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EXHIBIT 10.56
*CERTAIN CONFIDENTIAL
INFORMATION CONTAINED IN THIS
DOCUMENT, MARKED BY BRACKETS,
HAS BEEN OMITTED AND FILED WITH
THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE
24B-2 OF THE SECURITIES
EXCHANGE ACT OF 1934, AS
AMENDED.
COLLABORATION AGREEMENT
THIS COLLABORATION AGREEMENT (the "AGREEMENT"), effective as of
December
31, 2004 (the "EFFECTIVE DATE"), is by and between CELLADON
CORPORATION, a
California corporation ("CELLADON"), with its principal place of
business at
2223 Avenida de la Playa, Suite 300, c/o Enterprise Partners
Venture Capital, La
Jolla, CA 92037, and TARGETED GENETICS CORPORATION, a Washington
corporation
("TGC"), with its principal place of business at 1100 Olive Way,
Suite 100,
Seattle, WA 98101.
WHEREAS, TGC has developed substantial proprietary technology
and is
engaged in the discovery, development and manufacture of viral
and non-viral
gene-based product candidates and operates a cGMP-compliant
production facility
for the manufacture of such candidates;
WHEREAS, Celladon is engaged in the development of gene
vector-delivered
therapeutic products based on phospholamban and/or SERCA2a for
the treatment or
prevention of congestive heart failure;
WHEREAS, the parties wish to establish a collaborative
relationship
pursuant to which, among other things, TGC will assist Celladon
in: (a)
designing a cardiac gene therapy product based in part on
Celladon's proprietary
technology for clinical development by Celladon, (b) assessing
the intellectual
landscape associated with such product, and (c) the development
of a
manufacturing process and supplying such gene therapy product;
and
WHEREAS, concurrently herewith, the parties have entered into
a
manufacturing and supply agreement pursuant to which TGC will be
responsible for
the manufacture and supply of cardiac gene therapy products
developed pursuant
to this Agreement, subject to the terms and conditions set forth
therein (the
"MANUFACTURING AGREEMENT").
NOW, THEREFORE, 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. DEFINITIONS. Capitalized terms used but not otherwise defined
herein shall
have the meanings provided in the Manufacturing Agreement. In
addition, the
following terms shall have the meanings set forth below:
1.1 "AAV VECTOR" shall mean an adeno-associated virus gene
vector composed
of a viral capsid comprising three proteins known as VP1, VP2
and VP3, wherein
the genome is a single-strand DNA molecule flanked by inverted
terminal repeats
("ITRs").
1.2 "AFFILIATE" 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
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company which owns or controls, directly or indirectly, more
than 50% of the
voting stock of a party.
1.3 "ALLOCABLE OVERHEAD" shall mean the costs incurred by a
party or for
its account which are attributable to a party's supervisory
services, occupancy
costs, payroll and its payroll, information systems, human
relations or
purchasing functions and which are allocated to company
departments based on
space occupied or headcount or other activity-based method
consistently applied
by a party, or a standard rate if agreed to by the parties.
Allocable Overhead
shall not include any costs attributable to general corporate
activities,
including, by way of example, executive management, investor
relations, business
development, legal affairs and finance.
1.4 "APPROVAL APPLICATION" means any application necessary and
appropriate
to obtain a Regulatory Approval, together with all required
documents, data and
information concerning a Selected Product that is the subject of
such
application.
1.5 "BUDGET" shall have the meaning provided in Section 2.1.
1.6 "CELLADON COST OF GOODS" shall mean, with respect to any
Selected
Product in final form that is sold by Celladon or its Affiliates
hereunder:
(A) in the case of Selected Product in final form that is
manufactured in whole or in part by Celladon or its
Affiliate(s), the actual
fully allocated cost of manufacturing such Selected Product (in
accordance with
cGMP) determined in accordance with GAAP consistently applied
throughout the
organization of Celladon and its Affiliate(s), which includes
the direct and
indirect cost of any raw materials, packaging materials and
labor (including
benefits) utilized in such manufacturing (including formulation,
fill/finish,
quality assurance, quality control and stability testing,
labeling and
packaging, as applicable), plus an appropriate share of all
factory overhead,
both fixed and variable, allocated to the Selected Product being
manufactured,
in accordance with the normal accounting practices for all other
products
manufactured in the applicable facility; provided, however, that
"Cost of Goods"
shall exclude any allocation of cost related to idle capacity,
unless such
excess capacity is specifically reserved for Selected Product;
and
(B) in the case of Selected Product in final form that is
manufactured entirely by a Third Party, the actual price paid by
Celladon or its
Affiliate(s) to such Third Party for such Selected Product.
1.7 "CELLADON-ASSIGNED JOINT INVENTION" shall mean a Joint
Invention that
is not a TGC-Assigned Joint Invention.
1.8 "CELLADON PATENTS" shall mean, to the extent necessary or
useful for
the development, manufacture, use or sale of any Gene Therapy
Product, all
Patents that Celladon or any of its Affiliates Controls as of
the Effective Date
or during the Term.
1.9 "CELLADON TECHNOLOGY" shall mean: (a) the Celladon Patents;
and (b)
Information not included in the Celladon Patents that Celladon
or any of its
Affiliates Controls on the Effective Date or during the Term,
including, without
limitation, all such Information that is conceived or developed
by Celladon or
any of its Affiliates in the course and as part of the
Collaboration.
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1.10 "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).
1.11 "CMC" shall have the meaning provided in Section
3.2(b).
1.12 "COLLABORATION" shall have the meaning provided in Section
2.1.
1.13 "COLLABORATION TERM" shall have the meaning provided in
Section 2.11.
1.14 "COMMERCIALLY REASONABLE EFFORTS" means, with respect to
the efforts
to be expended by any entity with respect to any objective,
reasonable,
diligent, good faith efforts to accomplish such objective as
such entity would
normally use to accomplish a similar objective under similar
circumstances. With
respect to any objective relating to the commercialization of a
product by any
entity, "Commercially Reasonable Efforts" means efforts and
resources normally
used by such entity with respect to a product owned by such
entity or to which
such entity has similar rights which is of similar market
potential at a similar
stage in the development or life of such product, taking into
account issues of
safety, efficacy, product profile, the competitiveness of the
marketplace, the
proprietary position of the product, the regulatory structure
involved,
profitability of the product and other relevant commercial
factors.
1.15 "COMMITTEE" shall have the meaning provided in Section
2.2.
1.16 "CONFIDENTIAL INFORMATION" shall have the meaning provided
in Section
8.1.
1.17 "CONTROL" shall mean, with respect to any Information,
Patent or
other intellectual property right, possession by a party of the
ability (whether
by ownership, license or otherwise) to grant access, a license
or a sublicense
to such Information or intellectual property right without
violating the terms
of any agreement or other arrangement with any Third Party.
1.18 "DEVELOPMENT COSTS" shall mean costs actually incurred by
Celladon or
for its account that are specifically attributable to the
development of
Selected Products. Development Costs will include, but not be
limited to: (a)
costs of research and development of Selected Products,
including costs of
studies on the toxicological, pharmacokinetic, metabolic or
clinical aspects of
Selected Products conducted internally or by Third Parties; (b)
Cost of Goods
for Selected Product for use in preclinical studies or clinical
trials; (c)
costs of preparing and reviewing data or information for the
purpose of
submission to the FDA and foreign regulatory authorities for the
purpose of
obtaining Regulatory Approvals of Selected Products; (d) fees
associated with
regulatory filings or other governmental requirements related to
Selected
Products; and (e) applicable Allocable Overhead, including
expenses for data
management, statistical designs and studies, document
preparation, and other
administration expenses associated with clinical testing
programs.
1.19 "DEVELOPMENT PLAN" shall have the meaning provided in
Section 2.1.
1.20 "DMF" shall mean a drug master file (as such term is
defined in 21
C.F.R. Part 314.420, as it may be amended from time to time), or
any foreign
equivalent thereof, for a Selected Product.
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1.21 "FDA" shall mean the United States Food and Drug
Administration, or
any successor agency thereto.
1.22 "FIELD" shall mean the Therapeutic Field and/or the Pathway
Field.
1.23 "FINANCING" shall mean the purchase by Enterprise Partners
and
Venrock (and/or their respective affiliated entities) of shares
of the common
stock of TGC having an aggregate fair market value of
US$6,000,000 pursuant to
that certain Stock Purchase Agreement by and among TGC and such
entities dated
of even date herewith.
1.24 "FIRST COMMERCIAL SALE" shall mean, with respect to any
Product, the
first sale for end use or consumption of such Product in a
country after the
governing health regulatory authority of such country has
granted Regulatory
Approval. Sale to an Affiliate or Licensee shall not constitute
a First
Commercial Sale unless the Affiliate or Licensee is the end user
of the Product.
1.25 "GAAP" shall mean U.S. generally accepted accounting
principles
consistently applied.
1.26 "GCP" means, to the extent applicable, the then-current
good clinical
practices (under the regulations set forth in 21 C.F.R.
Subchapter A and the
requirement imposed thereunder by the FDA) and in effect from
time to time
during the Term, together with the then-current equivalent or
corresponding
regulations and requirements in jurisdictions outside the United
States.
1.27 "GENE THERAPY PRODUCT" shall mean an AAV Vector-delivered
therapeutic
product for the treatment or prevention of congestive heart
failure based on one
or more of the following: (a) phospholamban mutant gene
(S16EPLN) to inhibit
phospholamban-mediated events; (b) sarco(endo)plasmic reticulum
Ca(2+)-ATPase
("SERCA2a"); (c) [*]; and/or (d) [*].
1.28 "GROSS PROFIT" shall mean Gross Revenues, less the
following:
(A) (i) trade discounts, credits or allowances; (ii) credits
or
allowances additionally granted upon returns, rejections or
recalls; (iii)
freight, shipping and insurance charges; (iv) taxes, duties or
other
governmental tariffs (other than income taxes); and (v)
government mandated
rebates; all of the foregoing to the extent actually included in
the calculation
of gross revenues;
(B) the Celladon Cost of Goods of Selected Products sold by
Celladon
and its Affiliates;
(C) all royalties paid by Celladon or its Affiliates to
Third
Parties and all royalties paid by TGC or its Affiliates to Third
Parties with
respect to Patents and/or Information of such Third Parties that
Celladon and
TGC (in the case of TGC Licensed Technology), deem necessary or
useful for the
manufacture, use or sale of Selected Products (excluding any
such royalties paid
with respect to delivery devices, such as catheters); and
*CONFIDENTIAL TREATMENT REQUESTED.
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(D) all marketing and sales costs and revenue sharing (including
for
example, royalties on product sales and/or sales milestones
payments) incurred
by Celladon or its Affiliates with respect to marketing and
sales of Selected
Products in jurisdictions where one or more Third Parties
markets and sells
Selected Products on behalf of Celladon.
1.29 "GROSS REVENUES" shall mean the gross revenues (including
for
example, royalties on product sales and sales milestones)
actually received by
Celladon and its Affiliates from the commercial sale of Selected
Products after
Regulatory Approval thereof, determined in accordance with
GAAP.
1.30 "IND" shall mean an Investigational New Drug Application
filed with
the FDA, or the equivalent application or filing filed with any
equivalent
agency or governmental authority outside the United States of
America (including
any supra-national agency such as in the European Union)
necessary to commence
human clinical trials in such jurisdiction.
1.31 "INFORMATION" shall mean all tangible and intangible (a)
techniques,
technology, practices, trade secrets, inventions (whether
patentable or not),
methods, knowledge, know-how, skill, experience, test data and
results
(including pharmacological, toxicological and clinical test data
and results),
analytical and quality control data, results or descriptions,
software and
algorithms and (b) compositions of matter, cells, cell lines,
assays, animal
models and physical, biological or chemical material.
1.32 "JOINT INVENTION" shall mean any invention, whether
patentable or
not, which is conceived or reduced to practice, either as part
of the
Collaboration or under the Manufacturing Agreement, jointly by
one or more
employees or contractors of Celladon and one or more employees
or contractors of
TGC.
1.33 "LEAD PARTY" shall have the meaning provided in Section
6.2(c).
1.34 "LICENSEE" shall mean a Third Party to whom Celladon or any
of its
Affiliates has granted a license or sublicense of the right to
develop, make,
have made, use, distribute for sale, promote, market, offer for
sale, sell, have
sold, import or export Products, beyond the mere right to
purchase Products from
Celladon or its Affiliates.
1.35 "MANUFACTURING AGREEMENT" shall mean the Manufacturing
Agreement
between the parties dated the Effective Date and, as defined
therein, the
"Commercial Agreement" to be entered into by the parties in the
future.
1.36 "MANUFACTURING DOCUMENTS" shall have the meaning provided
in Section
3.2(b).
1.37 "MANUFACTURING PROCESS" shall mean the manufacturing
process for a
Selected Product developed by TGC pursuant to the terms of this
Agreement and
used by TGC, its Affiliates or Third Party subcontractors in
producing such
Selected Product under this Agreement.
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1.38 "NDA" shall mean a New Drug Application (as more fully
defined in 21
C.F.R. 314.5 et seq.) and all amendments and supplements thereto
filed with the
FDA, or the equivalent application filed with any equivalent
agency or
governmental authority outside the United States of America
(including any
supra-national agency such as in the European Union), including
all documents,
data, and other information concerning a pharmaceutical product
which are
necessary for gaining Regulatory Approval to market and sell
such pharmaceutical
product.
1.39 "PATENTS" shall mean (a) United States patents,
re-examinations,
reissues, renewals, extensions and term restorations, and
foreign counterparts
thereof, and (b) pending applications for United States patents,
including,
without limitation, provisional applications, continuations,
continuations-in-part, divisional and substitute applications,
including,
without limitation, inventors' certificates, and foreign
counterparts thereof.
1.40 "PATHWAY FIELD" shall mean modulation of the
phospholamban/SERCA
biological pathway [*].
1.41 "PHASE 1/2 CLINICAL TRIAL" shall mean a human clinical
trial that
would satisfy the requirements for a Phase 1 study as defined in
21 C.F.R.
312.21(a) (or its successor regulation) and/or the requirements
for a Phase 2
study as defined in 21 C.F.R. 312.21(b) (or its successor
regulation).
1.42 "PHASE 3 CLINICAL TRIAL" shall mean a human clinical trial
that would
satisfy the requirements for a Phase 3 study as defined in 21
C.F.R. 312.21(c)
(or its successor regulation).
1.43 "PRE-COMMERCIAL NET REVENUES" shall mean the amount (if
any) by which
Pre-Commercial Payments received by Celladon exceed Development
Costs paid by
Celladon.
1.44 "PRE-COMMERCIAL PAYMENTS" shall mean all amounts actually
received by
Celladon or an Affiliate of Celladon from any and all Licensees
prior to the
First Commercial Sale of a Selected Product arising from the
license or
sublicense of the right to develop, make, have made, use,
distribute for sale,
promote, market, offer for sale, sell, have sold, import or
export Selected
Products. Pre-Commercial Payments shall include up-front or
license fees,
milestone payments, premiums above the fair market value on
sales of securities,
annual maintenance fees and any other payments in respect of the
grant to such
Licensee of a license or sublicense of the right to develop,
make, have made,
use, distribute for sale, promote, market, offer for sale, sell,
have sold,
import or export Selected Products (with any of the foregoing
consideration
received by Celladon or its Affiliates other than in the form of
cash to be
valued at its fair market value as of the date of receipt);
provided, however,
that Pre-Commercial Payments shall not include any payments tied
directly to the
provision of goods and services by Celladon or its Affiliate to
such Licensee
(including research and development and manufacturing) to
compensate Celladon or
its Affiliate for the fair market value of the provision of such
goods and
services, or payments for securities (other than premiums above
the fair market
value of such securities).
1.45 "PROJECT LEADER" shall have the meaning provided in Section
2.2(d)
1.46 "REGULATORY APPROVAL" shall mean any and all approvals
(including
price and reimbursement approvals, if required), licenses,
registrations, or
authorizations of any country, federal, supranational, state or
local regulatory
agency, department, bureau or other government
*CONFIDENTIAL TREATMENT REQUESTED.
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entity that are necessary for the manufacture, use, storage,
import, transport
and/or sale of a Selected Product in such jurisdiction.
1.47 "ROYALTY TERM" shall mean, in the case of any Selected
Product, in
any country, the period of time commencing on the [*] of such
Selected Product
in such country and ending upon the later of (a) [*] after the
date of [*] of
such Selected Product in such country, and (b) the expiration of
the last to
expire of the [*] claiming the manufacture, use or sale of such
Selected Product
in such country.
1.48 "SELECTED PRODUCT" shall mean a Gene Therapy Product
selected by
Celladon, in its sole discretion, by written notice thereof to
TGC, as a
candidate for clinical development and commercialization by
Celladon in the
Field. Notwithstanding the foregoing, Selected Products shall
exclude TGC
Candidates.
1.49 "SELECTED PRODUCT PATENTS" shall have the meaning provided
in Section
6.1(b).
1.50 "TERM" shall have the meaning provided in Section 9.1.
1.51 "TGC ACCOUNTING METHOD" shall mean the method by which TGC
accounting
and budgeting under this Agreement will be conducted. The
details of such
accounting are set forth in Exhibit B. Exhibit B shall be
revised in advance of
each twelve (12) month period of the Collaboration.
1.52 "TGC-ASSIGNED JOINT INVENTION" shall mean a Joint Invention
directed
to the [*].
1.53 "TGC CANDIDATES" shall mean the adeno-associated
virus-delivered gene
therapy candidates Controlled by TGC as of the Effective Date
with potential
utility in the Field.
1.54 "TGC LICENSED PATENTS" shall mean, to the extent necessary
or useful
for the development, manufacture, use or sale of any Gene
Therapy Product, all
Patents that TGC or any of its Affiliates Controlled (but not
owned) as of the
Effective Date or during the Term, as a result of being licensed
to TGC by a
Third Party.
1.55 "TGC LICENSED TECHNOLOGY" shall mean: (a) the TGC Licensed
Patents;
and (b) to the extent necessary or useful for the development,
manufacture, use
or sale of any Gene Therapy Product, Information not included in
the TGC
Licensed Patents, TGC Patents, TGC Technology or Joint
Inventions that TGC or
any of its Affiliates Controls (but does not own) on the
Effective Date or
during the Term, including, without limitation, all such
Information that is
conceived or developed by TGC or any of its Affiliates, as a
result of being
licensed to TGC by a Third Party, in the course and as part of
the Collaboration
or in performing its obligations under the Manufacturing
Agreement.
1.56 "TGC PATENTS" shall mean, to the extent necessary or useful
for the
development, manufacture, use or sale of any Gene Therapy
Product, all Patents
that TGC or any of its Affiliates owns as of the Effective Date
or during the
Term.
*CONFIDENTIAL TREATMENT REQUESTED.
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1.57 "TGC TECHNOLOGY" shall mean: (a) the TGC Patents; and (b)
to the
extent necessary or useful for the development, manufacture, use
or sale of any
Gene Therapy Product, Information not included in the TGC
Patents that TGC or
any of its Affiliates owns on the Effective Date or during the
Term, including,
without limitation, all such Information that is conceived or
developed by TGC
or any of its Affiliates in the course and as part of the
Collaboration or in
performing its obligations under the Manufacturing
Agreement.
1.58 "THERAPEUTIC FIELD" shall mean the treatment or prevention
of
congestive heart failure.
1.59 "THIRD PARTY" shall mean any entity other than Celladon or
TGC or an
Affiliate of Celladon or TGC.
1.60 "TRANSFER PRICE" shall mean:
(A) with respect to bulk Selected Product commercialized
hereunder
that is supplied by TGC pursuant to the Manufacturing Agreement
or by a Third
Party, the price actually paid by Celladon, its Affiliate or a
Licensee for such
bulk Selected Product; and
(B) with respect to bulk Selected Product commercialized
hereunder
that is manufactured by Celladon or its Affiliate, Celladon's or
its Affiliate's
actual fully allocated cost of manufacturing bulk Selected
Product (in
accordance with cGMP) determined in accordance with GAAP
consistently applied
throughout the organization of Celladon and its Affiliate(s),
which includes the
direct and indirect cost of any raw materials, packaging
materials and labor
(including benefits) utilized in such manufacturing (including
formulation,
quality assurance, quality control and stability testing,
labeling and
packaging, as applicable), plus an appropriate share of all
factory overhead,
both fixed and variable, allocated to the Selected Product being
manufactured,
in accordance with the normal accounting practices for all other
products
manufactured in the applicable facility, provided that such cost
of manufacture
shall exclude any allocation of cost related to idle capacity,
unless such
excess capacity is specifically reserved for Selected
Product.
1.61 "VALID CLAIM" shall mean an unexpired claim of an issued
patent
within the Celladon Patents or TGC Patents which has not been
found to be
unpatentable, invalid or unenforceable by a court or other
authority in the
subject country, from which decision no appeal is taken or can
be taken.
2. COLLABORATION
2.1 COLLABORATIVE DEVELOPMENT PROGRAM. Subject to the terms and
conditions
of this Agreement, the parties shall conduct a collaborative
development program
to design one or more Gene Therapy Products suitable for
clinical development
and commercialization by Celladon in the Therapeutic Field, as
more fully
described below in this Article 2 (collectively, the
"COLLABORATION"). The
parties shall conduct the Collaboration during the Collaboration
Term in
accordance with a written development plan to be mutually agreed
upon within 60
days after the Effective Date and attached hereto as EXHIBIT A
(the "DEVELOPMENT
Plan"). A Development Plan shall be created and mutually agreed
upon by the
parties for each 12 month period of the Collaboration. The
Development Plan
shall set forth the activities to be performed by TGC, the
estimated timeline
for conduct of such activities and an estimated budget for the
Development Plan
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activities (the "BUDGET"). The parties shall report on the
progress made
pursuant to the goals of the Development Plan, revise and update
such
activities, Budget, and timeline as necessary, on a quarterly
basis during the
Collaboration Term. If modifications in the activities or
timeline of activities
conducted under the Development Plan are requested by Celladon,
TGC shall make
good faith efforts to accommodate such requests within the
parameters of
conducting its other programs, and taking into account its
facility, capacity
and resource constraints. If activities contemplated by the
Development Plan are
cancelled by Celladon less than [*] from their initiation,
Celladon shall be
responsible for non-cancelable costs incurred by TGC in
preparation for such
activities and shall be responsible for the hours or
manufacturing facility time
allocated to such activities [*]. At any time, and from time to
time, during the
Term or during any period when Celladon's license under Section
4.2(b) is in
effect, Celladon may, in its sole discretion, designate any
Selected Product by
written notice thereof to TGC.
2.2 COLLABORATION COMMITTEE. As promptly as practicable (but no
later than
30 days) following the Effective Date, the parties shall
establish a committee
(the "COMMITTEE") in accordance with this Section 2.2. The
Committee shall be
responsible for execution of the Development Plan within the
budget established
by the parties, and, in connection therewith, shall manage and
monitor the
progress and results of the Collaboration, allocate resources
(including,
without limitation, FTEs) among the various Development Plan
activities and
encourage and facilitate ongoing cooperation between the
parties.
(A) COMPOSITION OF THE COLLABORATION COMMITTEE. The Committee
shall
be composed of two named representatives of Celladon and two
named
representatives of TGC. Each party shall appoint its respective
representatives
to the Committee from time to time, and may substitute one or
more of its
representatives, in its sole discretion, effective upon notice
to the other
party of such change. These representatives shall have
appropriate technical
credentials, experience and knowledge, and ongoing familiarity
with the
Collaboration. Additional representatives or consultants may
from time to time,
by mutual consent of the parties, be invited to attend Committee
meetings,
subject to such representative's or consultant's written
agreement to comply
with confidentiality and non-use obligations equivalent to those
set forth in
Article 8. Each party shall bear its own expenses related to the
attendance of
such meetings by its representatives. The Committee shall be
chaired by a
representative of Celladon. Decisions of the Committee shall be
made by
unanimous vote, with each party's representatives on the
Committee collectively
having one vote. In the event that the Committee cannot or does
not, after good
faith efforts, reach agreement on an issue, such issue shall be
referred to the
Chief Executive Officers of Celladon and TGC. Such officers of
the parties shall
meet promptly thereafter and shall negotiate in good faith to
resolve such
issue.
(B) MEETINGS. The Committee shall meet in accordance with a
schedule
established by mutual written agreement of the parties, but no
less frequently
than once per calendar quarter, with the location for such
meetings alternating
between TGC and Celladon facilities (or such other locations as
is mutually
agreed by the parties). Alternatively, the Committee may meet by
means of
teleconference, videoconference or other similar communications
equipment or by
a signed unanimous written consent in lieu of a meeting, but not
by proxy. No
Committee meeting may be conducted unless both representatives
of each party are
participating.
*CONFIDENTIAL TREATMENT REQUESTED.
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(C) MINUTES. The hosting party shall have responsibility for
preparing definitive minutes of each Committee meeting, a draft
of which shall
be circulated for comment to all members of the Committee within
10 days after
the relevant meeting. Such minutes shall provide a description,
in reasonable
detail, of the Collaboration progress to date and of the
discussions at the
meeting, a list of any actions or determination approved by the
Committee and
any disagreements not resolved by the Committee. The Project
Leaders for the
parties shall discuss any comments on such minutes and finalize
the minutes by
no later than 30 days after the meeting. Any disagreement on the
minutes shall
be resolved in accordance with Section 2.2(a).
(D) PROJECT LEADERS. Celladon and TGC each shall appoint a
person
from the Committee or another representative of Celladon and TGC
not on the
Committee, but agreed upon by both parties to lead the project,
to coordinate
its part of the Collaboration and to be the primary contact
between the parties
with respect to the Collaboration ("PROJECT LEADERS"). Each
party shall notify
the other party as soon as practicable upon changing this
appointment.
2.3 CONDUCT OF THE COLLABORATIVE DEVELOPMENT PROGRAM. Subject to
the terms
and conditions of this Agreement, each party shall be
responsible for managing
and controlling its respective obligations under the Development
Plan. Each
party shall proceed diligently and in a timely manner with the
work set out in
the Development Plan by using its good faith efforts to allocate
sufficient
time, effort, equipment and facilities to the Collaboration and
to use personnel
with sufficient skills and experience as are required to
accomplish the
objectives of the Collaboration in accordance with the terms of
this Agreement.
Each party shall be entitled to utilize the service of Third
Parties to perform
its Collaboration responsibilities only upon the prior written
consent of the
other party (not to be unreasonably withheld) or as specifically
set forth in
the Development Plan or the Manufacturing Agreement.
Notwithstanding any such
consent, each party shall remain at all times responsible for
the performance of
its respective responsibilities under the Collaboration and
shall use
Commercially Reasonable Efforts to obtain the written agreement
of each such
Third Party, prior to the time such Third Party initiates work,
to assign
ownership of Inventions made in the course of Collaboration
activities to such
party.
2.4 FUNDING OF COLLABORATIVE DEVELOPMENT PROGRAM.
(A) FUNDING. Celladon shall be responsible for funding its
own
Collaboration activities. TGC hereby covenants to contribute to
the
Collaboration, up to US $2,000,000 ([*] through the performance
of activities
pursuant to the Development Plan. Such $2,000,000 contribution
of efforts shall
include payments to Third Parties contracted by TGC (raw
material purchases,
release testing etc.), with the remainder comprised of internal
research and
development and manufacturing efforts. Any Third Party costs
incurred in
accordance with the Development Plan that exceed $300,000 in the
aggregate shall
be borne by Celladon. For purposes of accounting for the
$2,000,000 contribution
of efforts, TGC shall utilize the TGC Accounting Method set
forth in Exhibit B.
If performance of TGC's obligations under the Development Plan
reasonably
requires funding in excess of US$2,000,000, Celladon shall be
responsible for
funding such excess expenses (in each case, to the extent of
[*]. TGC's
obligation to contribute up to $2,000,000 through the
contribution of efforts
under the Development Plan shall end on the second anniversary
of the Effective
Date of this Agreement. If TGC's performance of activities under
the Development
Plan does not reach $2,000,000 over the first 24 months of the
Collaboration,
TGC shall have no further obligation to perform activities
pursuant to the
Development Plan without compensation for
*CONFIDENTIAL TREATMENT REQUESTED.
10
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such activities by Celladon. All activities performed by TGC
pursuant to the
Collaboration shall be paid for at the then applicable FTE Rate
and
Manufacturing Rate specified in Exhibit B.
(B) REPORTING OF COSTS. Within 45 days of the end of each
quarter
during the Collaboration Term, TGC shall provide to Celladon a
reasonably
detailed written report of the costs incurred by TGC in
performing its
obligations under the Development Plan, including, without
limitation, the
number of hours dedicated to specific activities and an itemized
list of
out-of-pocket costs for materials, supplies and Third Party
services used in the
performance of the Development Plan. From and after such time
(if ever) as TGC
has applied US$2,000,000 to the performance of its obligations
under the
Development Plan in accordance with Section 2.4(a), TGC shall
provide an invoice
prior to the start of the quarter or partial quarter and
Celladon shall pay [*]
of the following partial quarter and/or whole quarter's
Development Plan
estimated budget within [*] days of the start of the next whole
quarter. Upon
receipt by Celladon of the written report of the costs incurred
by TGC in
performance of its obligations under the Development Plan during
the quarter,
Celladon shall pay TGC the amount remaining, calculated by
subtracting the
payment received by TGC for the estimated budget from the costs
incurred by TGC.
Each quarterly report of TGC under this Section 2.4(b) shall be
accompanied by
an itemized invoice for costs incurred by TGC in performance of
the Development
Plan that are in excess of US$2,000,000 in the aggregate. Each
such invoice
shall be due and payable upon receipt by Celladon. Failure to
make payments to
TGC within [*] business days of receipt by Celladon shall result
in the
obligation of Celladon to prepay the entire quarter estimated
budget in advance
of the start of each quarter.
(C) AUDIT OF COSTS. For a period of one year after each
Development
Plan year, TGC shall keep complete and accurate records of the
hours of
non-manufacturing time, the weeks of cGMP manufacturing facility
time (both
determined in accordance with Exhibit B) and the Third Party
costs utilized in
the performance of its obligations under the Development Plan,
in sufficient
detail to permit Celladon to verify the accuracy of TGC's
reports to Celladon
under Section 2.4(b). Such audit shall be limited to the
computation of the FTE
Rate and the Manufacturing Rate specified in Exhibit B, and the
compilation of
time, effort, and outside costs incurred by TGC in performance
of the
Development Plan. For a period of one (1) year following the
completion of each
calendar year, Celladon shall have the right to cause an
independent, certified
public accountant reasonably acceptable to TGC to audit such
records to confirm
such costs for a period covering not more than the preceding
year. Such audits
may be exercised during normal business hours upon reasonable
prior written
notice to TGC. Prompt adjustments shall be made by the parties
to reflect the
results of such audit. Celladon shall bear the full cost of such
audit unless
such audit discloses that TGC has overstated its costs in any
report delivered
by it with respect to the period audited by [*] or more, in
which case, TGC
shall bear the full cost of such audit and shall promptly
reimburse to Celladon
the amount of any overpayment.
2.5 EXCHANGE OF INFORMATION. Promptly following the Effective
Date and
from time to time as necessary thereafter during the
Collaboration Term, TGC
shall disclose to Celladon such TGC Technology as may be
necessary or useful for
the performance by Celladon of its responsibilities under the
Development Plan.
Promptly following the Effective Date and from time to time as
necessary
thereafter during the Collaboration Term, Celladon shall
disclose to TGC such
Celladon Technology as may be necessary or useful for the
performance by TGC of
its responsibilities under the Development Plan or the
Manufacturing Agreement.
*CONFIDENTIAL TREATMENT REQUESTED.
11
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2.6 RECORDS AND REPORTS.
(A) RECORDS. TGC and Celladon shall each maintain, and shall
use
Commercially Reasonable Efforts to cause any of their Third
Party contractors to
maintain, accurate and complete records that reflect all work
done and results
achieved in the performance of the Collaboration and all results
of any trials,
studies and other investigations conducted under this Agreement
by or on behalf
of TGC and Celladon, their Affiliates and Third Party
contractors, as
applicable.
(B) INSPECTION OF RECORDS. No more frequently than once per
calendar
year, a party shall have the right, during normal business hours
and upon
reasonable notice without undue interruption to normal business
operations and
provided such requests for visits are not otherwise
unreasonable, to inspect all
records of the other party referred to in Section 2.6(a) and
their Third Party
contractors (provided it is permitted under the agreement with
the Third Party
contractor); provided, however, that such party shall not have
the right to
review records to the extent that such records contain
information that does not
relate to the subject matter of this Agreement and/or the
Manufacturing
Agreement and access to such records shall be limited to the
narrowest
practicable group of other party's personnel who have a strict
need to know the
same for the purposes of such quality assurance inspections,
audits and
investigations. TGC shall permit representatives of Celladon to
enter TGC's
manufacturing facilities upon reasonable prior notice and at
intervals of no
more than once per year, during normal business hours for the
purpose of making
quality assurance audits of the facilities and of the procedures
and processes
used by TGC in storing, manufacturing and shipping any Selected
Product and to
inspect all related records. To the extent any such inspections,
notices,
responses, filings, audits and investigations could lead to the
disclosure of
any Confidential Information of TGC to Celladon: (i) access to
such Confidential
Information shall be limited to the narrowest practicable group
of Celladon's
quality assurance personnel who have a strict need to know the
same for the
purposes of such quality assurance inspections, audits and
investigations; and
(ii) any and all such Confidential Information and shall be
protected by
Celladon under Article 8. Each party shall maintain such records
and the
information disclosed therein in confidence in accordance with
Article 8.
(C) PROGRESS REPORTS. Within 45 days following the end of
each
calendar quarter during the Collaboration Term, each party shall
provide to the
other party a written progress report, or shall communicate by
some other
mechanism agreed to by both parties, including circulation of
the minutes of the
Committee, which shall describe the work performed by such party
to date on the
Collaboration, evaluate the work performed in relation to the
goals of the
Collaboration and provide such other information required by the
Collaboration
or reasonably requested by the other party relating to the
progress of the goals
or performance of the Collaboration. Such progress reports shall
include the
progress and results of activities conducted outside of the
Collaboration, by
Celladon or Third Parties on behalf of Celladon, on the Gene
Therapy Products
that are part of the Collaboration. Such activities would
include by example
preclinical, clinical and regulatory activities of the Gene
Therapy Products or
Selected Products.
2.7 INTELLECTUAL PROPERTY ANALYSIS AND LICENSING. Celladon and
TGC, [*],
shall conduct [*] analysis under Third Party intellectual
property rights with
respect to all elements of any Gene Therapy Product [*]. Third
Party Patents may
be identified as necessary for Celladon to develop, make, have
made, use, have
used, commercialize, offer for license, lease, sale or transfer
a Selected
Product. The parties agree to consult with, inform, and
collaborate on
identifying such
*CONFIDENTIAL TREATMENT REQUESTED.
12
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Third Party Patents and Information during the Term. Upon
identification of any
Third Party Patents, the parties will mutually agree to [*] to
obtain such
rights subject to the following conditions:
(A) Celladon shall be responsible for securing rights or
licenses to
Third Party Patents and Information directed to: (i) [*]; (ii)
[*]; (iii) [*];
and (iv) [*]. In the event Celladon determines it requires such
Third Party
Patent Rights and TGC makes a good faith determination that such
Third Party
Patent Rights are not necessary for TGC, Celladon will not [*].
Celladon will
involve TGC in the process of obtaining the Third Party Patent
Rights to the
extent necessary for TGC to ensure no such obligations are
created.
(B) TGC shall be responsible for securing rights or licenses
to
Third Party Patents and Information directed to: (i) [*], (ii)
[*], (iii) [*];
and (iv) [*].
All costs of [*] under Third Party intellectual property rights,
licensing,
complying with or obtaining other rights to any such Third Party
technology
shall be borne by [*] unless [*] in which case, Celladon and TGC
shall determine
the appropriate [*]. Royalty obligations associated with
obtaining such rights
shall be [*]. Each Party shall use Commercially Reasonable
Efforts to secure
rights or licenses identified in Sections 2.7(a) and 2.7(b), and
shall determine
a mutually agreeable solution if either Party is not able to
secure the licenses
or rights identified by the Parties.
2.8 COMPLIANCE. Each Party shall conduct the Collaboration in
good
scientific manner and in accordance with all applicable laws,
rules and
regulations, including, without limitation, and to the extent
applicable, all
current governmental regulatory requirements concerning cGMP.
Each party shall
notify the other party in writing of any material deviations
from applicable
regulatory or legal requirements. Celladon shall permit
representatives of TGC
to enter clinical trial sites upon reasonable prior notice at
reasonable
intervals, but no more frequently than once per year per site
unless a
significant adverse event has been reported to TGC, and with the
approval, such
approval shall not be unreasonably withheld or delayed, of the
appropriate
Celladon medical director, during normal business hours for the
purpose of
making quality assurance audits of the clinical trial sites and
of the
implementation of the clinical trial protocol according to the
appropriate
regulatory documents. Each party hereby certifies that it will
not and has not
employed or otherwise used in any capacity the services of any
person debarred
under Section 21 USC 335a in performing any activities under
this Agreement, the
Manufacturing Agreement or in performing activities, outside of
this Agreement,
that will be utilized in regulatory documents to support the
conduct of human
clinical trials of any Selected Product.
2.9 MATERIALS. In order to facilitate the Collaboration, each
party may
provide the other party with other chemical or biological
materials as necessary
for the conduct of the Collaboration. Each party shall use
materials supplied by
the other party solely: (a) for the purposes of carrying out its
respective
activities under the Collaboration in accordance with the terms
of this
Agreement during the Collaboration Term; (b) in the case of
Celladon, of
developing, commercializing and, if applicable, manufacturing
Selected Products
in accordance with this Agreement during the Term; and (c) in
the case of TGC,
manufacturing Selected Products in accordance with the
Manufacturing Agreement
during the Manufacturing Term. Neither party shall transfer,
deliver or disclose
any such materials of the other party, or any derivatives,
modifications or
components thereof, to any Third Party without the prior written
approval of the
providing party, except that: (A) TGC may transfer materials
provided by
Celladon (i) to TGC's subcontractors of its Collaboration
activities as
*CONFIDENTIAL TREATMENT REQUESTED.
13
<PAGE>
permitted in accordance with Section 2.3 for the sole purpose of
performing such
Collaboration activities or (ii) to TGC's Affiliates and Third
Party
subcontractors under the Manufacturing Agreement for the sole
purpose of
performing TGC's obligations thereunder; and (B) Celladon may
transfer Materials
provided by TGC (i) to Celladon's permitted subcontractors of
Collaboration
activities as permitted in accordance with Section 2.3 for the
sole purpose of
performing such Collaboration activities or (ii) to Celladon's
Affiliates,
licensees and agents without TGC's prior written consent for the
sole purpose of
developing, commercializing and, if applicable, manufacturing
Selected Products
in the Field; subject in each case to the terms and conditions
of this Agreement
and the Manufacturing Agreement. Neither party shall use any
materials provided
by the other party in humans, except as contemplated by this
Agreement and
permitted by applicable law. Materials supplied by a party
hereunder shall be
deemed to constitute Confidential Information of the supplying
party.
2.10 ACCESS TO OTHER TGC CAPABILITIES. Should Celladon wish to
have TGC
perform preclinical, regulatory and/or clinical development or
other services
not expressly contemplated by this Agreement (including, without
limitation,
EXHIBIT A hereto), TGC shall, in its sole discretion and
determination, provide
access to such capabilities, if and when available, at the rate
specified in
Exhibit B or, in light of the services that would be provided,
at a commercially
reasonable rate to be mutually agreed upon by the parties.
2.11 COLLABORATION TERM. The term of the Collaboration (the
"COLLABORATION
TERM") shall begin on the Effective Date and continue until the
earlier of (i)
completion of all activities under the Development Plan, or (ii)
the termination
of this Agreement by either party in accordance with Article 9.
Celladon may
terminate the Collaboration prior to its expiration upon written
notice to TGC;
provided, however, that Celladon shall pay to TGC within 30 days
of such
termination a termination fee in an amount equal to [*] as set
forth in the most
recently-approved budget included in a Development Plan. For the
avoidance of
doubt, in the event that Celladon terminates the Collaboration
under this
Section 2.11, then Article 2 shall terminate (subject to
Celladon's compliance
with any obligation incurred prior to such termination), TGC's
obligation
pursuant to Section 2.4(a) shall terminate, but this Agreement
shall otherwise
remain in full force and effect in accordance with its terms
related to
termination contained in Article 9.
3. DEVELOPMENT AND COMMERCIALIZATION OF SELECTED PRODUCTS.
3.1 DEVELOPMENT AND COMMERCIALIZATION OF SELECTED PRODUCTS.
Except as
otherwise expressly set forth in this Agreement or the
Manufacturing Agreement,
Celladon shall be solely responsible for the worldwide
development and
commercialization of Selected Products. Celladon agrees to use
Commercially
Reasonable Efforts to obtain Regulatory Approval of Selected
Products in the
United States and in such other countries as Celladon deems
appropriate and,
following Regulatory Approval, to commercialize Selected
Products. Celladon
shall provide quarterly updates to TGC of the progress of
clinical development
of Selected Products, the filing of any IND or NDA with respect
to a Selected
Product, and the Regulatory Approval of a Selected Product in
any jurisdiction.
Celladon shall, on a timely basis, provide TGC with information
in Celladon's
possession or control relevant to its or its Affiliates' or
Third Party
subcontractors' role as the holder of the INDs and NDAs and the
manager of the
clinical trials of Selected Products that is reasonably
necessary for and
relevant to TGC's obligations hereunder in complying with such
regulatory
requirements.
*CONFIDENTIAL TREATMENT REQUESTED.
14
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3.2 REGULATORY FILINGS AND APPROVALS.
(A) CELLADON RESPONSIBILITIES. Except as set forth in
Section
3.2(b) below or in the Manufacturing Agreement, Celladon or its
designee shall
be solely responsible for filing, obtaining and maintaining all
INDs, NDAs,
Regulatory Approvals and other licenses, registrations,
listings,
authorizations and approvals that may be required for the
manufacture,
development or commercialization of the Selected Products
throughout the world
(collectively, "REGULATORY DOCUMENTS"). Except as set forth in
Section 3.2(b)
below or in the Manufacturing Agreement, Celladon shall be the
sole and
exclusive owner of all Regulatory Documents. At Celladon's
request, TGC shall
take all actions necessary to assist Celladon in filing,
obtaining and
maintaining the Regulatory Documents. Celladon or its designee
shall serve as
the point of contact with the FDA and other regulatory agencies
concerning any
and all Regulatory Documents but may, as appropriate, request
TGC's assistance
with such matters. Celladon, with appropriate assistance from
TGC as and to the
extent provided under the appropriate Development Plan, will use
Commercially
Reasonable Efforts to assemble all Approval Applications needed
to conduct
clinical trials with any Selected Product developed or to be
developed under
the Agreement or supplied or to be supplied to Celladon under
the Manufacturing
Agreement. In connection with any Approval Application, Celladon
will have the
right to reference any relevant regulatory documents of TGC.
(B) TGC RESPONSIBILITIES. TGC shall use its Commercially
Reasonable
Efforts to prepare, file and permit Celladon, at Celladon's
request, to cross
reference the Selected Product chemistry, manufacture and
control ("CMC")
information in any Regulatory Document for a Selected Product.
For the
avoidance of doubt, TGC shall own all right, title and interest
in all TGC
regulatory documents and all Approval Applications filed by TGC
which are
necessary to obtain Regulatory Approvals required for
manufacture of Selected
Product by TGC, including the documents provided as part of the
CMC. With
respect to INDs and NDAs to be filed in the United States with
respect to
Selected Products, CMC information shall follow the format and
content set
forth in 21 C.F.R. Parts 312 and 314, respectively, and all
applicable rules,
regulations and guidelines promulgated thereunder. TGC shall
also be
responsible for obtaining and maintaining any filings, permits
and approvals
necessary for the manufacture of clinical and commercial supply
of Selected
Products, including, without limitation, DMFs for each Selected
Product and all
applicable permits and approvals required to operate TGC's
manufacturing
facilities (collectively, "MANUFACTURING DOCUMENTS"). Celladon
shall have, and
TGC hereby grants to Celladon, the right to reference the
Manufacturing
Documents for the purpose of obtaining and maintaining
Regulatory Approvals
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