OSAKA, Japan, January 5, 2018 /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) 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
SOURCE Takeda Pharmaceutical Company Limited