TiGenix and Takeda Announce Alofisel® (darvadstrocel) Receives Approval to Treat Complex Perianal Fistulas in Crohn's Disease in Europe

Leuven, Belgium and Osaka, Japan (ots/PRNewswire) -

- First allogeneic stem cell therapy to receive central marketing
authorization approval in Europe

- Alofisel offers a new treatment option for patients who do not
respond to current available therapies and may be subject to numerous
invasive surgeries[1]

TiGenix NV (Euronext Brussels and NASDAQ: TIG) ("TiGenix") and
Takeda Pharmaceutical Company Limited (TSE: 4502) ("Takeda") today
announced that the European Commission (EC) has approved Alofisel
(darvadstrocel), previously Cx601, for the treatment of complex
perianal fistulas in adult patients with nonactive/mildly active
luminal Crohn's disease, when fistulas have shown an inadequate
response to at least one conventional or biologic therapy. Alofisel
should be used after conditioning of fistula.[2] This marks the first
allogeneic stem cell therapy to receive central marketing
authorization (MA) approval in Europe.

(Logo: https://mma.prnewswire.com/media/658214/Takeda_Logo.jpg )

(Logo: https://mma.prnewswire.com/media/658215/TiGenix_Logo.jpg )

The European approval follows a positive opinion by the European
Medicines Agency (EMA) Committee for Medicinal Products for Human Use
(CHMP), in conjunction with the Committee for Advanced Therapies
(CAT), in December 2017. The recommendation was based on results from
TiGenix's Phase III ADMIRE-CD pivotal trial, which showed that
Alofisel achieved statistically significant superiority versus the
control group in the primary efficacy endpoint of combined remission
at 24 weeks,[*1] as well as further follow-up data that indicated
Alofisel maintained long-term remission of treatment refractory
complex perianal fistulas in patients with Crohn's disease over 52
weeks.[3]

"I am extremely excited about this approval, which brings
allogeneic stem cell therapy one step closer to patients in Europe,"
said Professor Julian Panes, Head of the Gastroenterology Department
at the Hospital Clinic of Barcelona (Spain) and President of the
European Crohn's and Colitis Organisation (ECCO). "Alofisel offers a
novel, minimally invasive and well tolerated alternative treatment
option for patients with Crohn's disease who do not respond to
currently available therapies, and who have until now had limited
treatment options available."

"This approval of Alofisel reflects our deep understanding and
recognized leadership in the development of allogeneic stem cells and
our firm commitment to developing innovative therapies for medical
needs," said Dr. Maria Pascual, VP Regulatory Affairs and Corporate
Quality at TiGenix. "We are pleased to offer the medical community an
important new treatment option for patients with Crohn's disease who
do not respond to currently available therapies."

Alofisel has been licensed to Takeda for the exclusive development
and commercialization outside of the US. Receipt of the MA will
trigger a milestone payment from Takeda to TiGenix of 15 million
Euro, and initiation of the process of transferring MA from TiGenix
to Takeda.

"Today's marketing authorization, the first for an allogeneic stem
cell therapy, represents a positive advancement in the treatment of
patients with complex perianal fistulas in Crohn's disease," said Dr.
Asit Parikh, Head of Takeda's Gastroenterology Therapeutic Area Unit.
"We look forward to bringing this much needed treatment option to
patients across Europe in the coming months."

The receipt of MA from the EC is one of the conditions to
completion of the tender offer announced by Takeda on January 5,
2018.

The consummation of the tender offer remains subject to other
conditions, including the tender into the offer (in Belgium and the
US), in aggregate, of a number of shares, warrants and American
Depositary Shares that, together with all shares, warrants and
American Depositary Shares owned by Takeda and its affiliates,
represents or gives access to 85% or more of the voting rights
represented or given access to by all of the outstanding shares,
warrants and American Depositary Shares of TiGenix on a fully diluted
basis as of the end of the initial acceptance period.

Takeda's Commitment to Gastroenterology

Gastrointestinal (GI) diseases can be complex, debilitating and
life-changing. Recognizing this unmet need, Takeda and our
collaboration partners have focused on improving the lives of
patients through the delivery of innovative medicines and dedicated
patient disease support programs for over 25 years. Takeda aspires to
advance how patients manage their disease. Additionally, Takeda is
leading in areas of gastroenterology associated with high unmet need,
such as inflammatory bowel disease, acid-related diseases and
motility disorders. Our GI research & development team is also
exploring solutions in celiac disease, advanced liver disease and
microbiome therapies.

About Takeda Pharmaceutical Company Limited

Takeda Pharmaceutical Company Limited (TSE: 4502
(https://www.takeda.com/investors/) ) is a global, research and
development-driven pharmaceutical company committed to bringing
better health and a brighter future to patients by translating
science into life-changing medicines. Takeda focuses its R&D efforts
on oncology, gastroenterology and neuroscience therapeutic areas plus
vaccines. Takeda conducts R&D both internally and with partners to
stay at the leading edge of innovation. Innovative products,
especially in oncology and gastroenterology, as well as Takeda's
presence in emerging markets, are currently fueling the growth of
Takeda. Approximately 30,000 Takeda employees are committed to
improving quality of life for patients, working with Takeda's
partners in health care in more than 70 countries. For more
information, visit https://www.takeda.com/newsroom/ .

About TiGenix

TiGenix NV (Euronext Brussels and NASDAQ: TIG) is an advanced
biopharmaceutical company developing novel therapies for serious
medical conditions by exploiting the anti-inflammatory properties of
allogeneic, or donor-derived, stem cells.

TiGenixÂ´ lead product, Alofisel, successfully completed a
European Phase III clinical trial for the treatment of complex
perianal fistulas - a severe, debilitating complication of Crohn's
disease. A global Phase III trial intended to support a future U.S.
Biologic License Application (BLA) started in 2017. TiGenix has
entered into a licensing agreement with Takeda, a global
pharmaceutical company active in gastroenterology, under which Takeda
acquired the exclusive right to develop and commercialize Alofisel
for complex perianal fistulas outside the U.S. TiGenix' second
adipose-derived product, Cx611, is undergoing a Phase I/II trial in
severe sepsis - a major cause of mortality in the developed world.
TiGenix is headquartered in Leuven (Belgium) and has operations in
Madrid (Spain) and Cambridge, MA (USA). For more information, please
visit http://www.tigenix.com

About Alofisel (darvadstrocel)

Alofisel is a local administration of allogeneic (or donor
derived) expanded adipose-derived stem cells (eASCs) for the
treatment of complex perianal fistulas in adult Crohn's disease
patients that have previously shown an inadequate response to at
least one conventional therapy or biologic therapy. Crohn's disease
is a chronic inflammatory disease of the intestine and complex
perianal fistulas are a severe and debilitating complication for
which there is currently no effective treatment. Alofisel was granted
orphan drug designation by the European Commission in 2009 and by the
U.S Food and Drug Administration (FDA) in 2017. TiGenix completed a
European Phase III clinical trial (ADMIRE-CD) in August 2015 in which
both the primary endpoint and the safety and efficacy profile were
met, with patients receiving Alofisel showing a 44% greater
probability of achieving combined remission compared to control
(placebo).[3] A follow-up analysis was completed at 52 weeks[3] and
104 weeks post-treatment, confirming the sustained efficacy and
safety profile of the product. The 24-week results of the Phase III
ADMIRE-CD trial were published in The Lancet in July 2016.[1] Based
on the positive 24 weeks Phase III study results, TiGenix submitted a
Marketing Authorization Application to the European Medicines Agency
(EMA). A global Phase III clinical trial (ADMIRE-CD II) intended to
support a future U.S. Biologic License Application (BLA) started in
2017, based on a trial protocol that has been agreed with the FDA
through a special protocol assessment procedure (SPA)
(clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT03279081?
cond=complex+perianal+fistulas&draw=1&rank=5) ; NCT03279081).
ADMIRE-CD II is a randomized, double-blind, placebo-controlled study
designed to confirm the efficacy and safety of a single
administration of Alofisel for the treatment of complex perianal
fistulas in Crohn's disease patients. In July 2016, TiGenix entered
into a licensing agreement with Takeda, a global pharmaceutical
company active in gastroenterology, under which Takeda acquired
exclusive rights to develop and commercialize Alofisel for complex
perianal fistulas in Crohn's patients outside of the U.S.

Forward-looking information

This press release may contain forward-looking statements and
estimates with respect to the anticipated future performance of
TiGenix and the market in which it operates and statements regarding
the expected consummation of the tender offer, which involves a
number of risks and uncertainties, including the satisfaction of
closing conditions for the tender offer, the possibility that the
transaction will not be completed, the impact of general economic,
industry, market or political conditions, and the other risks and
uncertainties discussed in TiGenix's public filings with the SEC,
including the "Risk Factors" section of TiGenix's Form 20-F filed on
April 6, 2017, as well as the tender offer documents to be filed by
Takeda and the solicitation/recommendation statement to be filed by
TiGenix. Certain of these statements, forecasts and estimates can be
recognised by the use of words such as, without limitation,
"believes", "anticipates", "expects", "intends", "plans", "seeks",
"estimates", "may", "will" and "continue" and similar expressions.
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 TiGenix's control. Therefore,
actual results, the financial condition, performance, timing 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. Given these uncertainties, no representations are made as
to the accuracy or fairness of such forward-looking statements,
forecasts and estimates. Furthermore, forward-looking statements,
forecasts and estimates only speak as of the date of the publication
of this press release. Takeda and TiGenix disclaim any obligation to
update any such forward-looking statement, forecast or estimates to
reflect any change in TiGenix's expectations with regard thereto, or
any change in events, conditions or circumstances on which any such
statement, forecast or estimate is based, except to the extent
required by Belgian law.

This communication constitutes communication within the scope of
article 31 and 33 of the Belgian Law of April 1, 2007 on public
takeover bids.

Prospectus and Response Memorandum

Following its approval by the Financial Services and Markets
Authority ("FSMA"), the prospectus (including the acceptance form and
the response memorandum) will be available free of charge by
telephone (+32 (0)2 433 41 13). An electronic version of the
prospectus (including the acceptance form and the response
memorandum) will also be available on the websites of BNP Paribas
Fortis SA/NV (http://www.bnpparibasfortis.be/epargneretplacer (French
and English) and http://www.bnpparibasfortis.be/sparenenbeleggen
(Dutch and English)), Takeda (http://www.takeda.com/newsroom) and
TiGenix (http://tigenix.com/takeda-takeover-bid).

Disclaimer

The tender offer for the outstanding shares, warrants and American
Depositary Shares has not yet commenced. This communication is for
informational purposes only and does not constitute an offer to
purchase securities of TiGenix nor a solicitation by anyone in any
jurisdiction in respect of such securities, any vote or approval. If
Takeda decides to proceed with an offer to purchase TiGenix's
securities through a public tender offer, such offer will and can
only be made on the basis of an approved offer document by the FSMA
and tender offer documents filed with the U.S. Securities and
Exchange Commission ("SEC"), which holders of TiGenix's securities
should read as they will contain important information. This
communication is not a substitute for such offer documents. Neither
this communication nor any other information in respect of the
matters contained herein may be supplied in any jurisdiction where a
registration, qualification or any other obligation is in force or
would be with regard to the content hereof or thereof. Any failure to
comply with these restrictions may constitute a violation of the
financial laws and regulations in such jurisdictions. Takeda, TiGenix
and their respective affiliates explicitly decline any liability for
breach of these restrictions by any person.

Important Additional Information for U.S. investors

The voluntary public takeover bid described herein has not yet
commenced. This communication is for informational purposes only and
is neither a recommendation, an offer to purchase nor a solicitation
of an offer to sell any securities of TiGenix.

At the time the voluntary public takeover bid is commenced,
security holders of TiGenix are urged to read the offer documents
which will be available at http://www.sec.gov. At the time the
voluntary public takeover bid is commenced, it shall be comprised of
two separate offers - (i) an offer for all ordinary shares issued by
TiGenix (the "Ordinary Shares") and warrants to acquire Ordinary
Shares in accordance with the applicable law in Belgium, and (ii) an
offer to holders of TiGenix's American Depositary Shares issued by
Deutsche Bank Trust Company Americas acting as depositary ("ADSs"),
and to holders of Ordinary Shares who are resident in the U.S. in
accordance with applicable U.S. law (the "U.S. Offer").

The U.S. Offer will only be made pursuant to an offer to purchase
and related materials. At the time the U.S. Offer is commenced,
Takeda will file, or cause to be filed, a tender offer statement on
Schedule TO with the SEC and thereafter, TiGenix will file a
solicitation/recommendation statement on Schedule 14D-9, in each case
with respect to the U.S. Offer.

Holders of ADSs and Ordinary Shares subject to the U.S. Offer who
wish to participate in the U.S. Offer, are urged to carefully review
the documents relating to the U.S. Offer that will be filed by Takeda
with the SEC since these documents will contain important
information, including the terms and conditions of the U.S. Offer.
Holders of ADSs and Ordinary Shares subject to the U.S. Offer who
wish to participate in the U.S. Offer, are also urged to read the
related solicitation/recommendation statement on Schedule 14D-9 that
will be filed with the SEC by TiGenix relating to the U.S. Offer
since it will contain important information. You may obtain a free
copy of these documents after they have been filed with the SEC, and
other documents filed by TiGenix and Takeda with the SEC, at the
SEC's website at http://www.sec.gov. Investors and security holders
may also obtain free copies of the solicitation/recommendation
statement on Schedule 14D-9 and other documents filed with the SEC by
TiGenix at http://www.tigenix.com. In addition to the offer and
certain other tender offer documents, as well as the
solicitation/recommendation statement, TiGenix files reports and
other information with the SEC. You may read and copy any reports or
other information filed by TiGenix at the SEC Public Reference Room
at 100 F Street, N.E., Washington, D.C. 20549. Please call the SEC at
1-800-SEC-0330 for further information on the Public Reference Room.
TiGenix's filings at the SEC are also available to the public from
commercial document-retrieval services and at the website maintained
by the SEC at http://www.sec.gov.

YOU SHOULD READ THE FILINGS MADE BY TAKEDA AND TIGENIX WITH THE SEC
CAREFULLY BEFORE MAKING A DECISION CONCERNING THE U.S. OFFER.

References

1. Panes J, Garcia-Olmo D, Van Assche G, et al., Expanded allogeneic
adipose-derived mesenchymal stem cells (Cx601) for complex perianal
fistulas in Crohn's disease: a phase 3 randomized, double-blind
controlled trial. The Lancet. 2016; 388(10051): 1281-1290.

2. Data on file.

3. Panes J, Garcia-Olmo D, Van Assche G, et al., Long-term Efficacy
and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas
in Patients With Crohn's Disease. Gastroenterology. 2017. Available
at:
http://www.gastrojournal.org/article/S0016-5085(17)36726-4/fulltext.
Accessed February 2018.

ots Originaltext: TiGenix and Takeda
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Claudia Jiménez
Senior Director
Investor Relations and Communications
T: +34-91-804-9264
claudia.jimenez@tigenix.com

Media enquiries: Consilium Strategic Communications
T: +44-20-3709-5700
tigenix@consilium-comms.com

For Takeda: Kazumi Kobayashi
Media in Japan
T: +81-33-278-2095
luke.willats@takeda.com

Luke Willats
Media outside of Japan
T: +41-44-555-1145
luke.willats@takeda.com

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