Exhibit 10.3
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*Confidential Treatment has been requested for
the marked portions of this exhibit pursuant to Rule 24b-2 of the
Securities Exchange Act of 1934, as amended.
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AMENDED AND RESTATED
MANUFACTURING AGREEMENT
T HIS A MENDED AND R ESTATED M ANUFACTURING A GREEMENT (the “Agreement” ) is
made effective as of February 25, 2009 (the
“Amendment Date” ) by and between
C ELLADON
C ORPORATION , a
California corporation, with its principal place of business at
2223 Avenida de la Playa, Suite 300, c/o Enterprise
Partners Venture Capital, La Jolla, CA 92037 (
“Celladon” ), and T
ARGETED G ENETICS C ORPORATION , a
Washington corporation with its principal offices at
1100 Olive Way, Suite 100, Seattle, Washington 98101 (
“TGC” ).
R ECITALS
W HEREAS , Celladon and TGC are parties to that certain
Manufacturing Agreement dated December 31, 2004 (the
“2004 Agreement” ), as amended by that
certain First Amendment to Manufacturing Agreement dated
March 19, 2008 (the “First
Amendment” and, collectively with the 2004 Agreement,
the “Original Agreement” ), pursuant to
which TGC is responsible for the manufacture and supply of certain
gene therapy products, subject to the terms and conditions set
forth therein;
W HEREAS , Celladon and TGC now wish to amend and restate
the Original Agreement as set forth herein;
W HEREAS , concurrently herewith, Celladon and TGC are
entering into a License Agreement (the “License
Agreement” ), which supersedes and replaces the
Collaboration Agreement between the parties dated December 31,
2004, as amended to date (the “Collaboration
Agreement” ), and pursuant to which TGC is granting
Celladon an exclusive license to develop and commercialize certain
gene therapy products; and
W HEREAS , this
Agreement and the Collaboration Agreement will supersede and
replace the letter agreement between the parties dated
January 16, 2009 (the
“2009 Letter” )
A GREEMENT
N OW ,
T HEREFORE
, in consideration of the foregoing and the mutual
promises and covenants hereinafter set forth, Celladon and TGC,
intending to be legally bound, hereby agree as follows:
1.1
“Affiliates” shall mean any company or entity controlled by,
controlling, or under common control with a party hereto and shall
include any company more than 50% of whose voting stock or
participating profit interest is owned or controlled, directly or
indirectly, by a party, and any company which owns or controls,
directly or indirectly, more than 50% of the voting stock of a
party.
1.2 “Applicable Laws” means all
laws, statutes, ordinances, codes, rules and regulations which have
been enacted by a Government Authority and are in force as of the
Amendment Date or come into force during the Term, in each case to
the extent that the same are applicable to the performance by the
parties of their respective obligations under this Agreement. For
purposes of this Agreement, cGMP shall be deemed to be within the
term “Applicable Laws.”
1.3 “Celladon
Designee” shall
have the meaning provided in Section 3.1.
1.4 “Celladon
Product” shall have
the meaning provided in the License Agreement.
1.5 “cGMP” shall mean current
good manufacturing practices for medicinal products established by
U.S. laws, rules and regulations (including 21 CFR
Parts 210 and 211, as amended, and any successor regulations
thereto, each as in effect from time to time).
1.6 “cGMP3” shall have the
meaning provided in Section 2.1(a).
1.7 “CMC”
shall mean chemistry, manufacture
and control.
1.8 “Commercially Reasonable
Efforts” shall mean, with respect to the efforts to be
expended by any entity with respect to any objective, the level of
reasonable, diligent, good faith efforts and resources devoted to
accomplish such objective as a typical biotechnology company would
normally use to accomplish a similar objective under similar
circumstances.
1.9 “Development
Plan” shall mean
the cGMP3 Development Plan attached to this Agreement as
Exhibit A .
1.10 “FFDCA” means the Federal
Food, Drug, and Cosmetic Act, 21 U.S.C. § 321 et seq. ,
as amended from time to time.
1.11 “Government Authority” means
any supranational, national, regional, state or local government,
court, governmental agency, authority, board, bureau,
instrumentality or regulatory body.
1.12
“Information” shall have the meaning provided in the License
Agreement.
1.13 “Manufacturing
Process” shall mean
the manufacturing process for the cGMP3 manufacturing campaign for
Mydicar developed by TGC pursuant to the First
Amendment.
1.14
“Mydicar” shall mean the Celladon Product
known as MYDICAR ® (AAV1/SERCA2a).
1.15 “Quality Agreement” shall
mean that certain Quality Agreement for cGMP Manufacturing of Phase
II/III and III AAV1/SERCA2a Purified Bulk Drug Substance and
Testing of Bulk Drug Substance and Drug Product entered into by the
parties prior to the Amendment Date.
1.16
“Term” shall
have the meaning provided in Article 10.
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2.
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*Confidential Treatment
Requested.
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1.17 “Third Party” means any
entity or individual other than TGC or Celladon or their respective
Affiliates.
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2.
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C
LINICAL M ANUFACTURING S ERVICES
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2.1 cGMP3 Pre-Bulk Drug Substance.
(a) Manufacture.
Subject to the terms and conditions
of this Agreement, TGC shall use Commercially Reasonable Efforts to
manufacture Mydicar pre-bulk drug substance using the Manufacturing
Process under a manufacturing campaign designated by the parties as
cGMP3, as more fully described in the Development Plan (
“cGMP3” ). TGC shall manufacture such
Mydicar pre-bulk drug substance in accordance with this
Section 2.1(a), the Development Plan, all applicable batch
records and test procedures for cGMP3 approved by Celladon and
communicated to TGC in writing prior to the Amendment Date, and all
Applicable Laws (including, without limitation, cGMP, to the extent
applicable to TGC’s manufacturing activities hereunder, as
demonstrated by the batch records and test procedures described
above as well as those steps and procedures which are
(i) specified in the Development Plan, (ii) previously
agreed to by the parties with respect to validation of equipment
and facilities used by TGC to manufacture Mydicar, or
(iii) otherwise agreed to by the parties in writing), provided
that TGC shall not be obligated to perform, and shall not perform,
analytical or other testing, nor any quality assurance or control,
except, in each case, as expressly set forth for TGC to perform in
the Development Plan (or as otherwise mutually agreed in
writing).
(b) Permitted Use of cGMP3
Pre-Bulk Drug Substance. Mydicar pre-bulk drug substance manufactured
pursuant to Section 2.1(a) shall be used solely for
preclinical or clinical development and regulatory approval
purposes.
2.2 Transfer of Analytical Methods. TGC shall
provide its existing analytical methods for Mydicar in accordance
with Section 3.1 hereof.
2.3 Mydicar Production Records. TGC shall
maintain, and allow Celladon to access or provide to Celladon (as
specified in the Development Plan), all records required to be
prepared by TGC under the Development Plan in connection with
TGC’s manufacture of Mydicar pre-bulk drug substance pursuant
to this Agreement. All such records shall be maintained by TGC for
such period as may be required by Applicable Laws; provided,
however, that any such records provided to Celladon shall be
maintained by Celladon for such period as may be required by
Applicable Law (and TGC shall have no such obligation with respect
thereto).
2.4 Product Delivery. TGC shall ship Mydicar
pre-bulk drug substance manufactured pursuant to
Section 2.1(a), under quarantine and stored frozen in
accordance with cGMP, to such Celladon Designee as Celladon
specifies in writing to TGC (and Celladon shall specify such
Celladon Designee and corresponding shipping destination prior to
March 31, 2009). TGC shall package all items in suitable
containers to permit safe transportation and handling. Each shipped
container will be labeled and marked to identify its contents
without having to be opened, and all boxes and packages must
contain packing sheets listing the contents. Celladon shall bear
all transportation, insurance, taxes, duties, and other costs and
risks
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3.
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*Confidential Treatment
Requested.
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of loss, spoilage and damage associated with the
shipping and delivery of Mydicar pre-bulk drug substance to such
Celladon Designee.
2.5 Limited Obligations. TGC provides no
warranties or guarantees hereunder that its manufacture of Mydicar
pre-bulk drug substance will be successful or result in drug
substance suitable for use in clinical trials. Except to the extent
TGC does not comply with its obligations set forth in
Sections 2.1 through 2.4, TGC shall have no liability
hereunder for any failures to manufacture or supply Mydicar
pre-bulk drug substance hereunder.
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3.
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M
ANUFACTURING
T ECHNOLOGY T RANSFER .
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3.1 Technology
Transfer. Subject to the
terms and conditions of this Agreement (including, without
limitation, Article 5 hereof), commencing promptly after the
Amendment Date and throughout the Term, TGC shall provide to a
Third Party contract manufacturing organization or contract
research organization (as applicable) designated by Celladon (each,
a “Celladon Designee” ) all manufacturing
and other technology and know-how in TGC’s possession (and,
if not owned by TGC, that TGC has a right to disclose), that is
necessary to practice the Manufacturing Process and to manufacture
and test the Mydicar pre-bulk drug substance manufactured hereunder
(the “Technology Transfer” ), as more
fully described below and in the Development Plan. It is
contemplated that the Celladon Designee [*] ; provided,
however, that TGC shall not be responsible for any delays or
failures to complete the Technology Transfer prior to the end of
the Term to the extent caused by [*] . It is the intention
of the parties that the Technology Transfer will enable the
Celladon Designee(s) to replicate the Manufacturing Process to
manufacture and test Mydicar in the same manner as TGC manufactures
Mydicar pursuant to this Agreement and in the same manner as TGC
tests or has tested Mydicar as of the Amendment Date or during the
Term. The Technology Transfer shall include at least the following
activities during the Term:
(a) TGC shall provide to Celladon or a Celladon
Designee the existing analytical methods for conformance testing of
Mydicar, including [*]
(b) TGC shall provide to Celladon or a Celladon
Designee [*] in all such cases (i) as are necessary to
manufacture Mydicar as manufactured hereunder, to test Mydicar or
to support regulatory filings for Mydicar, and (ii) to the
extent in the possession and control of TGC;
(c) TGC shall provide [*] in order to enable
such Celladon Designee to manufacture Mydicar as manufactured
hereunder and to test Mydicar [*]
(d) TGC shall provide Celladon or a Celladon
Designee [*] ; and
(e) TGC shall [*]
3.2 Limitations on Obligations In
Light of Available Personnel. The parties acknowledge that, in accordance with
the Development Plan and payment schedule attached hereto as
Exhibit B , TGC has a limited number of
personnel to perform its obligations hereunder [*] .
Accordingly, TGC’s obligations under Section 3.1 shall
be limited to the extent of what can reasonably be accomplished by
the anticipated personnel and staffing (working solely on
the
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4.
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*Confidential Treatment
Requested.
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obligations under this Agreement) during the
Term. Celladon shall designate the Celladon Designees who will
receive the Technology Transfer reasonably promptly after the
Amendment Date, and in any event within such time so that TGC,
using Commercially Reasonable Efforts and in accordance with the
Development Plan, can reasonably be expected to complete the
Technology Transfer as contemplated in the Development Plan
[*] . TGC is not responsible or liable for any delays or
failure to complete the Technology Transfer due to
(a) Celladon’s failure to provide timely designation of
the Celladon Designees as described above, or (b) the
inexperience of, or excessive need for consultation by, any
Celladon Designee.
3.3 Disclosure and Use of Technology
Transfer. All Information provided or disclosed to Celladon
under the Technology Transfer (or otherwise under Section 3.1)
shall be subject to the terms and conditions of Section 2.2(d)
of the License Agreement (“Disclosure and Use of Released
Materials”) and shall be deemed part of the “TGC
Manufacturing Information” thereunder with respect to the
application of such Section 2.2(d). All such Information shall
be used for the sole purpose of exercising and fully exploiting the
license granted to Celladon under Section 2.1 of the License
Agreement, subject to the terms and conditions of the License
Agreement (and Celladon and its Affiliates and Licensees, as
defined in the License Agreement, shall not use such Information
for any other purpose).
3.4 Retained Rights; TGC Use of Celladon
Designees. TGC and, if applicable, its licensors retain
ownership of, and all rights, title and interest in, to and under,
the Information provided or disclosed to Celladon under the
Technology Transfer or otherwise under this Agreement (except for
the equipment on Exhibit C hereto, which is
being sold to Celladon), subject only to Celladon’s rights
therein as expressly provided for in the License Agreement,
including, without limitation, Sections 2.1, 2.2 and 2.8 of
the License Agreement. Any use of the term “transfer”
or similar terms herein (including in any exhibit hereto) shall be
construed accordingly and not as an assignment or sale. For the
avoidance of doubt, TGC is entitled to retain and use copies and/or
originals of such Information (subject to the exclusive license
granted to Celladon under the License Agreement), and nothing
herein restricts TGC (or its Affiliates or licensees) from
utilizing any Celladon Designee and/or such Information to
manufacture or test products (subject to the exclusive license
granted to Celladon under the License Agreement). Furthermore,
Celladon shall not restrict, and shall otherwise