Takeda Announces Intention to Acquire TiGenix

PR71751

OSAKA, Japan, Jan 5 /PRNewswire=KYODO JBN/ --

Takeda Announces Intention to Acquire TiGenix

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.[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) 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