Transgene SA · EURONEXT:TNG
Transgene SA — FY2004 Earnings Presentation
59 slides from Transgene SA's earnings presentation, Feb 23, 2005
Slide 1: Corporate Presentation
CORPORATE PRESENTATION Paris February 23, 2005 1 transgene
Slide 2: Forward Looking Statement
Forward Looking Statement This presentation contains forward-looking statements, including statements regarding Transgene’s capital requirements and prospects. Statements that are not historical facts are based on the Company's current expectations, beliefs, estimates, forecasts and assumptions. The
Slide 3: Agenda
Agenda § PART 1 2004 FINANCIAL RESULTS § PART 2 TRANSGENE STRATEGIC DIRECTION ü New Strategic Direction & Priorities ü Latest clinical results & future clinical development § PART 3 CONCLUSION § PART 4 QUESTIONS & ANSWERS 3 transgene
Slide 4: Part 1: 2004 Financial Results
Part 1 2004 FINANCIAL RESULTS 4 transgene
Slide 5: Statement of Operations
Statement of Operations US GAAP; in € million ; unaudited 2004 2003 Revenues 2.5 2.5 Operating expenses (24.2) (24.5) R&D (20.0) (20.3) G&A (4.2) (4.3) Restructuring - 0.1 Loss from operations (21.7) (22.0) Interest income 0.5 1.1 Income tax benefit 0.7 - Net loss (20.5) (20.9) 5 transgene
Slide 6: Revenues
Revenues US GAAP; in million €; unaudited 2004 2003 Variation A.F.M. 1.1 1.2 (0.1) Contracts 0.7 * 0.3 + 0.4 Licenses 0.7 1.0 (0.3) 2.5 2.5 - * Productions for Eurovac/Karolinska during first half 2004 not included 6 transgene
Slide 7: 2004 Cash expenditures
2004 Cash expenditures US GAAP; in million €; unaudited 40 + 0,5 + 0,2 + 2,8 35 30 - 22,6 25 20 34,9 - 0,7 - 0,5 15 10 14,7 5 0 Cash & Cash Revenues R&D tax Interest Income Operating Capital Financing Cash & Cash equivalents credit refund expenses expenditures equivalents at 31.12.2003 excl. at 31.1
Slide 8: 2004 Net Cash expenditures
2004 Net Cash expenditures US GAAP; in € millions; unaudited 2004 2003 Net cash expenditures (20.3) (19.6) The 0,7 M€ additional cash expenditures is mostly due to: M€ ü R&D tax credit refund (ø) - 0.6 üInterest income(ø) - 0.6 üOperating expenditures (ø) 0.3 üCapital expenditures(ø) 0.3 - 0.6 8 tra
Slide 9: IFRS transition
IFRS transition § Financials under IFRS almost identical to US GAAP (only difference relies in actualisation of LT R&D tax credit) § Differences between French GAAP and IFRS accounts (unaudited - K€) : Impact on 2004 IFRS net result ü Capital increase costs 332 ü Stock-options (203) ü Unrecognized g
Slide 10: Market conditions
Market conditions 12 months - rebased to 100 as of 31 January 2004 180% 160% 140% 120% 105,03% 100% 93,62% 80% 60% 40% j-04 f-04 f-04 m -04 m-04 a-04 a-04 m -04 m -04 j-04 j-04 j-04 j-04 a-04 a-04 s-04 s-04 o-04 o-04 n-04 n-04 d-04 d-04 j-05 j-05 Nasdaq Biotech Index TRANSGENE NM 10 transgene
Slide 11: Part 2: Transgene Strategic Direction
Part 2 TRANSGENE STRATEGIC DIRECTION « Establish Transgene as a leader in Therapeutic vaccines in Cancer and Infectious Diseases » 11 transgene
Slide 12: Transgene initially positioned itself on the embryonic Gene Therapy segment
Transgene initially positioned itself on the embryonic Gene Therapy segment Chemical molecules Recombinant proteins Therapeutic Gene Vaccines therapy Embryonic Emerging Growing Mature Non validated technologies Products in development (no commercial product yet) 12 transgene
Slide 13: Transgene strategic direction is to move downstream towards growing segment
Transgene strategic direction is to move downstream towards growing segment… Chemical molecules Recombinant proteins Therapeutic Gene Vaccines therapy Nascent Emerging Growing Mature 13 transgene
Slide 14: Focus on therapeutic vaccines in Cancer and Infectious Diseases
… and focus on therapeutic vaccines in the fields of Cancer and Infectious Diseases Market opportunity Cancer 178 Almost 60% of all biopharmaceutical products are in the field of cancer and Infectious Diseases 68 infectious diseases (large unmet clinical Auto-immunity needs) 26 Neurology 22 Transgen
Slide 15: Rationale for Strategic Direction
Rationale for Strategic Direction § Large untapped market with no established entrenched players § Therapeutic vaccine is getting market appreciation on the back of post-9/11 vaccine boom and recent clinical trials § Infectious diseases and especially HCV is the best possible candidate to broaden Tr
Slide 16: Short term priorities
Short term priorities § Focus resources and capabilities towards achieving clinical proof of concept on most promising product and indications § Re-deploy research program to support product strategy ü Development of cancer & infectious disease vaccine candidates ü Broadening Transgene’s technology
Slide 17: Implication of new strategy on Transgene Development Engine
Implication of new strategy on Transgene Development Engine Research Vaccine Evaluation cGMP Clinical Technology Candidates Immunogenicity Production Trials bricks Preclinical • Immuno-adjuvants In vitro & In vivo Viral vectors • Oncolytic vectors • Oncology Evaluation Indication-specific • Viral ve
Slide 18: Consequences on clinical plan
Consequences on clinical plan MARKET REALITY RECOMMENDATION § The number of cancer vaccines in phase Streamline portfolio and focus on selected II and III is large. Competitors validating products in order to get significant proof of this therapeutic approach concept on a candidate for a given indic
Slide 19: 2004 Clinical program
2004 Clinical program Indication Preclinical Phase I Phase II Status (*) MVA-MUC1-IL2 Lung Completed 65 patients Completed MVA-MUC1-IL2 Prostate 40 patients Completed MVA-MUC1-IL2 Kidney 37 patients On-going MVA-HPV-IL2 CIN 2/3 (6 month follow up) 5 patients On-going Ad-IFNγ Cutaneous T-Cell Lymphom
Slide 20: 2005 Clinical Development Plan
2005 Clinical Development Plan Indication Preclinical Phase I Phase II Next step MVA-MUC1-IL2 Lung Phase IIb MVA-MUC1-IL2 Prostate Stand-By MVA-MUC1-IL2 Kidney Stand-By MVA-HPV-IL2 CIN 2/3 (6 month follow up) Phase IIb Ad-IFNγ Cutaneous T-Cell Lymphoma (CTCL) Phase II / III Ad-IL2 Malignant Melanoma
Slide 21: Latest Clinical Results
Latest Clinical Results 21 transgene
Slide 22: MVA-MUC1-IL2
MVA-MUC1-IL2 22 transgene
Slide 23: MVA-MUC1-IL2 Product profile
MVA-MUC1-IL2 Product profile Recombinant MVA (Modified Virus Ankara) ü non-replicative, highly immunogenic Skin poxvirus Immune cells Expressing MUC1 tumor-associated antigen Tumor ü MUC1 is found in most adenocarcinoma Skin Expressing human IL-2 cDNA ü stimulation of specific T-cell response Status
Slide 24: MUC1 expression in NSCLC associated with poor prognosis
NAB3 MUC1 expression in NSCLC Associated with poor prognosis MUC1+ cells <25% % overall survival MUC1+ cells > 25% Time (days) § MUC1 protein may have oncogenic activity (Li et al., 2003). § MUC1 attenuates the apoptotic response to oxydative stress (Yin et al., 2003). § MUC1 expression is a marker
Slide 25: Diapositive 24
Diapositive 24 NAB3 pour Wang 1999: article en chinois. Dans abstract : l'expression des mRNA MUC1 dans les ganglions médiastins est un mauvais fct progno. Nadine BIZOUARNE; 09/08/2004
Slide 26: MUC1 Expression in Major Cancers
MUC1 Expression in Major Cancers 90,0% 60,0% 60,0% MUC1+ MUC1+ MUC1+ Breast Lung Prostate 70,0% 80,0% 90,0% MUC1+ MUC1+ MUC1+ Colorectal Stomach Liver (cholangiocarcinoma) 25 transgene
Slide 27: MVA-MUC1-IL2 Clinical Trial Design
MVA-MUC1-IL2 Clinical Trial Design § Clinical settings and modalities Clinical Stage of Treatment Evaluation settings the disease modalities criteria Lung Stade IIIb/IV Combination with Tumor response cancer non resectable chemotherapy 2 arms Prostate Non-metastatic Monotherapy PSA level cancer PSA
Slide 28: MVA-MUC1-IL2 Phase II interim results
MVA-MUC1-IL2 Phase II interim results End points reached in NSCLC § Interim Results (February 2005) Arm 1 (TG4010 + chemo) : 35 evaluable patients 13/35 (37%) PR (validated by central reading) 11/35 (31%) SD > 12w 24/35 (68%) Clinical benefit Time to Progression 6.4 months Overall survival > 12month
Slide 29: MVA-MUC1-IL2 in NSCLC: Comparison with published clinical studies
MVA-MUC1-IL2 in NSCLC : Comparaison with published clinical studies using Navelbine / Cisplatine regimen Study % response Study TTP Study Overall survival Gebbia 44 TG4010 + chemo 6.4 m TG4010 + chemo >12 m TG4010 + chemo 37 % Gridelli 5.3 Fossela 10.1 Souquet 34.6 Fossela 5.1 Scagloitti 9.5 Le Chev
Slide 30: Clinical design Phase IIb in NSCLC
MVA-MUC1-IL2 Clinical design Phase IIb in NSCLC Targeted Intervention: Primary Decision Population: Endpoints to continue RR on phase III: Chemo. TTP +TG4010* Gain in response rate IIIB/IV Secondary higher than 7% MUC1+ Endpoint PS 0 or 1 R OS Gain in 100 patients Median TTP higher than Chemo. 1.5 M
Slide 31: MVA-MUC1-IL2: Prostate Cancer Study PSA Doubling Time
MVA-MUC1-IL2 : Prostate Cancer Study Patient PSA-DT (Slope calculated) Interim analysis Dec 2004 80 PSA - Doubling Time (months) Pre-Vaccination 70 During Immunotherapy 60 50 40 30 20 10 0 1001 1002 1003 1008 5001 5003 7002 7003 7005 7007 7010 7011 7012 8002 8004 1004 1005 1006 1007 5002 7001 7004 7
Slide 32: MVA-MUC1-IL2: Prostate Cancer Study
MVA-MUC1-IL2 : Prostate Cancer Study Patient PSA-DT (Slope calculated) Interim analysis Dec 2004 Immunisation schedule Weekly 3 weekly Pre-vac. Post-vac. Fold Pre-vac Post-vac Fold change change Mean 4.77 16.40 3.64 5.37 8.24 1.51 Median 4.70 7.10 1.93 5.60 6.50 1.34 P < 0.0001 ü80% of patients incr
Slide 33: MVA-MUC1-IL2 Market potential
MVA-MUC1-IL2 Market potential PROSTATE Patients with rising PSA after primary treatment (biochemical failure) Population incidence is estimated at 150.000 for Europe and US Metastatic NSCLC First line therapy for metastatic disease in combination with chemotherapy Mortality rate estimated at 350.000
Slide 34: MVA-MUC1-IL2 Future direction
MVA-MUC1-IL2 Future direction § Proven biological activity by slowing down or stopping the growth of tumour of several origins § Most encouraging results obtained in lung cancer with possible synergy between MVA-MUC1-IL2 and chemotherapy § Final data presentation at ASCO (13-17 May 2005) § Next step
Slide 35: MVA-HPV-IL2
transgene MVA-HPV-IL2
Slide 36: MVA-HPV-IL2 Potential product positioning
MVA-HPV-IL2 Potential product positioning HPV infection Prophylaxis Persistent infection. CIN2-3 Late-stage Cervix Cancer No vaccine No treatment Conisation Chemotherapy L1 ± L2 E1 ± E2 E7 ± E6 ± E1 E7 ± E6 35 transgene
Slide 37: MVA-HPV-IL2 Product profile
MVA-HPV-IL2 Product profile Recombinant MVA (Modified Virus Ankara) Skin ü non-replicative, highly immunogenic Immune cells poxvirus Tumor Expressing early genes Human Papilloma Virus 16 Skin ü CIN (cervical intraepithelial neoplasia) due to HPV: pre-cancerous stage of the HPV infection ü more than
Slide 38: MVA-HPV-IL2 Clinical Trial Design
MVA-HPV-IL2 Clinical Trial Design § Multicenter study in France § CIN2/3 in HPV16+ patients § 3 SC injections of TG4001, on Days 1-8-15 § 2 doses tested: 5x105 pfu and 5x107 pfu § Standard treatment (conization) on Week 6-8 37 transgene
Slide 39: MVA-HPV-IL2 Final results
MVA-HPV-IL2 Final results Summary table of TG4001 dose (pfu) secondary efficacy endpoints 5x105 5x107 Patients treated 14 17 Patients analyzed for efficacy 13 16 Viral clearance 0 4 Partial regression of histology signs 0 5 Reduction of grade (to CIN1) 0 2 Limited extent of histological lesion 0 3 H
Slide 40: MVA-HPV-IL2 Clinical Trial Design (on-going study)
MVA-HPV-IL2 Clinical Trial Design (on-going study) Phase IIb / CIN 2/3 Study design ü Open-label, 5x107 pfu ü 18 CIN2/3 patients Treatment plan ü Up to 6-month assessment period to study efficacy ü Follow-up every 2 months : Cytology + virology ± colposcopy ü Responder if (no need of LEEP at M6) • N
Slide 41: MVA-HPV-IL2 Incidence: HPV-related diseases
MVA-HPV-IL2 Incidence: HPV-related diseases Europe/US HPV16 Worldwide Cervix cancer 80,000 50% 470,000 CIN2/3 600,000 90% 1,000,000 CIN1 1,000,000 20% 10,000,000 Silent infection 10,000,000 20% 300,000,000 40 transgene
Slide 42: Adeno IFNγ
transgene Adeno IFNγ
Slide 43: Adeno IFNg Product profile
Adeno IFNg Product profile Recombinant adenovirus vector containing the sequence coding for the human IFN-g cDNA Mechanism of action ü Direct action on tumor cells: antiproliferative, induction of apoptosis ü Indirect actions on tumors: immune stimulation, antiangiogenic activities ü IFN-g is a majo
Slide 44: Adeno IFNg Clinical Trial Design
Adeno IFNg Clinical Trial Design Phase I/II : Primary Cutaneous Lymphoma ü Study design Dose escalation 3 dose levels 3.109 tp → 3.1011 tp 3 patients / dose level (Phase I) + 9 patients at highest dose + up to 18 patients (Phase I / II) ü Treatment plan Intra-tumoral administration Weekly injections
Slide 45: Phase I/II Cutaneous Lymphoma
Phase I/II Cutaneous Lymphoma § Efficacy results : (Interim data first 20 patients) ü Clinical responses observed locally 7 CR and 3 PR out of 18 evaluable patients (56%) ü Distant clinical responses : 2 CR – 1 PR out of 12 evaluable patients ü Overall response rate (53%) 44 transgene
Slide 46: Adeno IFNγ Market potential
Adeno IFNγ Market potential CTCL Patients with limited number of lesions and refractory / relapsing to at least two lines of standard therapy Population incidence is estimated at 38.000 in Europe and US Hepato Cellular Carcinoma Worldwide incidence is estimated at 600.000 Population incidence is est
Slide 47: Adeno IFNγ Future direction
Adeno IFNγ Future direction § Clinical development Cutaneous Lymphoma : ü Phase II / III study (Q1 06 – Q1 08) in CTCL pts ü Placebo controlled – 2 step study – 75 pts § Regulatory strategy : ü U.S. : • IND preparation and filing in process to be followed by SPA • Orphan drug designation submission
Slide 48: MVA HCV
transgene MVA HCV
Slide 49: MVA-HCV Market potential
MVA-HCV Market potential § 170 M people world-wide are infected by HCV, including 12 M chronically infected in the USA and Europe. § 10,000 to 12,000 deaths/year in the USA, predicted to increase dramatically in the next two decades § Leading indication for liver transplant § 50% pts infected with t
Slide 50: MVA-HCV Product design
MVA-HCV Product design § Genomic organization of HCV (RNA of 9.6 Kb) 5‘ NON CODING 3‘ NON CODING REGION STRUCTURAL REGION NON--STRUCTURAL REGION NON REGION NS4A P7 C E1 E2 NS2 NS3 NS4 B NS5 A NS5 B UUU 7 CORE GLYCOPROTEINS PROTEASE/HELICASE RNA POLYMERASE § Recombinant MVA (Modified Virus Ankara) ex
Slide 51: MVA-HCV: Clinical program
MVA-HCV: Clinical program Study design § MVA-HCV alone § Start Phase I / II in § Dose-escalating safety study in the USA (Q1 2006) chronically infected HCV patients Phase I ü Non-responder to reference treatment ü Treatment-naïve patients § Preparation of different « Prime- On-going boost » combinat
Slide 52: Muscular Dystrophy
transgene Muscular Dystrophy
Slide 53: Muscular dystrophy: AFM-financed development
Muscular distrophy AFM-financed development § First ever gene based trial in Duchenne Muscular Dystrophy § Phase I trial completed in 2003. Objectives fulfiled: ü expression of normal dystrophin detected in the injected muscle ü no immune rejection § On-going development financed by AFM ü Orphan Dru
Slide 54: Part 3: Conclusion
Part 3 CONCLUSION 53 transgene
Slide 55: 2005 Clinical Development Plan
2005 Clinical Development Plan Indication Preclinical Phase I Phase II Next step MVA-MUC1-IL2 Lung Phase IIb MVA-MUC1-IL2 Prostate Stand-By MVA-MUC1-IL2 Kidney Stand-By MVA-HPV-IL2 CIN 2/3 (6 month follow up) Phase II Ad-IFNγ Cutaneous T-Cell Lymphoma (CTCL) Phase II / III Ad-IL2 Malignant Melanoma
Slide 56: Development project Next Milestones and Newsflow
Development project Next Milestones and Newsflow PRODUCT INDICATION MILESTONE DATE Asco presentation of results for Lung & Prostate Q2 2005 MVA-MUC1-IL2 NSCLC / Lung Start of Phase IIb trial Q4 2005 MVA-HPV-IL2 CIN 2/3 Results on Phase II trial Q4 2005 Feedback on IND (and SPA) review Q2 2005 Ad-IFN
Slide 57: Transgene's technology value: potential for growth
Transgene ‘s technology value: potential for growth As of January 31, 2005 Technological Value (M$) 396 400 378 350 300 278 280 250 234 215 200 158 150 124 124 100 64 68 58 41 50 17 14 0 Epimmune Virax Vical Aphton Genvec Transgene Biomira Oxford Cancervax Dendreon Corixa Cell Antigenics Crucell Bav
Slide 58: Investment case
Investment case § Clinical pipeline with 3 phase II in active development § Products with large market potential aiming at fullfilling large unmet medical needs § Focused strategy in therapeutic vaccine field, leading to rich newsflow in 2005 § Large reservoir of opportunities (internal product cand
Slide 59: Transgene contact details
Transgene 11 rue de Molsheim 67082 Strasbourg Cedex France Contact : communication@transgene.fr Tel : +33-(0)3.88.27.91.02 Web Site : www.transgene.fr 58 transgene