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Exhibit 10.1
CONFIDENTIAL TREATMENT REQUESTED
WITH RESPECT TO CERTAIN PORTIONS HEREOF
DENOTED WITH "***"
RESEARCH COLLABORATION AND LICENSE AGREEMENT
This Research Collaboration and License Agreement (the
"Agreement" ) is made as of January 20, 2009. (the
"Effective Date" ), by and between BioDelivery Sciences
International, Inc. , a corporation having its principal
place of business at 801 Corporate Center, Suite 210, Raleigh,
North Carolina 27607, USA (" BDSI "), and THE DRUGS FOR
NEGLECTED DISEASES INITIATIVE , a not-for-profit foundation
organized under the laws of Switzerland, having its registered
office at 15 chemin Louis-Dunant, 1202 Geneva, Switzerland ("
DNDi "). BDSI and DNDi are referred to herein each
individually as a "Party" and collectively as the "Parties."
RECITALS
WHEREAS, BDSI possesses proprietary technology and know-how
related to the formulation of CAMB (as hereinafter defined);
WHEREAS, DNDi is developing drugs for neglected parasitic
diseases such as leishmaniasis and Chagas’ disease;
WHEREAS, the Parties wish to collaborate in the design
and conduct of a research and clinical collaboration to assess the
efficacy of CAMB in the treatment of visceral leishmaniasis and, if
such efficacy is established, DNDi desires to obtain rights to
register and distribute CAMB for use in the Field (as hereinafter
defined) in the Territory (as hereinafter defined) on the terms and
conditions hereinafter set out.
NOW, THEREFORE, in consideration of the foregoing
premises and the mutual covenants set forth below, and for other
good and valuable consideration, the receipt of which is hereby
acknowledged, DNDi and BDSI hereby agree as follows:
ARTICLE 1
DEFINITIONS
1.1 References in the body of this Agreement to "Sections" will
refer to the sections of this Agreement. In addition, as used
herein, the following initially capitalized terms will have the
following meanings:
1.2 "Affiliate" means any legal entity that directly or
indirectly owns or controls or is owned or controlled by, or is
under common control or ownership with, either Party, with
"control" (for purposes of this Section 1.1) meaning
the direct or indirect beneficial ownership of fifty-one percent
(51%) or more of the share capital, or the power to appoint a
majority of the managing directors of such legal entity.
1.3 "Agreement" means this Research Collaboration and
License Agreement.
1.
CONFIDENTIAL TREATMENT
REQUESTED
WITH RESPECT TO CERTAIN PORTIONS HEREOF
DENOTED WITH "***"
1.4 "Alliance Manager" means a single
individual appointed by each Party to assist in the administration
of the Agreement and to oversee the timing of events as described
herein take place when and how defined.
1.5 "BDSI Background IP" means (a) any Patents or
patent applications either granted or filed by BDSI and which are
necessary or useful in the optimization, development,
manufacturing, or distribution of CAMB and (b) any Know-How
developed by or on behalf of BDSI which relates to CAMB.
1.6 "Collaboration IP" means (a) any Know-How made,
developed or conceived under the R&D Plan according to this
Agreement in each case solely or jointly by an employee, consultant
or agent of DNDi or BDSI or their respective Affiliates,
subcontractors or sublicensees, (b) any Patents describing,
claiming or covering the Know-How developed according to section
1.6, a, and (c) any other intellectual property rights in or
to such Know-How.
1.7 "Fully-Burdened Manufacturing Costs" means: the costs
of all raw materials and labor used or consumed in such
manufacture, packaging costs and expenses, shipping, handling, and
delivery costs related to delivery of CAMB, quality assurances and
quality control related expenses and all overhead amounts allocable
to such manufacturing and delivery (including without limitation
amortized capital equipment costs) provided that: (1) all of
the foregoing shall be calculated in accordance with US GAAP,
(ii) BDSI shall, notwithstanding anything to the contrary in
the Agreement, use commercially reasonable efforts to minimize
Fully-Burdened Manufacturing Costs.
1.8 "Develop" or "Development" means the performance of
all pharmaceutical and pre-clinical development, clinical
development activities and any post Regulatory Approval
development, and regulatory activities that are required to obtain
or maintain Regulatory Approval.
1.9 "Distribution" means all activities that are
undertaken after obtaining Regulatory Approval to make CAMB
available to prescribers and/or users in the Territory for use in
the Field.
1.10 "Distribution Through the Public Sector" means
Distribution, disposition or use of CAMB in the Territory for use
in the Field by a Public Sector Agency.
1.11 "Governmental Authority" means any court, agency,
department or other instrumentality of any foreign, federal, state,
county, city or other political subdivision.
1.12 "Effective Date" means the date set forth in the
first paragraph of this Agreement.
1.13 "Field" means the treatment of, African Human
Trypanosomiasis (HAT), Chagas’ disease and both Visceral and
Cutaneous Leishmaniasis.
1.14 "Filing Party" has the meaning set out in
Section 6.1.
1.15 "Joint Research Committee" or "JRC" has the
meaning set out in Section 2.2(a).
1.16 "Know-How" means information or materials including,
without limitation, discoveries (whether patentable or not),
formulae, materials, practices, methods, knowledge, know-how,
processes, test data (including pharmacological, toxicological and
clinical information and test data), analytical and quality control
data, and manufacturing, marketing, pricing, distribution, cost and
sales data.
2.
CONFIDENTIAL TREATMENT
REQUESTED
WITH RESPECT TO CERTAIN PORTIONS HEREOF
DENOTED WITH "***"
1.17 "Intellectual Property Rights"
or "IPR" mean both Patents and Know-How.
1.18 "Laws" mean all (a) applicable laws, statutes,
rules, regulations, ordinances and other pronouncements having the
effect of law of any federal, national, multinational, state,
provincial, or other political subdivision, domestic or foreign;
and (b) any guideline or directive of the World Health
Organization or other applicable non-governmental agency.
1.19 "Non-Filing Party" has the meaning set out in
Section 6.1.
1.20 "Patent" means any and all (a) patents and
patent applications (provisional and non-provisional);
(b) continuations, divisionals, continuations-in-part,
continued prosecutions, re-examinations, reissues, utility models,
petty and other patent applications or any applications claiming
priority from any of the foregoing, and all patents that issue
therefrom; (c) counterparts, substitutions, restorations,
extensions (including, without limitation, patent term extensions
(both administrative and regulatory and including any pediatric
marketing exclusivity), supplementary protection certificates,
registrations, confirmations, validations and renewals of any of
the foregoing; and (d) invention certificates and other
government grants for the protection of inventions or industrial
designs.
1.21 "CAMB" means a pharmaceutical formulation of
Amphotericin B using BDSI’s encochleation technology
(Bioral™ CAMB), the manufacture, use, import or distribution
of which (a) incorporates BDSI Background IPR or
(b) would, in the absence of a license, infringe a claim of
any Patent forming part of BDSI Background IPR
1.22 "Program Data" has the meaning provided in
Section 2.7(a).
1.23 "Program Manager" means the representative from DNDi
responsible for managing the R&D Plan.
1.24 "Project Team" means a team composed of adequately
qualified representatives of both Parties which shall be
responsible for managing and guiding the research and development
activities conducted under this Agreement, under the direction of
the Program Manager.
1.25 "Project Plan" means a detailed plan setting forth the
Parties’ specific activities for one or more activities under
the R&D Plan, as approved and adopted from time to time by the
JRC as guided and managed by the Project Team.
1.26 "Public Sector Agency" means any Governmental Authority
(but specifically excludes any military or para-military
organization, branch, department or agency of any Governmental
Authority) or entity organized under applicable tax laws as a
non-profit or public benefit organization or entity, including,
without limitation, ministries of health, governmental
organizations such as the World Health Organization or UNICEF,
non-governmental organizations operating for the provision of
health care within the public health area such as Médecins
sans Frontières or recipients of funding from the Global
Fund to Fight Aids, Tuberculosis and Malaria. Public Sector
Agencies specifically exclude any non-state or government-supported
hospitals and clinics which wish to purchase CAMB for their own
use.
1.27 "Regulatory Approval" means any and all approvals
(including supplements, amendments, pre- and post-approvals),
licenses, registrations or authorizations of any national,
supra-national, regional, state or local regulatory agency,
department, bureau, commission, council or other governmental
entity, that are necessary for the manufacture, Distribution or use
of CAMB in the Field in any regulatory jurisdiction within the
Territory.
3.
CONFIDENTIAL TREATMENT
REQUESTED
WITH RESPECT TO CERTAIN PORTIONS HEREOF
DENOTED WITH "***"
1.28 "Regulatory Authority" means any
Governmental Authority and supranational authorities such as WHO
with responsibility for granting any licenses or approvals
necessary for the marketing, distribution and sale of
pharmaceutical products.
1.29 "Regulatory Documentation" means, with respect to CAMB in
the Field, all Regulatory Filings and supporting documents created
and submitted to a Regulatory Authority, and all data contained
therein, including, without limitation, any investigator’s
brochures, drug master files, details on the active pharmaceutical
ingredient, details on the analytical methods used for the active
drug substance and drug product, drug product manufacturing ,
process and controls, clinical and pre-clinical study reports,
summary analyses, and any and all other supporting documentation,
correspondence to and from a Regulatory Authority, minutes from
teleconferences with Regulatory Authorities, registrations and
licenses, regulatory drug lists, advertising and promotion
documents shared with Regulatory Authorities, adverse event files,
complaint files and manufacturing records.
1.30 "Regulatory Filing" means any and all filings required by
Regulatory Authorities relating to the study, Development,
manufacture or Distribution of CAMB in the Field.
1.31 "Research and Development Plan" or "R&D Plan"
means the overall strategic plan for the evaluation of the efficacy
of CAMB for use in the Field (and should efficacy be established,
the strategy for all Regulatory Filing in the Territory) including
all Project Plans. The R&D Plan will describe the individual
objectives for pharmaceutical, preclinical and clinical development
necessary for project completion and Regulatory Filing and
Regulatory Approval as well as the all associated timelines and
estimated budgets. The R&D Plan and the Project Plan will be
conducted by DNDi and BDSI under this Agreement and as set forth in
Exhibit A hereto, and may be amended from time to time after
the Effective Date by both Parties’ mutual written
agreement.
1.32 "Term" has the meaning provided in Section 10.1.
1.33 "Territory" means all countries of the world
excluding Japan, Australia, New Zealand, Russia, CIS countries,
China, and all countries in North America and any country in, or
that joins the European Union.
1.34 "Third Party" means a person or entity other than
(a) DNDi, (b) BDSI, or (c) an Affiliate of either
Party.
ARTICLE 2
RESEARCH AND DEVELOPMENT PROGRAM
2.1 Overview; R&D Plan. The Parties’ objective is to
jointly conduct the R&D Plan for the purpose of assessing the
efficacy of CAMB in the Field and, if such efficacy is established,
DNDi will be responsible for obtaining all Regulatory Approvals and
for the Distribution Through the Public Sector of CAMB under the
terms hereinafter set out. The Parties’ framework for their
activities hereunder is set forth in the R&D Plan, which may be
amended only by mutual written agreement of the Parties. If the
R&D Plan or any Project Plan conflicts with, or creates
ambiguities with, this Agreement, then this Agreement will
prevail.
4.
CONFIDENTIAL TREATMENT
REQUESTED
WITH RESPECT TO CERTAIN PORTIONS HEREOF
DENOTED WITH "***"
2.2 Joint Research Committee.
(a) Formation; Composition. Promptly after the Effective
Date, the Parties will appoint a joint research committee
consisting of two (2) representatives from each Party (the "
Joint Research Committee " or " JRC "). Either Party
may change its appointed JRC members upon written notice to the
other Party. The JRC will construct the R&D Plan and appoint
the necessary Project Team. The JRC will oversee the activities of
the Project Team including the review and approval of the Project
Plan and any modifications. The JRC will continue to operate for as
long as CAMB is being developed under this Agreement.
(b) Duties. The JRC will (a) oversee the conduct of
the R&D Plan, (b) serve as an information-sharing forum
between the Parties regarding the R&D Plan, (c) design,
manage and organize clinical trials, data storage and access,
(d) approve Project Plans detailing the conduct of the Project
Team and the Parties’ research activities, (e) review
the results of the R&D Plan, including the results of on-going
clinical trials, on a regular basis (to be agreed upon by the JRC),
and (f) propose to the Parties modifications to the R&D
Plan as appropriate. The JRC will have only those powers set forth
in this Section 2.2 and will have no power to amend or waive
compliance with this Agreement.
(c) Meetings. Within thirty (30) days after the
Effective Date, the JRC will meet, in person or by video or
teleconference to discuss and approve a Project Plan for the
Parties’ initial activities under this Agreement, and to
finalize within 60 days of the Effective Date a complete R&D
Plan to constitute the Annex A of the present Agreement.
Thereafter, the JRC will meet regularly as determined by its
members, in person or by video or teleconference. The JRC will be
chaired by a representative of DNDi. The JRC is required to and
will keep complete and accurate detailed minutes of its meetings,
including any decisions made. The chair (or his or her designee)
shall prepare and circulate an agenda ten (10) business days
before each meeting of the JRC and meeting minutes after each
meeting for review and approval by the JRC. In all cases the JRC
will comply with the timings described in this section and provide
the Alliance Managers with all dates and times for meetings and all
minutes described in this section.
(d) Decision-Making. The JRC representatives of each
Party will each have one (1) vote in the JRC. The JRC will
make all decisions by majority vote and in case of deadlock the JRC
shall refer the matter to the Alliance Managers who will attempt to
resolve the deadlock. The Alliance Managers shall consult with each
Parties executive management and attempt to resolve the dispute.
For the avoidance of doubt, DNDi shall have the final decision in
any matter regarding the funding of clinical trials. Should the
Alliance Managers with the input of the Parties executive
management be unable to resolve the dispute, the matter shall be
handled as defined in Section 11.
2.3 Project Team. The JRC will establish a Project Team
responsible for day-to-day management of all activities under the
R&D Plan and Project Plans. The purpose of the Project Team
will be to facilitate the efficient conduct of the R&D Plan, to
provide information and assistance with respect to specific
activities conducted under the R&D Plan, and to assist with
data analysis and interpretation. It is possible that members of
the Project Team could also be members of the JRC.
2.4 BDSI’s Performance of the R&D Plan
(a) Research and Development Activities. BDSI agrees to
use its best efforts to perform or have performed at its own cost
the responsibilities assigned to it in the R&D Plan and Project
Plans, all in accordance therewith and in a manner consistent with
any timelines set forth therein. In particular, BDSI agrees to
dedicate the appropriate number of FTEs to perform the tasks
described in the R&D Plan. BDSI will ensure that its
responsibilities under the R&D Plan and Project Plans are
conducted in compliance with all applicable Laws or guidelines
pertaining to good research practices and/or good laboratory
practices.
5.
CONFIDENTIAL TREATMENT
REQUESTED
WITH RESPECT TO CERTAIN PORTIONS HEREOF
DENOTED WITH "***"
(b) Know-How Contribution and Grant of
Rights. At its own cost, BDSI will provide to DNDi all
technical information and data relating to CAMB in its possession
and grant DNDi all rights under BDSI Background IP which are
reasonably necessary or useful for DNDi to conduct its activities
under this Agreement. Determination of "reasonably necessary" shall
be made in consultation with the JRC.
(c) Clinical Product Supply. BDSI will manufacture and
make available to DNDi samples of CAMB in such quantities as shall
be necessary for DNDi to conduct its activities under the R&D
Plan. Such samples will be subject to the provisions of
Section 2.6 below and sold by BDSI to DNDi at a price to be
agreed between the Parties once agreement on clinical trial
protocols have been reached by the JRC. DNDi and BDSI management
will base the cost of clinical trial materials on the cost of the
raw materials necessary for the production of CAMB and agree to a
reasonable and sufficient additional cost to cover BDSI’s
internal costs or the costs of using an external manufacturer. DNDi
acknowledges (a) any or all of BDSI’s supply obligations
hereunder can be supplied by Third Party subcontractors which will
provide the necessary staff, equipment, instruments, raw materials
and facilities to carry out BDSI’s manufacturing obligations,
(b) BDSI will remain responsible for the conduct of all of its
obligations under this Agreement, including those conducted by such
Third Party subcontractors and DNDi will have no responsibility for
managing such activities or such subcontractors, (c) BDSI will
keep the JRC informed of any Third Party subcontractor which BDSI
engages to perform its obligations under this section of the
Agreement.
2.5 DNDi’s Performance of the R&D Plan.
(a) Research and Development Activities. DNDi agrees to
use its best efforts to perform or have performed at its own cost
the responsibilities assigned to it in the R&D Plan and Project
Plans, all in accordance therewith and in the manner consistent
with any timelines set forth therein. In particular, DNDi agrees to
dedicate the appropriate number of FTEs to perform the tasks
described in the R&D Plan. DNDi will ensure that its
responsibilities under the R&D Plan and Project Plans are
conducted in compliance with all applicable Laws or guidelines
pertaining to good research practices and/or good laboratory
practices. BDSI acknowledges and agrees that (a) DNDi’s
research activities under the R&D Plan can be conducted by
Third Party subcontractors which will provide the research staff,
equipment, instruments, supplies and facilities necessary to carry
out DNDi’s responsibilities under the R&D Plan and
Project Plans, (b) DNDi will remain responsible for the
conduct of all of its obligations under this Agreement, including
those conducted by such subcontractors and BDSI will have no
responsibility for managing such activities or such subcontractors,
(c) DNDi will keep the JRC informed of any other Third Party
subcontractor which it may subsequently engage to perform its
obligations under this Agreement.
(b) Program Manager. DNDi will be responsible for the
overall management of the R&D Plan through the Program Manager
and the other representatives of the JRC and Project Team. DNDi,
promptly after the Effective Date will appoint a Program Manager
and will advise BDSI in writing of the name and qualifications of
the appointed Program Manager. The Program Manager maybe removed
from such appointment by a majority vote of the JRC. Should the
Program Manager be removed DNDi will appoint a new Program Manager
according to this section.
(c) Know-How Contribution and Grant of Rights. At its own
cost, DNDi will provide to BDSI all technical information and data
relating to CAMB in its possession and access to and a right of
reference to all Regulatory Documentation and Regulatory Filings
and grant BDSI all rights thereunder which are reasonably necessary
or useful for BDSI to conduct its activities related to CAMB.
6.
CONFIDENTIAL TREATMENT
REQUESTED
WITH RESPECT TO CERTAIN PORTIONS HEREOF
DENOTED WITH "***"
(d) Scientific Advisory Committee. BDSI
acknowledges that DNDi’s continued performance of the R&D
Plan is subject to review by DNDi’s Scientific Advisory
Committee, which may recommend to terminate DNDi’s
performance of the R&D Plan at any time.
2.6 Material Transfer. To the extent any material is
transferred by one Party to another under this Agreement the Party
receiving such material will use the material solely for the
purposes of performing its responsibilities assigned to it under
the R&D Plan and applicable Project Plan(s) in compliance with
all applicable Laws. Neither Party will use the other Party’s
material for any other purposes. Neither Party will sell, transfer,
disclose or otherwise provide access to the other Party’s
material without the prior written consent of the other Party;
provided that each Party may allow access to the other
Party’s material to such first Party’s employees,
consultants, agents and subcontractors for purposes of performing
the R&D Plan in accordance with the applicable Project Plan(s),
and provided further that such employees, agents and
subcontractors are apprised of the proprietary nature of such
material and are bound by written agreement to protect the
confidentiality of such material and any results obtained from
working with such material and to assign to the subcontracting
Party any IPR made in the course of working with such material.
Upon completion of all activities under the R&D Plan or the
earlier expiration or termination of this Agreement, each Party
will return any remaining quantities of the other Party’s
material to such other Party, or otherwise dispose of such material
as directed by such other Party and certify in writing to the other
Party such destruction has taken place.
2.7 Data and Reports.
(a) Data. Each Party will keep complete and accurate
notes, accounts and records of the data, results, materials, or
other information arising out of or resulting from the research
performed by such Party under this Agreement (collectively, "
Program Data "). The Program Data will be deemed the
Confidential Information of both Parties under this Agreement, and
both Parties shall have unfettered rights to access and reference
to the Program Data in support of their clinical and regulatory
activities.
(b) Reports. For so long as a Party has obligations to
conduct research or development activities under the R&D Plan,
such Party will provide written quarterly reports to the JRC, and
additional updates as requested by the JRC, summarizing all Program
Data created in the preceding quarter by such Party, including a
description of any inventions made, developed, conceived or reduced
to practice by such Party. The purpose of these reports is to
ensure the continuous sharing between the Parties of information
regarding results achieved under the R&D Plan and to enable any
Party to take prompt action to file any patent applications
covering the Collaboration IP. In addition, each Party will submit
to the JRC semi-annual written reports outlining the milestones
achieved by such Party, key decisions made, and progress toward
achieving the objectives set forth in the R&D Plan. The JRC
will provide to the Alliance Managers copies of all reports
required under this section and it will be the responsibility of
the Alliance Managers to assure the JRC and their respective Party
complies with all responsibilities under this section in a timely
manner.
7.
CONFIDENTIAL TREATMENT
REQUESTED
WITH RESPECT TO CERTAIN PORTIONS HEREOF
DENOTED WITH "***"
ARTICLE 3
REGULATORY APPROVALS, MANUFACTURE AND
DISTRIBUTION
3.1 Allocation of Responsibilities. Beginning with the
completion of the R&D Plan, DNDi will have sole responsibility
for seeking and obtaining Regulatory Approvals for CAMB, and for
the Distribution Through the Public Sector of CAMB in the Territory
for use in the Field. DNDi may use a third party for Regulatory
Approval activities, provided that the terms of the agreements with
such third party conform to the terms of the present Agreement.
BDSI shall have sole responsibility for the manufacture and supply
to DNDi of CAMB for DNDi’s Distribution.
3.2 Regulatory Approvals. DNDi will be responsible,
either directly or through a third party, and shall bear all costs
for developing Regulatory Documentation, preparing and submitting
Regulatory Filings, and seeking and maintaining Regulatory
Approvals in the Territory for CAMB’s use in the Field. BDSI
agrees to provide DNDi with all information and data in its
possession relating to CAMB and to cooperate with DNDi, as
reasonably requested by DNDi, in preparing and filing all
Regulatory Documentation. DNDi will have the right to use all parts
of the Program Data for developing Regulatory Documentation and
BDSI will have the right to access or reference any of DNDi’s
Regulatory Approvals for BDSI’s private sector Distribution
of CAMB in or outside the Territory. Prior to DNDi providing a
Regulatory Authority any Regulatory Documents in conjunction with
any Regulatory Filing, DNDi will engage BDSI for review and comment
on the Regulatory Documents prior to submission.
3.3 Manufacture and Supply. During the Term and subject
to the provisions of Section 4.1, BDSI will be responsible for
the exclusive, subject to section 3.3 (a), manufacture and supply
of CAMB to DNDi for Distribution in the Territory and for all costs
associated therewith. Prices at which BDSI will sell CAMB to DNDi
are set out in section 5.3 below.
(a) Should BDSI be unable to meet DNDi’s
Distribution needs as evidenced by failure to meet *** of
DNDi’s forecast needs for *** consecutive quarters,
DNDi shall be able to engage a secondary supplier to meet any BDSI
shortfall in DNDi’s supply needs with the assistance of BDSI.
However, in every instance, DNDi shall purchase the full quantity
of CAMB available from BDSI prior to engaging a secondary
manufacturer. Should DNDi engage a secondary supplier due to BDSI
shortfall of DNDi’s Distribution needs, DNDi will revert back
to BDSI as the exclusive supplier of DNDi’s needs once BDSI
is able to show manufacturing capacity equivalent to *** of
DNDi’s forecast needs for any upcoming quarter.
(b) Should BDSI determine, in its sole discretion, that
parallel importing, or divers
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