Virus-based immunotherapies to transform the fight against solid tumors and infectious diseases. March 2019 Full Year Results 2018 & Business Update

Transcription

1 Virus-based immunotherapies to transform the fight against solid tumors and infectious diseases March 2019 Full Year Results 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 2018 Highlights - Positioning Transgene for an Exciting 2019 Key clinical results Significant progress with our key late stage clinical products set to deliver multiple clinical data readouts in H Progress of our novel oncolytic virus platform Positive data from collaboration with BioInvent presented at SITC First Invir.IO products expected to enter the clinic in 2020 Highly innovative viral-based, individualized immunotherapy Strategic collaboration with NEC Using NEC s Artificial Intelligence Capabilities Lead candidate TG4050 to enter the clinic in Q $48 million Cash runway Sale of TG1050 and TG6002 rights in Greater China to Tasly Biopharmaceuticals - $48M in Tasly Biopharmaceuticals shares Financial visibility extended to mid-2020 through the monetization of the Tasly shares in a 20M loan with French bank Natixis 3

4 Clear need to improve treatment options for solid tumors Immune checkpoint blockade reshaping solid tumor therapies Commonly used as standard of care for various solid cancers However only effective in patients with a pre-existing immune response to their cancer and whose tumors are inflamed ( hot tumors ) Need to render all solid tumor patients responsive to immune checkpoint blockade Need to provide treatment to the 70% non-responding patients Need to develop optimised patient specific treatment options for multiple cancers 4

5 Transgene pipeline and strategy at a glance Products/Platforms Plans Operational: Deliver clinical readouts Strategic: Pursue further development and commercialisation through partnerships Transgene s key focus going forward Platforms are truly new and differentiated generation of vaccines and oncolytics First clinical trials 2019/2020 5

6 Cutting-edge molecular virology applied to solid tumors Next-generation of multifunctional oncolytic viruses based on a more potent OV Potential to express a range of anti-cancer weapons to better modulate the Tumor Micro Environment (TME) Sustained anti-tumor response via immunogenic cell death boosting both innate and adaptive immune response Large genome capacity to accommodate multiple transgenes TG6002 is paving the way for Invir.IO Individualized virotherapy based on patient s own tumor mutations called neoantigens Expected to induce broader and stronger T cell response for a better treatment outcomes Ability to prime/boost patient s immune system to overcome the immunosuppressive environment of the tumor sites The advantages of personalised treatment without the drawbacks of autologous approaches First Invir.IO candidate in the clinic in 2020 Lead candidate to enter the clinic in 2019 Oncolytic Viruses Therapeutic vaccines 6

7 Our Target Market Opportunity Global immunotherapy market for solid tumors worth $57bn in 2016 Market estimated to reach $144bn by 2023, growing 14% annually* Immunotherapy eligible patients CURRENTLY Immunotherapy eligible patients FUTURE Non-responsive. Target for combination therapies 70% 30% Immune Checkpoint responsive Oncolytic viruses, other targeted therapies and combined treatments 60% 30% 10% Immune Checkpoint responsive Cancer vaccines in combination therapies * Cancer Immunotherapy Market Report Global Industry Analysis , Research&Markets 7

8 Objectives for the coming 12 months Portfolio to deliver significant news flow Q TG4010 1L NSCLC: Recruitment completed Pexa-Vec Phase 3 1L HCC: Futility analysis Q H TG4010 1L NSCLC: Primary endpoint analysis (ORR) on 35 patients Pexa-Vec + nivo 1L HCC: Interim analysis (ORR) on 15 patients TG4001 HPV+ cancers: First efficacy readout TG6002 CRC - IV route: Phase 1 clinical readout TG4050: First Patients treated in 2 clinical trials TG6002 CRC - IHA route: First Patient treated H OV-Anti-CTLA-4: First Patient treated TG6002: Start Phase 1 in new indication 8

9 Our clinical products are making good progress Important clinical data read-outs expected in

10 TG4010 Our lead therapeutic vaccine in lung cancer MVA based therapeutic vaccine targeting the MUC1 TAA Being developed for the treatment of non-small cell lung cancer (NSCLC) Current lung cancer treatment landscape Need to increase response rate and OS Better therapeutic options still needed for nonresponders (ICIs) Still major unmet medical need in adenocarcinoma of the lung as majority of patients do not respond to ICIs NSCLC 1L treatment Min. 350 K patients * 30 % of 1L patients with PD-L1 50 % Pembrolizumab 70 % of 1L patients with no or low levels of PD-L1 (<50 %) Pembrolizumab in combination with CT / Atezolumab in combination with CT *Source: USA, EU, JP, Globocan, Company estimates 10

11 TG4010 1L To increase ORR with triple combination regimen in patients with non sq. NSCLC expressing low levels of PD-L1 (<50%) Protocol In collaboration with Study Proof-of-concept Phase 2 trial Collaborative agreement with BMS (supply of nivolumab) Target 35 evaluable patients Multi-center, single-arm, open label study First-line treatment, stage IIIB-IV, non sq. NSCLC with undetectable or low (<50%) PD-L1 expression Endpoints Primary endpoint: objective response rate (ORR) Secondary endpoints: duration of response, disease control rate, progression-free survival (PFS), overall survival (OS), and safety First patient treated in January 2018 Recruitment to be completed in Q Primary endpoint evaluation expected in H (ORR on 35 patients) 11

12 TG4001 HPV-positive cancers including Head & Neck Cancers (HNSCC) Phase 1b/2 in combination with avelumab (Bavencio ) MVA based therapeutic vaccine expressing HPV 16 E6 and E7 oncoproteins In collaboration with Target Population: patients Principal Investigator Pr Christophe Le Tourneau, Institut Curie Protocol Up to 50 patients (in EU) Multi-center, single-arm, open label trial Metastatic or refractory/recurrent HPV-16+ cancers including head & neck cancer, after failure 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 patient treated in September 2017 Following positive safety evaluation, Phase 2 part ongoing and additional sites being activated of standard therapy Next clinical readout expected in 2H 2019 Publication of prior study results in progress 12

13 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 treated in China in Sept Futility analysis expected in Q Interim analysis expected in 2020 Multi-center Phase 1/2 trial in France and Italy ; USA sites for the phase 2 part only Open-label, single-arm trial Phase 1 part: positive SRC in Q Interim analysis (15 patients) expected H (primary endpoint ORR) 13

14 Our next generation of oncolytic therapeutics Multi functional OVs based on our industry leading Vaccinia Virus (VV) backbone

15 Oncolytic viruses Three complementary ways to act on the tumor Oncolysis Specific replication in tumor cells, and direct lysis of infected cells Immune response Induction of immunogenic cell death, engagement of both innate and adaptive anti-tumor immunity Many routes to reach the tumor (i.e. IV, IT) Immuno-modulating payloads delivery Targeted delivery of anti-tumor modalities, synergistic with other MOAs (e.g. targeted Chemotherapy, or immune modulation of TME) 15

16 Vaccinia virus: The optimal oncolytic viral backbone Excellent Oncolytic activity of the Copenhagen vaccinia strain with double gene deletion (TK-RR-) Good immunological balance (Th1 vs Th2, anti-tumor vs anti-viral responses, etc.) Large genome capacity (up to 25 kb), to accommodate multiple transgenes Pure cytoplasmic replication (no risk for genome integration or mutagenesis) Well-established processes for GMP manufacturing 16

17 TG6002 In Phase 1/2a study in GI cancer (IV administration) Viral oncolysis + local production of chemotherapy (5-FU) Gastro-intestinal adenocarcinoma with liver metastasis (colon cancer) (Tumors known to be 5-FU sensitive) Protocol Multi-center Phase 1/2a trial Phase 1 part (dose escalation): up to 24 patients Phase 2a part (efficacy) in CRC: 35 patients Trial will include biodistribution analysis Principal investigator Prof Philippe Cassier, centre Léon Bérard (Lyon, France) Regimen TG6002 IV: D1, D8, D mg/kg/day Oral 5-FC prior to TG6002 Additional cycles until disease progression INDs granted in Belgium, Spain, France First patients treated in October 2018 Expected Ph 1 Readout: H New study in CRC patients via IHA route in preparation: FPI expected in Q

18 Multifunctional OVs to modulate the tumor micro-environment Immuno-armed oncolytic viruses based on the improved vaccinia virus The optimal oncolytic backbone Efficacy Flexible Versatile Safety Manufacturing Excellent oncolytic activity of the vaccinia virus (VV) strain Large genome capacity to accommodate multiple transgenes Tumor selective replication in a number of cancer cell types Good safety profile. Pure cytoplasmic replication (no risk of genome integration or mutagenesis) Well-established processes for GMP manufacturing Clinical First candidate to enter the clinic in

19 Generate a large portfolio of multifunctional immunotherapies aimed at modulating the tumor micro-environment Multiple options for immune modulation of the tumor microenvironment via immuno-armed oncolytic VVs Better release of tumor Ags, and of related immunostimulatory molecules Local expansion, and activation of APC and effectors cells Chemokines Favoring tumor infiltration Undisclosed sdabs Unlocking local immunosuppression Undisclosed targets Degradation of immunosuppressive metabolites and cells in the TME Undisclosed enzyme hcd Cytokines TNFR-Ls TCEs Agonistic sdabs ICIs Anti-CTLA-4 Collaboration with << 19

20 OV encoding for anti-ctla-4 mab in collaboration with BioInvent Building a potent multifunctional OV 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 non-tumor compartments Indications: multiple solid cancers First product expected to enter the clinic in H Transgene to use its Invir.IO oncolytic virus to deliver functional mab in the TME (1) BioInvent to provide full length human recombinant anti-ctla-4 Abs to promote depletion of intratumoral Treg cells (2) (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) 20

21 Key take aways OV encoding for anti-ctla-4 mab in collaboration with BioInvent First results presented at SITC in 2018 A functional antibody can be vectorized in the Invir.IO highly oncolytic and immunogenic vaccinia virus backbone The oncolytic vaccinia virus has demonstrated its ability to ensure the expression of BioInvent s anti- CTLA-4 antibody in the tumor with low systemic exposure Synergistic effect of combining ICI and oncolytic vaccinia virus in pre-clinical models triggering a massive immune infiltration into the tumor Better safety profile compared to combination of separate Ab and OV Therapeutic molecule accumulates in the tumor while the circulating concentrations are low compared to a regular combination 21

22 Creating individualized immunotherapies leveraging our MVA based platform First clinical trials in Q4 2019

23 Individualized immunotherapy Targets the patients own neoantigens Individualized Efficacy Safety Flexible immunotherapy Based on the patient s own cancer mutations Proven anti-tumor activity Established therapeutic class Versatile platform and AI integration MVA-based therapeutic vaccine Clinical First clinical trials to start in Q

24 Targeting unique patient specific set of mutations Because of deficient repair mechanisms and rapid proliferation, tumor cells accumulate DNA mutations Some mutations lead to the generation of non-self proteins (therefore immunogenic) called neoantigens These neoantigens are more immunogenic than classical tumor associated antigens Transgene s myvac vaccines against neoantigens are expected to induce broader and stronger T cell responses 24

25 Process for individualized neoantigen vaccination combines bioengineering and digital transformation Gene sequencing Data processing, Artificial intelligence Gene editing, Manufacturing Treatment 1. Routine Patient tumor biopsy 2. Next generation sequencing 3. Comparison, and selection of mutations 4. Vaccine generation and manufacturing 5. Viral vaccination of patient Patient s biopsies are sequenced to determine the mutations specific to the patient s tumor (neoantigens) Selection of top 30 mutations/neoantigens based on expression and immunogenicity In vitro synthesis of DNA plasmid containing said sequences DNA plasmid integrated into MVA* Resulting vaccine is produced and controlled to obtain enough product for treatment Vaccine contains sequences encoding for neoantigens Neoantigens are expressed in patient body Immune response is triggered by vaccine encoding for neoantigens *MVA: Modified vaccinia virus ankara 25

26 Our lead candidate TG4050 to enter the clinic in Q TG4050 In collaboration with Neoantigen therapeutic vaccine developed for individual patients Based on specific mutations identified in the patient s own tumor Project supported by Bpifrance, with partners: IND and CTA filed, with support of international KOLs Both studies will be co-funded by Transgene and NEC HPV negative head and neck cancers Ovarian cancer After surgery and adjuvant therapy After surgery and adjuvant chemotherapy Primary endpoints: Safety and immunogenicity of TG4050 Pave the way for combination studies with different classes of therapies 26

27 2018 Financial results Jean-Philippe DEL VP Finance

28 2018 FINANCIAL RESULTS P&L in million Var. Revenue Research and development expenses (27.3) (30.4) General and administrative expenses (7.0) (5.7) (1.3) Other expenses, net (1.2) (0.2) (1.0) Net operating expenses (35.6) (36.2) Operating income/(loss) 7.4 (28.1) Interest expenses, net (2.0) (2.3) Income from equity consolidated expenses 2.7 (1.9) Total net income/(loss) 8.0 (32.3) Net income/(loss) per share (in ) 0.13 (0.52) million in total net income compared with 32.3 million in net loss in million in net operating expenses compared with 36.2 million in

29 2018 FINANCIAL RESULTS Revenue 42.9 million in revenue compared with 8.1 million in 2017, driven by Tasly transaction In million Revenue from collaborative and licensing agreements Government financing for research expenditures Other revenue Revenue R&D Services: 1.3 million vs. 0.9 million in 2017 Licenses: 0.03 million vs. 1.2 million in Research tax credit: 5.7 million vs. 5.4 million in T101 patent rights sold to Tasly Biopharmaceuticals for 35.6 million 29

30 2018 FINANCIAL RESULTS R&D expenses 27.3 million in R&D expenses compared with 30.4 million in 2017 In million Var. 1 Staff costs % Share-based payments External IP and licensing costs % 3 External expenses on clinical projects % External expenses on other projects Operating expenses % Depreciation and amortization R&D expenses % 1 Staff costs +1% Stability in FTEs in R&D (117FTEs, 85% of total FTEs) 2 External IP and License costs -81% License: Milestone payment to Sillajen for 3.8 million for FPI in Phocus trial in External expenses on clinical projects + 0.9m Acceleration of clinical activities in

31 2018 FINANCIAL RESULTS Key Figures Cash and cash equivalents 50m 25m 41.4m 24.5m 16.9m zero Cash at 2017 Year end Cash BURN 2018 Cash at 2018 Year end 16.9 million in cash and cash equivalents at year end million of cash burn compared with 28.1 million in

32 Tasly Biopharmaceuticals deal - Monetization through 20M loan with Natixis In July 2018, Transgene became a shareholder of Tasly Biopharmaceuticals when it signed a series of agreements involving T601 and T101, two immunotherapeutics discovered by Transgene T601 ant101 are now being developed by Tasly in Greater China In March 2019, Transgene secured a 20 million loan (revolving credit) with Natixis, the French Corporate and Investment bank 30-month term Transgene can draw on the facility as needed Tasly shares used as collateral for this loan Financial visibility until mid-2020 (incl. 20M credit facility from Natixis) 32

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

34 Our key priorities for 2019/2020 Clinical pipeline Progress our clinical portfolio to deliver multiple key readouts Prepare and start one additional clinical trial for TG6002 Initiate clinical trial of our first candidate (OV encoding for anti-ctla-4) in H Select second clinical candidate new construct using our unique VV backbone TG Initiate two clinical trials by Q4 2019: Ovarian cancer and HPV-Negative head and neck cancer 34

35 Contact Jean-Philippe Transgene 400 Boulevard Gonthier d Andernach - Parc d Innovation - CS Illkirch Graffenstaden Cedex France Tél.: + 33 (0)