Takeda Announces Intention to Acquire TiGenix

Osaka, Japan (ots/PRNewswire) -

Expands Takeda's Late Stage Pipeline and Leadership in
Gastroenterology

Acquisition Highlights

- Deal reinforces Takeda's commitment to patients living with
Inflammatory Bowel Disease (IBD), an area of high unmet medical
need
- Acquisition extends existing collaboration between Takeda and
TiGenix to develop and commercialize Cx601 (darvadstrocel) - On
December 15, 2017, the Committee for Medicinal Products for
Human Use (CHMP) of the European Medicines Agency (EMA) adopted a
positive opinion recommending marketing authorization for Cx601
for the treatment of complex perianal fistulas in Crohn's
disease,
one of the most disabling manifestations of the disease
- A global, pivotal Phase III trial for U.S. registration has been
initiated with investigational medicine Cx601 for the treatment
of
complex perianal fistulas in patients with non-active/mildly
active luminal Crohn's disease
- Acquisition would expand Takeda's late stage gastroenterology
pipeline and strengthen presence in the U.S. specialty care market

Takeda Pharmaceutical Company Limited (TSE: 4502) ("Takeda") today
announced its intention to acquire TiGenix NV (Euronext Brussels and
NASDAQ: TIG) ("TiGenix"), an advanced biopharmaceutical company
developing novel stem cell therapies for serious medical conditions,
and as a result has entered into an offer and support agreement with
TiGenix which provides for a recommended potential voluntary public
takeover bid for TiGenix. The Takeda agreement has the unanimous
support of the TiGenix board of directors (including its CEO). The
acquisition is a natural extension of an existing partnership
agreement between Takeda and TiGenix, which aims to bring new
treatment options to patients with gastrointestinal disorders.

"As a leader in gastroenterology, Takeda recognizes the complex
physical, emotional and social barriers that people living with
fistulizing Crohn's disease experience," said Andrew Plump, Chief
Medical and Scientific Officer, Takeda. "Limited treatment options
exist today and I believe we can be most effective in serving this
population by working in collaboration with partners whose unique
skill sets allow us to more efficiently explore innovative
approaches, including stem cell therapies. I have had the opportunity
to work alongside the TiGenix team throughout our collaboration and
know that we have shared goals and varied, but complementary
expertise. I am thrilled at the prospect of welcoming them as part of
our organization."

In July 2016, Takeda and TiGenix entered into an exclusive ex-U.S.
license, development and commercialization agreement for Cx601, the
leading investigational therapy in TiGenix's pipeline. Cx601 is a
suspension of allogeneic expanded adipose-derived stem cells (eASC)
locally administered for the treatment of complex perianal fistulas
in patients with non-active/mildly active luminal Crohn's disease,
who have had an inadequate response to at least one conventional or
biologic therapy. In December 2017, the CHMP of the EMA adopted a
positive opinion recommending a marketing authorization for Cx601 in
this indication, the first allogeneic stem cell therapy to achieve
this. A decision from the EMA on the marketing authorization for
Cx601 is expected in the first half of 2018.

Complex perianal fistulas are considered one of the most disabling
manifestations of Crohn's disease and can cause intense pain,
infection and incontinence.[1,2] Despite modern and surgical
advancements, they currently remain challenging for clinicians to
treat and can have a severe impact on the lives of those affected.[3]

A global, pivotal Phase III trial investigating Cx601 for the
treatment of complex perianal fistulas in patients with
non-active/mildly active luminal Crohn's disease has been initiated
for U.S. registration. In the U.S., Takeda intends to work with the
U.S. FDA to facilitate the development and potential approval of
Cx601. Takeda is also exploring the steps required for regulatory
filing of Cx601 for patients in Japan, Canada and emerging markets.

Through the potential voluntary public takeover bid, Takeda
intends to acquire 100% of the securities with voting rights or
giving access to voting rights of TiGenix not already owned by Takeda
or its affiliates at an acquisition price of EUR 1.78 per share in
cash and an equivalent price per American Depositary Share, warrant
and convertible bond, representing a transaction value of
approximately EUR 520 million on a fully diluted basis. The bid will
be subject to certain conditions precedent as further described
below.

Subject to its fiduciary duties and review of the final bid
prospectus, the bid is unanimously supported by TiGenix's board of
directors (including its CEO). Takeda and TiGenix entered into an
offer and support agreement confirming TiGenix's support and the
terms and conditions of the bid set forth in this press release.
Gri-Cel S.A., holding 32,238,178 TiGenix shares, and its affiliate
Grifols Worldwide Operations Ltd., holding 7,189,800 TiGenix shares
in the form of American Depositary Shares, have irrevocably confirmed
that they will tender their shares and American Depositary Shares
into the potential public takeover bid.

Transaction terms

The acquisition is structured as an all cash voluntary public
takeover bid by Takeda with respect to 100% of the securities with
voting rights or giving access to voting rights of TiGenix that are
not already owned by Takeda or its affiliates. The transaction is
subject to the following conditions precedent: (i) the tender into
the offer, in aggregate, of a number of securities that, together
with all securities 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 securities on a fully diluted
basis as of the end of the first acceptance period, (ii) the absence
of a material adverse effect occurring at any time after the date of
this announcement, (iii) Cx601 obtaining marketing authorization in
the E.U. from the European Medicines Agency (EMA) and (iv) the
expiration, lapse or termination as appropriate of any applicable
waiting periods (including any extensions thereof) under the
Hart-Scott-Rodino Antitrust Improvements Act of 1976 in respect of
the offer.

Following closing of the potential voluntary public takeover bid,
Takeda intends to launch a squeeze-out if the applicable conditions
for such squeeze-out are met to delist the shares of TiGenix from
Euronext Brussels and NASDAQ. After the squeeze-out, TiGenix would
become a wholly-owned subsidiary of Takeda.

This communication does not constitute a formal notification of a
voluntary public takeover bid. In case Takeda would decide to
formally launch the voluntary public takeover bid, full details of
such public takeover bid will be covered by the prospectus to be
filed with the Belgian Financial Services and Markets Authority and
the offer documents which will be available at http://www.sec.gov. In
the event that Takeda would decide not to proceed with the potential
voluntary public takeover bid, then Takeda and TiGenix will issue a
further public announcement to that effect.

(1) Tender offeror Takeda Pharmaceutical Company
Limited

(2) Target company TiGenix NV (Euronext Brussels and
NASDAQ: TIG)

(3) Class of shares to be
acquired - all outstanding ordinary shares
(with the
exception of ordinary shares
represented by
American Depositary Shares);
- all outstanding American
Depositary Shares
(each representing 20 ordinary
shares);
- all outstanding warrants to
acquire
ordinary shares; and
- all outstanding convertible
bonds.

(4) Tender offer price EUR 1.78 per share (and an
equivalent price
per American Depositary Share,
warrant and
convertible bond)

(5) Acquisition amount Approximately EUR 520 million
(estimate)
(Aggregate tender offer * The amount is an estimated
amount calculated
price) by multiplying the number of
TiGenix's
ordinary shares (on a fully
diluted basis and
excluding the shares owned by
Takeda or its
affiliates) by the tender offer
price per
share. It does not include
advisory fees.

(6) Payment Funding from existing cash
balances

(7) Period of tender offer To be determined, subject to
regulatory
approvals being obtained.

(8) Minimum number of shares Consummation of the voluntary
public takeover
to be purchased bid will occur if a number of
securities is
tendered that, together with all
securities
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 securities on
a fully
diluted basis as of the end of
the first
acceptance period and other
customary
conditions precedent have been
satisfied.

(9) Financial advisor to Centerview Partners UK LLP
Takeda

(10) Legal counsel to Takeda DLA Piper UK LLP
DLA Piper US LLP

(11) Financial advisor to
TiGenix Cowen and Company, LLC

(12) Legal counsel to TiGenix Osborne Clarke CVBA
Davis Polk & Wardwell LLP

Overview of TiGenix

(1) Company name TiGenix NV (Euronext Brussels and
NASDAQ: TIG)

(2) Headquarters Romeinse straat 12 box 2, 3001 Leuven,
Belgium

(3) Representative Eduardo Bravo, Managing Director and
Chief Executive
Officer
(4) Business TiGenix is a biopharmaceutical company
focused on the
description development and commercialization of
therapeutics from
its platforms of allogeneic, or
donor-derived, expanded
stem cells
(5) Share capital EUR 27,428,719

(6) Date of 21 February 2000
establishment

(7) Major shareholders Gri-Cel, S.A./Grifols Worldwide
and percentage Operations Ltd.**
14.4%
of shares held* Cormorant Asset Management LLC
5.3%
Takeda Pharmaceuticals
International AG
4.2%
JPMorgan Securities LLC
2.9%
Others: BNP Paribas Investment Partners
SA

(8) Relationships
between Takeda Capital relationship Investee
Personnel relationship Not applicable
Transactional
relationship Licensor

(9) Operating results and financial condition for the last three
years (consolidated)

Accounting period Fiscal year Fiscal year
Fiscal year
ended December ended December
ended December
31, 2016 31, 2015
31, 2014
Net assets
(EUR in thousands) 79,679 13,145
34,757

Total assets
(EUR in thousands) 136,201 79,171
53,921

Net assets per share
(EUR) 0.40 0.08
0.22

Revenue
(EUR in thousands) 26,790 2,240
6,286

Operating profit
(EUR in thousands) (3,027) (24,076)
(12,563)

Net profit/(loss)
(EUR in thousands) 3,802 (35,069)
(12,990)

Net earnings/(loss) per
share
(EUR) 0.02 (0.21)
(0.08)

*Gri-Cel, S.A. and Grifols Worldwide Operations Ltd. holding as
per irrevocable undertaking given to Takeda. Cormorant Asset
Management holding as per TiGenix Schedule 13G dated February 14,
2017. Cormorant Asset Management liquidation of 129,032 American
Depositary Shares as per Cormorant Asset Management's filing Form 13F
(OMB 3235-0006). Percentage of shares is calculated by dividing the
respective shareholdings by the number of total shares outstanding of
the target company of 274,287,190 as reported on November 30, 2017.

**The potential voluntary public takeover bid is supported by
Gri-Cel S.A. and its affiliate Grifols Worldwide Operations Ltd.
Gri-Cel S.A. and Grifols Worldwide Operations Ltd. have irrevocably
confirmed that they will tender their shares and American Depositary
Shares in the potential voluntary public takeover bid.

Change in ownership before and after acquisition

(1) Number of shares already acquired 11,651,778 shares

Percentage of voting
rights: 4.2% of
total shares outstanding
(3.9% on a
fully diluted basis)

(2) Estimated number of shares to be
acquired (on a fully diluted basis) 290,288,172 shares***
Percentage of voting
rights: 96.1%
(planned)
(min. bid threshold is
85%)
***Excludes shares
already held by
Takeda or its affiliates.

Schedule

(1) Governance meeting resolution January 4, 2018

(2) Support and Offer Agreement
signature date January 5, 2018

(3) Commencement date and settlement To be determined, subject
to regulatory
date of the tender offer approvals being obtained.

(4) Completion of acquisition To be determined, subject
to regulatory
approvals being obtained
and completion
or waiver of any
conditions precedents.

Takeda Financial Outlook

As the completion of the acquisition is expected to occur near the
end of Q1 CY2018 or the beginning of Q2 CY2018, Takeda expects
minimal impact on its FY2017 earnings. We will incorporate the
financial impact in our FY2018 consolidated earnings forecast, which
will be announced at the FY2017 year-end earnings conference in May
2018.

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

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. Around 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/.

Forward-Looking Statements

This press release contains "forward-looking statements."
Forward-looking statements include all statements other than
statements of historical fact, including plans, strategies and
expectations for the future, statements regarding the expected timing
of filings and approvals relating to the transaction, the expected
timing of the completion of the transaction, the ability to complete
the transaction or to satisfy the various closing conditions, future
revenues and profitability from or growth or any assumptions
underlying any of the foregoing. Statements made in the future tense,
and words such as "anticipate," "expect," "project," "continue,"
"believe," "plan," "estimate," "pro forma," "intend," "potential,"
"target," "forecast," "guidance," "outlook," "seek," "assume,"
"will," "may," "should," and similar expressions are intended to
qualify as forward-looking statements. Forward-looking statements are
based on estimates and assumptions made by management of Takeda and
TiGenix that are believed to be reasonable, though they are
inherently uncertain and difficult to predict. Investors and security
holders are cautioned not to place undue reliance on these
forward-looking statements.

Forward-looking statements involve risks and uncertainties that
could cause actual results or experience to differ materially from
that expressed or implied by the forward-looking statements. Some of
these risks and uncertainties include, but are not limited to:
required regulatory approvals for the transaction may not be obtained
in a timely manner, if at all; the conditions to closing of the
transaction may not be satisfied; competitive pressures and
developments; applicable laws and regulations; the success or failure
of product development programs; actions of regulatory authorities
and the timing thereof; changes in exchange rates; and claims or
concerns regarding the safety or efficacy of marketed products or
product candidates in development.

The forward-looking statements contained in this press release
speak only as of the date of this press release, and neither TiGenix
nor Takeda undertakes any obligation to revise or update any
forward-looking statements to reflect new information, future events
or circumstances after the date of the forward-looking statement. If
one or more of these statements is updated or corrected, investors
and others should not conclude that additional updates or corrections
will be made.

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.

TiGenix´s lead product, Cx601, has successfully completed a
European Phase III clinical trial for the treatment of complex
perianal fistulas - a severe, debilitating complication of Crohn's
disease. Cx601 has been filed for regulatory approval in Europe and 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 Cx601 for complex perianal
fistulas outside the U.S. TiGenix's second adipose-derived product,
Cx611, is undergoing a Phase I/II trial in severe sepsis - a major
cause of mortality in the developed world. Finally, AlloCSC-01,
targeting acute ischemic heart disease, has demonstrated positive
results in a Phase I/II trial in acute myocardial infarction (AMI).
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 Cx601

Cx601 is an investigational administration of allogeneic (or donor
derived) expanded adipose-derived stem cells (eASCs) for the
treatment of complex perianal fistulas in adult patients with
non-active/mildly active luminal Crohn's disease 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.

Cx601 was granted orphan drug designation by the European
Commission in 2009 and by the FDA in 2017. TiGenix completed a
European Phase III clinical trial (ADMIRE-CD) in August 2015 in which
the primary endpoint was met, with a significantly greater proportion
of patients treated with Cx601 (50%, n=107) versus control (34%,
n=105) achieving combined remission as defined by clinical assessment
of closure of all treated external openings that were draining at
baseline and absence of collections > 2 cm of the treated perianal
fistulas confirmed by masked central MRI at week 24 (97·5% CI
0·2-30·3; p=0·024).[1] The most commonly reported treatment emergent
adverse events were proctalgia, anal abscess and nasopharyngitis. A
follow-up analysis was completed showing that the efficacy and safety
profile of Cx601 were maintained at 52 weeks.[4] 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 EMA,
with the CHMP adopting a positive opinion recommending the granting
of a marketing authorization.

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 U.S.
FDA through a special protocol assessment procedure (SPA)
(clinicaltrials.gov; NCT03279081). ADMIRE-CD II is a randomized,
double-blind, placebo-controlled study designed to confirm the
efficacy and safety of a single administration of Cx601 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
Cx601 for complex perianal fistulas in Crohn's patients outside of
the U.S.

Disclaimer

This communication 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 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,
shareholders 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 securities with voting rights
or giving access to voting rights, issued by TiGenix (except for
ADSs) (the "Securities"), 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 Securities 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 TiGenix ADSs and Securities 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 TiGenix ADSs and Securities 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. 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. 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] Panés J, García-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] Marzo M, Felice C, Pugliese D, et al., Management of perianal
fistulas in Crohn's disease: An up-to-date review. World J
Gastroenterol. 2015; 21(5): 1394-1395.

[3] Mahadev S, Young JM, Selby W, et al., Quality of life in
perianal Crohn's disease: what do patients consider important? Dis
Colon Rectum. 2011; 54(5): 579-585.

[4] Panés J, et al., Long-term efficacy and safety of stem cell
therapy (Cx601) for complex perianal fistulas in patients with
Crohn's disease. Gastroenterology. Published online 18th December
2017. http://dx.doi.org/10.1053/j.gastro.2017.12.020.

Media Contacts:

Kazumi Kobayashi

Media in Japan

T: +81-3-3278-2095

kazumi.kobayashi@takeda.com

Elissa Johnsen

Media outside of Japan

T: +1-224-554-3185

elissa.johnsen@takeda.com

Luke Willats

Media in Europe

T: +41-44-555-1145

luke.willats@takeda.com

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