Mediafin Investor Night: TiGenix NV. 23 September 2015

Transcription

1 Mediafin Investor Night: TiGenix NV 23 September 2015

2 Forward-looking Statements This document does not constitute or form part of any offer or invitation to sell or issue, or any solicitation of any offer to purchase or subscribe for, any shares in the Company, nor shall any part of it nor the fact of its distribution form part of or be relied on in connection with any contract or investment decision relating thereto, nor does it constitute a recommendation regarding the securities of the Company. This document may contain forward-looking statements and estimates made by the Company, including with respect to the anticipated future performance of TiGenix and the market in which it operates. They include all matters that are not historical facts. Such statements, forecasts and estimates are based on various assumptions and assessments of known and unknown risks, uncertainties and other factors, which were deemed reasonable when made but may or may not prove to be correct. Actual events are difficult to predict and may depend upon factors that are beyond the Company's control. Therefore, actual results, the financial condition, performance or achievements of TiGenix, or industry results, may turn out to be materially different from any future results, performance or achievements expressed or implied by such statements, forecasts and estimates. Forward-looking statements, forecasts and estimates only speak as of the date of this document and no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. TiGenix disclaims any obligation to update any such forward-looking statement, forecast or estimates to reflect any change in the Company s expectations with regard thereto, or any change in events, conditions or circumstances on which any such statement, forecast or estimate is based. 2

3 Multiple Product Candidates Product 1 Cell Type Indication Preclinical Phase I Phase II Phase III Market Cx601 (local) Allogeneic adipose-derived stem cells Complex perianal fistulas in Crohn s disease EMA granted Orphan Drug FDA endorsed SPA AlloCSC-01 (intracoronary) Allogeneic cardiac stem cells Acute myocardial infarction Cx611 (intravenous) Allogeneic adipose-derived stem cells Rheumatoid arthritis Severe sepsis Cx621 (intralymphatic) Allogeneic adipose-derived stem cells Autoimmune disorders AlloCSC-02 (intramyocardial) Allogeneic cardiac stem cells Cardiology ChondroCelect Characterised autologous chondrocytes Knee cartilage lesions Partnered 2 1 Covered by 25 patent families 2 Distributed through Swedish Orphan Biovitrum ( Sobi ) and the Finnish Red Cross Blood Service Product on hold 3

4 Cx601 Local injection of eascs for the treatment of complex perianal fistulas in Crohn s disease patients 4

5 Cx601: Addressing Perianal Fistulas in Crohn A significant commercial opportunity Almost 100,000 Crohn s disease patients suffer from complex perianal fistulas every year in Europe and US alone: Around 12% of Crohn s disease patients are affected by perianal fistulas Compromised QoL, pain, depression and risk of anal epithelial carcinoma Fistula Current treatment options have significant shortfalls: Limited efficacy High rate of relapse Serious side-effects A multi-billion euro market opportunity 5

6 Cx601: Phase III ADMIRE-CD 1 Trial A robust single pivotal study The largest RCT 2 in this indication: 289 patients recruited in 50 sites in 8 countries Patients with complex perianal fistulas with 2 internal openings and 3 external openings which accounts for the majority of the patients in real life Patients with inadequate response to at least one of the following: Antibiotics and/or Immunosuppressants and/or Anti-TNFs Continuation of medical standard of care was allowed during the duration of the trial in both groups Single injection of Cx601 Primary end-point: Combined Remission defined as closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections > 2 cm confirmed by MRI 3 at week 24 1 ADMIRE-CD:Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulising Crohn s Disease 2 RCT: Randomised Controlled Trial 3 MRI: Magnetic Resonance Imaging 6

7 Cx601: A Major Breakthrough Primary endpoint met (ITT 1 Population n= 212) (mitt 2 Population n= 204) 60 % p < % 60 p < % % % % Cx601 Placebo Cx601 Placebo Cx601 significantly superior to placebo in achieving Combined Remission Patients receiving Cx601 have 44% more chances to achieve Combined Remission than placebo patients Efficacy results consistent across all statistical populations Favourable safety and tolerability profile of Cx601 and comparable to placebo 1 ITT: Intention To Treat i.e. patients randomised 2 mitt: modified ITT i.e. patients randomized and treated, and with at least one post-baseline efficacy value 7

8 Cx601: A Regulatory De-risked And Fully-owned Asset Preparing for the European launch in 2017 Clear and fast pathway to the market built on a solid regulatory strategy Letter of intent submitted to the EMA 1 and MAA 2 filing planned for 1Q Scientific Advice Meetings held with EMA (2 pre-clinical, 2 CMC, 1 clinical) Team with previous experience in obtaining MAA of cell therapy product Major commercial opportunity 50,000 new patients every year in Europe with high medical need Protection obtained through EU patent and orphan designation Fully-owned commercial rights 1 EMA: European Medicines Agency 2 MAA: Marketing Authorisation Application 8

9 Cx601: Capturing The Value Of The Biggest Market Preparing for the US launch in 2020 Clear and fast pathway to the market built on a solid regulatory and clinical development strategy Type B meeting with FDA 1 confirmed: Adequacy of existing non-clinical package to support an IND 2 filing Acceptability of using data from the ADMIRE-CD trial to support BLA 3 FDA endorsement through SPA 4 of US Phase III protocol: Primary end-point identical to ADMIRE-CD trial p-value < 0.05 (vs p-value <0.025 in ADMIRE-CD trial) US Phase III trial scheduled to start 2H 2016 Lonza selected as US contract manufacturing organisation for Cx601 in the US Major commercial opportunity 50,000 new patients every year in the US with high medical need Protection obtained through US patent until 2030 Fully-owned commercial rights 1 FDA: Food and Drug Administration 2 IND: Investigational New Drug 3 BLA: Biological License Application 4 SPA: Special Protocol Assessment 9

10 AlloCSC-01 Intracoronary administration of allogeneic cardiac stem cells for the treatment of acute ischaemic heart disease 10

11 AlloCSC-01: Preventing Congestive Heart Failure Myocardial repair may be the only feasible alternative 1,9M Acute Myocardial Infarctions (US+EU) 1 occur annually, mostly treated by PCI 2 and stent implantation Successful treatment of AMI has contributed to a Chronic Heart Failure epidemic (26M patients worldwide 3 ) CHF post-ami is a terminal disease with an annual mortality rate of ~18% after the first episode, for which no curative treatment exists with the exception of heart transplantation In 2010, the AHA estimated that the direct and indirect cost of heart failure in the United States was $39 billion, half of which was related to repeated hospitalizations, and by 2030 the total cost of heart failure in the United States is projected to increase to $70 billion 4 An attractive market for a treatment able to mitigate or delay the onset of CHF 1. Datamonitor: Stakeholder Insight: Acute coronary syndromes, DMHC2347, PCI: Percutaneous Coronary Intervention 3. Ambrosy PA et al.. J Am Coll Cardiol. 2014;63: LloydJ ones et al Circulation 2010 Feb 23;121(7):e46-e

12 AlloCSC-01: A Regenerative Treatment Post-AMI Preventing the onset of chronic disease The formation of a non-functional scar tissue gives rise to a process of ventricular remodeling whereby the myocardium tries to compensate the effect of the injury Over time the heart dilates losing its contractile capacity causing the onset of CHF. This is a terminal condition with no treatment other than transplantation The severity of this process is related to the size of the scar resulting from the AMI. Smaller scars are related to better outcomes 1 Myocardial repair seems to be the only feasible treatment to address the post-acute phase of the disease and prevent the onset of chronic heart failure (CHF) 1. Konstam MA, Kramer DG, Patel AR, Maron MS, Udelson JE. Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment. JACC Cardiovasc Imaging. 2011;4:

13 AlloCSC-01: CAREMI Phase I/IIa Trial Safety and efficacy of intracoronary infusion of allogeneic cardiac stem cells in patients with Acute Myocardial Infarction (AMI) TRIAL SUMMARY Completion 1H 2017 (Interim data 2H 2016) Condition Study design Recruitment Acute Myocardial Infarction AlloCSC-01 administered 5-7 days after PCI 1 Phase 1. Open label dose escalation in 6 patients Phase 2: Placebo controlled, 49 patients randomised 2:1 (35M cell dose in active arm) Phase 1: Completed Phase 2: 36 of 49 treated, set to complete recruitment in 4Q 2015 # of centers 8 sites Primary endpoint Secondary endpoints (6 and 12 months) Mortality and MACE 2 from any cause at 30 days Safety: Mortality and MACE Efficacy: evolution of infarct size, biomechanical parameters by MRI Clinical parameters: 6m walk test, NYHA 3 scale PATIENT SELECTION Initial clinical pre-screening: Males, females 18 years and 80 years Patients who present a STEMI 4 Killip 2 on admission Successful revascularization by PCI (TIMI 5 = 3) within 12h after the onset of symptoms EF 50% by echocardiography (day 2 after infarct symptoms) EF 45% by MRI on D3-5 post-stemi Infarct size (1 st MRI) >25% in LV 6 Bare-metal stents or second generation drug eluting stent at PCI The infarct culprit coronary artery is adequate for treatment administration and the procedure is technically feasible The patient is stable and in adequate clinical condition to undergo the procedure 1 PCI: Percutaneous Coronary Intervention 2 MACE: Major Adverse Cardiac Events 3 NYHA: New York Heart Association 4 STEMI: ST-Segment-Elevation Myocardial Infarction 5 TIMI: Thrombolysis In Myocardial Infarction 6 LV: Left Ventricle 13

14 Cx611 Intravenous injection of eascs for the treatment of severe sepsis 14

15 Cx611: A Swiss Army Knife For Treating Sepsis Phase II in severe sepsis expected to start 4Q 2015 Unmet medical need An estimated 15-19M sepsis cases occur worldwide each year 1 Sepsis mortality was estimated at 36% in a recent major European study 2 No effective treatments available Current molecular approaches to the treatment of sepsis have inadequately addressed the complex immuno-modulatory pathways involved in sepsis pathogenesis Cellular therapies offer a novel multifaceted mechanism of action that is potentially able to address the underlying immune dysregulation through multiple pathways Cx611 data Its efficacy in significantly reducing mortality has been demonstrated in several animal models of sepsis through a combination of reduced inflammation, production of anti-microbial effectors, and increased phagocytosis Safety and tolerability confirmed in Phase I sepsis challenge trial 1 The Lancet Infectious Diseases; Volume 12; issue 2; page 89; February Vincent JL et al Sepsis in European intensive care units. Critical Care Medicine 2006; 34:

16 Key Milestones 16

17 Key Milestones Cx601 (local) AlloCSC-01 (IC) Cx611 (IV) Product Europe US acute myocardial infarction severe sepsis ChondroCelect Q14 Phase 3 enrolment completed 3Q14 CMO selection 4Q14 SPA submission 4Q14 Phase 1 initiated 1Q14 manufacturing facility sold 2Q14 licensed to SOBI 3Q15 Phase 3 primary endpoint met (24 weeks) 3Q15 positive SPA 1Q15 Phase 2 enrolment initiated 4Q15 Phase 2 enrolment completed 2Q15 Phase 1 study results 4Q15 Phase 2 enrolment initiated 2Q16 study results (1 year follow-up) 1Q16 EMA filing 2H16 tech transfer finalized 2H16 pivotal Phase 3 initiated 2H16 Phase 2 interim analysis 2H16 File IND increase market penetration in existing countries expand geographic reach through new market entry 2H17 EU launch 1H17 Phase 2 study results 2Q17 Phase 2 enrolment completed YE17 Phase 2 study results 17

18 Thank you for your attention!