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TiGenix NV

IPO Roadshow Presentation

March 2007

Gil Beyen Frank Hazevoets


CEO CFO
Important Notice

This presentation and any material distributed in connection with this presentation do not constitute an offer or
invitation, or solicitation of an offer, to subscribe for or purchase any securities, and neither this presentation nor any
material distributed in connection with this presentation or anything contained herein shall form the basis of any
contract or commitment whatsoever. This presentation, any material distributed in connection with this presentation
or any information contained herein are being furnished to you solely for your information and may not be
reproduced, disclosed or redistributed to any other person or published, in whole or in part. In particular, neither this
presentation nor any material distributed in connection with this presentation nor any copy hereof may be taken or
transmitted to, or distributed directly or indirectly in, the United States or to any resident thereof or to any “U.S.
Person" as such term is defined in the U.S. securities act of 1933. Additionally, this document may not be distributed
in Canada, Australia or Japan.
This presentation and any accompanying material are for distribution in the United Kingdom only to (i) persons who
have professional experience in matters relating to investments falling within article 19(5) of the Financial Services
and Markets Act 2000 (Financial Promotion) Order 2005 (as amended) (the “Order”) or (ii) high net worth entities
falling within Article 49(2)(a) to (d) of the Order (all such persons together being referred to as “Relevant Persons").
This presentation and any accompanying material are directed only at Relevant Persons and may not be acted on or
relied on by persons who are not Relevant Persons. Any investment or investment activity to which this presentation
and any accompanying material relate is available only to Relevant Persons and will be engaged in only with
Relevant Persons. The distribution of this presentation and any accompanying material in other jurisdictions may be
restricted by law and persons into whose possession this presentation and any accompanying material come should
inform themselves about, and observe, any such restrictions. By accepting this presentation and any accompanying
material , you agree to be bound by the foregoing limitations.
Neither TiGenix, nor any of its officers, employees, advisers, or agents, nor Piper Jaffray and ING make any
representation or warranty, express or implied, as to any matter or as to the truth, accuracy, or completeness of any
statement made in this presentation, made in conjunction therewith or in any accompanying materials or made at
any time, orally or otherwise, in connection with the matters referred to herein and all liability (in negligence or
otherwise) in respect of any such matter or statements is expressly excluded (except only in the case of fraud).
Piper Jaffray and ING are acting as lead managers in relation to the proposed equity fund raising and are not acting
for any other person and will not regard any other person (whether or not such person is present at the presentation)
as their customer in relation to the offering and will not be responsible to anyone other than TiGenix for providing the
protections afforded to their customers or for providing advice in relation to the proposed offering.

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Prospectus
If you intend to participate in the proposed offering, you are reminded that any such participation is to be made solely
on the basis of the information contained in the final prospectus of TiGenix (and any addenda thereto, as the case
may be). Before making an investment in the shares, you should carefully read the entire prospectus and should
give particular attention to the risk factors set forth therein.
When making any application or acceptance to acquire any shares or other securities in TiGenix, no reliance is to be
placed on the information contained in this presentation and any material distributed in connection with this
presentation (other than the prospectus), which in itself is not to be construed as an offer or invitation, or solicitation
of an offer, to subscribe for or purchase any securities and shall not form the basis of any contract or commitment
whatsoever.
The Dutch and English version of the prospectus and the French summary of the prospectus are available to
investors at no cost at the registered office of TiGenix, at the counters of ING Belgium NV/SA, Marnixlaan 24, 1000
Brussels, telephone numbers +32 (0)2 464 60 01 (Dutch), +32 (0)2 464 60 02 (French) or +32 (0)2 464 60 03
(English) and Petercam NV/SA, Sint-Goedeleplein 19, 1000 Brussels, telephone number +32 (0)2 229 64 46, and at
the following websites: www.tigenix.com, www.ing.be, www.petercam.be and on the websites of Euronext.

3
Introduction

4
Investment case

TiGenix is a late-stage biomedical company focused on


regenerative treatments for damaged and osteoarthritic joints
unique expertise in joint and cartilage biology
clear focus on a major unmet medical need
bridging the gap between pain relief and joint replacement
Product with successful Phase III data in cartilage repair
demonstration of clear structural superiority over standard of care
product set for registration in US and EU
targeting addressable market of more than 1 bn EUR
Innovative treatments in pipeline
strategic collaboration with FAB for next generation 3D product
scope to broaden indications into osteoarthritic joints and meniscal repair
Backed up by solid IP and experienced management team

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Experienced team
Founded 2000, spin-off of Universities of Leuven & Gent

Founders Prof. Frank Luyten, MD, PhD & Gil Beyen, MBA

Management Gil Beyen, CEO Arthur D. Little


Heico Breek, Commercial Dev. HMR, Aventis
Luc Dochez, Business Development ADL, Methexis
Frank Hazevoets, CFO ING, Puilaetco, Inbev
Koen Huygens, QA Operations Schering-Plough
Peter Tomme, R&D Tibotec, Galapagos
Nancy Veulemans, Clinical & Reg. AHP, BMS, Clintrials
Team 45 people of which 10 MD and/or PhD

Governance Board of Directors, chaired by Prof Koenraad Debackere


Scientific Advisory Board, chaired by Frank Luyten

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Market

7
Clear focus: joint function

Cartilage defects

>2 million articular


Femur Osteoarthritis
cartilage defects
diagnosed per year*

~130,000 grade 3-4 Articular cartilage


cartilage defects per year*

Tibia
2.5 to 5% of
adult population in
Western world has
symptomatic knee OA
Outer
meniscus

2.2 million menisci removed


or partially removed per year* Inner
Meniscus
Meniscus trauma

* Europe and US 8
Current treatments

Joint revision
Joint replacement
Severity of symptoms

Symptom relief Replacement


Microfracture
Debridement
HA-injections

Pain killers &


Nutraceuticals
Adapt lifestyle

Time: duration of symptoms

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Regenerative solutions to bridge the gap

GAP Joint revision


Joint replacement
Severity of symptoms

Symptom relief Regeneration Replacement


Microfracture
Debridement
HA-injections

Pain killers &


Nutraceuticals
Adapt lifestyle

Time: duration of symptoms


Î Biological solutions for durable regeneration
10
First: Autologous Chondrocyte Implantation (ACI)

1. Biopsy

2. Cell culture

Stable cartilage

? 3. Implantation

Fibrous repair tissue

11
Primary addressable market(1)
Cartilage damage
(in otherwise healthy knee)

1.2 million knee arthroscopies


65% Grade 1-2*
cartilage
defects

Other
24%
11%

Grade 3-4* cartilage defects

130,000 eligible patients

> €1.0 billion opportunity

Notes (1) US and EU * ICRS grading


Source: Aroen e.a., 2004; Johnsson e.a, 2004; Prismant database
12 2003, NL; Vital Health Stats US, 1998; Eurostat EU; Jackson e.a. 2001
Key drivers for market success

Potent, characterised cells forming stable cartilage

Clinical validation

Efficient manufacturing & supply

Ease of use and broad indication

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ChondroCelect

14
From ACI to CCI

ACI = CCI =
Autologous Chondrocyte Characterised Chondrocyte
Implantation Implantation

®
ChondroCelect
Cell Culture Service
Validated medicinal product
First of a new class!

Non-Characterised Cells Characterised Cells

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Forming stable cartilage: ChondroCelect®

ChondroCelect® utilises proprietary technology to produce and


characterise cells that are capable of generating stable cartilage

ChondroCelect®

Vascular invasion & Fibrous tissue Stable cartilage


bone formation
Unsuccessful Cartilage Repair Successful Repair

Dell’Accio et al, A&R, 2001


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ChondroCelect® key IP

ChondroCelect® is based on a proprietary molecular profile


of stable cartilage forming cells.

g2
Po 3

Ne 1
Po 2
s1

Ne 4
s

g
s

s
Po
Po
150 positive
Comparison of markers
populations that
pass and fail Stable cartilage
proprietary in- ChondroCelect®
vivo assay on score
gene

g2
Po 3

Ne 1
Po 2
s1

Ne 4
expression

g
s

s
Po
Po
profiles 60 negative
markers

Non-stable

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ChondroCelect® cells characterised by in-vivo potency

3
Histology score

2
Differentiated,
hyaline-like cartilage

0 Fibrous or no tissue
-5 -3 -1 0 1 3 5
ChondroCelect score
Non-ChondroCelect ChondroCelect

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Clinical validation: landmark trial
Prospective Randomized Controlled Trial of
ChondroCelect® versus Microfracture in the
Repair of Symptomatic Cartilage Defects of the Knee

Primary endpoint: superiority on structural repair at 12 months vs.


microfracture AND clinical non-inferiority at 12 and 18 months
118 patients treated in nine Belgian and three international centres
5 year patient follow-up to establish long term clinical benefit
State-of-the-art trial management and monitoring
Preparing for central approval track at EMEA and FDA

Primary endpoint reached

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Study Objectives/Hypothesis
Primary endpoints Secondary endpoints
40
Superiority on structural
35 repair parameters at 12
months as precursor of
L/T clinical benefit
Improvement from baseline

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L/T Clinical
benefit
25

20

15
Non-inferiority on
S/T clinical
10
outcome
ChondroCelect
5
Microfracture

0
Months FU:BL Baseline
6m 12m Short-term
18m 24m 30m 36m 42m 48m Long-term
52m 60m

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Primary Efficacy - Structural Outcome
CC is superior to MF on both primary efficacy parameters for structural repair

Histomorphometry Overall Histology


80
1.2 P = 0.012
P = 0.003
°

Mean Histology Score (VAS, mm)


1 60
*
Mean Sum of Ratios

0.8

40
0.6

0.4
20

0.2

0 0
Microfracture CCI
ChondroCelect Microfracture CCI
ChondroCelect
* Sum of staining intensities for Collagen II and Safranin-O, ° Mean histological scores (ICRS2) of two blinded histopathologists
indicators of characteristics of hyaline-like cartilage

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Primary Efficacy – Short-term Clinical Outcome
At 12 and 18 months, CC is as good as MF on all KOOS domains

KOOS: improvement from baseline at average of 12 & 18 months

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ChondroCelect
Microfracture
25
Mean improvement from BL

20

15

10

0
Overall° Pain Symptoms ADL Sports QoL
Knee Injury and Osteoarthritis Outcome Score (KOOS)

°
Average of all KOOS domains , except Sports
22
Secondary Efficacy – Evolution Clinical Outcome
During first 18 months, the CC group showed stronger clinical improvement

Example: evolution of Quality of Life during the first 18 months post-surgery follow-up

% Improvement
65 from Baseline:
P = 0.0002

60 60% 88%
P < 0.0001
Quality of Life domain of the KOOS°

55

50

45

40

35

30

25
N= 61 51 59 51 55 51 51 44
20 ChondroCelect
Baseline 6 months 12 months 18 months Microfracture

°
Average of all KOOS domains , except Sports
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Additional results

Subgroup of patients with less than 2 years since onset of symptoms


have statistically superior clinical improvement at 18 months

Clinical outcome at 12 & 18 months is positively correlated with the


ChondroCelect gene score

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Trial conclusions

The multiple primary endpoint was reached


The use of characterised chondrocytes in autologous cartilage repair
represents a new class of treatment which is associated with superior
structural repair of cartilage tissue, compared to microfracture. In the
short-term, the risk-benefit profile for ChondroCelect and microfracture
appears to be similar, and supporting a first-line use.

Long-term data will need to confirm the durability of repair. Patients


in the study will be followed up to 5 years

25
Regulatory approval

Well-positioned for regulatory approvals


First to go for central approval at EMEA (as cell therapy medicinal
product)
Study designed according to FDA guidelines for cell therapy products (in
view of approval for first line treatment)
Process for regulatory approvals has been initiated:
EMEA: MAA filing anticipated in H1 07
FDA: BLA filing targeted in 2008

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Reimbursement

Currently no systematic reimbursement for ACI products in Europe due


to lack of robust data from controlled clinical trials
TiGenix following medicinal products reimbursement route

In US, Carticel currently reimbursed by 85% of payers (private and


public health care coverage)

Company will engage with payers in 2007 to optimise reimbursement


strategy

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Commercialisation strategy

EU strategy
Compassionate use at selected reference centres prior to launch
Reference centre approach
Direct sales team, complemented by local partners
Launch anticipated in 2008

US strategy
Manufacturing in JV with local partner
Reference centre approach
Direct sales team, complemented by local partners
A strategic alliance with a specialised orthobiologics player may be
considered for the launch of the next generation product

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Key drivers for market success
ChondroCelect®

Potent, characterised cells forming stable cartilage 5


Demonstrated potency; quality controlled
Protected by solid IP

Clinical validation 5
Well designed, rigorous pre-clinical and clinical studies
Necessary to convince medical community, regulators and payers

Efficient manufacturing & supply 5


Rapid & effective process for cell extraction, expansion and
delivery

Ease of use and broad application 5


Minimally invasive surgery
Applicable in joints affected by early OA
29
Development portfolio

30
Pipeline

Stem cell
therapies
Broaden indication

MeniscoCelect

ChondroCelect-3D
Combination product
®
ChondroCelect
Validated medicinal
product

Increase ease of use and patient friendliness


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Next generation: ChondroCelect 3D

Agreement with Fidia Advanced Biopolymers for development of


next generation ChondroCelect:
Implantable 3D construct for minimally invasive/arthroscopic
procedure
Hyalograft scaffold has been used in over 4000 patients
Combination of ‘best cells and best scaffold’

Membrane 3D scaffold

No stitch approach opens perspective to treat focal defects in OA

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Development portfolio

Product Development
Preclinical Clinical Registration &
character- of potency
Product Indication development development launch
isation assay

Articular cartilage
ChondroCelect
defects

Articular cartilage
1)
defects
ChondroCelect-3D1)

Cartilage defects
in (early) OA

Traumatic
MeniscoCelect
meniscus lesions

1) Combination of ChondroCelect with proven biomaterial (Hyalograft C) may allow faster start of pivotal clinical development

LEGEND: Development steps completed

Development steps to be completed

33
Financials

34
Cash provided and used pre-IPO
30 M cash provided :
Incorporated in February 2000 – Two seed rounds
Two financing rounds (A and B) – Venture backed
Exercise of warrants by founders and management, …
22 M cash used from incorporation to positive phase III results
€ 29.8 mio.
CASH 7.7 mio.
B Round

USED 22.1 mio.


A Round

Seed Round

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Cash flow statement*
Years ended December 31
Thousands of Euro 2006 2005 2004

Cash at beginning of year 14,899 2,796 2,271

EBIT (8,550) (4,878) (3,797)


Total adjustments 807 334 419
Cash used in operating activities (7,743) (4,544) (3,378)

Cash used in investing activities (225) (54) (154)

Cash provided by financing activities 810 16,701 4,057

Net increase/(decrease) in cash (7,158) 12,103 525

Effect on exchange rate changes (3) 0 0

Cash at end of year 7,738 14,899 2,796

* The audited annual accounts are drawn up in accordance with IFRS

36
Income statement*
Years ended December 31
Thousands of Euro 2006 2005 2004
Sales 0 0 0
Other revenues 416 784 567
Revenues 416 784 567

Research and development expenses 5,765 3,817 3,025


Selling, general and admin. expenses 3,201 1,845 1,338
Total operating charges 8,966 5,662 4,364

Operating Result (EBIT) (8,550) (4,878) (3,797)


Financial result 304 75 50

Profit/(Loss) before taxes (8,246) (4,803) (3,747)


Income taxes 0 0 0

Net Profit/(Loss) (8,246) (4,803) (3,747)

* The audited annual accounts are drawn up in accordance with IFRS

37
Outstanding financial instruments pre-IPO

Shares : 14,157,014
Outstanding warrants* : 1,226,084

Shares Warrants Total


Management 9,750 613,750 623,500 4%
Founding shareholders 640,000 195,000 835,000 5%
Independent directors 0 120,000 120,000 1%
Institutional shareholders 13,345,442 12,500 13,357,942 87%
Other 161,822 284,834 446,656 3%
TOTAL 14,157,014 1,226,084 15,383,098

*Expected cash-in subject to exercising : € 2.9 M

38
Institutional shareholders

r s* Katholieke Universiteit Leuven


he
Ot Universiteit Gent
Gemma Frisius-Fonds
ING Belgium Universities
Baekeland Fonds
Capricorn Venture Fund II Venture
Fortis Private Equity & Fagus Capitalists
Auriga Ventures

* such as ITX Corporation (Japan), HSS Ventures (US), …

39
Cash provided and use of proceeds post-IPO
Up to € 69.8 mio.*
For our lead product ChondroCelect
Obtain the regulatory approvals and reimbursement
Pre-market and launch the product

IPO Put in place the required manufacturing capacity


Up to both in the US and Europe
CASH 47.7 mio.
For our next generation and pipeline products
Start clinical validation of ChondroCelect 3D
Accelerate development efforts for MeniscoCelect
Advance our other research programmes
B Round

USED 22.1 mio.


A Round
* Not taking into account the over-allotment option

40
Conclusions

41
Investment case

TiGenix is a late-stage biomedical company focused on


regenerative treatments for damaged and osteoarthritic joints
unique expertise in joint and cartilage biology
clear focus on a major unmet medical need
bridging the gap between symptom relief and joint replacement
Product with successful Phase III data in cartilage repair
demonstration of clear structural superiority over standard of care
product set for registration in US and EU
targeting addressable market of more than 1 bn EUR
Innovative treatments in pipeline
strategic collaboration with FAB for next generation 3D product
scope to broaden indications into osteoarthritic joints and meniscal repair
Backed up by solid IP and experienced management team

42
News flow

Filing of MAA for ChondroCelect


Additional long-term data ChondroCelect
Start of clinical trial ChondroCelect-3D
Filing of BLA for ChondroCelect
Start of exploratory trial for MeniscoCelect
Launch of ChondroCelect

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Details of Offering

44
Offering Summary
Offering Base deal of up to €40 million new shares plus 15%
greenshoe of new shares
Price range Price range: € 4.2 - € 5.5 or a pre-money valuation
between € 65 mln and € 85 mln
Offering Public offer in Belgium, institutional private placement
in Europe
Listing Listing on Eurolist by Euronext Brussels

Syndicate Joint-Lead managers: ING and Piper Jaffray –


Petercam is Co-lead manager
Lock-up & 12 month lock-up for the pre-IPO security holders and
standstill standstill for the company

45
Offering Summary
Key Dates March 9 : Press Conference
March 10 : Publication of the price range
in the press
March 12 - 23 : Bookbuilding
March 23 : End of bookbuilding
March 24 : Publication of final price
March 26 : Listing date
March 29 : Payment date
Early closing possible as of March 19

Syndicate

46
Thank you

More info:
Gil Beyen – CEO
Frank Hazevoets – CFO
investor@tigenix.com

TiGenix N.V.
Technologielaan 3
3001 Leuven
Belgium
+32 16 396060
www.tigenix.com

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