Final Agreement June 1, 2010
 
 Second Amendment
 Party Parties
 RECITALS
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 1
    
    The Agreement is amended to add the following new definitions.1.1
    
    Amendment Effective Date shall mean June 1, 2010.1.2
    
    Bridging Studyshall have the meaning set forth in Article 3.4.3 (b).
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1.3
    
    Cangrelorshall mean the Compound in such formulation for intravenous administration as
has been developed by TMC.1.4
    
    CHAMPION-PHOENIX Studyshall mean a repeat phase III prospective, randomised, double
blind, standard clopidogrel care controlled, parallel group, superiority study in which the
primary objective is to demonstrate that the efficacy of Cangrelor (combined with 600mg of
clopidogrel) is superior to that of usual care, in patients requiring percutaneous coronary
intervention (PCI) as measured by a composite of all cause mortality, myocardial infarction
(MI), IDR and stent thrombosis which will be performed under US IND 56,812.1.5
    
    Change of Controlmeans an event in which:
 1.5.1
    
    [**] or any of its Affiliates or a successor of any such entity (collectively
referred to herein as  [**]) (a)comes in possession, directly or indirectly, of
the power to direct the management or polices of TMC, whether through ownership of
voting securities, by contract or otherwise, or (b) acquires beneficial ownership,
directly or indirectly, of securities of TMC representing more than fifty percent
(50%) of the voting power of the then outstanding securities of TMC, or1.5.2
    
    TMC sells to [**], directly or indirectly, in one or more transactions, properties
or assets (i) representing more than fifty percent (50%) of TMCs consolidated total
assets or (ii) from which more than fifty percent (50%) of TMCs consolidated
operating income for its most recent fiscal year was derived.
 1.6
    
    Ticagrelor Product shall mean ASTRAZENECAs pharmaceutical product containing the
pharmaceutical compound known as ticagrelor, a reversibly binding oral P2Y12 adenosine
diphosphate (ADP) receptor antagonist.
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2
    
    The following Articles of the Agreement are hereby amended as follows:
 2.1
    
    A new Article 3.3.4 is added reading:
  2.2
    
    A new Article 3.4.3 is added reading:
  (a)
    
    as soon as practicable following the Amendment Effective Date, initiate the
CHAMPION-PHOENIX Study and use Commercially Reasonable Efforts to conduct the study in a
diligent and expeditious manner. Without prejudice to the immediately preceding sentence,
should ASTRAZENECA require by giving notice no later than two (2) months of the Amendment
Effective Date, TMC shall, whichever ASTRAZENECA may require, include in the
CHAMPION-PHOENIX Study (i) such number of patients from either of Korea or Thailand, or
both, that TMC has specified by giving notice to ASTRAZENECA that TMC desires to include in
patient enrolment in the CHAMPION-PHOENIX Study, and/or (ii) such number of patients from
either of China or Taiwan, or both, that ASTRAZENECA at its discretion considers sufficient
to obtain approved NDAs in such countries. The costs for any patient included as described
under (i) shall be carried by TMC and the costs for any patient included as described under
(ii) shall be carried by ASTRAZENECA. TMC shall give such notice of number of
patients mentioned under (i) within two (2) weeks of the Amendment Effective Date but,
without prejudice to ASTRAZENECAs rights hereunder in this regard, ASTRAZENECA shall
always have the right to provide its notice insofar it relates to the countries under (i)
within no less than six (6) weeks of the date of receipt of TMCs notice.Notwithstanding the foregoing, ASTRAZENECA shall have the right to withdraw its request
under (ii) at any time regarding either or both countries. In case of such ASTRAZENECAs
withdrawal, TMC shall as soon as reasonably possible, with full account taken to patient
safety, study ethics and Good Clinical Practice, terminate the CHAMPION-PHOENIX Study in
either or both, as notified by ASTRAZENECA, of those countries. ASTRAZENECA shall then carry
no further liability for any costs stated
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in this Article 3.4.3 (a) other than those relating to reasonably non-cancellable
expenses committed to by TMC at the date of ASTRAZENECAs withdrawal of such request for
completing the study in such country in accordance with the immediately preceding sentence.For the purpose of this Article 3.4.3 a) costs shall mean all expenses paid relating
specifically to the CHAMPION-PHOENIX Study to Third Parties (or payable to Third Parties and
accrued in accordance with TMCs accounting standards as generally and consistently applied
throughout TMCs organization) by TMC, and which costs cannot be reasonably incurred by TMC
using its own internal resource or FTEs or consultants otherwise engaged by TMC in
connection with activities outside the scope of the Agreement; and(b)
    
    perform a pharmacokinetics/pharmacodynamics study with Cangrelor and the Ticagrelor Product
(the Bridging Study). The Bridging Study shall be completed before the submission of the
first NDA for Cangrelor with the aim that the results could be included in all NDAs and other
regulatory submissions in the Territory. TMC shall provide ASTRAZENECA with proposals for the
study protocol and budget for performing the Bridging Study and the Parties shall in good
faith discuss and agree upon the definitive protocol and budget. ASTRAZENECA shall have the
right to request expansions or additional arms of the Bridging Study and TMC will include
such reasonable expansions or additional arms in the study. The Parties shall jointly analyse
and interpret the results of the Bridging Study and in good faith discuss the label strategy.
TMC shall bear the costs for performing the study, including expansions or additional arms
required by ASTRAZENECA, up to U.S. Dollars one million ($1,000, 000) (the Cap). ASTRAZENECA
will reimburse TMC for verified costs exceeding the Cap incurred as a result of the
performance of the Bridging Study, including expansions or additional arms required by
ASTRAZENECA. For the purpose of this Article 3.4.3 b) costs shall mean all expenses paid
relating specifically to the Bridging Study to Third Parties (or payable to Third Parties and
accrued in accordance with TMCs accounting standards as generally and consistently applied
throughout TMCs organization) by TMC, and which costs cannot be reasonably incurred by TMC
using its own internal resource or FTEs or
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consultants otherwise engaged by TMC in connection with activities
outside the scope of the Agreement.2.3
    
    Article 3.7.2 is modified to read as follows:TMC shall use Commercial Reasonable Efforts to diligently and expeditiously file NDAs in
the United States and all other Major Markets.2.4
    
    Article 3.7.3 is deleted.2.5
    
    The reference to Article 3.7.2 (a) in Article 3.8.1 b) is amended to refer to Article 3.7.2,
as amended in this Amendment. Article 3.8.1 c) is deleted.2.6
    
    A new Article 3.10 is added reading.ASTRAZENECA shall have the option to obtain from TMC critical care
strategic and secondary detail support for the promotion of the
Ticagrelor Product in the United States on a fee-for-service basis on
a then prevailing market rate. If and when ASTRAZENECA exercises this
option, the Parties shall in good faith discuss and agree (subject to
all applicable laws and regulations) upon the detailed terms for a
Commercial Assistance Agreement under which TMC shall provide to
ASTRAZENECA the support described above based on the terms attached
hereto Schedule 1.2.7
    
    A new Article 5.1.5. is added reading:In addition to Articles 5.1.1 to 5.1.4, TMC shall prepare and
maintain complete and accurate records and reports regarding the
development of Cangrelor. ASTRAZENECA shall have the right from time
to time and upon reasonable prior notice to TMC to examine TMCs
records regarding such activities. TMC shall provide ASTRAZENECA with
a quarterly report on the progress in the development of Cangrelor in
the Territory in order to keep ASTRAZENECA informed of its progress.
Such report shall cover general information on TMCs development
activities in the previous Quarter, a summary of the activities
planned in the next Quarter, and a timetable of planned and actual
submissions for NDAs. Notwithstanding the foregoing, TMC shall provide
to ASTRAZENECA
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interim analysis, if available, and summaries of the results of the CHAMPION-PHOENIX Study
and the Bridging Study as well as other studies performed by or on behalf of TMC in relation
to Cangrelor promptly upon completion of the studies. AstraZeneca shall only use the
information provided pursuant to this Article 5.1.5 for the purpose of ensuring that TMC is
complying with its obligations under the Agreement and may only share such information
internally consistent with Article 11.1..2.8
    
    A new Article 6.1 A is added reading:Amendment Fee.In consideration of the agreements set forth in this Amendment, TMC
shall pay to ASTRAZENECA a non-refundable amendment fee of U.S.
Dollars [**] within thirty (30) calendar days
following the Amendment Effective Date.2.9
    
    A new Article 6.1.4 is added reading:TMC shall make each of the milestone payments indicated below to ASTRAZENECA when
cumulative Net Sales across all indications in the Territory first reach the specified
dollar values in any Calendar Year. For clarity, each such milestone payment shall be
non-refundable against any other payment due under this agreement:
 Annual Net Sales in the Territory
    
    Milestone paymentUSD [**] ($[**])
    
    USD [**] ($[**])USD [**] ($[**])
    
    USD [**] ($[**])USD [**] ($[**])
    
    USD [**] ($[**])USD [**] ($[**])
    
    USD [**] ($[**])
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2.10
    
    The table under Article 6.2.1 is modified to read as follows:
 Annual Net Sales in the Territory
    
    Royalty Ratea) up to USD [**] ($ [**])
    
    [**] percent ([**]%)b) above USD [**] ($[**]) and up to USD [**] ($[**])
    
    [**] percent ([**]%)c) above USD [**] ($[**]) and up to USD [**] ($[**])
    
    [**] percent ([**]%)d) above USD [**] ($[**]) and up to USD [**] ($[**])
    
    [**] percent ([**]%)e) above USD [**] ($[**])
    
    [**] percent ([**]%)
 2.11
    
    Wire Transfer Instructions
 Article 6.9.1 is amended as follows:
  BANK ACCOUNT
 Beneficiary:
    
    AstraZeneca ABBank Name:
    
    [**]Account Number:
    
    [**]Swift:
    
    [**]IBAN:
    
    [**]
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2.12
    
    A new Article 14.3 A is added reading:

Termination for Change of Control of TMC. In the event that TMC
undergoes a Change of Control during such time as [**] is developing
or commercialising the pharmaceutical product known as [**] in any
country in the world, TMC shall promptly notify ASTRAZENECA in
writing and ASTRAZENECA shall have the right to terminate the
Agreement by written notice to TMC within one hundred twenty (120)
days following the receipt of the notice from TMC. The termination
shall become effective upon TMCs receipt of the termination
notice..2.13
    
    The second paragraph of Article 15.1 is modified to read:

Upon termination of this Agreement by TMC pursuant to Article 14.2
or by ASTRAZENECA pursuant to Articles 14.3 or 14.3A or by
ASTRAZENECA in a certain country pursuant to Article 3.8, the license
granted under Article 2.1 regarding the country (ies) contemplated by
the termination concerned shall cease, and TMC shall regarding the
Territory or country concerned, whichever is applicable:3
    
    No Other Amendments.Except as expressly amended hereby, all of the terms and
conditions of the Agreement shall remain in full force and effect.4
    
    Mutual Representations and Warranties.Each Party represents and warrants to the
other as of the date hereof that:
 Corporate Power
 Due Authorization
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Binding Agreement
 5
    
    Headings.
The headings used in this Amendment have been inserted for convenience of
reference only and do not define or limit the provisions hereof.6
    
    Entire Agreement.
This Amendment, together with the Agreement, constitutes the
entire agreement between the Parties with respect to the subject matter of the Agreement. The
Agreement together with this Amendment supersedes all prior agreements, whether written or
oral, with respect to the subject matter of the Agreement, as amended. Each Party confirms
that it is not relying on any statements, representations, warranties or covenants of any
person (whether a Party to this Agreement or not) except as specifically set out in the
Agreement as amended. Nothing in this Amendment is intended to limit or exclude any liability
for fraud. All Schedules referred to in this Amendment are intended to be and are hereby
specifically incorporated into and made a part of the Agreement. The Parties hereby agree that
subject to the modifications specifically stated in this Amendment, all terms and conditions
of the Agreement shall remain in full force and effect.
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7
    
    Counterparts; Facsimile Signatures.
This Amendment may be executed in two (2) or
more counterparts, each of which shall be deemed an original, but all of which together shall
constitute one (1) and the same instrument. This Amendment may be executed by facsimile
signatures and such signatures shall be deemed to bind each Party as if they were original
signatures.8
    
    Governing Law and Disputes.
This Amendment shall be governed by the laws of the
Agreement and any dispute arising out of or in connection with this Amendment shall be settled
in accordance with the procedure provided for in the Agreement.
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In Witness Whereof,
 THE MEDICINES COMPANY
    
    
    
    ASTRAZENECA AB(PUBL)By:
    
    /s/ Clive Meanwell
    
    
    
    By:
    
    /s/ Anders BurénName: Clive Meanwell
    
    
    
    
    
    Name: Anders BurénTitle: Chairman & CEO
    
    
    
    
    
    Title: Authorized Signatory
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