Corporate Presentation June 2, 2015

Transcription

1 Corporate Presentation June 2, 2015

2 SAFE HARBOR STATEMENT This presentation contains forward-looking statements. Although the Company believes its expectations are based on reasonable assumptions, these forward-looking statements 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 the Phase 2b part of the TIME trial will be predictive of future results with TG4010, (ii) regulatory authorities will agree with the Company s further development plans for TG4010, or (iii) the Company will find a development and commercialization partner for TG4010 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. The Company s ability to commercialize its products depends on but is not limited to the following factors: positive preclinical data may not be predictive of human clinical results, the success of clinical studies, the ability to obtain financing and/or partnerships for product development and commercialization, and marketing approval by government regulatory authorities. 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, which is 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 forward-looking statements, even if new information becomes available in the future. 2

3 TRANSGENE HIGHLIGHTS Discovering and Developing Targeted Immunotherapies to Treat Cancer and Infectious Diseases Immunotherapy approach complementary to other treatment types Viral vectors offer flexibility and adaptability based on indication and target Combine with traditional treatments such as chemotherapy and with new treatment paradigms such as immune checkpoint inhibitors (ICIs) Two late-stage oncology assets Broad pipeline of clinical and pre-clinical programs Multiple partnering and collaboration opportunities Transatlantic management team with solid biotech/pharma experience 3

4 COMPANY SNAPSHOT Discovering and Developing Targeted Immunotherapies to Treat Cancer and Infectious Diseases Euronext: TNG Market cap: ~$ 200 million Shares outstanding: 38.5 million HQ in Strasbourg, France Office in Lyon, France Satellite offices in U.S. and China 57 million in cash and equivalents at March 31, 2015 Cash reach to mid

5 TRANSGENE A LEADER IN VIRAL VECTOR-BASED IMMUNOTHERAPY Viral vector platforms a method for delivering genetic material into cells..used by Transgene in multiple ways in oncology and infectious diseases Therapeutic Vaccines Targeted delivery of tumoral or viral antigens to stimulate a specific immune response Oncolytic Viruses Targeted infection leads to cell lysis and death, and immune response Therapeutic Payloads Targeted delivery of suicide genes or chemotherapy enhancers 5

6 ACTIVE IMMUNOTHERAPEUTICS AND THE CANCER-IMMUNITY CYCLE*: Strong Logic for Combination with ICIs Vaccines and oncolytics ICIs *Chen and Mellman Immunity July

7 DIVERSIFIED DEVELOPMENT PIPELINE Internal Platforms have Delivered Multiple Programs Product Indications Pre-clinical ONCOLOGY TG4010 (MVA-MUC1-IL2) Pexa-Vec (JX594/TG6006) (VV-TK-GM-CSF) TG4001 (MVA-HPV-IL2) TG6002 (VV-TK-RR-FCU1) TG3003 (anti-cd-115 mab) INFECTIOUS DISEASES TG1050 (Ad5-HBV) Various candidates (MVA-TB) Non-small cell lung cancer Hepatocellular carcinoma Other solid tumors HPV-induced cancers Solid tumors Solid tumors Chronic hepatitis B Tuberculosis Combo w/chemo in 1 st line patients Combo w/ici 1 st line patients Combo w/ici 7

8 TG4010 CANCER IMMUNOTHERAPY: Phase 3 Ready in Non-small Cell Lung Cancer Target MUC1 Lead indication Non-small cell lung cancer (NSCLC) = large unmet medical need, large market opportunity Lung cancer accounts for more deaths than any other cancer type NSCLC global market expected to grow to $8-10 billion annually, mainly driven by treatment innovations Promising Phase 2b progression-free survival (PFS), overall survival (OS) and response rate data in NSCLC presented at recent medical conferences Plans for additional trials in NSCLC advancing Mechanism of action and safety profile = flexibility for potential combinations with other therapies Multiple drivers of exclusivity into late 2020s, early 2030s 8

9 TG4010: PHASE 2B PART OF PHASE 2B/3 TIME TRIAL Randomized, Double-blind, Multi-center Trial Results presented at ESMO 2014 & ASCO Stage IV NSCLC patients PS 0,1 MUC1+ No prior chemo normal TrPAL (170) high TrPAL (52) R A N D O M I Z E D TG4010 (10 8 pfu) 1 + chemotherapy 2 placebo 1 + chemotherapy 2 N O N P D Maintenance therapy (pemetrexed or erlotinib or bevacizumab) + TG4010 or placebo Primary endpoint: PFS (to prospectively validate TrPAL biomarker) Secondary endpoints: Overall Survival Overall Response Rate Duration of response Safety 1. TG4010/placebo administered subcutaneously on Day 1 of 1 st cycle, then weekly for 6 weeks, then once every 3 weeks until progression/discontinuation day cycle; 4-6 cycles; Type of chemotherapy (with or without bevacizumab) depends on tumor histology and physician choice 9

10 TG4010 CANCER IMMUNOTHERAPY: Promising Updated and New Data from TIME Trial Presented at ASCO 2015 More mature data confirm strength of improvements in PFS and OS, especially in non-squamous tumors 88% of patients in TIME trial had non-squamous tumors Phase 3 - plan to enroll only patients with non-squamous tumors Even more notable improvements in PFS and OS in low TrPAL * patients = potential utility of biomarker Improved response rate and longer duration of response seen with TG4010 vs. control Strong activity seen with TG4010 in patients with low levels (<5%) of tumor cells expressing PD-L1 Favorably positions TG4010 in combination with chemotherapy as well as with ICIs TG4010 well tolerated * Triple Positive Activated Lymphocytes: CD16+CD56+CD69+ cells 10

11 TG4010: PHASE 2B TIME TRIAL RESULTS Primary Endpoint Primary objective: PFS to prospectively validate the TrPAL predictive biomarker* As recommended by the FDA, primary endpoint based on a Bayesian design: pooling PFS data from TIME Phase 2b trial and earlier study in NSCLC to accelerate time to results and with fewer patients In Normal TrPAL group, probability that TG4010 induces reduction in disease progression or death - i.e., hazard ratio (HR) <1 is 98.4% o Thus, Phase 2b part of TIME study after 151 events of progression passes Bayesian probability threshold of 95% High TrPAL group no improvement observed All other analyses in study based on traditional Frequentist approach * The level of Triple Positive Activated Lymphocytes (TrPAL): CD16+CD56+CD69+ cells at baseline using a pre-defined threshold level, the so-called upper limit of normal or ULN; patients were classified as normal or high TrPAL using the ULN. 1 Quoix, E. et al. Results of the phase IIb part of TIME study evaluating TG4010 immunotherapy in stage IV non-small cell lung cancer (NSCLC) patients receiving first line chemotherapy. ASCO Annual Meeting

12 TG4010: PHASE 2B TIME TRIAL RESULTS Non-squamous : Statistically Significant PFS Results Quoix, E. et al. Results of the phase IIb part of TIME study evaluating TG4010 immunotherapy in stage IV non-small cell lung cancer (NSCLC) patients receiving first line chemotherapy. ASCO Annual Meeting

13 TG4010: PHASE 2B TIME TRIAL RESULTS Non-squamous : Compelling OS Results Quoix, E. et al. Results of the phase IIb part of TIME study evaluating TG4010 immunotherapy in stage IV non-small cell lung cancer (NSCLC) patients receiving first line chemotherapy. ASCO Annual Meeting

14 TG4010: PHASE 2B TIME TRIAL RESULTS Non-squamous, Low TrPAL* Even greater improvements seen in non-squamous, low TrPAL group PFS OS PFS (months) OS (months) The level of TrPAL cells at baseline as determined using a quartile approach; low TrPAL patients were in the three lowest quartiles. Quoix, E. et al. Results of the phase IIb part of TIME study evaluating TG4010 immunotherapy in stage IV non-small cell lung cancer (NSCLC) patients receiving first line chemotherapy. ASCO Annual Meeting

15 TG4010: PHASE 2B TIME TRIAL RESULTS Activity of TG4010 in Patients with Low PD-L1 Expressing Tumors PFS OS PFS (months) OS (months) In a retrospective analysis, PD-L1 expression was analyzed in 160 patients by immunohistochemistry staining on tumor slides using the E1L3N anti-pd-l1 antibody. The cut-off used to determine the level of positive PD-L1 expression was set at 5% of tumor cells. 138 patients had a non-squamous tumor, of which 97 patients (70%) had <5% PD-L1 tumor cell expression. 15

16 TG4010: PHASE 2B TIME TRIAL RESULTS Response Rate and Duration of Response Overall population (n) ORR Median duration of response (wks) Non-squamous (n) ORR Median duration of response (wks) Non-squamous, low TrPAL (n) ORR Median duration of response (wks) TG % % % 43.1 Placebo % % %

17 TG4010 TG4010: PHASE 2B TIME TRIAL RESULTS Conclusion TG4010 in combination with chemotherapy has demonstrated clinical efficacy Improved response rate and longer duration of response, including delayed and durable responses Significant improvement in PFS and in overall survival TG4010 greater efficacy in patients with low levels of TrPAL TG4010 shows activity in patients having <5% of tumor cells expressing PD-L1 (70% of patients in trial) Excellent safety profile of TG4010 when added to first-line chemotherapy Results warrant pursuing further development in NSCLC 17

18 TG4010: NEXT STEPS Initiate Phase 3 trial, subject to partnering Discussions with potential partners and with regulatory authorities ongoing Initiate exploratory Phase 2 trials in NSCLC in combination with ICIs Planning underway; potential collaborations with major cancer centers in France and US and pharmaceutical companies Initiation not subject to partnering 18

19 PEXA-VEC ONCOLYTIC IMMUNOTHERAPY: Oncolytic Immunotherapy for Liver and Other Cancers Lead indication: hepatocellular carcinoma (HCC, liver cancer) Major unmet medical need with only one drug (sorafenib) approved for use Global HCC market expected to grow to over $950 million by 2018 SPA with FDA for Phase 3 trial in first-line HCC Several exploratory trials in various other tumor types planned Transgene has development and commercialization rights in Europe, Commonwealth of Independent States and Middle East (>50 countries) 19

20 TG1050 ADENOVIRUS-BASED HBV IMMUNOTHERAPY Phase 1 Ready Large unmet medical need >240 million people have chronic liver infections; >780,000 deaths/yr due to consequences of hepatitis B Overall cure rate today = only ~3% of cases o Treatment duration = 15 years (in developed world), often for life HBV market >$1.2B for major markets (2013); expected to grow significantly Current status Strong pre-clinical package completed* Phase 1 trial - First patient expected to be enrolled in mid-2015 Strategy Proof of concept/first in humans: with standard-of-care (tenofovir or entecavir) Ultimate goal: improve cure rate (seroconversion) Plan to enter into co-development partnership to maximize chances of success * Martin P et al. TG1050, an immunotherapeutic to treat chronic hepatitis B, induces robust T cells and exerts an antiviral effect in HBV-persistent mice. Gut Nov 26, doi: /gutjnl

21 TG3003 ANTI-CD115 MONOCLONAL ANTIBODY Novel fully humanized mab against CD115 (CSF1 receptor) Targeting CD115 with TG3003 can skew the balance of macrophage cells towards dendritic (M1-type) cells away from M2-type macrophages M2 type associated with poor prognosis, while M1-type generally associated with good prognosis TG3003 may potentiate immune responses in patients TG3003 may impact tumor progression, metastasis and angiogenesis Current status Substantial pre-clinical package established confirming mechanism of action o Meaningful differentiation from other anti-cd115 programs Plan to partner before entering clinic 21

22 FINANCIALS Transgene is Sufficiently Funded until Mid-2016 Balance sheet At March 31, 2015: Cash and cash equivalents: 57.0 million Cash flow Cash burn for the 3 months ended March 31, 2015: 8.9 million Cash burn guidance for FY 2015: ~ 45 million 22

23 OWNERSHIP STRUCTURE 1 Retail investors 18% Institutional investors 30% Institut Mérieux 52% Institut Mérieux Institutional investors Retail investors 38.5 million shares outstanding million options and free shares 2 1. As of March 14, As of Dec 31,

24 POTENTIAL NEWSFLOW NEXT 12 MONTHS TG4010 Initiate further clinical development in NSCLC o o Start Phase 3 part of TIME trial, subject to partnering Initiate Phase 2 exploratory trials in combination with ICIs Present data at scientific/medical conferences Pexa-Vec Initiate additional clinical trials TG1050 Enrollment of first patient in Ph1/1b trial for chronic hepatitis B Pipeline Continued advancement of pre-clinical candidates towards clinic 24

25 CONTACT: Elisabetta Castelli, Director Investor Relations Laurie Doyle, Director Investor Relations U.S. & Corp Communications 400 Boulevard Gonthier d Andernach - Parc d Innovation - CS Illkirch Graffenstaden Cedex France Tél.: + 33 (0) Fax.: + 33 (0)