Virus-based immunotherapies to transform the fight against cancers and infectious diseases. September 2018 First Half 2018 & Business Update

Transcription

1 Virus-based immunotherapies to transform the fight against cancers and infectious diseases September 2018 First Half 2018 & Business Update

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 Risques ) 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 virus-based immunotherapies Focus on cancers High level of unmet medical need New treatments create significant opportunities 2 Cutting-edge technologies Therapeutic vaccines Oncolytic viruses 5 Immunotherapy products in clinical trials focus on combination regimens 4

5 Dense activity since January 2018 $48 million Sale of TG1050 and TG6002 rights in Greater China to Tasly Biopharmaceuticals (July 2018) $48 million in Tasly Biopharmaceuticals shares Key clinical trials Progress on key clinical trials to deliver results by the end of 2018 and in 2019 ASCO Invir.IO TM New positive data on Pexa-Vec IV Translational data showed strong anti-tumor activity and one pathological response (n=4) Progress of our novel oncolytic virus platform First candidate to enter the clinic in

6 Cutting-edge molecular virology applied to Immuno-Oncology Therapeutic vaccines Oncolytic Viruses Broad and sustained anti-tumor response Targeted response against selected TAAs Increase CD4+ and CD8+ T cells Synergies with other therapies Well tolerated Sustained anti-tumor response via immunogenic cell death Increase infiltration of T and NK cells Potential to express anti-cancer weapons to modulate the Tumor Micro Environment (TME) Synergies with other therapies Well tolerated 6

7 A broad pipeline of clinical-stage immunotherapeutics Transgene strategic trials Product THERAPEUTIC VACCINES Indication Preclinical Clinical Phase Phase 1 Phase 2 Phase 3 TG4010 Non-small cell lung cancer 1 st line + nivolumab (ICI) + CT * TG4001 Recurrent HPV-positive head and neck cancers + avelumab (ICI) * TG1050 Chronic hepatitis B + antiviral ** ONCOLYTIC VIRUSES Pexa-Vec Advanced HCC 1 st line (PHOCUS) + sorafenib *** Advanced HCC 1 st line + nivolumab (ICI) TG6002 Colorectal cancer ** * Clinical collaboration / ** Rights acquired for Greater China ***Transgene has commercial rights to Pexa-Vec in Europe and additional selected countries. 7

8 Invir.IO TM platform Oncolytic viruses with multiple MoAs Leverage our proprietary large capacity Vaccinia virus Enhanced modulation of the tumor micro-environment (TME) Designing the next generation of multifunctional oncolytic viruses ❶ Tumor cell lysis induced after specific viral replication in tumor cells ❷ Immunogenic cell death and recruitment of T cells ❸ Local release of active payload (transgenes) in the TME Preclinical candidates in development 2 research collaborations signed First candidate in clinic in 2019 IT and IV administrations 8

9 Therapeutic Vaccines Pioneering virus-based immunotherapeutics 9

10 TG4010 in non-small cell lung cancer (NSCLC) MVA coding for MUC1 and IL2

11 Lung cancer Better therapeutic options still needed for non-responders (ICIs) Dismal prognosis at late stage Need to increase response rate and OS Min. 350 K patients 1L* Min. 270 K patients 2L* First-line therapy Pembrolizumab registered in 2016 for patients whose tumor cells express high levels of PD-L1 ( 50 %) in 2017 (USA) and 2018 (EU) for all patients, in combination with pemetrexed/ carboplatin CT Second-line therapy Several anti PD-1/PD-L1 registered since 2015 (Nivolumab) Still a major unmet need as a majority of patients do not respond to ICIs *Source: USA, EU, JP, Globocan, Company estimates 11

12 TG4010 Compelling lung cancer clinical data Improved response rate & duration of response SUCCESSFUL PHASE 2B TRIAL (RANDOMIZED, PLACEBO-CONTROLLED, 222 PATIENTS) TG4010 in combination with chemotherapy for 1 st line NSCLC TG chemotherapy 40.9 [ ] wks Non-squamous (n) ORR Median duration of response (wks) TG CT 98 40% 41 Placebo + CT 98 28% 18 Chemotherapy (n=27) 18.1 [ ] wks Placebo + chemotherapy 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 Compelling 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 1L To increase ORR with triple combination regimen in patients expressing low levels of PD-L1 (<50%) Recruitment continues and additional centers are being activated Proof-of-concept Phase 2 trial Collaborative agreement with BMS (supply of nivolumab) First patient treated in January 2018 Recruitment to be completed in 2Q 2019 Primary endpoint evaluation expected in 2H 2019 (ORR on 35 patients) Endpoints Primary endpoint: Objective response rate (ORR) Secondary endpoints: duration of response, disease control rate, progression-free survival (PFS), overall survival (OS), and safety Protocol Up to 39 patients (35 evaluable patients) Multi-center, single-arm, open label study Stage IIIB-IV or delayed relapse, tumors with low or undetectable PD-L1 expression (<50%) 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 followed by pemetrexed maintenance Participating countries USA Belgium Denmark France Hungary 14

15 TG4001 & TG1050 Ongoing trials to deliver results in 2018 TG4001 HPV+ head & neck cancers MVA encoding for HPV16 E6 & E7 Clinical collaboration with Merck/Pfizer, supply of avelumab (ICI) Phase 1b/2 trial PI: Prof. Christophe Le Tourneau (Institut Curie, Paris) First patient treated in September 2017 Following positive safety evaluation, Phase 2 part ongoing and additional sites being activated Phase 1 results in 4Q 2018 (n=9 patients) Next clinical readout expected in 2H 2019 TG1050 Chronic hepatitis B Adeno encoding for 3 HBV antigens Phase 1 trial completed Primary endpoint met: good safety profile confirmed - single and multiple doses (AASLD 2017) Full results to be presented in 4Q 2018 at a major liver conference Rights for Greater China acquired by Tasly Pharmaceuticals (July 2018) 15

16 Oncolytic Viruses Pioneered by Transgene A new and highly promising therapeutic class in the fight against cancer. Transgene leading the development of multifunctional OVs for the enhanced modulation of the TME via a single therapeutic.

17 Oncolytic viruses Rising interest from Pharmas in exciting approach 1 st OV approved (Imlygic) M&As and collaborations signed (e.g. Viralytics, Benevir, PsiOxus ) Validates market potential of oncolytic approaches Jan st patient treated in Pexa-Vec Phase 3 Sep 2017 Launch OV platform for a new OV generation Oct st patient treated in TG6002 s Phase 1 Jun 2018 New data on Pexa-Vec presented at ASCO Jul 2018 Tasly Bio. acquires rights for TG6002 in China Mid 2019 Interim analysis on Pexa-Vec + nivo in HCC (ORR) 1 st product in clinic 17

18 Pexa-Vec Targeting solid tumors Replicative Vaccinia Virus expressing GM-CSF

19 Pexa-Vec Lead oncolytic virus Transgene owns development and commercialization rights in Europe Licensor: SillaJen (KOSDAQ: ) HCC 1L Global Phase 3 trial Combination Phase 2 trial conducted by Transgene Global clinical development plan Other solid tumors Exploratory Phase 2 trials conducted by Transgene Exploratory Phase 1 trials led by SillaJen (RCC 2L, CRC 2L/3L) 19

20 Pexa-Vec Large unmet medical need in HCC Dismal prognosis Better therapeutic options needed 25,000 eligible patients in Europe* First-line therapy Sorafenib - modest activity ORR: 2% ; median OS: 10.7 months Lenvatinib recently approved with non-inferiority results (USA, EU, Japan) Nivolumab could become a new therapeutic option: Promising activity in Phase 3 (still ongoing) Second-line therapy Regorafenib ORR: 10%; median OS: 10.6 months Nivolumab approved by FDA ORR: 18%; median OS: 15.6 months * Source: Globocan, Company estimates 20

21 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

22 Pexa-Vec Triggers antitumor immunity after single IV administration Prior to planned surgery of locally advanced, poor prognosis or metastatic cancers Pexa-Vec shown to Selectively target tumor tissue after single IV administration Stimulate the adaptive and innate anti-tumor immune response Induce expression of PD-L1 and PD-1 pathways One complete and one partial tumor pathological response at the time of surgery on four evaluable CRLM patients Presence of Pexa-Vec in tumor tissue Single i.v. Pexa-Vec Surgery PBMCs exhibited robust activation by 24 hrs post-infusion Expression of CD69 (an early activation marker) was enhanced on effector cell populations, notably NK & T cells Expression of PD-L1 was increased CD69 Post-surgery d1 d2 d3 d5 d14 ± 4d 1m 3m Peripheral blood samples collected n = 8 ; 3 with metastatic melanoma and 5 with colorectal cancer metastases to the liver (CRLM) PD-L1 Normal tissue CRLM tissue showing expression of Pexa-Vec, signs of inflammation and fibrosis, necrotic cells Data support ongoing development of Transgene s Vaccinia virus-based oncolytics Source: Samson, A. et al, Single intravenous preoperative administration of the oncolytic vaccinia virus Pexa-Vec to prime anti-tumor immunity, ASCO 2018, June

23 Pexa-Vec Clinical development plan in HCC - 1 st line Pivotal Phase 3 and combination Phase 2 Position Pexa-Vec with current and future standard of care Advanced HCC 1 st line Phase 3 Pexa-Vec + sorafenib Conducted by Advanced HCC 1 st line Phase 1/2 Pexa-Vec + Opdivo (nivolumab) Sponsor Multi-center Phase 3 trial in Europe, USA, Asia Randomized, two-arm trial Ongoing global recruitment First patient included in China in Sept First data (efficacy vs SoC) expected in 2019 Multi-center Phase 1/2 trial in France, Italy, USA Open-label, single-arm trial Safety review committee expected before year-end 2018 Interim analysis (15 patients) expected mid-2019 (primary endpoint ORR) 23

24 TG6002 Advanced OV already in the clinic Viral oncolysis + local production of chemotherapy administered IV Multiple MoAs: ❶ Excellent oncolytic properties ❷ Targeted chemotherapy with FCU1 gene allowing the production 5-FU in the tumor FCU1 gene Unique and proprietary High 5-FC to 5-FU conversion ratio No FCU1 related safety issue Preclinical results confirm potency Gastro-intestinal adenocarcinoma (colon cancer) Multi-center Phase 1/2a trial Regimen: TG6002: D1, D8, D mg/kg/day oral 5-FC prior to TG6002, additional cycles until disease progression Phase 1 part (dose escalation): up to 24 patients Phase 2a part (efficacy): 35 patients IND granted in Belgium, Spain, France First patient expected in coming weeks Glioblastoma Single-center Phase 1 trial Sponsor: AP-HP First patient treated in Oct Greater China rights acquired by Tasly Biopharmaceuticals (July 2018) 24

25 Engineering multifunctional oncolytic viruses Based on large capacity Vaccinia Virus

26 Invir.IO Engineer multifunctional oncolytic viruses To modulate the tumor micro-environment Proprietary virus Anti-cancer Weapons Enhanced modulation of TME + ICIs (Mabs/SdAbs) Enzymes Ligands Chemokines Restore T-cell/tumor interaction Depletion of Tregs Depletion of immuno-suppressive metabolites Activate immunological pathway Favor infiltration of CD8-T cells and/or DCs (Anti-CTLA-4 Abs)* (SdAbs) Oncolytic activity Immunogenic properties Tumor targeting from the IV route Cytokines Proliferation of NK, B, and T cells (not Tregs) Induction of memory CD8+-T cells Future pipeline of novel OV drugs * Vargas F. et al., Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies, Cancer Cell, April 2018, (33, 1-15) 26

27 OV encoding for anti-ctla-4 mab Improving on validated MoA of ipilimumab Preclinical PoC Building a potent multifunctional OV Transgene s OVs deliver functional mab in the TME (1) BioInvent s full length human recombinant anti-ctla-4 Abs promote depletion of intratumoral Treg cells (2) Improved efficacy compared to combination of separate Ab and OV (1) Longer duration of expression Expected improved tolerability owing to lower systemic antibody exposure in peripheral nontumor compartments Indications: multiple solid cancers (1) Kleinpeter P. et al., Vectorization in an oncolytic vaccinia virus of an antibody, a Fab and a scfv against programmed cell death -1 (PD-1) allows their intratumoral delivery and an improved tumor-growth inhibition, OncoImmunology, Oct (5:10) (2) Vargas F. et al., Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies, Cancer Cell, April 2018 (33: 1-15) 27

28 Outlook On track to deliver multiple value-enhancing clinical data readouts and preclinical milestones

29 Company funded to deliver multiple value generating milestones Key figures 33.0 million 3.5 million Cash and cash equivalents as of June 30, 2018 Operating revenues as of June 30, 2018 Key shareholders As of the end of mid September, % 8.4 million Cash burn for the first half 2018 Free float 43 % 25 million Expected cash burn for 2018 Financial visibility until the end of September 2019 Market capitalization: ~ 200 million as of September 18, million shares outstanding million options and restricted stocks Listed on Euronext Paris ISIN: FR Ticker: TNG 29

30 Significant anticipated value-creating news flow Portfolio to deliver news flow in the near-term 4Q H H 2019 TG6002 GI 1 st patient treated TG1050 Phase 1/1b results Pexa-Vec + nivo 1L HCC Safety review committee TG4001 SCCHN Phase 1 results on 9 patients TG4010 1L NSCLC Recruitment completed TG4010 1L NSCLC ORR on 35 patients Pexa-Vec + nivo 1L HCC Interim analysis (ORR) on 15 patients TG4001 SCCHN Next clinical readout Transgene to enter personalized medicine field Pexa-Vec Phase 3 1L HCC First readout Invir.IO 1 st product in clinic Clinical resuts Study milestone Preclinical activity 30

31 We would like to thank patients, clinicians and support personnel for their commitment to the fight against severe diseases 31

32 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)