nivolumab) TG6002 Glioblastoma First Phase 1 data 2H

39 Appendices 39

40 Company funded to deliver multiple value generating milestones Key figures Key shareholders As of September 30, 2017 ~ 30 million ~ 5 million 40 million Expected cash burn 2017 (~ 14 million for 4Q 2017) Operating revenues as of September 30, 2017 Cash and cash equivalents as of September 30, % Free float 40 % 10 million drawn down (Due 2021) Market capitalization: ~ 200 million as of September 30, million shares outstanding million options and restricted stocks Listed on Euronext Paris ISIN: FR Ticker: TNG 40

41 Our strategy Develop future disruptive innovation Engineer multifunctional oncolytic viruses Patented Viruses Anti-cancer Weapons VV TK - RR - + Enzyme Antibody SdAb Cytokines / Chemokines Receptor ligands Oncolytic activity Immunogenic properties Tumor targeting from the IV route Key effectors of the tumor microenvironment Potent immunomodulators benefiting from local delivery 41

42 Our strategy Develop future disruptive innovation Engineer viruses that attack the tumor at multiple points Cellular Improved replication in resistant tumor cells Improved lytic activity + release of immunogenic components Tumor microenvironment Attraction + infiltration of effector immune cells Breakdown of immunosuppressive mechanisms Organism Mobilization of innate + adaptive responses Systemic efficacy 42

43 ICI clinical collaboration scheme General approach Proof-of-concept trials Collaborative design of the protocol with shared expectations for outcomes Open-label trials with joint access to results No preferential rights granted over TG4010 or TG4001 Partner to provide ICI for the trial and participate in clinical sites selection Transgene to provide its product, fund the trials and ensure their execution 3 ongoing clinical collaborations TG4010, 1L, advanced lung cancer TG4010, 2L, advanced lung cancer TG4001, 2L, HPV+ head and neck cancers 43

44 TG4001 Positive Phase 2b in HPV-associated CIN 2/3 Demonstration of statistically significant curative activity at 6 months PHASE 2B TRIAL (RANDOMIZED, PLACEBO-CONTROLLED, 206 PATIENTS) in patients with cervical carcinoma in situ of high grade (2/3) Resolution (%) Viral clearance (%) Single agent TG4001 is active, and able P = P = HPV16 All Genotypes TG4001 monotherapy Placebo P = p = HPV16 All Genotypes to address HPV-related carcinomas Data represent a strong POC of active immunotherapy TG4001 was 5x superior in HPV16 patients compared to placebo to induce complete disease regression TG4001 showed an efficacy 4 fold superior compared to placebo regarding the viral clearance Clinical experience in 300+ subjects, demonstrating good safety profile Injection site reactions were the most common AE 44

45 Contact Lucie Larguier Director Corporate Communication and Investor Relations / larguier@transgene.fr / Transgene 400 Boulevard Gonthier d Andernach - Parc d Innovation - CS Illkirch Graffenstaden Cedex France Tél.: + 33 (0)