Corporate Presentation September 2014
Jan 12, 2015
Corporate Presentation
September 2014
2
Forward Looking Statement
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.
Management Team with Proven Track Record of Success
3
Managing Director and CEO: Eduardo Bravo, MBA
• More than 20 years experience in the pharma and biotech industries at Sanofi-Aventis, Recordati, Cephalon and SmithKline Beecham
CFO: Claudia D’Augusta, PhD
• More than 15 years experience in equity and debt financing at Aquanima (Santander Group), Apax Corporate Finance and Deloitte Corporate Finance
• More than 25 years experience in the pharma and biotech industries; previous engagements at GSK Biologicals and Transgène
VP Regulatory Affairs & Corporate Quality : María Pascual, PhD
• More than 10 years experience in cell therapy companies; specialised in regulatory affairs for advanced therapies; external adviser to EMA
CTO: Wilfried Dalemans, PhD
CMO: Marie Paule Richard, MD
• More than 25 years experience in the global biopharmaceutical industry at Aicuris, Crucell and Sanofi Pasteur
VP Medical Affairs & New Product Commercialisation: Mary Carmen Diez, MD
• More than 20 years experience in the biopharmaceutical industry at Meda Pharma, Asta Médica, Pfizer and Dupont Pharma
Investment Highlights
Pivotal Phase III Orphan Asset:
Cx601
• Perianal fistulas in Crohn’s patients in the US & EU represents a multi-billion dollar market opportunity
• Pivotal Phase III allogeneic stem cell asset (local administration of a single dose) with data expected in 3Q2015
• Phase II: 56% of patients achieved remission
• Positive Type B meeting held with the FDA
– Agreement on key parameters of future US Phase III trial
– Use of data from pivotal Phase III trial in EU to support a BLA
– Application for SPA to be filed Q4 2014
Clear US Approval Strategy:
Cx601
• Intravenously-administered allogeneic stem cell product for rheumatoid arthritis (Phase IIb) and severe sepsis (Phase Ib)
• Positive phase IIa data in refractory RA
Valuable Pipeline Opportunity:
Cx611
Proprietary Technology Platform
• Expanded adipose-derived stem cells (eASCs)
• Acts by controlling inflammation
• Well defined and fully characterized products
• Consistent and robust manufacturing process
• Up to 360 billion cells can be obtained from one donor
– 2,400 doses of Cx601 and 4,000 doses of Cx611
Established Uniform Manufacturing
Commercialized Product:
ChondroCelect
• First ever ATMP1 approved by EMA; valuable experience in regulatory approval / commercialization process
• Indicated for the repair of cartilage defects in the knee
• Established national reimbursement and partnered with Swedish Orphan Biovitrium
41 Advanced Therapy Medicinal Product
Multiple Product Candidates in Clinical Development
5
Preclinical Phase I Phase II Phase III Market
Cx601 (local)
Allogeneic Adipose Derived Stem Cells
Complex Perianal Fistulas in Crohn’s Patients
Cx611 (intravenous)
Allogeneic Adipose Derived Stem Cells
Rheumatoid Arthritis
Severe Sepsis
Cx621 (intralymphatic)
Allogeneic Adipose Derived Stem Cells
Autoimmune Disorders
ChondroCelectCharacterized Autologous Chondrocytes
Cartilage Lesions (knee)
Orphan Drug (EU)
IndicationProduct1
1 Covered by 24 patent families2 Distributed through Swedish Orphan Biovitrum and the Finnish Red Cross Blood Systems
Partnered2
Orphan Drug Filed (US)
Cell Type
Cx601 and Cx611 are our two key products in clinical development
6
Clear US Strategy Defined for Product Candidate
• Positive Type B meeting held with FDA in December 2013• Adequacy of the existing non-clinical package to support an IND1 filing for a
US-based pivotal Phase III trial
• Acceptability of using data from the ongoing ADMIRE-CD2 Phase III study in Europe to support a biologic license application (BLA)
• Agreement on key parameters of future US pivotal Phase III trial
• Development plan for the US being implemented• Selection of contract manufacturing organization for technology transfer
(3Q 2014)
• Application for special protocol assessment (submission 4Q 2014)
• IND1 to be filed as soon as technology transfer finalized
• Partnering discussions initiated
1 Investigational New Drug2 Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn’s Disease
MSCs1 Interact Closely with the Immune System
7
From: Singer and Caplan, 2011
PBMCs
Activated PBMCs
PBMCs+ASCs
activated PBMCs+ASCs
ASCs
0 5 10 15 20
IFN- (ng/ml)0 1 2 3 4 5
TNF- (ng/ml)
* *
* p<0.05 relative to supernatant from activated PBMCs Source: De la Rosa et al. Tissue Engineering 2009
1 MSCs: Mesenchymal Stem Cells
The ability to interact with many players in the immune system qualify MSCs (including
ASCs) as a potent anti-inflammatory agent
ACTIVATED PBMCs
ACTIVATED PBMCs +
ASCs
0
5
10
15
20
% O
F C
D4
+C
D2
5+
++
ON
T
OT
AL
CD
4
*
* p<0.05 relative to activated PBMCs without ASCs
Source: Tigenix data
eASCs as a Preferred Source of MSCs
8
Source and expansion
• Easily accessible
• Considerably higher yield than bone marrow
• Cell stability during expansion
Pharmacological profile
• Low immunogenicity, no tissue matching needed
• Enables allogeneic use
• Demonstrated anti-inflammatory capabilities
Validated eASC Platform
9
Quality• Consistent and robust manufacturing process• Quality control parameters defined: Identity, Purity, Potency
Safety
• No signs of toxicity, tumorigenicity, nor ectopic tissue growth in preclinical safety studies
• Clinical safety data obtained
Efficacy
• Demonstrated control of inflammation in 5 different preclinical models, including different routes of administration
• Clinical efficacy demonstrated
Reproducibility
• No tissue type matching needed, tissue dissociation and isolation of cells according to defined protocol, and expansion through a standardized cell culture process without pooling of cells
Cx601
Local injection of eASCs for the treatment of complex perianal fistulas in Crohn’s patients
10
11
Perianal Fistulas
• Fistulas: sores or ulcers that tunnel through the affected area into surrounding tissues
• 12% of Crohn’s patients are affected by perianal fistulas1
• 80% of these are complex
• Affect anal sphincters
• Present multiple tracts
• Are recurrent
• Are often associated with perianal abscess
> 100,000 Crohn’s patients suffer from complex perianal fistulas every year in Europe and the US alone => compromised QoL, pain, depression, risk of anal epithelial carcinoma
Large intestine
Fistula
1 Source: >60 publications (including Schwartz 2002, Lapidus 2006), the European Federation of Crohn’s and Colitis Associations, US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics
A Common Severe Complication of Crohn’s Disease
Perianal Fistulas: Treatment Options and Shortfalls
12
1 50% recurrence within 4 months of cessation of treatment (Bnernstein LH et al. (1980). Gastroenterology 79: 357–365) 2 Pearson DC et al. (1995) Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis. Ann Intern Med 123: 1323 ACCENT II clinical trial 4 54% for infliximab after 1 year (Sands BE et al. (2004). N Engl J Med 350: 876–885 5 CHARM clinical trial6 Schouten at al, Mizrahi et al, Sonoda et al, van der Hagen et al7 A. Soltani, A. Kaiser, Diseases of the Colon & Rectum vol.53:4 (2010)
Treatment Options Efficacy Safety
Antibiotics • Safety concerns with prolonged use• No long term healing data1
Infliximab(Remicade)
• Remission 23%3
• 20% need dose increase2
• High rate of relapse4
• Safety remains a concern with long term use of biologics
Adalimumab(Humira)
• Remission 33%5 • 20% need dose increase2
• High rate of relapse4
• Safety remains a concern with long term use of biologics
Immunossuppressants• Low healing rates• Relapse on drug cessation2
• High risk of infectious complications
Surgery • High risk of anal incontinence7• High proportion of recurrence6
0 250,000,000 500,000,000 750,000,000 1,000,000,000 1,250,000,000 1,500,000,000
16%12% 14%
60% 100%80%
70% 90%80%
20% 50%35%
$21k $48k
% CD patients with fistula2 (approximately 121,100 patients)
% Complex fistula – all fistula3 (approximately 97,000 patients)
% Patients failing biologic4 (approximately 77,500 patients)
% Market share (approximately 27,100 patients)
Average selling price $34k
1 TiGenix epidemiology report based on multiple publications 2 Schwartz et al, 2002, Vavricka et al., 2010, Pittet et al., 2010, KOL Interviews 3 Pittet et al., 2010, KOL Interviews4 Sands et al., 2004, Lichtiger et al., 2010, KOL Interviews
Market Potential: Perianal Fistula in Crohn’s Disease
Estimated peak year sales
•Assumptions:• Population EU28 + US: 824 million
• Prevalence of Crohn’s disease: 0.105% (865,200 patients)1
Note: Patient numbers refer to mid-point of the range given
13
Launch EU: 2017Launch US: 2020
2003 2004200
52006 2007 2008 2009 2010 2011 2012 2013 2014
Cx601: Developing a New Treatment Paradigm>10 years of experience, consistent efficacy and safety
14
I
Phase II
5 patients 1 center
50 patients 3 centers
214 patients 19 centers
Phase III (FATT 1)3
Cx601 (allogeneic)
Phase II
Phase II, IIS6
(ALOREVA)7
Phase III(ADMIRE-CD)8
Cx401 (autologous)
34 patients 6 centers
278 patients 52 centers
10 patients 1 center
Phase I
Note: Patient data refers to number of patients recruited
Crohn’s and non-Crohn’s perianal fistulas: 75% efficacy; open1
Crohn’s and non-Crohn’s perianal fistulas: 71% efficacy; p<0,0012
Non-Crohn’s perianal fistulas: 41% efficacy; p (n.s.)4
Crohn’s perianal fistulas: 56% efficacy; open5
Rectovaginal fistulas: 57% efficacy; open
1 García –Olmo, et al., 2005. Diseases of the Colon & Rectum 2 García –Olmo, et al., 2009. Diseases of the Colon & Rectum3 Fistula Advanced Therapy Trial 4 Herreros, et al., 2012. Diseases of the Colon & Rectum 5 de la Portilla, F. et al., 2012. Int. Journal of Colorectal Disease 6 Investigator Initiated Study7 Allogeneic adipose stem cells in rectovaginal fistulas8 Adipose Derived Mesenchymal Stem Cells for Induction of Remission in Perianal Fistulizing Crohn’s Disease
Cx601: Phase II
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Proof of concept for an allogeneic therapyTRIAL SUMMARY
Start June 2009
Completion September 2010
Conditions Complex perianal fistula in Crohn’s patients
Study design
• Single arm• Non-controlled• Safety/Efficacy study• One fistula/tract treated • Maximum of 2 doses1
Enrollment 34 patients recruited; 24 treated
# of centers 6 sites
Primary endpoint
Incidence of treatment emergent adverse-events
Secondary endpoints
• Closure of external openings (clinically and MRI)
• Reduce number of draining fistulas
Efficacy 56%
PATIENT SELECTION
• Older than 18 years: both genders • Complex perianal fistula fulfilling
some of the following conditions:• Associated fecal incontinence• Risk factors of anal incontinence• At least 1 previous treatment for a
fistulous disorder• Crohn’s disease (CDAI≤200)• Less than 3 fistulous tracts
• Wash out of anti-TNF of at least 8 weeks prior to inclusion
• No concomitant administration of anti-TNF allowed during the duration of the trial
• Efficacy confirmed by second gastroenterologist not involved in the direct care of the patient
1 First dose of 20M cells; Second dose of 40M cells injected if fistula has not closed after 12 weeks
Cx601: Phase II Results
16
Safety of allogeneic cells confirmed
• Repeated treatment with allogeneic eASCs well tolerated
• Favorable side effect profile•
Overview of adverse events. Full analysis set (n=24)
• Patients with at least one TEAE1 during the study: 13 (54.2%)
• Patients with at least one TEAE possibly related to eASCs during the study 5 (20.8%)
• Serious adverse events reported leading to withdrawal 22 (8.3%) (Events considered to be possibly related to the study treatment; no clinically relevant abnormalities found during physical examination or in vital signs)
1 Treatment Emergent Adverse Event2 Local abscess and pyrexia
Cx601: Phase II Results
17
Allogeneic eASCs confirmed efficacy of autologous cells
Closure of external openings of treated perianal fistula tracts
After 12 weeks (N=21) After 24 weeks (N=16)0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
38.1%
56.3%
Reduction in number of draining fistulas
Nº fistulas: 12
• Significant efficacy in closure of treated fistula tracts
• Reduction of drainage in treated fistulas that have not achieved complete closure
• Positive effect on adjacent fistula tracts that have not directly been treated
N= Patients with available information. Missing data not included in percentage calculations
(only 1 dose received) (week 26 if 2 doses received) (only 1 dose received)
After 12 weeks (N=21) After 24 weeks (N=16)0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
50.0%
61.5%
10.0% 7.7%
After 12 weeks (N=20) After 24 weeks (N=13)
(week 26 if 2 doses received)
Cx601: Investigator-Initiated Study ALOREVA
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Therapeutic effect of eASCs also confirmed in extremely tough condition
TRIAL SUMMARY
Start September 2009
Completion December 2011
ConditionsRectovaginal fistulas (RV) in
Crohn’s patients
Study design
• Open label• Non-controlled• Safety and efficacy study
Enrollment 10 patients
# of centers 1 site
Primary endpoint
Closure of the external opening of the treated RV fistula
Secondary endpoints
• Quality of life (SF-36)• Number of adverse events • Clinically relevant variations in
laboratory test
Efficacy 57% (1 year)
PATIENT SELECTION and RESULTS PATIENT SELECTION and RESULTS
• Women of a childbearing age (>18)• Rectovaginal fistula• Patients with Crohn’s disease
diagnosed at least 12 months earlier with either one previous surgery for fistulous disease or a physical status which discourage liposuction
• 7 patients completed the study• 4 out of these showed complete
closure of the fistula• All 10 patients avoided the previously
indicated colostomy
Cx601: Phase III ADMIRE-CD Trial
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Robust Phase III designed to qualify as a single pivotal study
TRIAL SUMMARY
Start July 2012
Completion Ongoing
ConditionComplex perianal fistula in Crohn’s
patients
Study design
• Randomized, double blind, placebo controlled trial
• All tracts treated. Fixed single dose1
Enrollment278 patients screened
208 patients randomized
# of centers 52 sites in 8 countries
Primary endpoint
Remission2 at week 24
Secondary endpoints
• Response3 • Time to remission / time to
response• PDAI score and QoL assessment
(IBDQ4)
PATIENT SELECTIONPATIENT SELECTION
• Older than 18 years: both genders • Patients with perianal fistulizing Crohn’s
disease refractory to antibiotics, immunosuppressants and/or anti-TNF
• Exclusion of naïve patients• Limit of patients refractory to antibiotics to
< 25% of total recruited patients• ≤ 2 internal openings (fistulas) and ≤ 3
external openings (tracts)• Non active luminal CD (CDAI5 ≤ 220)• CD diagnosed for ≥ 6 months; Fistula
draining < 6 weeks prior to inclusion• Concomitant treatments allowed without
modification of treatment dose or regimen
1 120 million cells2 Closure of all draining tracts at baseline despite gentle finger compression confirmed by MRI (no collections > 2cm) 3 Closure of 50% draining tracts at baseline despite gentle finger compression confirmed by MRI (no collections > 2cm) 4 Inflammatory Bowel Disease Questionnaire 5 Crohn's Disease Activity Index
Cx601: Phase III ADMIRE-CD Trial
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• Statistical plan:
• Evaluations at weeks 6, 12, 18 and 24 (after dosing)
• Final evaluation at week 52
• Blind clinical and MRI assessment
• Statistical pre-determination:
• α = 0.025
• β = 0.20
• Power: Designed for finding at least 25% difference among study groups
• Patient enrollment: More than 95% completed
• Follow-up: Initial follow up of six months completed with 1 year long-term follow-up study expected 3Q 2015 and 1Q 2016, respectively
Robust Phase III designed to qualify as a single pivotal study
Cx611
Intravenous injection of eASCs for the treatment of early rheumatoid arthritis
21
Rheumatoid Arthritis: A Huge Market Opportunity
22
• On a dollar basis, the market is dominated by biologic drugs (>80% of the market), and especially by antibodies which block tumor necrosis factor TNF1 (5 out of the 9 currently approved biologicals2)
• TNF inhibitors dominate the market with yearly average cost of ~$19k
• The overall RA market is expected to grow at a CAGR of slightly above 7% to approximately $23.4Bn in 2016
• Despite a wide variety of therapeutic options, a high level of unmet patient need exists
1 Wiki Analysis: Arthritis Drug market 2 Humira, Enbrel, Remicade, Simponi and Cimzia
• Induce and maintain low disease activity
• Target acute & inflammatory disease state
• Indication of activity evidenced in refractory patients in Phase IIa trial
Early Rheumatoid Arthritis
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eASCs are Functional in RA Models
Source: TiGenix data on file
Days after treatment
Arthritic score after three i.v. doses of eASCs TNF - alpha
% c
ytok
ine-
secr
etin
g T
cel
ls
* p<0.001
IL - 10
% c
ytok
ine-
secr
etin
g T
cel
ls
Source: González-Rey et al. Ann. Rheum. Dis. 2009
Intravenous administration of eASCs does protect animals from rapid progress to arthritic joints (CIA model)
T cells from RA patients reduce their inflammatory profile upon contact with
eASCs (in vitro experiment)
* p<0.001
Phase IIa Trial
First randomized trial with eASCs in refractory RA patients
24
TRIAL SUMMARY
Start March 2011
Completion January 2013
ConditionPatients with RA refractory to at
least two biologics
Study design
• Dose escalation, single blind, placebo-controlled (Cx611+ DMARD1 vs. placebo + DMARD)
Enrollment 53 patients
# of centers 23 sites
Primary endpoint
Safety (tolerability and treatment- emergent adverse events)
Secondary endpoints
• Efficacy measured by: – ACR2 remission (ACR 20,
ACR50, ACR 70)– EULAR3 (DAS4 28, VSG5)– Imaging (RAMRIS)– Quality of life (SF-36)
PATIENT SELECTION
• Heterogeneous patient population: Median range of diagnoses 5 – 69 years
• Patients with severe grade of RA: Median DAS 28 score: 3.2 – 7.9
• Patients refractory to at least two biologics
• Mean nº of previous DMARDs: 3.38 => 74% of patients received 3 or more DMARDs
• Mean nº of previous biologics: 2.92 => 45% of patients received 3 or more biologics
• 66% of patients had received Enbrel• 64% of patients had received Humira• 51% of patients had received Infliximab
1 DMARD: Disease-modifying anti-rheumatic drugs2 American College of Rheumatology 3 European League Against Rheumatism 4 Disease Activity Score 5 Variable Surface Glycoprotein
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Safety profile Cx611+DMARD(N=46)
Placebo+DMARD (N=7)
Patients with any adverse events (AE) 38 (83%) 4 (57%)
Patients with any related AE 22 (48%) 1 (14%)
Patients with any grade 3-4 related AE 1 (2%) 1 (14%)
Patients with any AE leading to discontinuation 1 (2%) 0 (0%)
• Only one patient experienced a serious adverse event leading to discontinuation of the treatment1
• All other side effects were mild and transient: most common related adverse events in the Cx611+DMARD group: fever (15%), headache (9%), asthenia (6%)
1 Lacunar infarction, which is defined as a type of stroke in the brain's deep structures
Phase IIa Trial
Favorable safety profile of all three doses of Cx611
Phase IIa Results
Encouraging therapeutic activity
26
ACR20 ACR50 ACR70
M1 M2 M3 FV0
10
20
30
40 3326
20 20
29
14
0 0
M1 M2 M3 FV0
10
20
30
11 13 11 1114
0 0 0
1 2 3 40
5
10
15
20
4 4 42
0 0 0 0
% % %
M
ACR criteria
M6 (FV) M6 (FV) M M M6 (FV)
Results shown are response rates in percentageM1, M2, M3 and M6 (FV) refers to month 1, 2, 3 and 6 (Final Visit) respectively;
For all graphs: N=46 for Cx611+DMARD cohort and N=7 for placebo + DMARD cohort
M1 M2 M3 FV0
10
20
30
4037 35
39
24
43
29
0 0
EULAR response Good + Moderate
DAS 28 (CRP) <3.2 DAS 28 (CRP) <2.6(remission)
M1 M2 M3 FV05
10152025
1520 20
1315 15
0 0
M1 M2 M3 FV0
5
10
15
20
711 11
9
0 0 0 0
M6 (FV) M6 (FV)
% % %
M6 (FV)
Cx611 + DMARD
Placebo + DMARD
EULAR criteria
Cx611
Intravenous injection of eASCs for the treatment of severe sepsis
27
eASCs Can Protect in Severe Sepsis
28
LPS Model
• Cx611 reduces mortality in animal models of sepsis
• This effect is due to a combination of reducing pro-inflammatory and increasing anti-inflammatory mediators, production of anti-microbial effectors and increased phagocytosis
Source: Gonzalez-Rey, 2009
CLP Model
ChondroCelect
Characterized autologous chondrocytes for the treatment of cartilage lesions in the knee
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ChondroCelect
• Suspension of characterized autologous chondrocytes injected intra-articularly
• Indicated for the repair of single symptomatic cartilage defects of the femoral condyle of the knee (ICRS III or IV) in adults
• Market: Between 17,000 – 28,000 new patients per year in Europe
• Additional expansion opportunity ex-Europe and Middle East
• Currently on the market in BE, NL, ES, UK and Finland => 2013 gross sales of €4.3M
• Further market penetration to be achieved through distribution agreement with Swedish Orphan International (Sobi), effective as of 1st June 20141
• 20% royalty on ChondroCelect net sales (22% in year 1) and reimbursement of almost all ChondroCelect expenses => ChondroCelect becomes a cash-flow positive asset for TiGenix
30
First ever ATMP approved by EMA (2009)
First, and so far, only cell therapy product with national reimbursement
1 Sobi Territory: European Union (excl. Finland), Switzerland, Norway, Russia, Turkey and the MENA region, whereby certain countries within MENA will only become part of Sobi’s territory as of Nov. 12th, 2014
Manufacturing, Intellectual Property, and Milestones
31
eASC Manufacturing
32
Isolation of Stromal Vascular Fraction(SVF)
Cellular expansion
Freezing Cell Banks
Schematic manufacturing overview
Manufacturing Process Scheme
33
Uniform manufacturing scheme for all products
Liposuction
Cell isolation and expansion
Frozen Drug Substance (FDS)
Finished Product
Master cell bank (cryo)
• Up to 360 billion cells can be obtained from 1 donor
• Finished product units at current doses (clinical trials):
• 2,400 doses of Cx6011
• 4,000 doses of Cx6112
1 Based on ongoing Phase III trial (120M cells per patient)2 Assumes 1 million eASCs/ Kg, weight average 80Kgs
A Growing Patent Portfolio in Cell Therapy
• 24 patent families related to cell therapy products
• Pending & granted patents in over 20 jurisdictions including the US; expiry dates 2024 onwards
• Key patent for Cx601 (PCX007) granted in AU, RU, MX, IL and NZ• Patent protects use of ASCs in treatment of fistula• Complementary protection possible through additional patents under review
• Portfolio covers key features of TiGenix’ chondrocyte and stem cell platforms• Expanded cell compositions and preparations• Use of expanded cells in treatment of broad range of indications• Cell preparation methods & delivery systems
• FTO for indications in clinical development confirmed by external counsels • US: Morrison & Foerster• Europe: Carpmaels & Ransford
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Key Milestones
35
2014 2015 2016 2017
Cx601 (local)
Europe
US
Cx611 (IV)
RA
Severe Sepsis
ChondroCelect
Product
3Q15 primary endpoint results (24 weeks)
1Q16 study results (1 year follow-up)
1H16 EMA filing
3Q14 CMO selection 1H16 tech transfer finalized
4Q14 SPA submission
Increase market penetration in existing countries
Expand geographic reach through new market entry
4Q14 Phase 3 enrollment completed
2H16 pivotal Phase 3 initiated
3Q15 Phase 2 enrollment initiated
YE16 Phase 2 enrollment completed
1H17 Phase 2 study results
1H17 EU launch
1Q15 Phase 1b initiated
3Q15 Phase 1b study results
3Q16 Phase 2 enrollment initiated
Key Facts about TiGenix
36
1 Exchange rate as of 14 July 2014 (oanda)
Headquarter Leuven, Belgium
Operations Madrid, Spain
Employees Approximately 50 employees
Stock Exchange Traded on NYSE Euronext Brussels (TIG)
Market Capitalization Approximately $130M
Reference Shareholders 30% held by Grifols, Roche, and Novartis
Liquidity ≈ 70% free-float of which 30% held by institutional investors
Analyst Coverage 6 analysts covering the stock, of which four are independent
Cash Balance $29M as of Q2 20141
Investment Highlights
Pivotal Phase III Orphan Asset:
Cx601
• Perianal fistulas in Crohn’s patients in the US & EU represents a multi-billion dollar market opportunity
• Pivotal Phase III allogeneic stem cell asset (local administration of a single dose) with data expected in 3Q2015
• Phase II: 56% of patients achieved remission
• Positive Type B meeting held with the FDA
– Agreement on key parameters of future US Phase III trial
– Use of data from pivotal Phase III trial in EU to support a BLA
– Application for SPA to be filed Q4 2014
Clear US Approval Strategy:
Cx601
• Intravenously-administered allogeneic stem cell product for rheumatoid arthritis (Phase IIb) and severe sepsis (Phase Ib)
• Positive phase IIa data in refractory RA
Valuable Pipeline Opportunity:
Cx611
Proprietary Technology Platform
• Expanded adipose-derived stem cells (eASCs)
• Acts by controlling inflammation
• Well defined and fully characterized products
• Consistent and robust manufacturing process
• Up to 360 billion cells can be obtained from one donor
– 2,400 doses of Cx601 and 4,000 doses of Cx611
Established Uniform Manufacturing
Commercialized Product:
ChondroCelect
• First ever ATMP1 approved by EMA; valuable experience in regulatory approval / commercialization process
• Indicated for the repair of cartilage defects in the knee
• Established national reimbursement and partnered with Swedish Orphan Biovitrium
371 Advanced Therapy Medicinal Product
Corporate Presentation
September 2014
38