<PAGE>
EXHIBIT 10.52
CONFIDENTIAL MATERIALS OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION. ASTERISKS DENOTE OMISSIONS.
COLLABORATION AGREEMENT
BY AND BETWEEN
PFIZER INC.
AND
EYETECH PHARMACEUTICALS, INC.
DATED AS OF DECEMBER
17, 2002
<PAGE>
TABLE OF CONTENTS
<TABLE>
<CAPTION>
PAGE
----
<S>
<C>
ARTICLE 1
DEFINITIONS.........................................................................................
2
ARTICLE 2 CO-PROMOTION OF PRODUCTS IN THE US
TERRITORY........................................................
18
2.1
Co-Promotion........................................................................................
18
2.2
License
Grants......................................................................................
18
2.3
Compliance With
Law.................................................................................
18
2.4
Detailing
Obligations...............................................................................
18
2.5
Training............................................................................................
18
2.6
Promotional Materials
and Call Center
Communications................................................
20
2.7
Samples.............................................................................................
20
2.8
Distribution and
Booking of
Sales...................................................................
21
2.9
Contract Sales
Forces...............................................................................
21
2.10
Delivery Technology
Development
Agreement..........................................................
21
ARTICLE 3 MANAGEMENT OF
ALLIANCE..............................................................................
22
3.1
Committee/Subcommittees.............................................................................
22
3.2
Meetings............................................................................................
22
3.3
Clinical
Development/Regulatory
Subcommittee........................................................
23
3.4
Commercialization
Subcommittee......................................................................
26
3.5
Manufacturing
Subcommittee..........................................................................
27
3.6
Joint Operating
Committee...........................................................................
29
3.7
Deadlocks...........................................................................................
30
3.8
Limitation on
Decision-Making
Authority.............................................................
30
ARTICLE 4 CLINICAL AND REGULATORY
MATTERS.....................................................................
31
4.1
Clinical and
Regulatory Matters in the US
Territory.................................................
31
4.2
Clinical and
Regulatory Matters in the ROW
Territory................................................
33
4.3 Inquiries, Adverse Events, etc.
....................................................................
35
4.4
Pfizer's Performance
of Regulatory Services Agreement
Obligations................................... 36
ARTICLE 5 PRODUCT
DEVELOPMENT.................................................................................
37
5.1
Development Plan and
Budget.........................................................................
37
5.2
AMD Product and DME
Product
Development.............................................................
38
5.3
Development of
Products for Additional Indications in the
Field..................................... 38
ARTICLE 6 LAUNCH,
CO-PROMOTION AND
DETAILING.................................................................
39
6.1
Co-Promotion of
Products............................................................................
39
6.2
Marketing Plan and
Budget...........................................................................
39
6.3
Detailing...........................................................................................
40
6.4
Detailing
Reports...................................................................................
40
6.5
Detail
Shortfalls...................................................................................
41
</TABLE>
i
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<TABLE>
<S>
<C>
6.6
Sales Force
Responsibilities........................................................................
44
6.7
Product
Information.................................................................................
45
6.8
Orders..............................................................................................
45
6.9
Audit...............................................................................................
45
6.10
Third Party
Reports................................................................................
45
6.11
Medical
Claims.....................................................................................
45
6.12
Manufacturing......................................................................................
46
6.13
Customer
Support...................................................................................
50
ARTICLE 7 PAYMENT
PROVISIONS..................................................................................
50
7.1
Payment
Currency....................................................................................
50
7.2
Payments............................................................................................
50
ARTICLE 8 EXPENSE SHARING AND
COMPENSATION....................................................................
51
8.1
Sharing of Development
Costs........................................................................
51
8.2
Responsibility for
Regulatory
Costs.................................................................
53
8.3
Responsibility for
Cost of Goods
Sold...............................................................
53
8.4
Responsibility for
Marketing
Expenses...............................................................
54
8.5
Net Sales
Reports...................................................................................
54
8.6
Quarterly
Reconciliation of Net Sales and
Expenses..................................................
54
8.7
Offset..............................................................................................
56
ARTICLE 9 ACCOUNTING AND
REPORTS..............................................................................
56
9.1
Books and
Records...................................................................................
56
9.2
Audits..............................................................................................
56
9.3
Sales Force
Efforts.................................................................................
57
ARTICLE 10
INTELLECTUAL PROPERTY RIGHTS AND
LABELING.........................................................
58
10.1
Trademark and
Corporate
Logos......................................................................
58
10.2
Copyrights and
Proprietary
Programs................................................................
61
10.3
Developments.......................................................................................
62
10.4
Third Party
Agreements.............................................................................
62
ARTICLE 11
CONFIDENTIAL
INFORMATION..........................................................................
63
11.1
Treatment of
Confidential
Information..............................................................
63
11.2
Confidential
Information...........................................................................
64
ARTICLE 12
REPRESENTATIONS, WARRANTIES AND
INDEMNIFICATION...................................................
65
12.1
Eyetech's
Representations..........................................................................
65
12.2
Pfizer's
Representations...........................................................................
66
12.3
No
Warranties......................................................................................
67
12.4
General
Indemnification in Favor of
Pfizer.........................................................
67
12.5
General
Indemnification in Favor of
Eyetech........................................................
68
12.6
Product Liability and
Intellectual Property Infringement
Indemnification........................... 69
12.7
"Losses"...........................................................................................
72
12.8
No Consequential or
Punitive
Damages...............................................................
73
12.9
General
Indemnification
Procedures.................................................................
73
</TABLE>
ii
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<TABLE>
<S>
<C>
ARTICLE 13 TERM AND
TERMINATION..............................................................................
77
13.1
Term...............................................................................................
77
13.2
Termination for
Breach.............................................................................
77
13.3
HSR
Denial.........................................................................................
79
13.4
Detail
Shortfalls..................................................................................
79
13.5
Breach of
Non-Competition
Obligations..............................................................
80
13.6
Changes of
Control.................................................................................
80
13.7
Termination of License
Agreement...................................................................
80
13.8
Sales Threshold
Termination........................................................................
81
13.9
Survival of
Obligations............................................................................
81
ARTICLE 14
NON-COMPETITION; DETAILING SERVICES
AGREEMENT.....................................................
84
14.1
Non-Competition....................................................................................
84
14.2
Acquisitions Involving
Competing
Products..........................................................
86
14.3
Detailing Services
Agreement; Additional
Agreements................................................
87
ARTICLE 15 DISPUTE
RESOLUTION................................................................................
88
15.1
Arbitration........................................................................................
88
15.2
No
Limitation......................................................................................
89
ARTICLE 16 HSR
MATTERS.......................................................................................
90
16.1
HSR
Filings........................................................................................
90
16.2
HSR Cooperation;
Further
Assurances................................................................
90
16.3
Activities Prior to
the Effective
Date.............................................................
91
ARTICLE 17
MISCELLANEOUS......................................................................................
91
17.1
Governing
Law......................................................................................
91
17.2
Jurisdiction.......................................................................................
91
17.3
Waiver.............................................................................................
91
17.4
Notices............................................................................................
92
17.5
Entire
Agreement...................................................................................
93
17.6
Headings...........................................................................................
93
17.7
Severability.......................................................................................
93
17.8
Registration and
Filing of the
Agreement...........................................................
94
17.9
Assignment.........................................................................................
94
17.10 Successors and
Assigns.............................................................................
94
17.11 Divestiture by
Pfizer..............................................................................
95
17.12
Counterparts.......................................................................................
96
17.13 Force
Majeure......................................................................................
96
17.14 Non-Solicitation of
Employees......................................................................
97
17.15 Press Releases
and Other
Disclosures..............................................................
97
17.16 Third-Party
Beneficiaries.........................................................................
98
17.17 Relationship of
the
Parties.......................................................................
98
17.18 Performance and
Compliance by
Affiliates..........................................................
100
</TABLE>
iii
<PAGE>
<TABLE>
<S>
<C>
EXHIBIT 1.20
-
Group/Joint Details
EXHIBIT 1.52
-
Call Center Costs
EXHIBIT 2.5
-
Sales Force Training Program
EXHIBIT 3.4(d)
-
Matters where Eyetech Possesses Special Expertise
or has Special Relationships
EXHIBIT 3.4(e)
-
Initially Planned Phase III(b)/IV Product Studies
EXHIBIT 5.1(a)
-
Development Programs for the AMD Product and the DME
Product
EXHIBIT 5.1(b)
-
AMD Agreed Development Costs and the DME Agreed
Development Costs
EXHIBIT 6.2
-
Marketing Budgets and Detailing Requirements
EXHIBIT 6.12(a)
-
Pre-Existing Clinical Supply Agreements
EXHIBIT 10.4
-
Third Party Agreements
EXHIBIT 12.6(a)(iii) -
Certain Product Liability Matters
EXHIBIT 12.6(b)(iii)(A) -
Eyetech 2002 Clinical Supply Costs
EXHIBIT 12.6(b)(iii)(B) -
Certain Third Party Intellectual Property
EXHIBIT 17.15
-
Joint Press Release
EXHIBIT 17.15(c)
-
Permitted Disclosures
</TABLE>
iv
<PAGE>
COLLABORATION AGREEMENT
THIS COLLABORATION AGREEMENT dated as of December 17, 2002 (the
"Execution Date"), between Pfizer Inc. ("Pfizer"), a corporation
organized under
the laws of the State of Delaware, having a business address at 235
East 42nd
Street, New York, New York 10017-5755, and Eyetech Pharmaceuticals,
Inc.
("Eyetech"), a corporation organized under the laws of the State of
Delaware,
having a business address at 500 Seventh Avenue, 18th Floor, New
York, New York
10018.
WHEREAS, the Parties have executed the Other Product-Related
Agreements
(as defined below) with respect to the aptamer known as
Macugen;
WHEREAS, the Parties have also executed the Equity Agreements
(as
defined below) with respect to purchases of shares of Eyetech
capital stock that
have been and/or will be made from Eyetech by Pfizer, Pfizer
Ireland
Pharmaceuticals, a Pfizer Affiliate organized under the laws of the
Republic of
Ireland ("Pfizer Ireland"), and/or another Pfizer Affiliate
designated by
Pfizer;
WHEREAS, the Parties have also executed the Detailing Services
Agreement (as defined below); and
WHEREAS, the Parties would like to set forth the terms and
conditions
pursuant to which they will collaborate in connection with the
worldwide
development and commercialization of products containing or based
on the Macugen
aptamer and with respect to certain other matters as described in
this Agreement
and in the Other Product-Related Agreements.
NOW, THEREFORE, the Parties agree as follows:
<PAGE>
ARTICLE 1
DEFINITIONS
The following terms, whether used in the singular or plural, shall
have
the following meanings:
1.1 "Act"
means both the United States Food, Drug and Cosmetic
Act, as amended, and the regulations promulgated under the
foregoing.
1.2
"Affiliate" means any Person directly or indirectly controlled
by, controlling or under common control with, a Party, but only for
so long as
such control shall continue. For purposes of this definition,
"control"
(including, with correlative meanings, "controlled by",
"controlling" and "under
common control with") means, with respect to a Person, possession,
direct or
indirect, of (a) the power to direct or cause direction of the
management and
policies of such Person (whether through ownership of securities or
partnership
or other ownership interests, by contract or otherwise), or (b) at
least 50% of
the voting securities (whether directly or pursuant to any option,
warrant or
other similar arrangement) or other comparable equity interests.
For the
avoidance of doubt, neither of the Parties shall be deemed to be an
"Affiliate"
of the other.
1.3 "AMD
Product" means a Product developed for use in the
treatment of age-related macular degeneration.
1.4 "API Bulk
Drug Substance Supplier" means a third-party
supplier of active pharmaceutical ingredient bulk drug substance
for Products
with which Eyetech or Pfizer enters into a supply agreement
pursuant to Section
6.12.
1.5 "Approval"
means receipt from FDA of approval to market a drug
product in the US Territory.
2
<PAGE>
1.6
"Bankruptcy Code" means 11 USC Sections 101-1330, as amended.
1.7
"beneficial ownership" (and other correlative terms) by a
Person means, with respect to any security: (a) such Person or any
of such
Person's Affiliates directly or indirectly owns such security; (b)
such Person
or any of such Person's Affiliates has the right to acquire such
security
(whether such right is exercisable immediately or only after the
passage of
time) pursuant to any agreement, arrangement or understanding
(whether or not in
writing) or upon the exercise of conversion rights, exchange
rights, rights,
warrants or options, or otherwise; or (c) ownership, direct or
indirect, by any
other Person with which such Person or any of such Person's
Affiliates has any
agreement, arrangement or understanding for the purpose of
acquiring, holding,
voting or disposing of such security; provided, however, that a
Person shall not
be deemed to have beneficial ownership of any security by virtue of
an
agreement, arrangement or understanding to vote such security that
arises solely
from a revocable proxy or consent given to such Person in response
to a public
proxy or consent solicitation made pursuant to, and in accordance
with, the
applicable rules and regulations of the Securities Exchange Act of
1934, as
amended.
1.8 "Business
Day" means a day that is not a Saturday, Sunday or a
day on which banking institutions in New York, New York are
authorized by Law to
remain closed.
1.9 "Call
Center" means the call center to be established by
Pfizer and substantially dedicated to receiving and answering
Product-related
inquiries and complaints from or on behalf of, as applicable,
Product-users,
physicians, managed care organizations, and others residing in the
US Territory.
3
<PAGE>
1.10
"Change in Control" means, with respect to a Party, an event
where:
(a)
any Person
or group of Persons (as the term "group"
is interpreted pursuant to Rule 13d-5 under the Securities Exchange
Act of 1934,
as amended) acquires beneficial ownership of capital stock of the
Party (other
than (x) directly from such Party or (y) from underwriter(s) of
such Party's
capital stock in a public offering) entitling the holder(s) thereof
to at least
a majority of the voting power of the then outstanding capital
stock of such
Party with respect to the election of directors of such Party,
or
(b) the Party
enters into a merger, consolidation,
reorganization or similar transaction with another Person (the
"Acquiring
Corporation") in which less than a majority of the voting power of
the
outstanding capital stock of such Party (if it is the surviving
entity) or of
the Acquiring Corporation (if it is the surviving entity) with
respect to the
election of directors following such transaction is held by Persons
who were
shareholders of such Party immediately prior to such transaction,
or
(c) the Party
sells to any Person(s) in one or more
related transactions properties or assets representing all or
substantially all
of the properties and assets of such Party.
1.11
"CMC" means the chemistry, manufacturing and controls section
of the Product NDA.
1.12
"Code" or "Codes" means the Code on Interactions with
Healthcare Professionals promulgated by the Pharmaceutical Research
and
Manufacturers of America (PhRMA), the American Medical Association
Guidelines on
Gifts to Physicians, and the PhRMA Principles on Conduct of
Clinical Trials and
Communication of Clinical Trial Results, as any of the foregoing
may be amended.
4
<PAGE>
1.13
"Commercially Reasonable Efforts" means, with respect to a
Product, commercially reasonable efforts, which in no event will be
less than
the efforts the Party required to make such efforts generally uses
(as
applicable in the context used in this Agreement) in developing,
seeking
Approvals, manufacturing, promoting, detailing and marketing its
other
pharmaceutical products (if any) that are comparable to such
Product, taking
into account product labeling or anticipated labeling, market
potential, past
performance (if any), economic return potential, medical and
clinical
considerations, the regulatory environment, and competitive market
conditions in
the therapeutic area, all as measured by the facts and
circumstances at the time
such efforts are due.
1.14
"Competing Product" means [**].
1.15
"Consumer Price Index" or "CPI" means the Consumer Price Index
- Urban Wage Earners and Clerical Workers, U.S. City Average, All
Items, 1982-84
= 100, published by the United States Department of Labor, Bureau
of Statistics
(or its successor equivalent index).
1.16
"Co-Promotion" means the joint marketing and promotion
(including without limitation Detailing) of the Products in the US
Territory as
described in Article 6. "Co-Promote" when used as a verb shall mean
to engage in
the activities described in Article 6.
1.17
"Co-Promotion Budget" is defined in Section 6.2.
1.18
"Co-Promotion Term" means the period from the Effective Date
until the later of (a) the expiration of the last to expire Valid
Claim (as such
term is defined in the License Agreement) in the United States of
America and
(b) 15 years after Launch of the last Product in the US Territory,
unless sooner
terminated as provided in this Agreement.
1.19
"Cost of Goods Sold" means Manufacturing Costs plus or minus
an adjustment to be mutually agreed by the Parties from time to
time for
variances between the standard cost
5
<PAGE>
component(s) of Manufacturing Costs and the actual costs incurred
by the Parties
that such standard cost component(s) are intended to cover.
1.20
"Detail" means a face-to-face contact of either an Eyetech or
Pfizer Sales Representative, as the case may be, with a medical
professional
with prescribing authority during which scientific and/or medical
information
about a Product is discussed. A Detail does not include a reminder
or sample
drop. With respect to certain group or institutional presentations,
or joint
details by Sales Representatives of both parties, Exhibit 1.20 sets
forth how
such presentations will be counted for determination of the number
of Details.
Details shall be measured by each Party's internal recording of
such activity,
provided that such measurement shall be on the same basis as the
recording
Party's measurement for its sales representatives detailing of such
recording
Party's other products (if any), consistently applied throughout
the
Co-Promotion Term. When used as a verb, the term "Detailing" means
to engage in
the activity of a Detail.
1.21
"Detailing Services Agreement" means the Detailing Services
Agreement dated as of the Execution Date between the Parties
relating to an
arrangement by which Eyetech may, at its option, detail for Pfizer
on a contract
basis Xalatan, Xalcom, and any other products approved for use in
the Field
containing latanoprost as an active ingredient, including without
limitation
Xalatan and Xalcom life-cycle products, that are owned by Pfizer or
its
Affiliates.
1.22
"Detailing Report" is defined in Section 6.4.
1.23
"Detail Requirement" means the number of Details that each
Party's Sales Representatives are required to perform in the US
Territory
pursuant to a Marketing Plan.
1.24
"Development Costs" means the costs, including without
limitation Out-of-Pocket Costs in relation to the preclinical and
clinical
development of Products and the conduct
6
<PAGE>
of Product Studies and direct and identifiable variable personnel
costs in
relation to preclinical development of Products and the conduct of
preclinical
Product Studies, as set forth in each relevant Development Plan;
provided,
however, Development Costs shall not include any (a) Out-of-Pocket
Costs paid by
either Party prior to December 1, 2002, (b) [**], or (c) except for
direct and
identifiable variable personnel costs explicitly provided for in
this Section
1.24, Internal Costs.
In addition, Development Costs shall include Out-of-Pocket Costs
and
direct and identifiable variable personnel costs of (w)
manufacturing clinical
supplies of Products, (x) process development for clinical and
commercial scale
manufacture of Products, including without limitation manufacturing
process
optimization in accordance with Section 6.12(h), (y) stability
studies and (z)
providing manufacturing transition support in accordance with
Section 6.12.
1.25
"Development Plan" is defined in Section 5.1.
1.26
"Distribution Agreement" means the Distribution Agreement
dated as of the Execution Date between the Parties relating to the
provision by
Pfizer of Product distribution services in the US Territory on a
contract basis
for Eyetech.
1.27
"DME Product" means a Product developed for use in the
treatment of diabetic macular edema.
1.28
"DOJ" means the United States Department of Justice.
1.29
"Effective Date" means the HSR Clearance Date.
1.30
"Equity Agreements" means (a) the Series D Preferred Stock
Purchase Agreement dated as of the Execution Date, to which the
Parties and
Pfizer Ireland are parties, and (b) the Amended and Restated
Investors' Rights
Agreement, the Amended and Restated Right of First
7
<PAGE>
Refusal and Co-Sale Agreement and the Amended and Restated Voting
Agreement,
each to be entered into by Eyetech and Pfizer Ireland after the
Execution Date
in accordance with the aforementioned Series D Preferred Stock
Purchase
Agreement.
1.31
"FDA" means the United States Food and Drug Administration and
any successor agency thereto.
1.32
"Field" means the prevention, treatment or control of all
ophthalmic diseases or conditions.
1.33
"Fill and Finish Services Supplier" means a third party
supplier of fill and finish services necessary to produce Products
in finished
(i.e., ready for administration to patients) form for sale in the
US Territory
with which Eyetech or Pfizer enters into an agreement pursuant to
Section 6.12.
1.34
"First Approval" means the first Approval of a Product.
1.35
"FTC" means the United States Federal Trade Commission.
1.36
"Funded Inventory Build Costs" means the amount of pre-Launch
Manufacturing Costs funded by each of the Parties pursuant to
Section 6.12(f).
Each Party's Funded Inventory Build Costs shall be increased by
amounts funded
pursuant to Section 6.12(f) and reduced by the Inventory Build
Credit applied
pursuant to Section 8.3.
1.37
"GAAP" means accounting principles generally accepted in the
United States of America.
1.38
"GMP" means the Good Manufacturing Practices regulations
promulgated by the FDA under the Act as of the time of manufacture
of the
applicable Products.
1.39
"Governmental Authority" means any court, agency, department
or other instrumentality of any foreign, federal, state, county,
city or other
political subdivision.
8
<PAGE>
1.40
"HSR Act" means the Hart-Scott-Rodino Antitrust Improvements
Act of 1976, as amended (15 U.S.C. Sec. 18a), and the rules and
regulations
promulgated thereunder.
1.41
"HSR Clearance" means either (a) early termination of the
applicable waiting period under the HSR Act with respect to the HSR
Filings or
(b) expiration of the applicable waiting period under the HSR Act
with respect
to the HSR Filings.
1.42
"HSR Clearance Date" means the earlier of (a) the date on
which the FTC or DOJ shall notify Eyetech and Pfizer of early
termination of the
applicable waiting period under the HSR Act or (b) the day after
the date on
which the applicable waiting period under the HSR Act expires.
1.43
"HSR Filings" means the filings by Pfizer and Eyetech with the
FTC and the Antitrust Division of the DOJ of a Notification and
Report Form for
Certain Mergers and Acquisitions (as that term is defined in the
HSR Act) with
respect to the matters set forth in the Transaction Agreements,
together with
all required documentary attachments thereto.
1.44
"IND" means an investigational new drug application filed with
the FDA with respect to a Product.
1.45
"Internal Costs" means a Party's and/or its Affiliate's costs
and expenses for overhead, personnel, rent, depreciation and
amortization,
utilities, equipment leases, general and administrative expenses
and similar
items.
1.46
"Know-How" means unpatented technical and other information
which is not known to the public, including information comprising
or relating
to concepts, discoveries, data, designs, formulae, methods, models,
assays,
research plans, procedures, designs for experiments and tests and
results of
experimentation and testing (including results of research or
development),
together with processes, including manufacturing processes,
specifications,
9
<PAGE>
techniques, chemical, pharmacological, toxicological, clinical,
analytical and
quality control data, trial data, case report forms, data analyses,
reports or
summaries, including documents (which shall include paper,
notebooks, books,
files, ledgers, records, tapes, discs, diskettes, CD-ROM and any
other media on
which the foregoing information can be permanently stored)
containing any of the
foregoing information. The fact that an item is known to the public
shall not be
taken to exclude the possibility that a compilation including the
item, and/or a
development related to the item, is (or remains) not known to the
public.
1.47
"Launch" means the initial shipping of a Product as a, or for,
commercial sale to an unaffiliated third party, excluding any
shipping for test
marketing, clinical trial purposes or compassionate or similar
use.
1.48
"Law" or "Laws" means all laws, statutes, rules, Codes,
regulations, orders, judgments and/or ordinances of any
Governmental Authority.
1.49
"License Agreement" means the License Agreement dated as of
the Execution Date between the Parties.
1.50
"Major Country" means France, Germany, Italy, Spain or the
United Kingdom.
1.51
"Manufacturing Costs" means costs that relate to (a) Products
supplied by a non-Affiliate third party, or (b) Products
manufactured directly
by a Party or an Affiliate of a Party. In the case of (a),
Manufacturing Costs
shall be a "standard cost" per unit, which standard cost shall
include (i) the
amount paid to such a third party, plus (ii) the manufacturing
Party's (i.e.,
the Party then responsible for manufacturing pursuant to Section
6.12) direct
and identifiable Internal Costs and Out-of-Pocket Costs, which
amounts shall be
subject to the other Party's reasonable approval, incurred or
accrued by the
manufacturing Party in connection with quality assurance, supply
chain
management, and similar activities comprising the manufacturing
10
<PAGE>
Party's oversight of the manufacturing process of the non-Affiliate
third party.
In the case of (b), Manufacturing Costs shall be a "standard cost"
per unit,
which standard cost shall include the cost of raw materials, labor,
and other
direct and identifiable variable costs and appropriate costs for
equipment
pools, plant operations and plant support services. The costs for
plant
operations and support services would include utilities,
maintenance,
engineering, safety, human resources, finance, plant management and
other
similar activities. The plant operations and support services costs
would be
allocated on a mutually agreed basis consistent with GAAP. Costs
which cannot be
identified to a specific activity supporting product manufacturing,
such as
charges for corporate overhead which are not controllable by the
manufacturing
plant, shall not be included in standard cost.
1.52
"Marketing Expenses" means all Out-of-Pocket Costs paid or
accrued by a Party pursuant to a Marketing Plan and directly
related to the
Co-Promotion of the Products in the US Territory, including those
in connection
with:
(a) [**]
(b) [**] for the Products [**]; (iii) [**] the Products [**];
(iv) [**]; (v) [**] the Products [**]; and (vi) [**] the Products
[**]. With
respect to [**] as determined in accordance with [**] subject to
[**]; and
(c) [**] the Products.
Notwithstanding the foregoing, Marketing Expenses shall not include
any
costs or expenses incurred prior to the Execution Date, and shall
include (i)
Eyetech's Out-of-Pocket Costs and direct and identifiable variable
personnel
costs incurred pursuant to Section 6.13 and amounts paid by Eyetech
to Pfizer
pursuant to the Distribution Agreement and (ii) filing or other
user fees or
maintenance fees paid to the FDA in order for Eyetech or Pfizer, as
the case may
be, to obtain or maintain regulatory approval for the Products.
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All other Out-of-Pocket Costs incurred in the Co-Promotion of
the
Products in the US Territory, but not specifically identified
above, but which
have been approved by the CSC or provided for in the Marketing
Plan, shall be
accounted for and deemed Marketing Expenses for all purposes of
this Agreement.
1.53
"Marketing Plan" is defined in Section 6.2.
1.54
"NDA" means a New Drug Application filed with the FDA with
respect to a Product.
1.55
"Net Sales" means the gross amounts billed or invoiced by
Eyetech and its Affiliates for Products in the US Territory, less
the following
deductions:
(a) trade,
quantity and cash discounts allowed, but
expressly excluding discounts or allowances offered as part of a
package of
products that includes a Product sold by Eyetech or its
Affiliates;
(b) refunds,
chargebacks and any other allowances which
effectively reduce the net selling price;
(c) actual
product returns, credits and allowances
allowed to customers, and actual bad debts;
(d) rebates
actually paid or credited to any governmental
agency (or branch thereof) or to any third party payor,
administrator or
contractee;
(e) discounts
mandated by, or granted to meet the
requirements of, applicable state, provincial or federal law,
wholesaler,
including required chargebacks and retroactive price
reductions;
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(f)
transportation, freight, postage charges and other
charges, such as insurance, relating thereto, in each case included
as a
specific line item on an invoice to such third parties; and
(g) taxes,
excises or other governmental charges upon or
measured by the production, sale, transportation, delivery or use
of goods, in
each case included as a specific line item on an invoice to such
third parties.
If any such sales to third parties are made in transactions that
are
not at arm's length between the buyer and the seller, then the
gross amount to
be included in the calculation of Net Sales shall be the amount
that would have
been invoiced had the transaction been conducted at arm's length.
Such amount
that would have been invoiced shall be determined, wherever
possible, by
reference to the average selling price of the relevant Product in
arm's-length
transactions in the US Territory.
If Eyetech or its Affiliate sells a Product in unfinished form to
a
third party for resale, then the gross amount to be included in the
calculation
of Net Sales arising from such sale shall be the amount invoiced by
the third
party upon resale, in lieu of the amounts invoiced by Eyetech or
its Affiliates
when selling the Product in unfinished form. Otherwise, where
Eyetech or its
Affiliate sells a Product in finished form to a third party that
does not
require a sublicense under the Eyetech Patents for further resale
(each such
third party hereinafter a "Distributor"), the amount to be included
in the
calculation of Net Sales shall be the price invoiced from Eyetech
or its
Affiliate to the third party, not the amount invoiced by the third
party upon
resale.
If, in addition to or in lieu of a transfer price paid for
quantities
of Product supplied, any Distributor provides consideration to
Eyetech or its
Affiliate in connection with any Product or the Distributor's
rights or
relationship with Eyetech or its Affiliate in relation thereto,
then such
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consideration shall be included in the calculation of Net Sales in
the Quarter
in which it becomes due to Eyetech or its Affiliate (as
applicable).
Notwithstanding the foregoing, amounts received by Eyetech or
its
Affiliates (x) for the sale of Products among Eyetech and its
Affiliates for
resale or (y) for the sale of Products by Eyetech or its Affiliates
to Pfizer or
its Affiliates or sublicensees for resale in the ROW Territory,
shall not be
included in the computation of Net Sales hereunder.
Net Sales shall be determined from books and records maintained
in
accordance with GAAP, consistently applied throughout the
organization and
across all products of the entity whose sales of Product are giving
rise to Net
Sales.
1.56
"Other Product-Related Agreements" means the License
Agreement, the Distribution Agreement and the Regulatory Services
Agreement.
1.57
"Out-of-Pocket Costs" means costs and expenses paid to third
parties (or payable to third parties and accrued in accordance with
GAAP), other
than Affiliates or employees, by either Party after the Execution
Date (or, in
the case of Development Costs, after December 1, 2002).
1.58
"Party" means either Eyetech or Pfizer; "Parties" means both
Eyetech and Pfizer.
1.59
"Person" means any natural person or any corporation, company,
partnership, joint venture, firm or other entity, including without
limitation a
Party.
1.60
"Pharmacia Merger" means the merger contemplated by the
Agreement and Plan of Merger dated as of July 13, 2002 among
Pfizer, Pilsner
Acquisition Sub Corp., a wholly owned Subsidiary of Pfizer, and
Pharmacia
Corporation ("Pharmacia") (as the same may be amended or
supplemented or
restated from time to time, the "Pharmacia Merger Agreement")
providing for the
merger of Pilsner Acquisition Sub Corp. with and into
Pharmacia.
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1.61
"Phase III Clinical Study" means a Product Study with study
design and statistical power intended to meet the requirement for
Approval by
the FDA.
1.62
"Phase III(b)/IV Product Study" means a clinical study
designed to support or profile a Product or intended to be the
basis of a
post-approval Product filing, including without limitation proposed
label
changes not explicitly described in Section 1.64 below, but not
including any
clinical study intended to be the basis of any regulatory filing
for initial FDA
or other Governmental Authority approval for marketing of Products
or conducted
as a condition to the prior receipt of any regulatory approval for
marketing of
Products. Phase III(b)/IV Product Studies shall include, without
limitation,
epidemiological studies and modeling and pharmacoeconomic
studies.
1.63
"Product" means any product, that (a) contains or is based on
the anti-VEGF aptamer known as "Macugen" or "EYE001", including any
metabolites
or prodrugs of such aptamer or any hydrates, conjugates, salts,
esters, isomers,
polymorphs or analogues of any of the foregoing, either alone or in
combination
with one or more other therapeutically active substances, and (b)
is for use in
the Field; including for the avoidance of doubt any AMD Product,
DME Product or
other product developed in accordance with the terms of this
Agreement for any
indication in the Field other than AMD or DME, or as a new
un-pegylated
formulation of any such AMD Product, DME Product or other product
(each such
other product, an "Additional Developed Product").
1.64
"Product Studies" means clinical, preclinical, safety, and
other studies that are designed to support FDA or other
Governmental Authority
approval for marketing of Products. For the avoidance of doubt,
Product Studies
shall not include [**], but shall include [**].
1.65
"PSURs" means periodic safety update reports.
15
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1.66
"Quarter" means (i) with respect to Eyetech, each of the
periods ending on March 31, June 30, September 30 and December 31,
and (ii) with
respect to Pfizer each of the periods ending at the end of each of
the four (4)
thirteen (13) week periods as used by Pfizer as reported in its
filings with the
Securities and Exchange Commission, the first such period
commencing on January
1 of any year, and the terms "Eyetech Quarter" and "Pfizer Quarter"
shall be
construed accordingly.
1.67
"Regulatory Costs" means the costs, including without
limitation the Out-of-Pocket Costs and direct and identifiable
variable
personnel costs, in relation to making or supporting regulatory
filings in the
US Territory; provided, however, Regulatory Costs shall not include
any (a)
Out-of-Pocket Costs paid by either Party prior to the Execution
Date, (b) costs
of making or supporting regulatory filings in the ROW Territory, or
(c) except
for direct and identifiable variable personnel costs explicitly
provided for in
this Section 1.67, Internal Costs. In addition, Regulatory Costs
shall include
amounts paid by Eyetech to Pfizer under the Regulatory Services
Agreement.
1.68
"Regulatory Services Agreement" means the Regulatory Services
Agreement dated as of the Execution Date between the Parties
relating to the
provision by Pfizer of specified regulatory services in the US
Territory on a
contract basis for Eyetech.
1.69
"ROW Territory" means all countries in the world other than
the US Territory.
1.70
"Sales Representative" means an individual who engages in
Detailing and other promotional efforts in the Field with respect
to the
Products and who has been trained and is employed by either Pfizer
or Eyetech or
their respective Affiliates.
1.71
"Senior Executive" means, with respect to Eyetech, the Chief
Executive Officer of Eyetech, and with respect to Pfizer, a
corporate officer of
Pfizer with senior decision-making
16
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authority; "Senior Executives" means both such officers. Pfizer
shall initially
designate Karen Katen as its Senior Executive.
1.72
"Specifications" means the specifications for the manufacture
and packaging of the Products consistent with the NDA.
1.73
"Subsidiary" means, with respect to a Party, a majority or
wholly-owned direct or indirect subsidiary of such Party.
1.74
"Territory" means the US Territory and the ROW Territory.
1.75
"Trademark" means (i) MACUGEN and (ii) any other trademark
associated with the Products that may be selected by the Parties in
accordance
with Section 10.1(e), excluding the respective corporate names and
logos of the
Parties.
1.76
"Transaction Agreements" means this Agreement, the Other
Product-Related Agreements, the Equity Agreements and the Detailing
Services
Agreement.
1.77
"US Territory" means the United States of America, including
its territories, possessions and Puerto Rico.
1.78
"Xalatan" means latanoprost ophthalmic solution which is
presently sold by Pharmacia under the trademark Xalatan(R) as a
single entity.
1.79
"Xalcom" means product containing as active ingredients
latanoprost and timolol and which is presently sold by Pharmacia
under the
trademark Xalcom(R) as a single entity.
1.80
"Year" means each calendar year during the Co-Promotion Term.
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ARTICLE 2
CO-PROMOTION OF PRODUCTS IN THE US TERRITORY
2.1
Co-Promotion. Subject to the terms of this Agreement, the
Parties shall Co-Promote Products in the US Territory
co-exclusively with each
other as provided in this Agreement.
2.2 License
Grants. Each Party's rights under intellectual
property rights owned or controlled by the other Party, with
respect to the
development, manufacture and Co-Promotion of Products in the US
Territory, are
as set forth in the License Agreement.
2.3 Compliance
With Law. Both Pfizer and Eyetech shall Co-Promote
the Products in the US Territory in accordance with applicable Law,
the terms of
this Agreement and the then-current Marketing Plan. Neither Party
shall be
required to undertake any action or inaction, or to incur
expenditures in
connection with any such action or inaction under this Agreement
that it
believes, in good faith, may violate any Law.
2.4 Detailing
Obligations. Subject to Exhibit 6.2, the Detailing
obligations of the Parties in respect of the Products shall be as
set out in the
then-current Marketing Plan.
2.5
Training.
(a) Pfizer
shall, at its sole expense, provide initial
sales and product training in connection with the first Product
Detailed by
Eyetech Sales Representatives in the US Territory pursuant to this
Agreement for
up to forty (40) Eyetech Sales Representatives. Eyetech may also
elect to have
Pfizer provide such initial sales and product training to an
additional fifteen
(15) Eyetech Sales Representatives, in which case Eyetech shall
reimburse Pfizer
for Pfizer's Out-of-Pocket Costs and direct and identifiable
variable personnel
costs incurred in connection with such training for such additional
Sales
Representatives. Such training shall, at Eyetech's option,
18
<PAGE>
be conducted in multiple program sessions; provided that Pfizer
shall not be
required to provide more than four (4) separate program sessions,
the first
three (3) of which shall be for not less than ten (10) Eyetech
Sales
Representatives each. A description of Pfizer's current initial
sales force
training program is described in Exhibit 2.5. Such program is
subject to
revision from time to time by Pfizer, provided that the initial
training
provided by Pfizer to Eyetech from time to time shall be the same
as the initial
training that Pfizer contemporaneously provides to Pfizer's
Sales
Representatives that Detail Products. Pfizer will provide ongoing
training
relating to Products for the trainers of Eyetech's Sales
Representatives. All
training programs for Eyetech's Sales Representatives other than
the initial
sales and product training will be the responsibility of Eyetech,
at its sole
expense; provided, however, that Pfizer will provide follow-up
training for such
Eyetech Sales Representatives at Eyetech's reasonable request,
provided that
Eyetech reimburses Pfizer for the reasonable costs and expenses
incurred by
Pfizer in connection with such follow-up training. In order to
coordinate the
training of Eyetech Sales Representatives with training of Pfizer
Sales
Representatives, any training provided by Pfizer to Eyetech
Sales
Representatives pursuant to this Section 2.5(a) shall take place at
times and at
locations reasonably selected by Pfizer in consultation with
Eyetech.
(b) Pfizer and
Eyetech shall, each at its own expense
(except as otherwise set forth in Section 2.5(a)), comply with any
training plan
for the Products contained in the applicable Marketing Plan.
(c) If a Party
organizes Co-Promotion-related meetings of
its employees (such as periodic briefings of its Sales
Representatives), it will
make reasonable efforts to keep the Product-related portions of
such meetings
independent from other matters and to give the other Party advance
notice of
such meetings. If requested by the other Party, the Party
organizing such
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<PAGE>
meeting will permit Sales Representatives of the other Party to
attend and
participate in such meetings or such portions thereof which relate
to the
Co-Promotion of Products.
2.6
Promotional Materials and Call Center Communications. The
Parties will only utilize promotional, advertising, communication
and
educational materials relating to the Products in the US Territory
(collectively
"Promotional Materials") and only conduct promotional activities
for the
Products which, in each case, have been approved in the Marketing
Plan or
otherwise by the CSC (as defined in Section 3.1). All Promotional
Materials
shall name and feature both Parties with equal prominence. All
promotional
activities conducted by the Parties shall be consistent with the
Promotional
Materials so approved and the then-current Marketing Plan. Promptly
after the
Effective Date, the Parties will mutually agree upon procedures
whereby
designated representatives of each of them representing the
marketing, medical,
regulatory and legal functions, will meet, whether in person, by
telephone or by
videoconference, in order to discuss all promotional activities
(except for
Detailing) and Promotional Materials prior to final approval
thereof by the CSC.
In addition, as a prominent part of each communication with
customers and other
third parties, the Call Center shall clearly identify the Products
as joint
products of Eyetech and Pfizer. Eyetech shall own all rights to all
Promotional
Materials, including all copyrights thereto, and Pfizer hereby
assigns to
Eyetech all rights, title and interests of Pfizer in and to such
Promotional
Materials, including without limitation all copyright interests of
Pfizer
therein. Unless and until Promotional Materials are approved by the
CSC for
publication or other general dissemination, each Party shall
maintain them in
confidence pursuant to the terms of Article 11.
2.7 Samples.
The Parties, through the CSC, shall determine whether
it is necessary and appropriate to undertake a sampling program for
the first
Product and, if so, the appropriate
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terms and allocation of responsibilities for satisfying such
sampling program;
provided that any samples will be allocated fairly between the
Parties'
respective Sales Representatives in accordance with the Detailing
arrangements
set forth in the Marketing Plan; and provided further that each
Party shall be
responsible, at its sole expense, for (a) accounting for samples
held, disposed
of or distributed by such Party or its Sales Representatives, (b)
destroying and
disposing of samples after the latest date on which such samples
are usable and
(c) complying with the requirements of all applicable Laws,
including without
limitation the requirements of the Prescription Drug Marketing Act
of 1987, as
amended.
2.8
Distribution and Booking of Sales. Eyetech shall be
responsible for distribution, invoicing, credit and collection for
the Products
in the US Territory. Eyetech will book all sales of Products in the
US
Territory; provided that this Section 2.8 shall not be construed as
an assurance
by Pfizer to Eyetech regarding the appropriate accounting treatment
of such
sales.
2.9 Contract
Sales Forces. Without the consent of the other Party,
neither Pfizer nor Eyetech may use any contract sales force to
Co-Promote or
Detail any Product.
2.10
Delivery Technology Development Agreement. Promptly after the
Effective Date, the Parties shall in good faith discuss entering
into a separate
agreement to provide for the development by the Parties of
additional Product
delivery technology. The Parties intend to provide in such
agreement for a
sharing between the Parties of the costs and benefits of developing
and
commercializing such additional delivery technology on the same
basis as
development costs and commercialization benefits are shared under
this Agreement
and the License Agreement; provided that, for the avoidance of
doubt, it is
agreed that neither Party would be required to make any upfront
license fee
payments to the other Party in connection with such separate
agreement.
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ARTICLE 3
MANAGEMENT OF ALLIANCE
3.1
Committee/Subcommittees. In order to fulfill the objectives of
this Agreement, the Parties agree to establish a Joint Operating
Committee
("JOC"), a Commercialization Subcommittee ("CSC"), a Clinical
Development/Regulatory Subcommittee ("CDRSC"), and a Manufacturing
Subcommittee
("MSC"), and such other committees and subcommittees as may be
established by
mutual consent of Eyetech and Pfizer. Each committee and
subcommittee shall have
two co-chairpersons, one designated by each of Eyetech and Pfizer.
All decisions
of the committees and subcommittees shall be by a vote of the
co-chairpersons,
each co-chairperson having one vote, and all decisions shall be by
unanimous
consent of the co-chairpersons.
3.2 Meetings.
The chairpersons of the JOC, CSC, CDRSC, MSC, or any
other committee or subcommittee, shall call meetings quarterly, or
as otherwise
requested by one of the Parties. Meetings may be held in person, by
telephone,
or by video conference call, and the location of each meeting shall
alternate
between sites located in New York, New York selected by each
co-chairperson.
Additional participants may be invited by any representative to
attend meetings
where appropriate. The Parties shall cause their respective
representatives on
the committees and subcommittees to use diligent efforts, acting in
good faith,
to resolve all matters presented to them as expeditiously as
possible.
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3.3 Clinical
Development/Regulatory Subcommittee.
(a) The CDRSC
shall consist of research and development,
commercial, regulatory and marketing/medical managers (as needed)
from each of
Eyetech and Pfizer, each of which shall confirm to the other its
designees. The
CDRSC will establish a clinical development working group that
shall be
responsible for:
(i) Preparing
annual Development Plans;
(ii)
Monitoring progress of all Product Studies
in the Territory (including reviewing costs and activities against
the annual
Development Plan);
(iii)
Facilitating the exchange of all development
information and data relating to all Product Studies in the
Territory;
(iv)
Review and approval of statistical analysis
plans and protocols for all Product Studies in the Territory and
revising any
investigator's brochure(s); and
(v) Providing
updates on its activities and
achievements to the JOC.
(b) The CDRSC
will also establish a regulatory working
group that will be responsible for:
(i)
Overseeing, monitoring and coordinating all
regulatory (FDA) aspects of the US Territory Product Approval
program, including
all US Territory regulatory actions, communications and filings
(including
matters pertaining to Product labeling) and submissions (including
filings and
submissions of supplements and amendments to FDA with respect to
the Products);
(ii)
Establishing the schedule and implementation
strategy for all FDA filings;
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<PAGE>
(iii)
Coordinating preparation for and attendance
at FDA advisory committee meetings;
(iv)
Coordinating responses to additional FDA
requirements and FDA inquiries;
(v) Proposing,
overseeing and agreeing upon a
regulatory strategy and plan for obtaining regulatory approvals for
the Products
in the Territory;
(vi)
Facilitating the exchange of all regulatory
information and data relating to Products in the Territory;
(vii)
Facilitating the exchange of information in
conjunction with Section 4.3 of this Agreement in order to ensure
that
significant issues concerning adverse event information and safety
issues are
addressed consistently among Governmental Authorities in the
Territory; and
(viii) Providing
updates on its activities and
achievements to the JOC.
(c) Neither
Party shall make any change to any annual
Development Plan without the prior approval of the CDRSC, and all
Development
Plans and Development Costs provided therein shall be consistent
with the terms
of this Agreement. If the CDRSC is unable to reach a decision on
any issue
within fifteen (15) Business Days after presentation, either Party
may refer the
issue to the JOC for resolution.
(d) Following
a referral to the Senior Executives of the
Parties pursuant to Section 3.7 below, the final decision-making
authorities set
out in Sections 3.3 (e), (f), (g) and (h) shall apply.
(e) [**] shall
have the final decision-making authority
for matters relating to [**] for such Product [**] to such Product
[**];
provided, however, that [**] shall have the final
24
<PAGE>
decision-making authority as to [**], provided that [**]. For
purposes of the
previous sentence, [**]; provided, however, that [**].
(f) [**] shall have
final decision-making authority with
respect to [**] the Parties shall [**]. Except as otherwise set
forth in this
Agreement, [**] shall have final decision-making authority with
respect to [**].
(g)
Notwithstanding the Parties' joint approval rights
set forth in Section 3.3(f), [**] may not prevent [**] from [**]
for the
applicable Product, [**].
(h) Subject to
Pfizer's fulfillment of its obligations
under the Regulatory Services Agreement, which shall require Pfizer
to perform
its obligations thereunder in a commercially reasonable manner, in
the event
that Eyetech materially fails to discharge its regulatory
obligations in the US
Territory in a commercially reasonable manner applying accepted
pharmaceutical
industry standards, and in compliance with all Laws, and fails to
cure such
failure following written notice thereof from Pfizer and a
reasonable
opportunity to cure, then the final decision-making authority with
respect to
[**] the Products [**] shall be transferred to Pfizer for the
balance of the
Co-Promotion Term; provided that in the event that after such
transfer (x)
Pfizer closes a Divestiture Transaction pursuant to Section 17.11
or (y)
materially fails to discharge its regulatory obligations in the US
Territory in
a commercially reasonable manner applying accepted pharmaceutical
industry
standards, and in compliance with all Laws, and fails to cure such
failure
following written notice thereof from Eyetech and a reasonable
opportunity to
cure, then the final decision-making authority with respect to [**]
the Products
[**] shall thereafter be exercised jointly by the Parties for the
balance of the
Co-Promotion Term.
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3.4
Commercialization Subcommittee.
(a) The CSC
shall consist of members from each of Eyetech
and Pfizer, each of which shall confirm to the other its designees.
The CSC
shall be responsible with respect to the US Territory for:
(i) Preparing
and implementing annually the
Marketing Plan;
(ii)
Monitoring progress under and compliance
with the Marketing Plan;
(iii)
Coordinating with the CDRSC with respect to
regulatory issues and future Product development activities to be
undertaken
pursuant to the Development Plans;
(iv)
Developing positioning and market strategies
consistent with the Marketing Plan, including decisions to seek or
include any
new indication, formulation or usage for the Products, such as for
life cycle
management;
(v) Developing
advertising material and
strategies and promotional materials for the Parties' Sales
Representatives for
the Products, designing packaging, and planning and overseeing
educational and
professional symposia and speaker and activity programs for the
Products in the
US Territory;
(vi)
Providing updates on the CSC's activities
and achievements to the JOC; and
(vii)
Discussing the prices at which the Products
will be sold to unaffiliated third parties throughout the
Territory.
(b) Following
a referral to the Senior Executives of the
Parties pursuant to Section 3.7 below, the final decision-making
authorities set
out in Sections 3.4(c), (d) and (e) shall apply.
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(c) Subject to
Sections 3.4(d), (e) and (f) below, Pfizer
shall have final decision-making authority with respect to
[**]:
(i) activities
[**];
(ii) [**]
(iii) [**] the Products; and
(iv) [**], including [**],
(d) [**] shall have final decision-making authority with
respect to:
(i) [**] Eyetech shall
[**]; and
(ii) [**] Eyetech [**]
(e)
The Parties shall mutually agree upon [**] Products [**]
covered by [**] shall have [**].
(f) Notwithstanding the provisions of Section 3.4(c), but
subject to the provisions of Section 3.4(g), in the event that
Pfizer closes a
Divestiture Transaction pursuant to Section 17.11, the final
decision-making
authority with respect to all US Territory marketing and other
commercial
activities for the Products pursuant to this Section 3.4, [**]
Eyetech [**]
pursuant to [**] shall thereafter be exercised jointly by the
Parties for the
balance of the Co-Promotion Term.
(g) All
Marketing Plans shall be consistent with the
terms of this Agreement. If the CSC is unable to reach a decision
on any issue
within fifteen (15) Business Days after presentation, either Party
may refer the
issue to the JOC for resolution.
3.5
Manufacturing Subcommittee.
(a) The MSC
shall consist of members from each of Eyetech
and Pfizer, each of which shall confirm to the other its designees.
The MSC
shall be responsible for:
(i) Overseeing
manufacturing activities underway
as of the Effective Date, including formulation development,
product
characterization studies, stability studies, and management of
clinical supplies
of the Products;
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<PAGE>
(ii)
Overseeing the manufacturing of registration
batches of Product;
(iii)
Overseeing process development plans;
(iv)
Monitoring worldwide quality assurance
efforts and ensuring that all Products are manufactured in
accordance with the
Parties' quality standards;
(v)
Overseeing supply
relationships with any
third party manufacturers;
(vi)
Subject to Section 4.1(c), review of the CMC
section of the NDA for each Product, provided that the time period
for reviewing
any such CMC section shall, notwithstanding the provisions of
Section 4.1(c), be
thirty (30) days from the date on which Eyetech, through the CDRSC,
provides
Pfizer with a draft of the NDA pursuant to Section 4.1(c);
(vii)
Overseeing manufacture of the Products;
(viii) Reviewing
and approving Specifications for
purposes of the NDA and for Launch;
(ix)
Commencing and overseeing any new
manufacturing activities, including Product manufacturing process
validation
prior to NDA approval and any pre-approval inspection of the
Product
manufacturing subcontractors;
(x)
Coordinating with the CSC and CDRSC as
appropriate;
(xi)
Preparation for FDA inspections and ensuring
adherence to compliance standards;
(xii)
Evaluating the forecasts provided in each
Marketing Plan as well as inventory levels for the Product and
future logistic
strategies and capacity planning;
28
<PAGE>
(xiii) Reviewing
quality-related issues concerning
the Product or any component thereof; and
(xiv)
Providing updates on the MSC's activities
and achievements to the JOC.
(b) If the MSC
is unable to reach a decision on any issue
within fifteen (15) Business Days after presentation, either Party
may refer the
issue to the JOC for resolution. Following a referral to the Senior
Executives
of the Parties pursuant to Section 3.7 below, [**]shall have
final
decision-making authority with respect to [**]; provided that:
(i) Pfizer
shall [**] any agreement [**] entered
into [**] (ii) [**] Pfizer [**] and/or [**] that otherwise would
[**], and
Pfizer [**] pursuant to this Section 3.5 [**],
(iii) [**]
Pfizer [**] pursuant to Section 17.11,
[**],
(iv)
[**] the Parties, and
(v)
[**] all
Products [**].
3.6 Joint Operating Committee.
(a) The Joint
Operating Committee ("JOC") shall consist
of an equal number of members from each of Eyetech and Pfizer. Each
of Eyetech
and Pfizer shall confirm to the other its designees. At least one
of Pfizer's
designees shall be the Vice President in Pfizer's Pharmaceuticals
Group with
global responsibility for the therapeutic area covering the
Products. The JOC
shall address all of the significant and strategic issues within
the purview of
the various subcommittees, and shall be responsible for resolving
any issues
referred by the subcommittees. The JOC will be presented with
updates on the
activities and achievements of the subcommittees. All decisions of
the JOC will
be unanimous votes of the co-chairpersons.
29
<PAGE>
(b) If the JOC
is unable to resolve any issue within ten
(10) Business Days after presentation, either Party may refer the
issue to the
Senior Executives for resolution pursuant to Section 3.7.
3.7 Deadlocks.
If for any reason the JOC cannot resolve any matter
properly referred to it, either Party may refer the matter to the
Senior
Executives for resolution. If after discussing the matter in good
faith and
attempting to find a mutually satisfactory resolution to the issue,
the Senior
Executives fail to come to consensus within five (5) Business Days
of the date
on which the matter is referred to the Senior Executives, the
provisions of
Sections 3.3(d), 3.4(b), and 3.5(b), as applicable, shall apply and
resolutions
reached through such provisions shall be binding on the Parties;
provided that
such decisions are made in good faith and are consistent with the
provisions of
this Agreement.
3.8 Limitation
on Decision-Making Authority. Notwithstanding
anything to the contrary, none of the committees or subcommittees
contemplated
by this Article 3 nor any Senior Executive pursuant to this Article
3 shall be
entitled to determine any matters for which: (a) one or more of the
Parties is
allocated decision-making authority elsewhere in this Agreement; or
(b) such
determination would violate or permit the violation of any express
provision of
this Agreement, including, without limitation, the provisions of
Sections
3.3(f), 3.3(g), 3.3(h), 3.4(e) and 3.5(b) that provide explicitly
for mutual or
joint decision-making; or (c) this Agreement provides that neither
Party shall
have final decision-making authority or provides that a decision
shall not be
made without the approval or consent of a particular Party.
30
<PAGE>
ARTICLE 4
CLINICAL AND REGULATORY MATTERS
4.1 Clinical and
Regulatory Matters in the US Territory. This
Section 4.1 shall apply to clinical and regulatory matters relating
to Products
in the US Territory.
(a) Subject to
Section 3.3, [**]FDA for the Products [**]
for each of the Products.
(b) All NDAs
and Approvals within the US Territory
relating to the Products shall be the property of Eyetech and held
in the name
of Eyetech or its designated Affiliates. Eyetech's designated
representative
shall serve as the designated regulatory official for Products in
the US
Territory for purposes of receiving communications from the
FDA.
(c) Eyetech
will provide Pfizer with copies, which copies
may be in draft form, of the following submissions to the FDA
through the CDRSC.
If reasonably practicable, Eyetech will provide Pfizer with such
copies at least
fifteen (15) days prior to planned submission to the FDA by
Eyetech, whereupon
Pfizer shall provide comments to Eyetech regarding such submission
at least ten
(10) days prior to such planned submission, and, Eyetech shall
reasonably
consider the comments given by Pfizer prior to making such
submission:
(i) all annual
reports regarding a Product prior
to First Approval of such Product, including without limitation the
annual
reports required under 21 C.F.R. 312.33 as it may be amended;
and
(ii)
all other filings that are not subject to a
deadline imposed by the Act of less than twenty-one (21) days after
discovery of
an event that triggers the filing requirement and that are not
otherwise
required to be jointly agreed upon pursuant to Section 4.1(d).
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<PAGE>
(d) Eyetech
shall provide notice to Pfizer within two (2)
Business Days of discovery by Eyetech of any event that triggers an
FDA filing
requirement that is subject to a deadline imposed by the Act of
less than
twenty-one (21) days after the discovery of such an event. Eyetech
shall
promptly provide copies of any correspondence or other submission
subject to
this Section 4.1(d) to Pfizer, and the chairpersons of the CDRSC
shall discuss
in good faith and on a timely basis determine the most effective
and expeditious
means of responding to such FDA filing requirement.
(e) Eyetech
shall provide notice to Pfizer of any
additional FDA requirements which FDA may impose with respect to
the First
Approval, (including without limitation, additional clinical
studies) and of all
FDA inquiries requiring a response within two (2) Business Days of
receipt
thereof by Eyetech. Eyetech will promptly provide Pfizer with
copies of all
correspondence between Eyetech and FDA and copies of all FDA
contact reports
produced by Eyetech.
(f) In
connection with Sections 4.1(a), (b) and (c)
above, Eyetech shall provide Pfizer with notice of all meetings,
conferences,
and discussions (including without limitation, advisory committee
meetings and
any other meeting of experts convened by FDA concerning any topic
relevant to
the Products) scheduled with FDA concerning any pending NDA or
other regulatory
matters relating to the Products within two (2) Business Days after
Eyetech
receives notice of the scheduling of such meeting, conference, or
discussion.
Pfizer shall be entitled to have reasonable representation present
at all such
meetings. Eyetech and Pfizer, through the CDRSC, shall use
reasonable efforts to
agree (subject to Section 3.3(f)(i) to the extent applicable) in
advance on the
scheduling of such meetings and on the objectives to be
32
<PAGE>
accomplished at such meetings, conferences, and discussions and the
agenda for
the meetings, conferences, and discussions with FDA.
(g) Each Party
shall provide to the other Party, through
the CDRSC, on a timely basis copies of all material pre-clinical
and clinical
data compiled in support of an NDA or other regulatory filings in
the US
Territory with respect to the Products.
(h) Any
decision to initiate a recall or withdrawal of
Product in the US Territory shall be made by the CDRSC. Before the
CDRSC
initiates a recall or withdrawal, and upon the request for a recall
or
withdrawal by either Party, the Parties shall promptly and in good
faith discuss
the reasons therefor. Under no circumstances shall either Party
unreasonably
object to a recall or withdrawal requested by the other Party, and
neither Party
shall have any right to object to a recall or withdrawal requested
by the other
Party for failure of a Product to meet the Specifications, for
material safety
concerns or for noncompliance with the Act. In the event of any
recall or
withdrawal, Pfizer shall implement any necessary action, with
assistance from
Eyetech as reasonably requested by Pfizer.
4.2 Clinical
and Regulatory Matters in the ROW Territory. This
Section 4.2 shall apply to clinical and regulatory matters relating
to Products
in the ROW Territory.
(a) After the
Effective Date, Pfizer will assume sole
ownership, control of and responsibility for all regulatory filings
in the ROW
Territory, and Eyetech shall cooperate with Pfizer in connection
with such
filings as reasonably requested by Pfizer and at Pfizer's sole cost
and expense.
Prior to Pfizer taking over responsibility for contracting with API
Bulk Drug
Substance Supplier(s) and/or Fill and Finish Services Supplier(s)
or performing,
either directly or through Affiliates, services that otherwise
would be
performed by API Bulk Drug Substance Supplier(s) and/or Fill and
Finish Services
Supplier(s) in accordance with Section 6.12, Eyetech
33
<PAGE>
shall be responsible for providing Pfizer with Product samples for
use in
connection with regulatory filings relating to Products in the ROW
Territory at
Pfizer's sole cost and expense.
(b) All
regulatory approvals in the ROW Territory
relating to the Products shall be deemed the property of Pfizer and
held in
Pfizer's or its Affiliate's name.
(c) Pfizer's
rights under Sections 4.2(a) and (b) above
are subject to the following: Pfizer shall provide Eyetech with
notice of all
meetings, conferences, and discussions (including without
limitation, any
meeting of experts convened by regulatory authorities concerning
any topic
relevant to the Products) scheduled with Governmental Authorities
concerning any
material regulatory matters relating to the Products within two (2)
Business
Days after the scheduling of such meeting, conference, or
discussion. Eyetech
shall be entitled to have reasonable representation present at all
such
meetings. In addition, with respect to clinical and regulatory
matters in the
ROW Territory, Pfizer shall promptly provide Eyetech with (i)
copies of all
pre-clinical and clinical data compiled in support of regulatory
filings in the
ROW Territory, (ii) copies of all material regulatory
correspondence with EMEA,
as defined in the License Agreement, (or any Governmental Authority
in a Major
Country) and with Japanese Governmental Authorities, (iii) advance
copies of
material submissions to EMEA (or any Governmental Authority in a
Major Country)
and to Japanese Governmental Authorities, and the same opportunity
to comment in
advance on such submissions (and to have its comments reasonably
taken into
account) as Pfizer is provided with respect to the submissions to
FDA under
Section 4.1(c), provided, however, that an inadvertent failure by
Pfizer to
submit Eyetech advance copies pursuant to this Section 4.2(c)(iii)
shall not be
considered a material breach of this Agreement if Pfizer has
implemented
procedures reasonably designed to avoid any such failure and cures
any such
failure promptly after its discovery, (iv) notices of any
revocations of
34
<PAGE>
Product marketing approvals and any Product recalls, and (v)
reasonable
responses to inquiries by Eyetech regarding the regulatory approval
and
commercialization processes for each Product in the ROW Territory,
including
without limitation reasonable access to Pfizer personnel, documents
and files in
connection with such inquiries.
4.3 Inquiries,
Adverse Events, etc.
(a) Eyetech
and Pfizer shall be responsible for the
surveillance, receipt, evaluation, and reporting of product
complaints and
reports of adverse drug experiences, for the Products in the US
Territory and
the ROW Territory, respectively; provided, however, during the term
of the
Regulatory Services Agreement, Pfizer shall perform certain of such
US Territory
responsibilities on behalf of Eyetech under the terms of the
Regulatory Services
Agreement.
(b) Eyetech
shall be responsible for promptly
investigating Product complaints and reports of adverse drug
experiences and
other required safety information (e.g., PSURs and annual safety
reports)
associated with the use of any Product in the US Territory. As to
each Product,
Eyetech shall submit reports of all adverse drug experiences
associated with the
use of the Product(s) and other required safety information to the
FDA in
accordance with applicable Law. Eyetech shall submit a copy of each
such report
to Pfizer contemporaneously with its submission of the report to
FDA, or in
advance of such submission if, and as, reasonably necessary to
permit Pfizer to
comply with legal requirements applicable to it, if
practicable.
(c) Pfizer
shall promptly investigate Product complaints
and reports of adverse drug experiences and other required safety
information
(e.g., PSURs and annual safety reports) associated with the use of
any Product
in the ROW Territory. As to each Product, Pfizer shall submit
reports of all
adverse drug experiences associated with the use of the Product(s)
and other
required safety information to the applicable Governmental
Authorities in the
ROW
35
<PAGE>
Territory in accordance with applicable Law. Pfizer shall submit a
copy of each
such report to Eyetech contemporaneously with its submission of the
report to
the applicable Governmental Authority in the ROW Territory, or in
advance of
such submission if, and as, reasonably necessary to permit Eyetech
to comply
with legal requirements applicable to it, if practicable.
(d) Eyetech
shall have the sole responsibility for
revising the Product labeling for the US Territory, and Pfizer for
the ROW
Territory, as needed, to adequately warn of the potential risks
identified by
reports of adverse drug experiences associated with the use of the
Product and
from Product complaints. In addition, the Parties agree to jointly
develop
additional written procedures including the mechanics for the
surveillance,
receipt, evaluation, and reporting of Product complaints and
adverse drug
experiences, including the possible maintenance of a worldwide
safety database,
in accordance with this Article 4 and subject to the oversight of
the CDRSC.
(e) Each Party
shall notify the other Party within two
(2) Business Days after it receives information about the
initiation of any
investigation, review or inquiry by FDA or other Governmental
Authority
concerning the distribution, promotion or sale of the Product, not
otherwise
described above.
4.4 Pfizer's
Performance of Regulatory Services Agreement
Obligations. During the term of the Regulatory Services Agreement,
all of
Eyetech's regulatory obligations under this Agreement are subject
to Pfizer's
performance of its obligations under the Regulatory Services
Agreement to the
extent Eyetech's performance of Eyetech's obligations depends on
Pfizer's
performance of Pfizer's obligations under the Regulatory Services
Agreement.
36
<PAGE>
ARTICLE 5
PRODUCT DEVELOPMENT
5.1
Development Plan and Budget. The CDRSC shall develop an annual
development plan, which shall include preclinical and clinical
plans and a
budget (a "Development Plan") in respect of the Products consistent
with the
terms of this Agreement for each Year during the Co-Promotion Term.
The CDRSC
shall meet to discuss the first Development Plan within ninety (90)
days after
the Execution Date. A description of the overall development
programs for
development of the AMD Product and DME Product is attached as
Exhibit 5.1(a),
and a summary of the budgets for agreed upon Development Costs for
such programs
(respectively, the "AMD Agreed Development Costs" and the "DME
Agreed
Development Costs") are attached as Exhibit 5.1(b) to this
Agreement. Each
annual Development Plan may be updated throughout the Year as
deemed appropriate
by the CDRSC. Cumulative Development Costs for each of the AMD
Product and DME
Product shall not exceed the AMD Agreed Development Costs and the
DME Agreed
Development Costs, respectively, for such Products absent mutual
consent of the
Parties. The Parties' respective obligations with respect to
Development Costs
shall be as set forth in Section 8.1, provided that, unless
otherwise agreed by
the Parties, neither Party shall be obligated to pay for any
Development Costs
in excess of the AMD Agreed Development Costs or the DME Agreed
Development
Costs, respectively, except to the extent a Party exercises its
final
decision-making authority in accordance with Article 3 to approve
such excess
Development Costs over the objection of the other Party or
otherwise
unilaterally incurs such excess Development Costs, in which case
the Party
exercising such final decision-making authority or unilaterally
incurring excess
Development Costs shall be solely responsible for such excess
Development Costs.
The Parties
37
<PAGE>
acknowledge that the budgets set forth in Exhibit 5.1(b) do not
cover
preclinical Development Costs for periods after the end of 2003 and
do not cover
Development Costs for manufacturing process development and
optimization. With
respect to such Development Costs not covered by the budgets set
forth in
Exhibit 5.1(b), the Parties shall discuss reasonably necessary
preclinical
Development Costs for subsequent periods and Development Costs for
manufacturing
process development and optimization, and amend Exhibit 5.1(b) to
cover such
additional Development Costs.
5.2 AMD
Product and DME Product Development. Each of the Parties
shall, during the Co-Promotion Term, use Commercially Reasonable
Efforts to
develop and obtain Approvals for at least one AMD Product and one
DME Product as
provided in this Agreement. In the event that a party fails to
exercise such
Commercially Reasonable Efforts, such Party's sole liability and
the other
Party's sole remedy for such failure shall be termination of this
Agreement in
accordance with Section 13.2.
5.3
Development of Products for Additional Indications in the
Field. At the request of either Party, the Parties shall in good
faith meet and
discuss jointly developing Additional Developed Products where
preclinical
and/or clinical results provide a reasonable basis for pursuing
such additional
development or the pursuit of such additional development is
otherwise
potentially commercially attractive. If the Parties agree to pursue
such
additional development, the Parties shall amend the applicable
Development
Plan(s) accordingly. If the Parties do not agree to pursue such
additional
development, either Party shall have the right to pursue
development of such
Additional Developed Products at its sole expense, subject to the
other Party's
rights under this Agreement with respect to the Co-Promotion of
Products
(including Additional Developed Products); provided, however, that
such
additional development would
38
<PAGE>
not, based on the best available scientific evidence, be reasonably
likely to
have a materially adverse effect on the Co-Promotion of the
Products.
ARTICLE 6
LAUNCH, CO-PROMOTION AND DETAILING
6.1
Co-Promotion of Products. Eyetech and Pfizer shall be jointly
responsible for the Co-Promotion of Products in the US Territory,
with each
Party participating (except as otherwise expressly provided in this
Agreement)
in all types of marketing activity in the US Territory. Each of the
Parties
shall Co-Promote the Products in the US Territory during the
Co-Promotion Term
in accordance with the terms of this Agreement and the applicable
Marketing
Plan, and in compliance with all Laws. In conducting Co-Promotion
activities,
each Party shall use Commercially Reasonable Efforts to Co-Promote
the sale of
the Products in the US Territory. In the event that a Party fails
to exercise
such Commercially Reasonable Efforts, such Party's sole liability
and the other
Party's sole remedy for such failure shall be (a) termination of
this Agreement
in accordance with Section 13.2 and (b) if applicable to such
failure, the
remedies set forth in Section 6.5 below. All aspects of each
Marketing Plan will
be determined pursuant to the committee system set forth in Article
3.
6.2 Marketing
Plan and Budget.
(a) The CSC
shall, subject to the provisions of Sections
3.4(c), (d), (e) and (f), develop a Marketing Plan (a "Marketing
Plan") and a
marketing budget (a "Co-Promotion Budget") for the period from the
Effective
Date through Launch of the first Product in the US Territory and
for each Year
thereafter during the Co-Promotion Term consistent with Exhibit 6.2
and the
other terms of this Agreement. The first Marketing Plan shall be a
pre-Launch
Marketing Plan, such Marketing Plan to be as approved by the JOC
within six (6)
months of the
39
<PAGE>
Effective Date (the "Pre-Launch Marketing Plan"). The Pre-Launch
Marketing Plan
shall contain a pre-Launch Co-Promotion Budget covering the period
of time from
the Effective Date through the Launch of the first Product in the
US Territory
of up to $[**] or such higher amount as is agreed between the
Parties. The
pre-Launch Co-Promotion Budget shall not exceed $[**] unless
otherwise agreed by
both Parties, and neither Party's election to withhold such
agreement shall be
subject to the other Party's decision-making authority. Neither
Party shall
engage in any Co-Promotion activities except as provided in the
applicable
Marketing Plan. Subsequent annual Marketing Plans will describe the
plan for
commercialization of the Products in the US Territory, including:
(a) general
strategies for the Detailing and marketing of the Products and
allocation of
responsibilities for marketing activities; (b) Detail Requirements
and sampling
activities, if any; (c) market and sales forecasts; (d) pricing and
discounting
analysis; (e) advertising, public relations and other promotional
programs,
including professional symposia and speaker and activity programs
to be used in
the Co-Promotion of the Products; and (f) [**]. Each Marketing Plan
and the
Co-Promotion Budget may, subject to the provisions of Sections
3.4(c), (d), (e)
and (f), be updated from time to time as deemed appropriate by the
CSC.
(b) Exhibit
5.1(b) also includes [**], which Product
Studies will be performed absent mutual agreement by the Parties to
the
contrary. [**] these [**] of Products, [**].
6.3 Detailing.
The Parties shall be responsible for performing the
Detail Requirements specified in each then-current Marketing
Plan.
6.4 Detailing
Reports. Each Party shall provide the other Party
and the CSC with a report as soon as practicable but in no event
later than
forty-five (45) days following the end of each Quarter during the
Co-Promotion
Term setting forth, in such detail and form as the Parties shall
agree, the
number of Details made by such Party's Sales Representatives of
Products in the
40
<PAGE>
US Territory during such Quarter (each, a "Detailing Report"),
provided,
however, that the Detailing Report for the fourth such Quarter in
each Year
shall be cumulative and reflect the number of Details made by such
Party's
respective Sales Representatives in the US Territory during such
Year. Eyetech
covenants that it shall develop an internal system for the purpose
of reporting
the number of Details of its Sales Representatives, and that it
shall have such
system implemented by the time it begins Detailing the
Products.
6.5 Detail
Shortfalls.
(a) In the
event that either Party fails to perform (such
Party, a "Shortfall Party") at least [**] percent ([**]%) of its
Detail
Requirement in any Year as reported pursuant to Section 6.4 or
verified pursuant
to Section 9.3, the Shortfall Party shall pay to the other Party as
liquidated
damages an amount equal to the Detail Cost (as hereinafter
defined), multiplied
by the applicable factor set forth below (the "Shortfall Factor")
multiplied by
the total number of Details in the shortfall (the Detail Cost,
multiplied by the
number of Details in the shortfall, multiplied by the Shortfall
Factor, the
"Detail Shortfall Payment Amount"), on an incremental basis as set
forth below:
41
<PAGE>
<TABLE>
<CAPTION>
-----------------------------------------------------------------------------------------
Shortfall
Detail Shortfall Level
Factor
-----------------------------------------------------------------------------------------
<S>
<C>
<C>
For such portion of shortfall which is: > or = [**]% but <
[**]% of Detail
[**]
Requirement
-----------------------------------------------------------------------------------------
For such portion of shortfall which is: > or = [**]% but <
[**]% of Detail
[**]
Requirement
-----------------------------------------------------------------------------------------
For such portion of shortfall which is: < [**]% of Detail
Requirement
[**]
-----------------------------------------------------------------------------------------
</TABLE>
For purposes of this Section 6.5, "Detail Cost" means $[**]. If a
Party wishes
to verify the Details performed by the other Party in any Year,
such Party shall
give notice to the other Party that the notifying Party wishes to
verify Details
pursuant to Section 9.3 within forty-five (45) days after receipt
of the other
Party's last Detailing Report set forth in Section 6.4 for such
Year.
(b) With
respect to any Year in which onl
