Exhibit 10.41

***Text Omitted and Filed Separately
with the Securities and Exchange Commission.
Confidential Treatment Requested
Under 17 C.F.R. Sections 200.80(b)(4)
and 240.24b-2.

C O N F I D E N T I AL

AMENDMENT TO COLLABORATION AGREEMENT

THIS AMENDMENT TO COLLABORATION AGREEMENT (the “Amendment”) is entered into and
effective as of October 31, 2006 (the “Amendment Date”) for the purpose of
amending that certain Collaboration Agreement dated September 19, 2002, as
amended (the “Agreement”) by and between:

ELI LILLY AND COMPANY, a corporation organized and existing under the laws of
the State of Indiana, whose principal place of business is Lilly Corporate
Center, Indianapolis, Indiana, 46285, United States of America (“Lilly”); and

AMYLIN PHARMACEUTICALS, INC., a corporation organized and existing under the
laws of Delaware, whose principal place of business is 9360 Towne Centre Drive,
San Diego, California 92121, United States of America (“Amylin”).

In consideration of the mutual covenants contained herein and other good and
valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, Lilly and Amylin agree as follows:

1.             Defined Terms.  Capitalized terms used but not otherwise defined
herein shall have the meanings provided in the Agreement.  Any reference herein
to a numbered “Section” shall be deemed to refer to such numbered Section of the
Agreement, and any reference herein to a numbered “paragraph” shall be deemed to
refer to such numbered paragraph of this Amendment.  The following terms shall
have the meanings set forth below:

(a)           “BID Product” shall mean the Product sold under the Product
Trademark “BYETTA®” (or such other Trademark if BYETTA is unavailable as a
Trademark in a given country) as a fixed-dose injection of exenatide
administered twice per day for any indication provided for in the first
Marketing Approval received in a relevant country (included in such indication
would be any subsequent label expansion(s) relating to use of the BID Product
for the same indication, e.g., new indication for combination use with TZDs for
treatment of the same indication as provided for in the first Marketing
Approval). For the avoidance of doubt, it is understood that any subsequent
indication relating to any disease or condition not included in the first
Marketing Approval shall be regarded as a Non-BID Product (e.g., a Product
indicated for treatment of obesity or Type I diabetes is a Non-BID Product).

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(b)           “BID Study” shall mean a clinical trial of a BID Product; but
excluding any Non-BID Study.

(c)           “Cost of Product Sold (OUS)” shall mean, solely for purposes of
calculation of Gross Margin (OUS) and for no other purpose, the Cost of Product
Sold for Product sold outside the U.S., determined in accordance with Section
1.33 of the Agreement, plus Lilly’s manufacturing costs for labeling, packaging,
or other manufacturing-related activity that may be undertaken by Lilly for
Product sold outside the U.S.  Lilly’s manufacturing costs included in Cost of
Product Sold (OUS) shall include, without limitation, the standard cost of
product sold expensed by Lilly for Product sold outside the U.S. plus
manufacturing variances expensed by Lilly for Product sold outside the U.S., in
each case, determined in accordance with U.S. GAAP.   It is understood that
Lilly’s Cost of Product Sold (OUS) may or may not be the same as Lilly’s
internal transfer pricing to its Affiliates for Product sold outside of the U.S.
and Lilly’s Cost of Product Sold (OUS) shall not include any mark-up or profit
margin in addition to actual Product cost.

Lilly’s standard cost of product sold may include, without limitation, the
following components:

(i)               the total invoice price, outside processing costs, freight,
duties, taxes, and brokers fees, with any volume or trade discounts being
reflected in the calculation and purchase of inventory from either Amylin or
Third Party suppliers being considered a Third Party cost;

(ii)             conversion costs (including, without limitation, direct labor
and direct overhead) directly associated with the manufacturing of Product;

(iii)            replacement costs for Products that are determined to be
defective or recalled or for Products that are returned to Lilly from the
customer;

(iv)             an allocation of service and administrative departments
performing functions which support Manufacturing operations directly associated
with the Manufacturing of Products;

(v)              depreciation of Product-specific capital investments for
equipment;

(vi)             depreciation of general manufacturing equipment and facilities
directly associated with Manufacturing of Products, in the case of equipment, to
the extent used specifically for Product, based on a percentage of
throughput/utilization (hours of utilization) and, in the case of facilities,
based upon percentage of square footage utilized.

(vii)            Product breakage;

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(viii)          obsolete Products; and

(ix)             to the extent attributable to the Manufacture of Products, any
other costs considered inventory costs or costs of products sold under U.S.
Generally Accepted Accounting Principles.

  All of these costs, and the methodology to be used in allocating indirect or
overhead costs among Manufacturing operations hereunder and other Lilly
manufacturing operations, shall be determined in a manner consistent with
Generally Accepted Accounting Principles in the U.S., and Lilly shall share with
Amylin such details relating to the allocation relating to operations outside
the U.S. used by Lilly as Amylin may reasonably request.  In the event that
Lilly does not use Dedicated Capacity for primary equipment for the Manufacture
of Products, an appropriate allocation of costs associated with the Manufacture
of Products shall be determined in a manner consistent with Generally Accepted
Accounting Principles in the U.S.  It is understood and agreed by the Parties
that Lilly will report all costs using its then current systems and procedures,
subject to audit and adjustment as required to be consistent with this
Amendment.

(d)           “Cumulative Gross Margin (OUS)” shall mean the cumulative Gross
Margin (OUS) calculated beginning upon the first Product Launch for Product
outside the U.S.

(e)           “Gross Margin (OUS)” shall mean Net Sales of Products outside the
U.S., less: (i) Cost of Product Sold (OUS) and (ii) Product Sample Costs for
Product Samples supplied for distribution outside the U.S.  Notwithstanding the
foregoing, for purposes of calculating Gross Margin (OUS), in no event shall
Product Sample Costs for Product Samples distributed outside the U.S. exceed
commercially reasonable sample quantities.

(f)            “Major OUS Market” shall mean the following countries:  France,
Germany, Italy, Spain, United Kingdom, and Japan.

(g)           “Non-BID Product” shall mean a Product other than BID Product.

(h)           “Non-BID Study” shall mean a clinical trial of a BID Product that
compares a Non-BID Product to a BID Product or that includes a Non-BID Product.

(i)            “Non-Major OUS Market” shall mean any country outside the U.S.
that is not a Major OUS Market.

(j)            “OUS BID Development Trial Costs” shall mean Development Costs
specifically attributable to all BID Studies (excluding BID Studies that are not
required for Marketing Approval such as Phase 3B Clinical Trials and Phase 4
Clinical Trials), other than any such BID Study that is required to be
undertaken to obtain Marketing Approval of BID Product in the U.S.

3

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(k)           “OUS BID Commercialization Trial Costs” shall mean
Commercialization Costs specifically attributable to all BID Studies undertaken
to support Commercialization outside the U.S. that are not required for
Marketing Approval such as Phase 3B Clinical Trials and Phase 4 Clinical Trials.

(l)            “OUS Non-BID Development Trial Costs” shall mean Development
Costs specifically attributable to all Non-BID Studies (excluding Non-BID
Studies that are not required for Marketing Approval such as Phase 3B Clinical
Trials and Phase 4 Clinical Trials), other than any such Non-BID Study that is
required to be undertaken to obtain Marketing Approval of Non-BID Product in the
U.S.

(m)          “OUS Non-BID Commercialization Trial Costs” shall mean
Commercialization Costs specifically attributable to all Non-BID Studies 
undertaken to support Commercialization outside the U.S. that are not required
for Marketing Approval such as Phase 3B Clinical Trials and Phase 4 Clinical
Trials.

(n)           “Product Plan” shall mean, for a particular Major OUS Market, the
strategic and tactical medical, marketing and sales plans for Product(s) of the
type and format used from time to time by Lilly for its own products. For the
avoidance of doubt, as of the Amendment Date, the referenced plans are known
internally as “Lilly Affiliate Brand Plans.”

(o)           “Product Sample” shall mean a sample (or a voucher for a sample)
of Product supplied for distribution to health care professionals without charge
for promotional, patient initiation, or familiarization purposes.

(p)           “Product Sample Costs” shall mean the standard unit cost plus
variances of Product Samples actually distributed in a country after Marketing
Approval in such country, calculated in accordance with GAAP samples  accounting
methods, consistently applied.    Distribution costs shall be excluded from the
standard unit cost.  However, Product Sample Costs will be included in the Cost
of Product Sold (OUS) (rather than in the marketing and selling expense line),
and shall reflect the standard Cost of Product Sold plus variances.

2.             Allocation of OUS Revenues.  Effective for OUS revenues accrued
on or after January 1, 2007, Section 4.5(b) of the Agreement shall be eliminated
in its entirety and replaced with the royalty-based structure set forth in this
paragraph 2, pursuant to which Lilly will retain all revenues from sales of
Product in the Territory outside the U.S. and pay a royalty to Amylin based upon
a percentage of Gross Margin (OUS).  Commencing on the date when Cumulative
Gross Margin (OUS) exceeds $[***] and continuing during the term of the
Agreement, Lilly shall pay to Amylin royalties based on the aggregate annual
Gross Margin (OUS) (without adjustment for partial calendar years) at the rates
set forth below:

(a)           [***]% of the portion of aggregate Gross Margin (OUS) during a
calendar year that is equal to or less than $[***];

(b)           [***]% of the portion of aggregate Gross Margin (OUS) during a

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***CONFIDENTIAL TREATMENT REQUESTED

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calendar year that is greater than $[***] but equal to or less than $[***]; and

(c)           [***]% of the portion of aggregate Gross Margin (OUS) during a
calendar year that is greater than $[***] but equal to or less than $[***]; and

(d)           [***]% of the portion of aggregate Gross Margin (OUS) during a
calendar year that is greater than $[***].

For the avoidance of doubt, the Parties acknowledge and agree that no royalty
shall be due on the first $[***] of Cumulative Gross Margin (OUS), nor shall
such amount be included in determining the applicable royalty rates set forth
above.  The exclusion of the first $[***] in Cumulative Gross Margin (OUS) is to
be applied one time and not on a product-by-product or country-by-country
basis.  The following sample calculation is provided for purposes of
illustration and clarification only:

 

Year

 

Annual Gross 
Margin (OUS)

 

Cumulative Gross 
Margin (OUS)

 

Royalty Payable 
to Amylin

 

2006

 

$

[***]

 

$

[***]

 

[***]

 

2007

 

$

[***]

 

$

[***]

 

[***]

 

2008

 

$

[***]

 

$

[***]

 

[***]

 

2009

 

$

[***]

 

$

[***]

 

$

[***] (1)

 

2010

 

$

[***]

 

$

[***]

 

$

[***] (2)

 

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(1)During [***], Cumulative Gross Margin (OUS) first exceeds $[***], and
calculation of royalties payable with respect to Gross Margin (OUS) in excess of
$[***] (i.e., $[***]) begins. The royalty for [***] would therefore equal $[***]
x [***]%, or $[***].

(2)For [***] (the year after Cumulative Gross Margin (OUS) first exceeds
$[***]), the royalty payable would be calculated as follows: ($[***] x [***]%) +
($[***] x [***]%) = $[***].

Also effective as of January 1, 2007, all references to “Adjusted OUS Operating
Profit/Loss” in Section 4.9 (a) shall be deleted, and the “OUS Operating Profit
Sharing” example calculations found in Schedule 4.5 shall be deleted in their
entirety.  Royalties due under this paragraph 2 shall be paid by Lilly to Amylin
on a [***] basis within [***] ([***]) days after the end of [***] for Products
sold outside of the U.S. during such [***].  At Lilly’s option, such payment may
be made by providing Amylin a credit in the amount of the royalty due as part of
the calculation of periodic settlement payments between the Parties contemplated
by Section 4.9(a).  Royalties due each [***] under this paragraph 2 shall be
subject to simple interest as follows:  royalties due from Product sales from
the [***] of each [***] shall be increased by an amount equal to simple interest
for a period of [***], and royalties due from Product sales from the [***] of
each [***] shall be increased by an amount equal to simple interest for a period
of [***].  The interest factor used for a particular [***] shall be equal to the
rate specified in the Agreement for calculating amounts owed under Section
4.9(a) (as described in the letter agreement between the Parties dated June 12,
2006.)

3.             Allocation of OUS Development and Commercialization Costs.  In
partial

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***CONFIDENTIAL TREATMENT REQUESTED

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consideration of Amylin foregoing its right to receive any share of the first
$[***] of Cumulative Gross Margin (OUS), the Parties hereby agree to the
following allocations with respect to costs outside the U.S.:

(a)           BID Products.  Lilly shall be solely responsible for 100% of BID
Product Commercialization Costs relating to the Commercialization of BID
Products outside of the U.S. (including without limitation OUS BID
Commercialization Trial Costs), and regardless of whether such Commercialization
Costs were incurred before or after the Amendment Date. Effective as to expenses
accrued on or after January 1, 2007, Lilly shall also be solely responsible for
100% of BID Product Development Costs relating to Development of BID Product for
sale outside of the U.S. (including without limitation OUS BID Development Trial
Costs).  Accordingly, BID Product Commercialization Costs relating specifically
to sale of Product outside of the U.S., and effective January 1, 2007, BID
Product Development Costs specifically relating to development of BID Product
for sale outside of the U.S., shall not be included in the calculation of the
periodic settlement payments between the Parties contemplated by Section 4.9(a)
of the Agreement.  Exhibit C sets forth those clinical trials or other
development activities underway as of the Amendment Date and indicates how the
expenses thereof shall be shared by the Parties, subject to potential adjustment
as provided in Paragraph 3(c).   For the avoidance of doubt, it is understood
that any Development Costs related to development of Non-BID Product for sale
outside the US shall continue to be allocated 80% to Lilly and 20% to Amylin as
contemplated by Section 4.3(a)(ii) of the Agreement.  It is also understood that
Amylin shall not be entitled to reimbursement of any OUS BID Product
Commercialization Costs unless reimbursement is approved in advance by Lilly.

(b)           Non-BID Products.  Section 4.4(a)(ii) of the Agreement is amended
in its entirety, effective January 1, 2007, to read as follows:

“(ii)   Rest of World.  Lilly shall pay one hundred percent (100%) of the
Commercialization Costs for Commercialization of Products in all countries in
the Territory outside the U.S. and Amylin shall pay 0% of such Commercialization
Costs, with the sole exception of OUS Non-BID Commercialization Trial Costs
which shall be allocated 80% to Lilly and 20% to Amylin.”

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***CONFIDENTIAL TREATMENT REQUESTED

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Lilly will prepare and deliver to Amylin, in addition to and concurrently with
the [***] composite reports due pursuant to Section 4.9(a), a separate composite
report of OUS Non-BID Commercialization Trial Costs substantially the same in
scope, content and format to the [***] reports of Development Costs due pursuant
to Section 4.3(b), and the amounts reported in such composite report of OUS
Non-BID Commercialization Trial Costs shall be aggregated with the amounts
reported in the composite reports specified in Section 4.9(a) and included in
the calculation of periodic settlement payments between the Parties contemplated
by Section 4.9(a).  The parties recognize that Lilly does not formally track
time spent by OUS FTE’s on Development matters versus time spent by the same
individuals on Commercialization matters so that good faith allocations of FTEs
between the categories of Non-BID Commercial Trial Costs and Non-BID Development
Trial Costs may be necessary.

(c)           Costs for OUS Studies Utilized in U.S.

(i)                                    The Parties recognize that data from
certain clinical, health outcomes or other studies undertaken for Development or
Commercialization purposes relating to countries outside the U.S. (an “OUS
Study”) may generate data that could also be utilized for U.S. purposes. 
Accordingly, the Parties agree as follows:

a.               Except with respect to any Required Study, the Global
Development and Commercialization Committee (“GDCC”) shall, prior to the
initiation of any OUS Study, review whether such OUS Study is also expected to
generate data that will be utilized for U.S. purposes.  If the GDCC agrees that
the OUS Study will also be used for U.S. purposes, (a “Dual Use Study”) then the
expense of such Dual Use Study shall be shared in accordance with the Dual Use
Cost Allocation. In all other cases, the expenses of the OUS Study shall be
shared in accordance with the OUS Study Cost Allocation, but shall be subject to
possible later recharacterization as provided in paragraph (d) below. The
Parties agree that their respective representatives to the GDCC will act in a
reasonable manner with respect to any proposal that an OUS Study be regarded as
a Dual Use Study.

b.              Except as provided in paragraph (c) below, if the OUS Study is a
Required Study, the expenses thereof shall be shared in accordance with the OUS
Study Cost Allocation regardless of whether such OUS Study is also used in the
U.S., and the provisions of paragraph (d) below shall not apply.

c.               Notwithstanding paragraph (b) above, any OUS Study relating to
Non-BID Product that is a Required Study for Marketing Approval in the European
Union (“Europe Non-BID Product Registration Study”) shall be prospectively
reviewed by the GDCC upon request of either Party to determine whether data from
such Europe Non-BID Product Registration Study is also expected to be used for
U.S. purposes.  If the GDCC agrees

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***CONFIDENTIAL TREATMENT REQUESTED

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that data from such Europe Non-BID Product Registration Study will be used for
U.S. purposes, then such study shall be deemed a Dual Use Study and the expenses
thereof shall be shared in accordance with the Dual Use Cost Allocation.  In all
other cases, the expense of the Europe Non-BID Product Registration Study shall
be shared in accordance with the OUS Study Cost Allocation, but shall be subject
to possible later recharacterization as provided in paragraph (d) below.  The
Parties agree that their respective representatives to the GDCC will act in a
reasonable manner with respect to any proposal that an OUS Study be regarded as
a Dual Use Study.

d.              With respect to (i) any OUS Study that is not a Required Study
and that has not previously been determined to be a Dual Use Study and (ii) any
Europe Non- BID Product Registration Study that has not previously been
determined to be a Dual Use Study, either Party shall have the right to request
that the allocation of costs of any such study be reviewed based upon actual or
intended use or non-use (as defined below in (c) (iii)) of the data therefrom. 
In the event either party requests such a review, the GDCC shall review such
issue in good faith, and if it concludes that the study is a Dual Use Study the
expenses of such study previously incurred shall be reallocated as appropriate
in accordance with the Dual Use Study Cost Allocation. If necessary, an
appropriate adjustment shall be made in the next [***] settlement contemplated
by Section 4.9 of the Agreement.  Thereafter, any future expenses of such study
shall be shared in accordance with the Dual Use Cost Allocation, and
appropriately reflected in the [***] settlement.  The Parties agree that their
respective representatives to the GDCC will act in a reasonable manner with
respect to any proposal that data from an OUS Study be used in the U.S. In the
event the GDCC is unable to agree upon proposed U.S. use of data from an OUS
Study, Lilly may if applicable exercise its right under of Section 3.1(e) (ii)
to require that data from an OUS Study be utilized in the U.S., but if Lilly
exercises such right, the fact that such data was used in the U.S. shall not be
a basis for recharacterization of the expenses of such OUS Study.

(ii)                                As used herein:

a.               “OUS Study Cost Allocation” shall mean (i) in the event such
expenses are related to a BID Product and incurred prior to January 1, 2007, the
expenses shall be borne 80% by Lilly and 20% by Amylin, (ii) in the event such
expenses are related to a BID Product and incurred on or after January 1, 2007,
the expenses shall be borne 100% by Lilly, and (iii) in the event such expenses
are related to Non-BID Product (regardless of whether such expenses are incurred
before or after January 1, 2007), the expenses shall be borne 80% by Lilly and
20% by Amylin.

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b.              “Dual Use Cost Allocation” shall mean 50% of such expenses are
borne by Lilly and 50% by Amylin.

c.               “Required Study” shall mean any study required as part of the
minimum data package necessary for receipt of Marketing Approval in the relevant
country.  The Parties recognize that the application for Marketing Approval may
include additional OUS Studies that are useful, but not required, and that any
such additional study shall not be deemed a Required Study.

(iii)                            Data will be considered utilized for U.S.
purposes if such data is (i) contained in materials approved for use in the U.S.
by any joint U.S. promotion or U.S. medical/legal/regulatory review body
established by the Parties (e.g., the committee currently known as SMART), (ii) 
included in materials utilized by U.S. sales representatives, medical liaisons,
or managed care account representatives, such as promotional slide sets,
materials for use in health professional to health professional programs,
marketing materials, brochures, or authorized reprints utilized by alliance
personnel in field or congress settings, (iii) is disclosed for U.S. promotional
purposes at U.S. congresses or in U.S. publications or (iv) included in any
direct to consumer advertising or consumer directed promotional materials
distributed in the U.S.  Data will not be considered utilized for U.S. purposes
merely because such data is (i) used in Third Party U.S. continuing medical
education programs, (ii) released by Lilly in U.S. venues  or U.S. publications
to service OUS needs, (iii) used with advisory boards,  (iv) filed as required
with U.S. Regulatory Authorities (but not any pivotal studies) , (v) used in
medical information letters, used to answer unsolicited medical questions, used
in reprints used at congresses to answer unsolicited medical questions, (vi)
used in scientific slide decks provided only upon request, (vii) presented at
Lilly’s request in poster or abstract form at scientific meetings or congresses
or by independent investigators where such presentation was not requested by
Lilly, or (viii) any meta based data analysis.

(iv)                               The provisions of Section 4.3(a)(iii) of the
Agreement shall continue in effect.

(d)  [***] Report Adjustment.  The Parties have previously disagreed as to the
responsibility for certain OUS Commercialization Costs.  In order to resolve
this dispute, the periodic settlement payment contemplated by Section 4.9(a) of
the Agreement due to Lilly for the [***] after the Amendment Date will include
an additional $[***] beyond any actual amount due to Lilly, for such [***], with
the effect that the amount that would otherwise be due to Lilly will be
increased by $[***].  All future OUS Commercialization Costs shall be borne by
Lilly as provided in paragraph 3.

(e)           Conforming Changes. 

(i)            Section 8.1(c) of the Agreement is hereby amended to read

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in its entirety as follows:  “In the event of any product liability or other
Third Party claim in which both Parties are asserted to be liable and neither is
entitled to indemnification hereunder, the Parties shall treat such Damages as
Commercialization Costs if such claim relates to the U.S. or share such Damages
80% by Lilly and 20% by Amylin if such claim relates to the Territory outside
the U.S.  In the case of any such claim relating to the Territory outside the
U.S., (i) any amounts owed to Lilly pursuant to this Section 8.1(c) shall be
paid as part of the periodic settlement process contemplated under Section
4.9(a) of the Agreement and (ii) in the event such amount is due to Lilly at
anytime prior to the expiration of one year from the date of the first Product
Launch in the first country outside the U.S., the amount due to Lilly shall
initially be treated as a credit against royalties due from Lilly hereunder for
such first year, and thereafter any remaining amount due shall be paid through
the periodic settlement process for the [***] immediately following such first
year. ”

(ii)           Section 10.4(e) of the Agreement is hereby amended to read in its
entirety as follows:  “Each Party shall pay 50% of any expenses (except for the
expenses of the non-controlling Party’s counsel, if any) and shall receive 50%
of any recovery realized as a result of any litigation pursuant to this Section
10.4 until each Party’s reimbursable expenses have been recovered and thereafter
share recovery in accordance with each Party’s proportionate interest in
Operating Profits and Losses for the U.S., or if such litigation relates to the
Territory outside the U.S., 80% to Lilly and 20% to Amylin.”

4.               Audit Rights.  The Parties acknowledge each Party’s right to
audit under Section 4.9(e) of the Agreement shall include the right to audit any
Affiliates of the other Party as part of an audit where a Party audits the U.S.
and/or one or more countries outside the U.S.  It is understood that for
purposes of determining responsibility for payment of audit expenses pursuant to
Section 4.9(e), the 5% materiality threshold shall be applied to the U.S. and
any audited OUS countries taken as a whole.

5.               Reporting.          (a) Lilly shall provide royalty reporting
to Amylin in a form to be mutually agreed by the Parties.  Royalty reporting
shall be provided [***] together with royalty payments.  Lilly also agrees to
undertake [***] updates to Amylin in any [***] where Lilly anticipates material
variances so as to allow Amylin to make financial adjustments in its financial
reporting.  It is the Parties’ intention to structure reports to fulfill Amylin
reporting needs and be as consistent as possible within existing internal Lilly
systems to the extent practical to do so.  Attached hereto as Exhibit A and
described below are examples of the royalty reports to be provided.

(b)           Lilly shall provide Amylin with the following reports:

(i)            a [***] royalty report substantially in the form of Exhibit A
within [***] ([***]) days of [***].

(ii)           [***] planning report(s) as follows:

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(A)    showing a preliminary [***] ([***]) year royalty projection by country
for Major OUS Markets and in the aggregate for all other countries, the timing
of such report to be consistent with the alliance financial calendar agreed upon
by the GDCC each year; and

(B)    showing a final [***] ([***]) year royalty projection by country for
Major OUS Markets and in the aggregate for all other countries, the timing of
such report to be consistent with the alliance financial calendar agreed upon by
the GDCC each year;

(iii)         [***] rolling forecasts showing projections of [***] within [***]
days after the forecasts are finalized each [***] by Lilly.

Lilly represents and warrants that Exhibit B to this Amendment fairly and
accurately describes how Lilly currently calculates foreign currency conversions
as referenced in Section 4.9(a) of the Agreement.  It is understood that Lilly
may from time to time change its methodology for currency conversions.

6.          OUS Commercialization Activities.  Lilly shall have responsibility
for Commercialization activities outside the U.S., including development,
approval and implementation of the Commercialization Plan as it relates to the
Territory outside the U.S. (the “OUS Commercialization Plan”).  Amylin will have
advisory input into the OUS Commercialization Plan, but all decisions as to the
content of the OUS Commercialization Plan, the OUS Commercialization Budget, and
the Commercialization activities to be conducted outside the U.S. shall be made
by Lilly, provided, however, that Lilly shall comply with its obligations under
the Agreement as modified by this Amendment.  Notwithstanding the foregoing, any
portion of the Commercialization Plan specifically relating to Non-BID
Commercialization Trial Costs shall be subject to the approval pursuant to the
Binding Budget process of the Agreement. Nothing in this Amendment shall be
construed as modifying the provisions in the Agreement related to Manufacturing
or to selection of trademarks, or any other rights that are not specifically
changed by this Amendment, all of which shall continue in effect, or any other
right of review, approval or participation of Amylin under the Agreement except
to the extent specifically provided in this Amendment. The terms of the Clinical
Research Quality Agreement between the Parties dated May 14, 2004 shall continue
in effect. Through the GDCC, Amylin and Lilly agree to modify the roles and
responsibilities guidance for activities outside of the U.S. such that Amylin
retains its current participation in the Lilly Brand Council I and II
processes.  In addition, GDCC will modify the OUS roles and responsibilities to
maintain Amylin’s current ability to review and provide input into the Affiliate
Brand Plans for the Major OUS Markets.  Lilly and Amylin anticipate the OUS
roles and responsibilities document will be updated to include the following
topics.

·                              Addition of Amylin Medical and Team management
into the Brand Council I and II process.

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·                              Clarification of Amylin’s ability to review and
provide input on OUS Major Market affiliate plans versus review and input of
Non-Major OUS Market affiliate plans.

·                              Clarification of a Brand Council III alliance
process that provides Amylin representatives the appropriate venue and access to
personnel to review and provide input on OUS Major Market affiliate plans.

(a)           Non-Major OUS Markets.  If Amylin has business questions regarding
brand management for Product(s) in any Non-Major OUS Market, Lilly’s
representatives shall address such questions on an ad hoc basis to the extent
included as approved GDCC agenda items.

(b)           Budget Summary.  Consistent with the Brand Council Process and
Product Plans of Lilly Affiliates, Lilly will provide to Amylin on an [***]
basis, a budget summary covering the next [***] for each of the Major OUS
Markets in such level of detail and format as the parties shall agree.  Such
summaries shall include external marketing and medical spending as well as sales
force FTEs.  It is understood that any such budget shall reflect Lilly’s plans
at the time such budget is created but shall not be binding upon Lilly.  Each
such budget summary may be modified from time to time by the applicable Lilly
Affiliate, but Lilly shall provide to Amylin a final Lilly-approved copy that
represents the next year’s approved budget plan for such Major OUS Market
promptly following approval of such plan.

(c)           Long Range Business Plan.  [***], Lilly shall present to Amylin a
long-range business plan for Commercialization of Products outside the U.S.,
including [***].  Such long-range business plans shall be presented for each
Major OUS Market and in summary fashion for all Non-Major OUS Markets.  In
addition, the business plan shall also include, at an OUS consolidated level,
[***].

(d)           Budget Summary and Business Plan Updates.  In the [***], Lilly
shall provide Amylin (through the GDCC) with updates of the annual budget
summary delivered to Amylin pursuant to paragraph 6(b) and any material update
to the business plan for the Products.  Each such update shall cover the [***]. 
The budget summary updates will include, without limitation, [***].  In the
budget summary updates, for any [***]% or greater discrepancy (provided the
discrepancy is at least $[***]) between actual and forecasted amounts, Lilly
shall also provide brief explanatory comments regarding the reason(s) for such
discrepancy.  At Amylin’s reasonable request, additional discussions and/or
questions relating to such updates shall occur to the extent approved as a GDCC
topic.

(e)           Existing Obligations.   The Parties existing obligations under
Sections 2.2 and 2.6 of the Agreement shall be deemed modified as necessary to
be consistent with the provisions of this Amendment.

7.             Exclusions from Binding Budgets.  The Parties agree that
Development Costs

--------------------------------------------------------------------------------

***CONFIDENTIAL TREATMENT REQUESTED

12

--------------------------------------------------------------------------------

outside the U.S. and Commercialization Costs outside the U.S. that are borne
entirely by Lilly are not subject to the provisions of the Agreement that are
specifically applicable to Binding Budgets.  This provision shall not relieve
Lilly from the obligation to use Commercially Reasonable Efforts to
Commercialize the Products on a worldwide basis as provided in the Agreement.

8.          Medical Meetings.

(a)           Lilly Meetings.  To the extent that certain Lilly-organized
medical meetings relating to commercialization of Product OUS contain sections
on Product, Lilly shall invite Amylin to attend the specific sections related to
Product and provide Amylin with at least [***] prior written notice of such
meetings.  For purposes of clarity, this paragraph shall be applicable only to
the following global and regional conferences (or any successor conferences
covering substantially the same topics):

(i)            European Clinical Advisory Boards;

(ii)           Global Medical Conferences (GMC’s);

(iii)         Regional Medical Conferences (RMC’s); and

(iv)          Taking Control Peaks and Valleys Conferences (TCPV).

(b)           Amylin Meetings.  To the extent that certain Amylin-organized
medical meetings contain sections on Product, Amylin shall invite Lilly to
attend the specific sections related to Product and provide Lilly with at least
[***] prior written notice of such meetings.  For purposes of clarity, this
paragraph shall be applicable only to the following meetings (or any successor
meetings covering substantially the same topics):

(i)            Amylin’s non-US medical meetings; and

(ii)           Amylin’s non-US advisory board meetings.

9.                              Recalls.  Section 3.1(e)(ii) (A) of the
Agreement is hereby deleted.  Section 5.11 of the Agreement is hereby amended to
read in its entirety as follows:

“In the event either Party believes that a recall or removal from the market of
the Product is necessary in any Regulatory Jurisdiction, it shall immediately
notify the other Party, and the Parties shall discuss the appropriate course of
action.  In the event of any disagreement between the Parties regarding the
necessity of a recall or removal, the Marketing Approval holder for the
Regulatory Jurisdiction in question shall make the final determination after
considering in good faith the views of the other Party.  In the event that a
Regulatory Authority issues a request, directive, or order, or the Marketing
Approval holder determines to recall or remove the Product from the market, the
recall shall be the responsibility of the Marketing Approval holder.  Both
Parties will cooperate fully with one another in conducting the recall.”

--------------------------------------------------------------------------------

***CONFIDENTIAL TREATMENT REQUESTED

13

--------------------------------------------------------------------------------

10.        Entire Agreement.  The Agreement, as amended by this Amendment,
embodies the entire understanding of the Parties and shall supersede all
previous communications, representations and understandings, whether oral,
written or otherwise, between the Parties relating to the subject matter
hereof.  Except as specifically amended by this Amendment, the terms and
conditions of the Agreement shall remain in full force and effect.

11.        Governing Law.  This Amendment shall be governed by, and construed
and enforced in accordance with, the laws of the State of New York, excluding
its conflicts of laws principles.

12.        Counterparts.  This Amendment may be executed in counterparts, each
of which shall be deemed an original document, and all of which, together with
this writing, shall be deemed one instrument.

IN WITNESS WHEREOF, the Parties hereto have duly executed this Amendment as of
the Amendment Date.

ELI LILLY AND COMPANY

 

AMYLIN PHARMACEUTICALS, INC.

 

 

 

By:

/s/ Bryce D. Carmine

 

By:

/s/ Daniel M. Bradbury

 

 

 

Name:

Bryce D. Carmine

 

Name:

Daniel M. Bradbury

 

 

 

Title:

President, Global Brand Dev.

 

Title:

President and Chief Operating Officer

 

14

--------------------------------------------------------------------------------

EXHIBIT A

REPORTS

 

 

Byetta OUS Gross Margin Royalty Calculation

 

 

 

 

 

 

 

 

 

For the [***]

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Country/Affiliate

 

Net Sales

 

Foreign
Exchange Rate

 

Net Sales

 

Std. Cost
COPS

 

Std. Cost
Samples

 

Gross
Margin

 

 

 

Local Currency

 

 

 

US Dollars

 

 

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

[***]

 

[***]

 

$[***]

 

 

 

 

 

 

 

$[***]

 

[***]

 

$[***]

 

$[***]

 

 

OUS Distribution

  [***]

OUS Mfg Variances - favorable/(unfavorable)

$[***]

 

 

Total PUS Gross Margin

$[***]

 

 

OUS G.M. Royalty*

$[***]

 

*Illustrative only — early years will also have to reflect adjustment for
cumulative

gross margin on which no royalty will be due.

--------------------------------------------------------------------------------

***CONFIDENTIAL TREATMENT REQUESTED

--------------------------------------------------------------------------------

Byetta 5mcg Sales Supplemental

For the [***]

All in [***]

Country/Affiliate

 

Sales Units

 

Net Sales

 

Foreign
Exchange
Rate

 

Net Sales

 

Std. Cost
 COPS

 

 

 

Local Currency

 

 

 

US Dollars

 

 

 

 

 

In mils

 

 

 

 

 

 

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

 

 

[***]

 

 

 

 

 

$[***]

 

$[***]

 

 

--------------------------------------------------------------------------------

***CONFIDENTIAL TREATMENT REQUESTED

 

2

--------------------------------------------------------------------------------

Byetta 10mcg Sales Supplemental

For the [***]

Country/Affiliate

 

Sales Units

 

Net Sales

 

Foreign
Exchange
Rate

 

Net Sales

 

Std. Cost
 COPS

 

 

 

Local Currency

 

 

 

US Dollars

 

 

 

 

 

in mils

 

 

 

 

 

 

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

[***]

 

[***]

 

[***]

 

[***]

 

$[***]

 

$[***]

 

 

 

[***]

 

 

 

 

 

$[***]

 

$[***]

 

 

Byetta Samples Supplemental

For the [***]

 

Country/Affiliate

 

Sample Units
in mils

 

 

 

Std. Cost
Samples
in mils

 

 

[***]

 

[***]

 

 

 

 

 

$[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

[***]

 

[***]

 

 

 

 

 

[***]

 

 

 

 

[***]

 

 

 

 

 

$[***]

 

 

 

--------------------------------------------------------------------------------

***CONFIDENTIAL TREATMENT REQUESTED

3

--------------------------------------------------------------------------------

EXHIBIT B

Lilly Foreign Currency Conversion Methodology

Month end FX spot exchange rates are pulled from a reliable source, or
calculated by the affiliate when required for statutory purposes, at each month
end and loaded into Lilly Enterprise System.  These rates are used to translate
income statement totals into U.S. dollars for reporting purposes in the
subsequent month.  For example, the EUR/USD spot exchange rate pulled on or near
April 30 becomes the rate for translation of income statement transactions
recorded during the month of May for all EUR-denominated subsidiaries for
consolidated reporting purposes.  The end result is a weighted average exchange
rate being used to convert foreign currency income statement totals into U.S.
dollars throughout the quarter/year.  Except as may otherwise be required by
law, these rates shall conform to an independent worldwide exchange rate
authority such as Reuters or the Wall Street Journal (based on rates posted on
or near the last business day of the applicable month).

 

4

--------------------------------------------------------------------------------

EXHIBIT C

Ongoing Development and Commercialization Study Costs*

 Trial/Study Description

 

US Split
50/50

 

OUS Split
80L/20A

 

Beginning 1/1/07
OUS 100% Lilly

 

Beginning 1/1/06
OUS 100% Lilly

 

[***]

 

 

 

 

 

 

 

 

 

[***]

 

 

 

 

 

X

 

 

 

[***]

 

 

 

 

 

X

 

 

 

[***]

 

 

 

 

 

X

 

 

 

[***]

 

 

 

 

 

X

 

 

 

[***]

 

 

 

 

 

X

 

 

 

[***]

 

 

 

 

 

X

 

 

 

[***]

 

 

 

 

 

 

 

 

 

[***]

 

 

 

 

 

X

 

 

 

[***]

 

 

 

 

 

X

 

 

 

[***]

 

 

 

 

 

X

 

 

 

[***]

 

 

 

 

 

X

 

 

 

[***]

 

 

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

 

*Subject to recharacterization as provided in Paragraph 3(c) of this Amendment.

--------------------------------------------------------------------------------

***CONFIDENTIAL TREATMENT REQUESTED

--------------------------------------------------------------------------------

 

Trial/Study Description

 

US Split
50/50

 

OUS Split
80L/20A

 

Beginning 1/1/07
OUS 100% Lilly

 

Beginning 1/1/06
OUS 100% Lilly

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

 

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

 

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

 

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

X

 

 

 

 

 

 

 

[***]

 

 

 

 

 

 

 

 

 

[***]

 

 

 

 

 

 

 

X

 

[***]

 

 

 

 

 

 

 

X

 

[***]

 

 

 

 

 

 

 

X

 

[***]

 

 

 

 

 

 

 

X

 

[***]

 

 

 

 

 

 

 

X

 

 

--------------------------------------------------------------------------------

***CONFIDENTIAL TREATMENT REQUESTED

 

2

--------------------------------------------------------------------------------