Exhibit 10.19
THIS (the "AGREEMENT") is entered into as of
August 19, 2004 (the "EFFECTIVE DATE"), by and between SPINAL MUSCULAR ATROPHY
FOUNDATION (the "FOUNDATION"), having its principal place of business located at
0000 Xxxxxxxx, 00xx Xxxxx, Xxx Xxxx, Xxx Xxxx, 00000, and COMBINATORX,
INCORPORATED ("COMBINATORX"), having its principal place of business located at
000 Xxxxxx Xxxxxx, Xxxxxx, Xxxxxxxxxxxxx 00000.
RECITALS
WHEREAS, CombinatoRx has developed a proprietary combination drug discovery
platform and is engaged in the identification and development of new combination
therapies;
WHEREAS, the Foundation is dedicated to accelerating the development of a
treatment or cure for spinal muscular atrophy;
WHEREAS, the Foundation wishes to sponsor, and CombinatoRx wishes to
perform, research focused on identifying clinical combination drug candidates as
potential treatments for spinal muscular atrophy, subject to the terms and
conditions of this Agreement, including the Res3arch Plan attached hereto as
EXHIBIT A; and
WHEREAS, it is the intent of the Foundation and CombinatoRx to disseminate
the results of the Research to other investigators in the spinal muscular
atrophy research community and to medical professionals treating spinal muscular
atrophy patients and to provide a mechanism for transfer of rights to the
patents and intellectual property developed by CombinatoRx as a result of the
Research to the Foundation if CombinatoRx elects not to pursue commercial
development of any drug candidates identified during the Research.
NOW, THEREFORE, in consideration of the foregoing and the mutual covenants
and premises contained in this Agreement, the parties hereto agree as follows:
1. DEFINITIONS.
1.1 "ADDITIONAL PAYMENTS" shall mean all amounts actually paid to
or on behalf of CombinatoRx pursuant to Section 4.2.
1.2 "AFFILIATE" shall mean any corporation or other entity that
controls, is controlled by, or is under common control with, a party. A
corporation or other entity shall be regarded as in control of another
corporation or entity if it owns or directly or indirectly controls more that
50% of the voting securities or other ownership interest of the other
corporation or entity, or if it possesses, directly or indirectly, the power to
direct or cause the direction of the management and policies of the corporation
or other entity.
1.3 "AVAILABLE PRODUCT" shall mean a Drug Candidate that either:
1.
(a) is composed of a combination of two or more
Pharmaceutical Products, each said Pharmaceutical Product being suitable for
administration to patients as part of a co-therapy regimen in which neither
Pharmaceutical Product is in any way altered with respect to its registration in
the FDA Orange Book registry; or
(b) is a single Pharmaceutical Product suitable for
administration to patients without being in any way altered with respect to its
registration in the FDA Orange Book registry.
For the purposes of this definition, "PHARMACEUTICAL PRODUCT" shall mean a drug
product which has been approved by the FDA with a corresponding dosage and
formulation registered in the FDA Orange Book, and is legally available for sale
in the United States.
1.4 "COMBINATORX TECHNOLOGY" shall have the meaning provided in
Section 6.1(b).
1.5 "CONFIDENTIAL INFORMATION" shall mean any confidential or
proprietary information of a party, including, without limitation, information
relating to any compound, product specifications, data, know-how, formulations,
research project, work in process, future development, scientific, engineering,
manufacturing, marketing, business plan, financial or personnel matter relating
to such party, its present or future products, sales, suppliers, customers,
employees, investors or business, whether in oral, written, graphic or
electronic form, subject to the limitations specified in Section 5.2 hereof.
Without limiting the generality of the foregoing, the terms of this Agreement
shall be deemed the Confidential Information of both parties.
1.6 "DATA" shall have the meaning provided in Section 6.1(a).
1.7 "DILIGENCE MILESTONE" shall have the meaning provided in
Section 3.2.
1.8 "DRUG CANDIDATE" shall have the meaning provided in Section
2.3(b).
1.9 "FDA" shall mean the United States Food and Drug Administration
(or its successor agency).
1.10 "FIELD" shall mean the treatment of SMA, any neurodegenerative
condition, or any other disease or disorder affecting motor neurons.
1.11 "HIT" Shall have the meaning provided in Section 2.3(a).
1.12 "IND" shall mean an Investigational New Drug Application filed
with the FDA.
1.13 "INFORMATION" shall mean all tangible and intangible
techniques, technology, practices, trade secrets, inventions (whether or not
patentable), 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,
2.
software, algorithms, compositions of matter, cells, cell lines, assays, animal
models and physical, biological or chemical material.
1.14 "IP FILING PERIOD" shall have the meaning provided in Section
5.4.
1.15 "LEAD CANDIDATE" shall have the meaning provided in Section
2.3(b).
1.16 "LICENSEE" shall mean a Third Party to whom CombinatoRx 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 Drug Candidate or Product, beyond the mere
right to purchase Drug Candidate or Product from CombinatoRx or its Affiliates.
1.17 "MOUSE MODEL" shall have the meaning provided in Section 2.2.
1.18 "NET SALES" shall mean the gross amounts received by
CombinatoRx and its Affiliates (but not their respective Licensees) for sales of
Products to Third Parties that are not Affiliates or Licensees of the selling
party (unless such Affiliate or Licensee is the end user of such Product, in
which case the amount billed therefor shall be deemed to be the amount that
would be billed to a Third Party end user in an arm's-length transaction), less
the following items, as allocable to such Product (if not previously deducted
from the amount invoiced): (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.
1.19 "PATENTS" shall mean (a) United States and foreign patents,
re-examinations, reissues, renewals, extensions and term restorations, and
foreign counterparts thereof, and (b) pending applications for United States and
foreign patents, including, without limitation, provisional applications,
continuations, continuations-in-part, divisional and substitute applications,
including, without limitation, inventors' certificates, and foreign counterparts
thereof.
1.20 "PRE-CLINICAL MODULE" shall have the meaning provided in
Section 2.3(b).
1.21 "PRODUCT" shall mean a pharmaceutical product comprising or
containing a Drug Candidate, or any analog or derivative of any such Drug
Candidate, including, in each case, all formulations, line extensions and modes
of administration thereof.
1.22 "PRODUCT REVENUES" shall mean Net Sales of Products by
CombinatoRx and its Affiliates, plus all royalties, license fees, milestone
payments, annual maintenance fee or similar payment or consideration paid by a
Licensee to CombinatoRx or its Affiliates in consideration for the grant by
CombinatoRx or its Affiliate of a license to develop, make, have made, use,
distribute for sale, promote, market, offer for sale, sell, have sold, import or
export Drug Candidates or Products (with any of the foregoing consideration
received by CombinatoRx other than in the form of cash to be valued as its fair
market value as of the date of receipt); PROVIDED, HOWEVER, that "Product
Revenues" shall in any event exclude any funds paid to directly
3.
support research and/or development actually being performed by CombinatoRx or
its Affiliates (in amounts that are commercially reasonable in light of the
research and/or development services being performed), and payments for equity
or debt securities of CombinatoRx or its Affiliates (except to the extent such
payments exceed the fair market value of such securities upon date of receipt,
in which event such excess over fair market value shall be included in the
calculation of Product Revenues).
1.23 "RESEARCH" shall mean the activities conducted pursuant to the
Research Plan.
1.24 "RESEARCH FUNDS" shall mean all amounts actually paid to
CombinatoRx pursuant to Section 4.1.
1.25 "RESEARCH PLAN" shall mean the research plan attached hereto as
EXHIBIT A, which is incorporated herein by this reference, as such research plan
may be modified from time to time by mutual written agreement of the Foundation
and CombinatoRx.
1.26 "RESEARCH INTELLECTUAL PROPERTY" shall mean (a) Information
developed by or on behalf of CombinatoRx in the course of performing the
Research and (b) Patents claiming such Information. Without limiting the
generality of the foregoing, "Research Intellectual Property" shall include any
and all Hits, Lead Candidates, Drug Candidates, other candidate co-therapy
regimens, combination drugs, drug admixtures, drug co-formulations and
processing technology, in each case, to the extent developed by CombinatoRx
during the Research.
1.27 "TERM" shall have the meaning provided in Section 2.5.
1.28 "SCREENING MODULE" shall have the meaning provided in Section
2.3(a).
1.29 "SMA" shall mean spinal muscular atrophy.
1.30 "THIRD PARTY" shall mean any entity other than the Foundation
or CombinatoRx or an Affiliate of the Foundation or CombinatoRx.
2. CONDUCT OF THE RESEARCH.
2.1 OBJECTIVE. Subject to the terms and conditions of this
Agreement, the parties agree that, during the Research Term, CombinatoRx shall
perform the Research in accordance with the Research Plan with the goal of
identifying and advancing to IND stage at least one Drug Candidate for the
treatment of SMA.
2.2 RESEARCH PLAN; CONTRIBUTIONS. The Research Plan sets forth the
activities to be conducted by CombinatoRx, together with an anticipated schedule
for completion of such activities. CombinatoRx agrees to use commercially
reasonable efforts to perform the Research on the schedule specified in the
Research Plan. The parties may, by mutual written agreement, amend the Research
Plan from time to time during the course of the Research and, in connection
therewith, may modify the funding amounts and schedule set forth in Section 4.1
or
4.
provide for Additional Payments, as appropriate. Each party shall contribute to
the Research the materials and services specified in the Research Plan. Without
limiting the generality of the foregoing, the parties acknowledge that the
performance of some of the responsibilities borne by CombinatoRx in the
Pre-Clinical Module will require a validated animal model of SMA (the "MOUSE
MODEL"). The Foundation agrees that it will have primary responsibility to
identify a source for, and take necessary steps to arrange for the availability
to CombinatoRx of, the Mouse Model for use in the Research. Subject to the
provisions of Section 4.2 hereof, CombinatoRx agrees that it will work
diligently and cooperatively with the Foundation, as appropriate, to arrange for
the use of the Mouse Model by CombinatoRx in the conduct of the Research. The
parties' objective is that the Mouse Model be available to be transferred to
CombinatoRx within nine months of the Effective Date in order to keep the
Research on schedule. If for any reason, the Mouse Model cannot be made
available to CombinatoRx in a timely manner relative to the Research Plan, the
parties will meet to discuss options for amending the Research Plan; said
options may include, but are not limited to (i) using another methodology or
animal model of SMA; (ii) preparing an IND for submission to the FDA without the
research results generated from the Mouse Model; or (iii) attempting to initiate
a human clinical study of a Lead Candidate under regulatory or Institutional
Review Board approval in a non-United States jurisdiction (collectively the
"PRE-CLINICAL OPTIONS"). To the extent that the parties agree upon a revision to
the Research Plan to include a Pre-Clinical Option, the Foundation agrees to be
responsible for any charges, costs, or expenses associated with the revised
Research Plan as provided under Section 4.2 of this Agreement, and the parties
agree that the Diligence Milestones set forth in Section 3.2 of this Agreement
will also be adjusted as a result of the revised Research Plan. Further, if the
Mouse Model cannot be made available to CombinatoRx and the Foundation is
unwilling to underwrite the additional costs and expenses (if any) associated
with the revised Research Plan including a suitable Pre-Clinical Option, then
this Agreement will automatically terminate after the selection of the Lead
Candidates and submission of the PK/PD Final Report as described in the Research
Plan for the Pre-Clinical Module, subject to the provisions of Section 7.3
hereof. In the event of such termination, the Foundation will be responsible for
all costs and expenses incurred and/or accrued to the date of termination, and
CombinatoRx will retain sole ownership of all Data, research results, and
Research Intellectual Property.
2.3 THE RESEARCH. As more fully described in the Research Plan, the
Research will be conducted in two modules:
(a) SCREENING MODULE. In the first module of the Research
(the "SCREENING MODULE"), CombinatoRx shall screen a library of approximately
500 drug compounds in order to identify promising combination drugs for the
potential treatment of SMA. The parties agree that the screening library will
consist of drug molecules which are known to be able to cross the human
blood-brain barrier. As promptly as practicable following the Effective Date,
the parties shall work together to define the screening library for the
Screening Module. For such screening, CombinatoRx shall use a fibroblast SMN
protein induction assay optimized for combination high-throughput screening by
CombinatoRx. CombinatoRx shall disclose the results of such screening to the
Foundation in accordance with Section 2.6, and the parties shall consult with
each other to select one or more combination drug candidates meeting the
criteria set forth in the Research Plan (or otherwise mutually agreed upon by
the parties) for further
5.
evaluation in animal models (each such combination drug candidate being
hereinafter referred to as a "HIT").
(b) PRE-CLINICAL MODULE. In the second module of the
Research (the "PRE-CLINICAL MODULE"), CombinatoRx shall: (i) assess the
pharmacokinetics of each Hit (and, as the parties deem appropriate consistent
with the Research Plan, any analog, derivative or formulation thereof) in
animals with the goal of identifying one or more lead candidates for further
pre-clinical research (each such lead candidate being hereinafter referred to as
a "LEAD CANDIDATE"); and (ii) evaluate each Lead Candidate (and, as the parties
deem appropriate consistent with the Research Plan, any analog, derivative or
formulation thereof) for evidence of efficacy against the Mouse Model. The
parties shall mutually agree upon a strategy for progressing Hits and Lead
Candidates into human clinical trails in the most expeditious manner.
CombinatoRx shall disclose the results of all Pre-Clinical Module activities to
the Foundation in accordance with Section 2.6, and the parties shall consult
with each other with the objective of identifying at least one combination drug
candidate suitable for the preparation and filing of an IND (each such
combination drug candidate being hereinafter referred to as a "DRUG CANDIDATE").
2.4 PERFORMANCE STANDARDS. CombinatoRx shall conduct the Research
in good scientific manner, and in compliance in all material respects with the
requirements of applicable laws and regulations and with applicable good
laboratory practices, to attempt to achieve its objectives efficiently and
expeditiously. CombinatoRx shall maintain laboratories, offices and all other
facilities reasonably necessary to carry out the activities to be performed by
it pursuant to the Research Plan. In conformity with standard pharmaceutical and
biotechnology industry practices and the terms and conditions of this Agreement,
CombinatoRx shall prepare and maintain, or shall cause to be prepared and
maintained, complete and accurate written records, accounts, notes, reports and
data with respect to activities conducted pursuant to the Research Plan and,
upon the Foundation's written request, shall send legible copies of the
aforesaid to the Foundation. Upon reasonable advance notice, CombinatoRx agrees
to make its employees and non-employee consultants reasonably available at their
respective places of employment to consult with the Foundation on issues or
questions arising during the Research Term.
2.5 RESEARCH TERM. The Research is expected to require two years to
reach the primary overall objective of a filed IND and an additional 30 days (or
such longer period as may be necessary) to achieve acceptance for filing by the
FDA of an IND for a Drug Candidate (such entire period being hereinafter
referred to as the "RESEARCH TERM"). The parties expect that it will take
approximately 18 months to complete the Screening Module in its entirety. The
parties acknowledge that potential Lead Candidates may emerge from Screening
Module activities before the completion of the Screening Module in its entirety,
in which event such Lead Candidates will be advanced to the Pre-Clinical Module
as they become available from the Screening Module. The parties further expect
that it will take approximately 18 months to complete the Pre-Clinical Module in
its entirety. The parties may, from time to time, extend or modify the scope of
the Research by mutual written agreement.
6.
2.6 RESEARCH REPORTS. CombinatoRx shall keep the Foundation fully
informed as to all results and discoveries (including, without limitation, all
Hits and potential Lead Candidates and Drug Candidates) made in the course of
performing activities under the Research Program. In furtherance of the
foregoing, on a quarterly basis, CombinatoRx shall prepare, and deliver to the
Foundation no later than 30 days after the conclusion of each quarter during the
Research Term, a reasonably detailed written summary report of the results and
progress of the Research during such quarter (each, a "RESEARCH REPORT"). In
addition, the Foundation may, at its option, schedule up to two yearly formal
program review meetings with CombinatoRx personnel and Third Party advisors to
the Foundation. Such meetings will be held at the times and locations mutually
agreed upon by the parties. The purpose of such meetings will be to review the
progress of the Research relative to the Research Plan.
2.7 SUBCONTRACTS. CombinatoRx may perform some of its obligations
under the Research Plan through one or more subcontractors, provided that (a)
none of the Foundation's rights hereunder are diminished or otherwise adversely
affected as a result of such subcontracting, and (b) CombinatoRx will at all
times be responsible for the performance and, except as otherwise agreed by the
parties in writing, payment of such subcontractor.
3. DEVELOPMENT OF PRODUCTS.
3.1 CLINICAL DEVELOPMENT STRATEGY. As soon as CombinatoRx
reasonably believes that it has identified a Drug Candidate for which it
proposes to file an IND, CombinatoRx will notify the Foundation in writing, and
the parties will promptly discuss in good faith how to proceed with development
of such Drug Candidate, taking into consideration both the interests of SMA
patients and the commercial potential of the Drug Candidate. The parties
acknowledge that if the Drug Candidate is an Available Product, investment by
CombinatoRx in further development of such Drug Candidate may not be in the best
interests of CombinatoRx's stockholders. In such case, the parties may wish to
enter into an additional under which the Foundation
would provide funding for further development efforts by CombinatoRx, but
neither party shall have any obligation to enter into such additional agreement.
If CombinatoRx wishes to pursue further development of a Drug Candidate, the
parties will work together to identify an appropriate clinical trial network.
The parties currently expect to use the clinical trial network established by
the Foundation. In addition, if CombinatoRx identifies a Drug Candidate for
which it proposes to file an IND, CombinatoRx will seek, and use commercially
reasonable efforts to obtain, Orphan Product Designation of the Drug Candidate
with the FDA, as well as funding from the FDA's Office of Rare Diseases to
support clinical trials of the Drug Candidate.
3.2 CONDUCT OF CLINICAL DEVELOPMENT. Except as set forth in Section
3.1 above or as otherwise agreed by the parties in writing, CombinatoRx shall be
responsible for clinical development of any Drug Candidate for which CombinatoRx
files an IND. CombinatoRx shall use commercially reasonable efforts to develop
and commercialize (whether directly, in collaboration with one or more third
parties, through licensing or some combination of the foregoing) at least one
Product. Without limiting the generality of the foregoing, CombinatoRx shall
achieve the milestones set forth below on or before the applicable date (each, a
"DILIGENCE MILESTONE"):
7.
(a) CombinatoRx shall file an IND within six (6) months of
identifying a Drug Candidate; and
(b) CombinatoRx shall initiate human clinical trials of
such Drug Candidate within six (6) months of the FDA's approval of an IND. The
initiation of human clinical trials shall mean (i) the definition of a trial
protocol; (ii) the identification and establishment of the investigator sites at
which the trials will be conducted; and (iii) the beginning of active
recruitment of patients by the investigators.
Notwithstanding the preceding provisions of this Section 3.2, in no event shall
CombinatoRx have any obligation to pursue clinical development or
commercialization of any Available Product.
3.3 DISCLOSURE REGARDING COMBINATORX EFFORTS. CombinatoRx will keep
the Foundation appropriately informed about clinical trial progress and
commercialization efforts with respect to Products, and in any event,
CombinatoRx shall provide the Foundation with semi-annual written reports
summarizing any significant development or commercialization events that have
occurred during the applicable six-month period.
3.4 ACCESS TO CLINICAL TRIAL MATERIAL. CombinatoRx hereby agrees
that up to one hundred (100) SMA patients meeting the enrollment criteria of a
CombinatoRx Clinical Trial and identified by the Foundation or any licensed
physician treating SMA patients will be invited by CombinatoRx to enroll in any
CombinatoRx Clinical Trial. "COMBINATORX CLINICAL TRIAL" shall mean any human
clinical trial of a Drug Candidate or Product (i) conducted in compliance with a
clinical trial protocol submitted by CombinatoRx and approved by the FDA (or
equivalent foreign regulatory agencies); and (ii) conducted by or on behalf of
CombinatoRx, its Affiliate or any Licensee, except to the extent such
participation is prohibited by law (provided that CombinatoRx shall use
commercially reasonable efforts to enable such patients to be enrolled in such
trial). In the event that a SMA patient identified by the Foundation or any
licensed physician treating SMA patients does not meet the enrollment criteria
for a CombinatoRx Clinical Trial, CombinatoRx agrees to work with the Foundation
to establish a compassionate use program in which such SMA patients may gain
access to the Drug Candidate or Product; PROVIDED HOWEVER, that treatment of any
SMA patients under such compassionate use program (i) must be conducted by a
licensed physician experienced with SMA patients; (ii) must be compliant with
all applicable laws; and (iii) must not adversely affect the ability to gain
regulatory approval of a Product as a result of the CombinatoRx Clinical Trials.
CombinatoRx shall obtain the written agreement of each Licensee to comply with
the provisions of this Section 3.4.
4. PAYMENTS.
4.1 RESEARCH FUNDING BY THE FOUNDATION. For the conduct of the
Research, the Foundation shall pay a total of US$2,040,000 to CombinatoRx on the
schedule specified below:
8.
(a) SCREENING MODULE. For conduct of the Screening Module,
the Foundation shall pay the following amounts to CombinatoRx upon occurrence of
the applicable event specified below:
(i) Within 10 days of the Effective Date, the
Foundation will pay to CombinatoRx US$190,000;
(ii) Within 30 days of the Foundation's receipt of
the Research Report for the first quarter of the Research Term, the Foundation
will pay to CombinatoRx US$190,000;
(iii) Within 30 days of the Foundation's receipt of
the Research Report for the second quarter of the Research Term, the Foundation
will pay to CombinatoRx US$190,000;
(iv) Within 30 days of the Foundation's receipt of
the Research Report for the third quarter of the Research Term, the Foundation
will pay to CombinatoRx US$190,000;
(v) Within 30 days of the Foundation's receipt of
the Research Report for the fourth quarter of the Research Term, the Foundation
will pay to CombinatoRx US$190,000; and
(vi) Within 30 days of the Foundation's receipt of
the Research Report for the fifth quarter of the Research Term, the Foundation
will pay to CombinatoRx US$190,000;
(b) PRE-CLINICAL MODULE. For conduct of the Pre-Clinical
Module, the Foundation shall pay the following amounts to CombinatoRx upon
occurrence of the applicable even specified below:
(i) Within 30 days of the initiation of
pharmacokinetic studies of a Hit, the Foundation will pay to CombinatoRx
US$100,000;
(ii) Within 30 days of the selection of the first
Lead Candidate, the Foundation will pay to CombinatoRx US$370,000;
(iii) Within 30 days of the selection of the first
Drug Candidate, the Foundation will pay to CombinatoRx US$330,000; and
(iv) Within 30 days of filing of the first IND for a
Drug Candidate or Product, the Foundation will pay to CombinatoRx US$100,000.
For purposes of clarification, each of the foregoing payments shall be payable
only once. In addition, except as agreed pursuant to Section 4.2, the foregoing
payments reflect the full cost of doing the Research, and the Foundation will
not be obligated expected to pay any additional amounts in connection with the
Research.
9.
4.2 ADDITIONAL PAYMENTS. In addition to the amounts specified in
Section 4.1, the Foundation shall pay, or reimburse CombinatoRx for, the cost of
acquiring the Mouse Model, and, upon mutual written agreement of the parties,
the Foundation may make additional research funding payments to CombinatoRx in
connection with any modification of the Research Plan.
4.3 DONATION BY COMBINATORX. Within one year after such time
(if ever) as CombinatoRx has received an aggregate of US$100,000,000 in Product
Revenues, CombinatoRx shall donate to the Foundation (or, at the Foundation's
option, one or more other non-profit organizations or academic or research
institutions designated by the Foundation in writing) an amount equal to 200% of
the sum of the Research Funds and the Additional Payments.
4.4 REPORTING OF PRODUCT REVENUES. From and after such time as
CombinatoRx first receives any Product Revenues and until such time as
CombinatoRx has paid in full the amount due under Section 4.3 (if any),
CombinatoRx shall deliver to the Foundation (or a Third Party designated in
writing by the Foundation) quarterly written reports of Product Revenues
received by CombinatoRx and its Affiliates, which reports shall indicate the
amount of each type of Product Revenues received. CombinatoRx shall keep, and
shall cause its Affiliates to keep, complete and accurate records pertaining to
the receipt of Product Revenues in sufficient detail to permit the Foundation to
confirm the accuracy of such reports.
4.5 EXCHANGE RATE; MANNER AND PLACE OF PAYMENT. All payments
hereunder shall be payable in U.S. dollars. When conversion of payments from any
foreign currency is required for purposes of calculating Product Revenues, such
conversion shall be at the exchange rate used by CombinatoRx throughout its
accounting system (which shall, in any event, be commercially reasonable)
during the quarter for which such report is due. All payments owed under this
Agreement shall be made by check, or by wire transfer in immediately available
funds to a bank and account designated in writing by party entitled to receive
payment, unless otherwise specified in writing by such party.
4.6 TAXES. CombinatoRx will pay any and all taxes levied on account
of any payments made to it under this Agreement. If any taxes are required to be
withheld by the Foundation, the Foundation will (a) deduct such taxes from the
payment made to CombinatoRx, (b) timely pay the taxes to the proper taxing
authority, and (c) send proof of payment to CombinatoRx and certify its receipt
by the taxing authority within 30 days following such payment.
4.7 AUDITS. The Foundation shall have the right to cause an
independent, certified public accountant reasonably acceptable to CombinatoRx to
audit the records of CombinatoRx and its Affiliates to confirm the accuracy of
CombinatoRx's reports of Product Revenues for a period covering not more than
the preceding three (3) years. Such audits may be exercised during normal
business hours upon reasonable prior written notice to CombinatoRx and no more
than once per year. Prompt adjustments shall be made by the parties to reflect
the results of such audit. The Foundation shall bear the full cost of such audit
unless such audit discloses and underreporting of Product Revenues by
CombinatoRx of more than 10%, in which case, CombinatoRx shall bear the full
cost of such audit.
10.
5. CONFIDENTIALITY.
5.1 CONFIDENTIALITY. Except to the extent expressly authorized by
this Agreement or otherwise agreed in writing by the parties, the parties agree
that, during the Research Term and for a period of five years thereafter, each
party (the "RECEIVING PARTY") will maintain in confidence all Confidential
Information disclosed by the other party (the "DISCLOSING PARTY"). The Receiving
Party may use the Confidential Information of the Disclosing Party only to the
extent required to accomplish the purposes of this Agreement. The Receiving
Party shall use at least the same standard of care as it uses to protect
proprietary or confidential information of its own to ensure that its employees,
agents, consultants and other representatives do not disclose or make any
unauthorized use of the Disclosing Party's Confidential Information. Each party
will promptly notify the other upon discovery of any unauthorized use or
disclosure of the other party's Confidential Information.
5.2 EXCEPTIONS. The obligations of confidentiality contained in
Section 5.1 will not apply to the extent that it can be established by the
Receiving Party by competent proof that such Confidential Information: (a) was
already known to the Receiving Party, other than under an obligation of
confidentiality, at the time of disclosure by the Disclosing Party; (b) was
generally available to the public or otherwise part of the public domain at the
time of its disclosure to the Receiving Party; (c) became generally available to
the public or otherwise part of the public domain after its disclosure and other
than through any act or omission of the Receiving Party in breach of this
Agreement; (d) is independently discovered or developed by the Receiving Party,
and can be documented by the Receiving Party's written records, without the use
of Confidential Information of the Disclosing Party; or (e) was disclosed to the
Receiving Party, other than under an obligation of confidentiality, by a Third
Party who had no obligation to the Disclosing Party not to disclose such
information to others.
5.3 AUTHORIZED DISCLOSURE. Notwithstanding any other provision of
this Agreement, disclosure of Confidential Information shall not be precluded if
such disclosure is in response to a valid order of a court or other governmental
body of competent jurisdiction of the United States or any political subdivision
thereof or is otherwise required by law or regulation; PROVIDED, HOWEVER, that
the Receiving party shall first have given notice to the Disclosing Party and
shall have made a reasonable effort to obtain a protective order requiring that
the Confidential Information so disclosed be used only for the purposes for
which the order was issued or the law or regulation required or to seek other
confidential treatment of such information.
5.4 PUBLICATION. The parties acknowledge and agree that the SMA research
community and medical professionals treating SMA patients will benefit from
disclosure of the Data as soon as practicable. Accordingly, CombinatoRx shall
have a period of ninety (90) days following the submission of each Research
Report to the Foundation (the "IP FILING PERIOD") to file patent applications
covering the Research Intellectual Property disclosed in such Research Report.
During the IP Filing Period, the Foundation shall maintain as confidential the
Data and the Research Report provided to Foundation by CombinatoRx. Except as
expressly set forth in this Agreement, the Foundation shall not have the right
to use the Data to develop, commercialize, market or sublicense any commercial
offering of any product or service based on
11.
the Data. Notwithstanding the foregoing or any other provision of this Agreement
to the contrary, after the expiration of the applicable IP Filing Period for a
particular Research Report, CombinatoRx shall release copies of each Research
Report and supporting Data to any Third Party investigator who requests such
material from CombinatoRx in writing; PROVIDED, HOWEVER, that said Third Party
investigator first executes CombinatoRx's non-disclosure agreement and other
appropriate transactional agreements (e.g. Materials Transfer Agreement). It is
understood that such non-disclosure or other transactional agreements between
CombinatoRx and said Third Party investigator shall not prohibit a Third Party
investigator from the conduct of work to further SMA research and/or to treat
SMA patients, but shall define the terms under which the Third Party
investigator may use or disclose the Data or Research Intellectual Property to
further SMA research and/or to treat SMA patients. After the selection of the
Lead Candidate(s) and the Pre-Clinical Module, the parties shall cooperate in
good faith to publish the Data, and the Foundation shall in any event have the
unrestricted right to publish, have published or otherwise disseminate such
Research Report and the Data disclosed therein to the SMA research community and
/or to medical professionals treating SMA patients; PROVIDED, HOWEVER, that in
doing so the Foundation and/or a Third Party investigator does not disclose any
Confidential Information regarding CombinatoRx. Technology as defined in Section
6.1(b). To the extent that any journal or other forum in which the Foundation
proposes to publish or disseminate the Data requires the authorship or
participation of one or more CombinatoRx employees or contractors who
participated in the Research or in the development of a Drug Candidate or
Product, CombinatoRx shall use commercially reasonable efforts to cause such
individuals to cooperate with the Foundation in making such publication and, as
necessary or appropriate, to be named as authors (or co-authors) of such
publication.
5.5 PUBLICITY. It is understood that the parties intend to issue a
joint press release announcing the execution of this Agreement, and the parties
agree that each party may desire or be required to issue subsequent press
release relating to this Agreement or activities hereunder. The parties agree to
consult with each other reasonably and in good faith with respect to the text
and timing of such press releases prior to the issuance thereof, provided that a
party may not unreasonably withhold consent to such releases, and that either
party may issue such press releases as it determines, based on advice of
counsel, are reasonably necessary to comply with laws or regulations or for
appropriate market disclosure. In addition, following the initial joint press
release announcing this Agreement, either party shall be free to disclose,
without the other party's prior written consent, the existence of this
Agreement, the identity of the other party and those terms of the Agreement
which have already been publicly disclosed in accordance herewith.
6. OWNERSHIP AND USE OF DATA AND INTELLECTUAL PROPERTY.
6.1 OWNERSHIP.
(a) DATA. CombinatoRx shall solely own all data generated
as a result of the Research (the "DATA"). Notwithstanding the foregoing, in the
event that (i) CombinatoRx elects not to continue the Research or subsequent
development of a Drug Candidate or Product, (ii) CombinatoRx fails to achieve
any Diligence Milestone or does not comply with its diligence
12.
obligations under Section 3.2 and is unable to remedy such failure to comply
within 60 days of notice thereof from the Foundation, or (iii) CombinatoRx is
otherwise in material breach of this Agreement and is unable to remedy such
breach within 60 days of notice of such breach from the Foundation, then, in any
such case, CombinatoRx shall transfer, assign and convey to the Foundation all
of CombinatoRx's right, title and interest in and to the Data; PROVIDED,
HOWEVER, that CombinatoRx may continue to use the Data in the context of its
internal research programs. CombinatoRx agrees to execute, at the Foundation's
request and expense, all documents and other instruments necessary or desirable
to confirm such transfer, assignment and conveyance.
(b) COMBINATORX TECHNOLOGY; RESEARCH INTELLECTUAL PROPERTY.
CombinatoRx shall at all times retain sole ownership of all Information which
may be employed in the conduct of the Research and which CombinatoRx can
establish by competent evidence to have been proprietary to CombinatoRx on the
Effective Date, and all Patents claiming any of the foregoing (collectively,
"COMBINATORX TECHNOLOGY"). In addition, CombinatoRx shall solely own all
Research Intellectual Property. Notwithstanding the foregoing, in the event that
CombinatoRx is obligated to assign the Data to the Foundation as described in
Section 6.1(a) above, then CombinatoRx shall, and it hereby does, grant to the
Foundation an exclusive, worldwide, royalty-free, paid-up license, including the
right to sublicense, under the Research Intellectual Property to research,
develop, make, have made, use, sell, have sold, offer for sale and import Lead
Candidates, Drug Candidates and Products in the Field.
6.2 PATENT FILINGS. CombinatoRx shall file, prosecute and maintain
all Patents on the Research Intellectual Property at its sole expense.
Notwithstanding the foregoing, if CombinatoRx is obligated to assign the Data to
the Foundation as described in Section 6.1(a) above, then the Foundation shall
have the right, itself or through its designee, to file, prosecute and maintain
Patents on the Research Intellectual Property at its sole expense. In such
event, CombinatoRx shall execute all papers and instruments, and require its
employees and contractors to execute all papers and instruments, so as to enable
the Foundation to exercise such right.
6.3 AVAILABLE PRODUCT LICENSE; COVENANT NOT TO XXX. The parties
recognize the critical need for availability of therapeutic regimens to treat
SMA. In the event that the Research identifies an Available Product, CombinatoRx
will, at the request of the Foundation or any licensed physician, grant a
limited royalty-free, paid-up license to the Research Intellectual Property to
any licensed physician who may wish to treat spinal muscular atrophy patients by
co-prescribing the individual drugs identified as components of such Available
Product. In addition, CombinatoRx hereby covenants not to xxx any licensed
physician or other medical professional who uses or prescribes an Available
Product for use in the Field.
6.4 NO OTHER LICENSE. Other than any license granted pursuant to
Section 6.1(b) or 6.3, no license is granted or implied with respect to any
CombinatoRx Technology, Data or Research Intellectual Property for any use,
including, without limitation, development, manufacture, sale or distribution of
any Hit, Lead Candidate, Drug Candidate or Product.
13.
7. TERM; TERMINATION.
7.1 TERM. The term of this Agreement shall commence on the
Effective Date and shall continue until expiration of the Research Term, unless
this Agreement is earlier terminated in accordance with Section 2.2 or this
Article 7.
7.2 TERMINATION FOR CAUSE. Each party shall have the right to
terminate this Agreement upon 60 days' prior written notice to the other upon
the occurrence of any of the following:
(a) Upon or after the bankruptcy, insolvency, dissolution
or winding up of the other party (other than a dissolution or winding up for the
purpose of reconstruction or amalgamation); or
(b) Upon or after the breach of any material provision of
this Agreement by the other party if the breaching party has not cured such
breach within the 60-day period following written notice of termination by the
non-breaching party.
7.3 CONSEQUENCES OF EXPIRATION OR TERMINATION. Expiration or
termination of this Agreement will not relieve the parties of any obligation
accruing prior to such expiration or termination (including, without limitation,
any accrued obligation of the Foundation to make payments pursuant to Section
4.1 and/or 4.2). Notwithstanding any other provision of this Agreement to the
contrary, the provisions of Sections 4.3, 4.4, 4.5, 4.6, 4.7, 7.3 and 7.4, and
Articles 3,5,6,8, and 9 will survive expiration or termination of this
Agreement.
7.4 RIGHTS IN BANKRUPTCY. All rights and licenses granted under or
pursuant to this Agreement by CombinatoRx are, and will otherwise be deemed to
be, for purposes of Section 365(n) of the U.S. Bankruptcy Code, licenses of
right to "intellectual property" as defined under Section 101 of the U.S.
Bankruptcy Code. The parties agree that the Foundation, as licensee of such
rights under this Agreement, will retain and may fully exercise all of its
rights and elections under the U.S. Bankruptcy Code. The parties further agree
that, in the event of the commencement of a bankruptcy proceeding-by or against
CombinatoRx under the U.S. Bankruptcy Code, the Foundation will be entitled to a
complete duplicate of (or complete access to, as appropriate) any such
intellectual property and all embodiments of such intellectual property, and
same, if not already in the Foundation's possession, will be promptly delivered
to the Foundation (a) upon any such commencement of a bankruptcy proceeding upon
its written request therefor, unless CombinatoRx elects to continue to perform
all of its obligations under this Agreement, or (b) if not delivered under
clause (a) above, following the rejection of this Agreement by or on behalf of
CombinatoRx upon written request therefor by the Foundation.
8. INDEMNIFICATION.
8.1 INDEMNIFICATION BY COMBINATORX. CombinatoRx hereby agrees to
save, defend, indemnify and hold harmless the Foundation, its trustees,
officers, employees and agents (each, a "FOUNDATION INDEMNITEE") from and
against any and all losses, damages, liabilities, expenses and costs, including
reasonable legal expenses and attorneys' fees ("LOSSES"), to which a Foundation
Indemnitee may become subject as a result of any claim, demand, action or other
14.
proceeding by any Third Party to the extent such Losses arise directly or
indirectly out of (a) the development, manufacture, handling, storage, sale or
other disposition of any Drug Candidate or Product by CombinatoRx, its Affiliate
or Licensee, or (b) the breach of this Agreement by CombinatoRx or the gross
negligence or willful misconduct of any CombinatoRx Indemnitee, except in each
case to the extent such Losses result from the breach of this Agreement by the
Foundation or the gross negligence or willful misconduct of any Foundation
Indemnitee.
8.2 CONDITIONS TO INDEMNIFICATION. The obligations of CombinatoRx
under Section 8.1 are conditioned upon the Foundation's delivery of written
notice to CombinatoRx of any potential Losses promptly after the Foundation
becomes aware of such potential Losses. CombinatoRx shall have the right to
assume the defense of any suit or claim related to the Losses if it has assumed
responsibility for the suit or claim in writing. If CombinatoRx defends the suit
or claim, the Foundation may participate in (but not control) the defense
thereof at its sole cost and expense.
8.3 SETTLEMENTS. Neither party may settle a claim or action related
to any Losses subject to indemnification under Section 8.1 without the consent
of the other party, if such settlement would impose any monetary obligation on
the other party or require the other party to submit to an injunction or
otherwise limit the other party, its Affiliates, trustees, employees, agents,
officers or directors.
8.4 INSURANCE. During any period when CombinatoRx, its Affiliate or
any Licensee is clinically developing or commercializing any Drug Candidate or
Product and for three years thereafter, CombinatoRx, at its own expense, shall
maintain clinical trial and/or product liability insurance, as applicable, in an
amount consistent with industry standards and shall name the Foundation as an
additional insured with respect to such insurance. CombinatoRx shall provide a
certificate of insurance evidencing such coverage to the Foundation upon
request.
8.5 LIABILITY OF THE FOUNDATION'S. The Foundation assumes any and
all risk of personal injury and property damage attributable to the practice by
the Foundation or its designee or sublicensee of any license granted by
CombinatoRx to the Foundation hereunder, the breach of this Agreement by the
Foundation, or the gross negligence or willful misconduct of any Foundation
Indemnitee.
9. MISCELLANEOUS.
9.1 ASSIGNMENT. Except as expressly provided hereunder, neither
this Agreement nor any rights or obligations hereunder may be assigned or
otherwise transferred by CombinatoRx without the prior written consent of the
Foundation (which consent shall not be unreasonably withheld). The Foundation
shall have the right to assign or transfer any or all of its rights or
obligations under this Agreement to a Third Party upon written notice to
CombinatoRx, provided that the Foundation shall remain liable for any payment
obligations accruing hereunder to the extent that such Third Party does not
comply with such obligations. The rights and obligations of the parties under
this Agreement shall be binding upon and inure to the benefit of the successors
and permitted assigns of the parties. Any assignment not in accordance with this
Agreement shall be void.
15.
9.2 FORCE MAJEURE. Neither party shall be held liable or
responsible to the other party nor be deemed to have defaulted under or breached
this Agreement for failure or delay in fulfilling or performing any term of the
Agreement when such failure or delay is caused by or results from causes beyond
the reasonable control of the affected party, including, without limitation,
fire, floods, earthquakes, natural disasters, embargoes, war, acts of war
(whether war be declared or not), insurrections, riots, civil commotions,
strikes, lockouts or other labor disturbances, acts of God or acts, omissions or
delays in acting by any governmental authority or the other party.
9.3 GOVERNING LAW. This Agreement shall be governed by, and
construed and enforced in accordance with, the laws of the State of New York,
without regard to its choice of law provisions.
9.4 WAIVER. Except as specifically provided for herein, the waiver
from time to time by either party of any right or failure to exercise any remedy
shall not operate or be construed as a continuing waiver of the same right or
remedy or of any other of such party's rights or remedies provided under this
Agreement.
9.5 SEVERABILITY. In case any provision of this Agreement shall be
invalid, illegal or unenforceable, the validity, legality and enforceability of
the remaining provisions shall not in any way be affected or impaired thereby.
9.6 INDEPENDENT CONTRACTORS. It is expressly agreed that
CombinatoRx and the Foundation shall be independent contractors and that the
relationship between the two parties shall not constitute a partnership, joint
venture or agency of any kind. Neither party shall have the authority to make
any statements, representations or commitments of any kind, or to take any
action, which shall be binding on the other party, without the prior written
consent of the other party.
9.7 NOTICES. All notices and other communications provided for
hereunder shall be in writing and shall be mailed by first-class, registered or
certified mail, postage paid, or delivered personally, by overnight delivery
service or by facsimile, with confirmation of receipt, addressed as follows:
If to the Foundation: Spinal Muscular Atrophy Foundation
0000 Xxxxxxxx, 00xx Xxxxx
Xxx Xxxx, XX 00000
Fax: (000) 000-0000
Attention: Xx. Xxxxxxx Xxxxx, Executive Director
With a copy to: Xxxxxx Godward LLP
0000 Xxxxxxxx Xxxx
Xxx Xxxxx, XX 00000
Fax: (000) 000-0000
Attention: Xxxx X. Xxxxx, Esq.
16.
If to CombinatoRx: CombinatoRx, Incorporated
000 Xxxxxx Xxxxxx
Xxxxxx, XX 00000
Fax: (000) 000-0000
Attention: Xxxxxx X. Xxxx, Vice President
With a copy to: Xxxxx and Xxxxxx LLP
00 Xxxxx Xxxxx
Xxxxxx, XX 00000
Fax: (000) 000-0000
Attention: Xxxxx X. Xxxx, Esq.
Either party may by like notice specify or change an address to which notices
and communications shall thereafter be sent. Notices sent by facsimile shall be
effective upon confirmation of receipt, notices sent by mail or overnight
delivery service shall be effective upon receipt, and notices given personally
shall be effective when delivered.
9.8 ENTIRE AGREEMENT; AMENDMENT. This Agreement (including the
Exhibit hereto, as such Exhibit may be amended from time to time by mutual
written agreement of the parties) sets forth all of the agreements and
understandings between the parties hereto with respect to the subject matter
hereof and thereof, and supersedes and terminates all prior agreements and
understandings between the parties with respect to the subject matter hereof and
thereof. There are no other agreements or understandings with respect to the
subject matter hereof, either oral or written, between the parties. Except as
expressly set forth in this Agreement, no subsequent amendment, modification or
addition to this Agreement shall be binding upon the parties hereto unless
reduced to writing and signed by the respective authorized officers of the
parties.
9.9 HEADINGS. The captions contained in this Agreement are not a
part of this Agreement, but are merely guides or labels to assist in locating
and reading the several Articles and Sections hereof.
9.10 COUNTERPARTS. This Agreement may be executed in counterparts,
each of which shall be deemed an original, but all of which together shall
constitute one and the same instrument.
[REMAINDER OF THIS PAGE INTENTIONALLY LEFT BLANK]
17.
IN WITNESS WHEREOF, the parties hereto have executed this Agreement on the
Effective Date.
By: /s/ Xxxxx Eng By: /s/ Xxxxxx X. Xxxx
-------------------------- ----------------------------------------
Printed Name: Xxxxx Eng Printed Name: Xxxxxx X. Xxxx
----------------
Title: President Title: Vice President, Corporate Development
----------------------- & Strategy
[SIGNATURE PAGE TO ]
