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Corporate PresentationDecember 2015Dual listed company
Lead asset on track for EU approval
Partnered with tier-one, big pharma company
June 2017
2
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 statements 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.
Forward-Looking Statements
3
Compelling Investment CaseLead product near approval in Europe, strong partner, significant upside potential
Seasoned management team with deep experience in drug development
Well capitalized
Traded on the Nasdaq and Euronext (TIG)
Ex-US rights licensed to Takeda; key strategic partner for commercial launch
Up to EUR 380M in potential milestones plus double-digit royalties
Lead product Cx601 in development for complex perianal fistulas, an orphanindication with high unmet medical need
Filed for approval in EU; decision expected in 2H2017
Clear development plan for global pivotal phase III trial to start in 1H2017
Multiple assets in clinical-stage development
4
PipelineClear commercial potential with future growth opportunities
5
Cx601
Novel, locally administered treatment for a severe
complication of Crohn’s disease
EU approval decision expected 2H2017
6
Adipose-Derived Stem Cells are Potent Anti-inflammatory AgentsMechanism of Action (MoA) is IDO1-mediated
• eACSs broadly interact with many players
in the immune system
• One of their key in vivo biological roles is
the control of inflammation to prepare the
return to homeostasis through:
• Inhibition of T cell proliferation and pro-
inflammatory cytokine secretion
• Induction of anti-inflammatory cytokines
• Induction of increased number of Tregs
• Control of NK cell mediated killing
• Control of monocyte and B cell maturation
• IDO enzyme is a key player in the MoA
1 IDO: Indoleamine 2,3-dioxygenase
Image representation of the proprietary research that supports the key characteristics of eASC mechanism of action.
7
GMP Facility Approved for Commercial ManufacturingConsistent and robust process
1 liposuction from healthy donor
Allogeneic model translates into production scalability
2,400 patients (Cx601)
8
Complex Perianal FistulasA common and severe complication of Crohn’s disease
Fistula
Fistula
Perianal fistulas are chronic, abnormal
communication between the epithelialized
surface of the anal canal and the perianal skin
Perianal fistulas are a complication of Crohn’s
disease for 30−50% of patients1
Perianal fistulas in Crohn’s disease are
difficult to treat with currently available
therapies and often leads to pain, swelling,
infection and incontinence
70−80% of perianal fistulas are classified as
complex2,3
• Most challenging to treat
• Often refractory to conventional treatment
and anti-TNF agents4-6
1. Schwartz DA, et al. Gastroenterology. 2002;122:875-80; 2. Eglinton TW, et al. Dis Colon Rectum. 2012;55:773-7; 3. Bell SJ, et al
Aliment Pharmacol Ther. 2003;17:1145-51; 4. Present DH, et al. N Engl J Med. 1999;340:1398-405; 5. Sands BE, et al. N Engl J Med.
2004;350:876-85; 6. Pearson DC, et al. Ann Intern Med. 1995;123:132-42;
9
Cx601: A Completely Different and Simple ApproachA single administration with long-term efficacy
Method of administration of Cx601: Injection
10
1 Schwartz et al 2002. Gastroenterology 122:875-8802 Kappelman et al 2013. Dig Dis Sci, 58:519-5253 Khalili et al 2012. Gut :1686-16924 Study commissioned to Vencore Health Analytics Inc based on Truven MarketScan database5 Göttgens et al 2017. Eur J Gastroenterol Hepatol [Epub ahead of print]6 Burisch et al 2013. J Crohn’s Colitis 7:322-337
Estimation of prevalence of Crohn’s Disease patients
with perianal fistulas
Adult Crohn’s patients with perianal fistulas (93% CD
patients are adults 2)
Crohn’s patients with perianal fistulas
50,153 57,359
80,849
From European published data 5,6From US published data 1,2,3 From US real world data (claims
database) 4
53,756Crohn’s patients with perianal fistulas (average)
Adult Crohn’s patients with perianal fistulas (93%
CD patients are adults 2)75,19049,993
Over 125,000 Adult Crohn’s Patients Suffer Perianal Fistulas40% of these patients are in the US
11
With complex perianal fistulas:
Adult Crohn’s Disease patients with perianal fistulas:
37,495
24,746
22,272
With complex perianal fistulas and controlled luminal disease:
With refractory complex perianal fistulas and controlled luminal disease:
56,392
37,219
33,497
1 Bell et al 2003. Aliment Pharmacol Ther 17:1145-11512 Eglinton et al 2012. Dis Colon Rectum 55:773-7773 Riss et al 2013. Tech Coloproctol 17:89-944 Molendijk et al 2014. Inflamm Bowel Dis 20:2022-2028
In ~75% CD patients perianal fistulas are complex 1-5
In ~66% CD patients with perianal fistulas luminal disease is controlled
in ~90% CD patients perianal fistulas are treatment refractory 6-8
5 Molendijk et al 2015. Gastroenterology 149:918-927 6 Sands et al 2004. N Engl J Med 350:876-8857 Domenech et al 2005. Aliment Pharmacol Ther 22:1107-11138 Rayen et al 2017. Tech Coloproctol 21:119-124
More than 55,000 Patients Fit the Expected LabelNon-controlled luminal disease patients represent a very meaningful opportunity
49,993 75,190
Expected label
12
A Real Need for New Treatment OptionsAvailable treatments lack long term efficacy and present safety issues
1 Sands et al 2004. N Engl J Med 350:876-8852 Grimaud et al 2010. Gastroenterology 138:2275-22813 Domenech et al 2005. Aliment Pharmacol Ther
22:1107-11134 Rayen et al 2017. Tech Coloproctol 21:119-1245 Present et al 1999. N Engl J Med 349:1398-14056 Poritz et al 2002. Dis Colon Rectum 45:771-775
● Only ~1/5 patients see a response after 1 year of
continued treatment (IV infusion every 8 weeks) 1,2
● Upon treatment discontinuation healed fistulas relapse
in 2/3 patients within the next year 3
● Rarely achieves complete healing in the long-term (13%
of patients) 4
● Efficacy does not increase in combination with
immunosuppressants 5
● Treatment does not abolish the need for surgery 6
● Associated with serious infections in 9% of patients and
to infusion reactions in 11% of patients 7
● An average of 4 surgeries over a period of years 9,10 with
only half of patients healed 9
● Fistula surgery is linked to risk of sphincter damage
leading to faecal incontinence 11,12
● 30% and 54% of patients report post-operative
incontinence to solid and liquid stools 13
● High rate of recurrences and failures 8
● 33% and 13% of patients with complex anal fistulas
require ostomy and proctectomy 14 , with no guarantee of
healing 15,16
Infliximab (anti-TNFα)
7 D’Haens et al 2016. J Crohn’s Colitis [Epub]8 Schwartz et al 2015. Inflamm Bowel Dis 21:723-7309 Graf et al 2015. Colorectal Dis 18:80-85110 Galandiuk et al 2005. Ann Surg 241:796-80211 Norton et al 2013. J Crohn’s Colitis 7:e302-311 12 Geltzeiler et al 2014. Ann Gastro 27:320-33013 Riss et al 2013. Tech Coloproctol 17:89-94
Surgery
14 Molendijk et al 2014. Inflamm Bowel Dis 20:2022-2028
15 Figg et al 2009. Dis Colon Rectum 52:646-65016 Lee et al 2017. Colorectal Dis 19:418-429
Only medical treatment approved for fistulas in Crohn’s
disease
Complex fistulas require surgical intervention 8
13
Pivotal Phase III Design Validated by EMA and FDAComplex fistulas refractory to best available standard of care
• Randomized, double-blind, placebo controlled
• 212 patients randomized 1:1
• Patients with non-active or mildly-active Crohn’s Disease
• 40% of patients with multiple tract fistulas
• Draining fistulas despite active treatment (majority anti-TNF)
• All patients stayed on their best standard of care treatment
• All draining tracts treated
• Efficacy defined as combined remission: clinical remission and lack of
abscesses with magnetic resonance imaging
• Efficacy measured at 24 and 52 weeks. Safety follow up to 104 weeks
14
Cx601: Primary Endpoint Met at Week 24
Patients receiving Cx601 had a 44% greater probability of achieving Combined
Remission1 than placebo patients. Results published in The Lancet in July 2016
Shorter median time to clinical remission (6.7 weeks for Cx601 vs 14.6 weeks in
the control group)
51.5%
35.6%
0
20
40
60%
Combined Remission at W24 (mITT2 Population n= 204)
p = 0.021
1 Closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections > 2cm
by MRI (Magnetic Resonance Imaging)2 mITT: modified Intention To Treat i.e. patients randomized, treated and with ≥1 post-baseline assessment. Efficacy results are
consistent across all statistical populations
Cx601 Control
15
Cx601: Benefit Sustained, Lower Relapse Rate at Week 52
1 Closure of all treated external openings draining at baseline despite gentle finger compression, and absence of collections > 2cm by MRI
(Magnetic Resonance Imaging)2 Relapse: reopening of any of the treated external openings with active drainage as clinically assessed, or development of perianal collection ≥2cm
of the treated perianal fistula confirmed by centrally blinded MRI assessment in patients with clinical remission at any previous visit3 mITT: modified Intention To Treat i.e. patients randomized, treated and with ≥1 post-baseline assessment. Efficacy results are consistent across all
statistical populations
75.0% of the patients treated with Cx601 who were in combined remission at W24 did not
relapse2, compared to 55.9% for patients in the placebo arm
75.0%
55.9%
0
20
40
60
80
56.3%
38.6%
0
20
40
60
More than 50% of the patients receiving Cx601 had all treated fistulas in Combined
Remission1 one year after a single administration of the product
Combined Remission at W52
(mITT3 Population n= 204)
p = 0.010
No Relapse Rate at W52
Cx601 Control Cx601 Control
16
Cx601: KOLs Voice Excitement Over AMDIRE-CD ResultsECCO1 (EU), DDW2 (US), The Lancet3
Dr. Panés: Oral presentation, ECCO 2016
Dr. Van Assche: Satellite Symposium, ECCO 2016
1 European Crohn’s and Colitis Organization (ECCO), Amsterdam, March 16 – 19, 2016
2 Digestive Disease Week (DDW) in San Diego, May 24, 2016 and Chicago, May 4, 2017
3 The Lancet [online]. Published online July 28, 2016, available at http://dx.doi.org/10.1016/S0140-6736(16)31203-X
17
“Key Opinion Leader” Event, 8th May 2017, ChicagoDoctors express disappointment with current treatments
1 Key Opinion Leader event webcast: http://www.wsw.com/webcast/cc/tig/
“Gastroenterology is one of Takeda’s core therapeutic
areas of focus. When we look at leadership in GI it is all
about delivering very innovative drugs in a population
which has high unmet need. And Cx601 truly
underscores that commitment.” 1
Dr. Uthra Sundaram, VP of the GI Therapeutic Area
and Global Commercial Leader at Takeda
Pharmaceuticals
“…This is a really debilitating, serious medical condition. The more complex fistulas historically have had poor
healing rates, which is one of the unmet need areas that stem cell therapy could potentially help. Fistulizing Crohn's
disease is fairly common and the incidence increases as the disease duration goes up. Gastroenterologists,
surgeons and radiologists collaborate to take care of these patients and what we really need is some new treatment,
which is what brings us here today.“ 1
Dr. William J. Sandborn, MD, Professor of Medicine and Adjunct Professor of Surgery Chief, Division of
Gastroenterology Vice Chair for Clinical Operations, Department of Medicine Director, UCSD IBD Center University
of California San Diego and UC San Diego Health System
18
• Team with previous experience in obtaining MA1 of cell therapy product
• Orphan Designation received 2009
• 5 Scientific Advice Meetings held with EMA2 (2 pre-clinical, 2 CMC3, 1 clinical)
• Approved PIP4 with 20 patients to be started not before 2020
• GMP license for commercial manufacturing granted
• Final approval expected in 2H2017
Cx601: EU Approval Decision Expected 2H2017Clear and fast pathway to the market built on a solid regulatory strategy
1 MA: Marketing Authorization2 EMA: European Medicines Agency3 CMC: Chemistry Manufacturing and Controls4 PIP: Pediatric Investigational Plan5 MAA: Marketing Authorization Application
6 AR: Assessment Report7 LoQ: List of Questions8 LoOI: List of Outstanding Issues9 CHMP: Committee of Human Medicinal Products (within
EMA)
AR6 LoQ7 Responses Joint AR LoOI8 Responses
D121 D181
CHMP9
Opinion
D2101st Clock
Stop
2nd Clock
Stop
MAA5
Submitted
1Q2016
EU Decision
D277
D1 D80 D120
Start of the
procedure
D150
D180
Current status
19
Ex-US Rights of Cx601 Licensed to TakedaTiGenix keeps significant upside potential
• Takeda acquired the exclusive ex-US development and commercialization
rights to Cx601 for the treatment of complex perianal fistulas in Crohn’s
disease patients
• TiGenix retains the right to develop Cx601 in new indications
• Takeda paid EUR 25M up front and a EUR 10M equity investment
• TiGenix eligible to receive potentially up to EUR 355M in regulatory and
sales milestones, including a EUR 15M EU marketing approval milestone
• Double-digit royalties on net sales, tiered to reimbursement price
• Takeda will assume manufacturing responsibilities for Cx601 after an initial
period of product supply by TiGenix at cost for the EU
20
Takeda is the Best Potential Partner for Cx601A global leader with strategic focus in GI
Source: Takeda presentation (JPM event 2017)
2121
Cx601: A Key Pillar in Takeda’s GI StrategyPerfect fit with existing IBD portfolio
Source: Takeda presentation (JPM event 2017)
22
Cx601: European Launch Expected 1H2018Significant progress since signing licensing agreement
1 European Crohn’s and Colitis Organization2 Digestive Disease Week, May 6-9 Chicago, IL, USA
First wave of pre-launch activities completed or ongoing by Takeda
Value proposition, positioning and branding
Large-scale multi-stakeholder market research to understand unmet need, value perception and potential usage
Price and market access research
Preliminary structure of cost-effectiveness model
Centers mapping
Sizing of potential population eligible for Cx601 treatment
Stakeholder facing function training
Oral presentation on Cx601 and symposium at ECCO1 2017
Oral presentation at the 2017 DDW2 session dedicated to Controlled Clinical Trials in Inflammatory Bowel Diseases
23
Cx601: Approach to US MarketLeveraging EU data with approved phase III protocol
• Solid regulatory and clinical development strategy
• Type B meeting with FDA1 confirmed:
• Adequacy of existing non-clinical package to support an IND2 filing
• Acceptability of using data from the ADMIRE-CD trial to support BLA
• SPA3 for US Phase III protocol agreed with FDA:
• Primary end-point identical to ADMIRE-CD trial
• p-value < 0.05 (vs. p-value <0.025 in ADMIRE-CD trial)
• Global phase III trial scheduled to start in 1H2017
• Lonza selected as contract manufacturing organization for Cx601 in the US,
technology transfer ongoing
• Exploring different expedited pathways with the FDA
1 FDA: Food and Drug Administration 2 IND: Investigational New Drug 3 SPA: Special Protocol Assessment
24
The 21st Century Cures Act and the New RMAT Designation A potential avenue to accelerate Cx601 availability up to 24 months
The 21st Century Cures Act is an extremely significant healthcare legislation that
may have a direct and beneficial impact on TiGenix’s clinical development
programs and progress towards approvals with at least 4 RMAT designationsgranted since program launch in January 2017
Human acellular vessel in Vascular Access for Hemodialysis (Humacyte), 20 March 2017
Allogeneic thymic tissue in complete DiGeorge Syndrome (Enzyvant), 17 April 2017
Human retinal progenitor cells in Retinitis Pigmentosa treatment (jCyte), 2 May 2017
Autologous bone marrow derived multicellular therapy in Advanced Heart Failure Due to Ischemic Dilated Cardiomyopathy (Vericel), 10 May 2017
Expedited approval pathway specific for regenerative advanced therapies
Allows shorter timeline for marketing approval
Creates medical and economic benefits for the healthcare system and reduces costs of
development Facilitates early patient access to therapies with proven efficacy
Definition
Real cases
Benefits
25
“Group A”Controlled
luminal disease
Antib. / Immuno.
Not responding
“Group B” Controlled
luminal disease
Infliximab
Not responding
“Group C”Controlled
luminal disease
Second biologic
Not responding
“Group D” Controlled
luminal disease
After failure of
repair surgery
Non-controlled
luminal disease
Infliximab
Not responding
21% 38% 17% 24% ∆ 54% patients upside
50% 45% 85% 90% 60%
11% 17% 14% 21% ∆ 51%patients upside
% of patients in US within each subgroup
25
Patient subgroups within expected label in US
% patients in US within each group treated with Cx601
% patients in US treated with Cx601 (from total within expected label)
Sources: Simon-Kucher & Partners; Expert discussions in June 2016 with 5 medical directors, 2 ex-Medicare carriers, 2 hospital pharmacy directors, 5 KOLs and 16 HVPs (gastroenterologists and colorectal surgeons) in the US
Cx601 Product Profile is Extremely CompetitiveUS doctors may also use Cx601 in other patient groups
Physicians in the US would prescribe Cx601 to around two thirds of all patients included in
the expected label
26
46%
59%
90%100% 95%
99%
0%
20%
40%
60%
80%
100%
120%
At increasing prices, physicians would prescribe Cx601 to less patients given likely
restrictions of payers. However, profits would be optimized between $60 and $120k
Sources: Simon-Kucher & Partners; expert discussions June 2016 with 5 medical directors, 2 ex-Medicare carriers, 2
hospital pharmacy directors, 5 KOLs and 16 HVPs. Assumptions on costs provided by TiGenix
Pre
fere
nce
sh
are
fo
r C
x6
01
34%29%
27%
21%
16%14%
0%
10%
20%
30%
40%
50%
WAC price per treatment (thousand $)
Aggregated price-response curve
(physicians’ coverage and payers’ Rx)
Pro
fit
ind
ex (
incl
ud
ing
CO
GS
)
WAC price per treatment (thousand $)
Profit index function for Cx601
(physicians’ coverage and payers’ Rx)
30 40 60 80 100 12030 40 60 80 100 120
Payer adjusted scenario
Profit-optimal price range
Cx601: US Price Range Allows Significant Margin Research indicates profit-optimal prices between $60 and $120k
27
Addressable patient population70,000 – 37,000
10% - 30%
USD 40,000 – 50,000
Penetration rate
Price per dose
70,000 – 40,000
15% - 25%
USD 20,000 – 30,000
Peak Year Sales
Cx601 Peak Year Sales Analysts’ ConsensusSeveral variables kept today on the “conservative side” provide future upside
USD 270M – 663M USD 205M – 300M
28
Cx601: Pipeline Expansion Under EvaluationPotential for Cx601 growth beyond complex perianal fistulas
• Rectovaginal fistulas in Crohn’s
• Enterocutaneous fistulas in Crohn’s
• Complex anal fistulas in non-Crohn’s
• Intestinal ulcers in Crohn’s disease
• Intestinal ulcers in Ulcerative Colitis
Other gastrointestinal fistulasGastrointestinal indications other than fistulas
Other indications
29
Cx601: Significant Potential in Other Gastrointestinal FistulasAddressable population could be four times larger
1 Study Commissioned to Vencore Health Analytics Inc, 2016
Patients under
expected label Cx601
Patients with other
fistulas
* Complex perianal fistulas out of the expected label include those in patients with non-controlled luminal
symptoms, those that are not refractory to currently available therapies, and those affecting children
Source: Truven MarketScan® database1
Estimated Patient Populations in US (2014)
30
Pipeline
Cx611 – novel treatment for severe sepsis
AlloCSC-01 – allogeneic cardiac stem cells to treat heart
disease
31
1 The Lancet Infectious Diseases; Volume 12; issue 2; page 89; February 20122 Martin GS Expert Rev Anti Infect Ther. 2012 June ; 10(6): 701–706. 3 Adapted from Lagu, T., et al. Critical Care Medicine, 40(3):754-761; 2012 4 Adapted from: Elixhauser et al. Septicemia in U.S. Hospitals 2009, AHRQ, Healthcare Cost Brief No. 122 October 2011
Cx611 – A Novel Treatment Approach to Severe SepsisLeading cause of mortality in the developed world
• Sepsis is a life-threatening complication of infection
leading to systemic inflammation and organ failure
• Between 15M to 19M sepsis cases occur worldwide
each year1. Mortality reaches 50% for severe
sepsis raising to 80% in septic shock2
• Cx611’s novel mechanism of action may offer an
innovative alternative to the treatment of severe
sepsis: efficacy in in vivo models and good Phase I
results
• TiGenix’ Phase II trial (SEPCELL) has received the
support of the Horizon 2020 European Commission
Program and the endorsement of Key Opinion
Leaders
• SEPCELL is a randomised, multicentre, double-
blind, placebo-controlled study. Recruitment
ongoing in patients with severe community-acquired
bacterial pneumonia (sCABP). Primary endpoint
safety; secondary endpoints include improved
survival, and/or clinical cure of the CABP, and other
infection-related endpoints (at 90 days)
600
800
1000
1200
1400
1600
1800
2000 2002 2004 2006 2008 2010
Dis
ch
arg
es th
ou
sa
nd
s
Trend in U.S. hospital stays with septicemia 2000−20094
8% CAGR
750,000
466,000
375,000
84.000
0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
Sepsis Breast, Prostate Cancer &AIDS
Diagnosed cases and mortality of Sepsis vs. Breast Cancer, Prostate Cancer & AIDS3
Diagnosis
32
AlloCSC-01: Allogeneic Cardiac Stem CellsTop-line results met all safety objectives. Study revealed valuable insight
“First-in-human” phase I/II trial focused on a safety primary objective and the
evaluation of the feasibility of an intracoronary infusion of 35 million of AlloCSC-01 in
patients following a high-risk AMI
The main findings were:
• Safety primary objective was met: no death or major cardiac adverse events at 30
days. Same results at 6 or 12 months; no immune-related adverse events
throughout the trial
• A larger reduction in infarct size was found in the AlloCSC-01 arm in a pre-
specified subgroup of patients with poor long-term prognosis associated with a
characteristic MRI signature, offering an exciting prospect for further targeted trials in
this population
• Top-line results announced on March 13, 2017. Full results to be presented at
upcoming medical congress
33
Outlook
34
Strong Financial PositionSignificant fundraising completed in 2016; marquee investors on board
• EUR 23,75 million raised in private placement with specialized investors
• USD 35,65 million raised with NASDAQ IPO. 4 US analysts coverage
• EUR 10 million equity investment from Takeda
• EUR 78 million (18 – 24 months runway) at Dec 31, 2016
• Shareholders over 3%1
• Grifols (16%)
• Cormorant (6%)
• Takeda (5%)
• Hillhouse (4%)
• Source: transparency notification, 13-F Reports, Nasdaq IR insight
35
2017
2018
2019
• Cx601 IND and start of recruitment in US centers
• Takeda to launch Cx601 in EU markets
• Start of global phase III for Cx601 BLA at FDA
• Cx601 EU marketing approval decision
• €15M milestone on Cx601 EU MA decision
• Plan on new indications for Cx601
Several Key Future Milestones Short-term catalysts and long-term value-creation opportunities
• End of Cx601 recruitment
• Sepsis phase II data
36