Document:

Exhibit 10.29

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

MASTER AGREEMENT FOR SERVICES

 

This Master Agreement for Services (the “Agreement”) is made and entered into on August 27, 2014 (the “Effective Date”), by and between Insmed Incorporated, a Virginia corporation having offices at 10 Finderne Avenue, Building 10, Bridgewater, NJ  08807-3365 (“Sponsor”) and SynteractHCR, Inc., a California Corporation with offices at 5759 Fleet Street, Suite 100, Carlsbad, CA 92008 and its affiliate SynteractHCR Deutschland GmbH office with an address of Albrechtstrasse 14 80636 Munich, Germany (collectively “SynteractHCR”).  Sponsor and SynteractHCR may each be hereinafter referred to as a “Party” or collectively, as the “Parties”.

 

WHEREAS, SynteractHCR is engaged in the business of providing services related to the design, implementation and management of clinical development programs for the pharmaceutical, biotechnology and medical device industries; and

 

WHEREAS, Sponsor desires to engage SynteractHCR to perform implementation and management services in connection with certain clinical trials pursuant to a specific protocol (“Protocol”) of pharmaceutical products (“Study Drug”) under development by or under control of Sponsor (each a “Study”);

 

NOW, THEREFORE in consideration of the premises and mutual promises and undertakings herein, the receipt and sufficiency of which are hereby acknowledged, the Parties intending to be legally bound do hereby agree as follows:

 

1.0          Services.  SynteractHCR shall use commercially reasonable efforts to provide services, including without limit maintaining study documentation, and manage the services provided by SynteractHCR Subcontractors (as defined in section 3.3), approved by Sponsor as specified in this Agreement and any associated Work Order(s) and Changes in Scope (both as defined below in Section 2.0) in accordance with the terms and conditions of this Agreement, the associated Work Order and any applicable Change in Scope, the applicable Protocol, applicable standard operating procedures, and all international, regional, federal, state and local laws, rules and regulations governing the performance of clinical investigations, human subjects research and subject data privacy, including without limit the Federal Food Drug, and Cosmetic Act (the “Act”), United States Food and Drug Administration  (“FDA”) regulations 21 C.F.R. Parts 50 and 56, guidances of the FDA, generally accepted standards of Good Clinical Practice (“GCP”) as set forth in Title 21 of the U.S. Code of Federal Regulations (“CFR”), the Health Insurance Portability and Accountability Act and implementing regulations (“HIPAA”) and United States Department of Health and Human Services (“HHS”) regulations 45 C.F.R. Part 46 and applicable guidances of the Office for Human Research Protection, the Federal Corrupt Practices Act, the UK Bribery Act and similar statutes or laws, and the EU/Swiss Safe Harbor certification (“Applicable Law”) (collectively the “Services”).  The Parties will agree on all Services to be provided and the performance of those Services will be authorized in writing through the execution of a Work Order.  SynteractHCR will dedicate qualified and appropriate resources to perform activities related to the project(s), to achieve mutually agreed to milestones and meet mutually agreed to timelines as set forth in each Work Order.  SynteractHCR shall keep appropriate records of the status and progress of a Study as required by the relevant Work Order and Applicable Law.

 

2.0          Work Orders.  SynteractHCR will provide Services as specified in one or more Work Order substantially in the form set out in Appendix A (each a “Work Order”).  Each Work Order will include

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

detailed information with respect to a specific project, including the specifications; the deliverables (“Deliverables”); the nature and scope of the Services to be provided by SynteractHCR; Subcontractors (as defined in section 3.3), and any subcontractors SynteractHCR is requested to contract on behalf of the Sponsor with one or more Sponsor-Designated Vendors (as defined in section 3.1); any transfer of obligations from Sponsor to SynteractHCR; the timeline; milestones; the budget, including without limit projected pass-through expenses; and payment schedule.  To the extent any terms set forth in a Work Order conflict with the terms of this Agreement, the terms of this Agreement shall control.

 

2.1          Change Order Form.  The Parties will agree and document in a written amendment to the Work Order (each a “Change in Scope”) when there are any changes requested by Sponsor with regard to a Work Order.

 

2.2          Incorporation.      Work Orders and Changes in Scope will become effective when signed and delivered by respective authorized representatives of the Parties.  Once fully executed and delivered, the Work Order and Change in Scope shall be incorporated into this Agreement and will be subject to the terms and conditions set forth herein.

 

2.3          Project Staffing.  In performing the Services, SynteractHCR will assign personnel who are adequately trained, qualified, experienced and have the appropriate time and resources to conduct the work as specified in a Work Order.  SynteractHCR will ensure that all persons performing Services are bound by provisions at least as stringent as the  obligations of confidentiality, intellectual property, debarment, patient privacy, financial disclosure and adherence to Applicable Law of this Agreement (applicable to their performance of Services) prior to commencing such performance.  SynteractHCR shall provide Sponsor with the curriculum vitae of persons it identifies as key personnel providing Services, and also of other personnel providing Services as requested by Sponsor.  Sponsor shall have the right to request replacement of assigned personnel for cause, including but not limited to unsatisfactory performance or interpersonal conflicts.  SynteractHCR will promptly respond to any such request and make reasonable efforts to correct the situation in order to improve performance, or to provide a replacement, at its own expense, within a mutually agreeable timeframe.

 

2.4          Acceptance of Services.  Sponsor shall have the right to accept or reject the Service and/or Deliverable, or any portion thereof, in writing within *** (***) business days from receipt thereof.  Such acceptance or rejection shall be consistent with the criteria set forth in the Work Order, if any.  If Sponsor does not reject in writing within *** (***) business days, the Service and/or Deliverable shall be considered accepted by Sponsor, however this shall not prevent Sponsor from exercising other remedies in order to address unacceptable Services or Deliverables it discovers after the *** (***) days. Sponsor shall clearly state in writing the reasons for any rejection. Within *** (***) business days of any notice of rejection, SynteractHCR shall present a corrective plan of action to Sponsor.  Upon approval by Sponsor of the corrective plan, SynteractHCR, at no additional expense to Sponsor, shall then make the corrections and, where applicable, SynteractHCR shall resubmit the corrected Service or Deliverable to Sponsor.

 

2.5       Quality Agreement.  Within *** (***) days of the Effective Date, Sponsor and SynteractHCR will discuss and negotiate in good faith a formal Quality Agreement that establishes the quality strategies and team monitoring criteria to ensure that controls are in place to comply with ICH/GCP guidelines, applicable regulatory and legal requirements, as well as applicable Insmed/SynteractHCR standards and procedures for clinical studies.

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

3.0          Third Party Vendors and Subcontracting.

 

3.1          Sponsor-Designated Vendors.  If Sponsor requests that SynteractHCR uses a particular third party vendor in connection with the Services (a “Sponsor-Designated Vendor”), the Work Order will incorporate the Sponsor-Designated Vendor agreement entered into by SynteractHCR on behalf of Sponsor (“Sponsor-Designated Vendor Contract”) budget, projected pass-through expenses, payment terms, and if applicable, a letter of indemnification.  Sponsor shall only be responsible for financial terms under a Sponsor-Designated Vendor Contract if Sponsor has provided prior written approval of such financial terms.  In the event that a Sponsor-Designated Vendor Contract is to be executed after the execution of the Work Order, then the additional Sponsor-Designated Vendor Contract terms and budget will be incorporated by written Change in Scope and incorporated into the Work Order.  Upon Sponsor’s request, SynteractHCR will contract with such Sponsor-Designated Vendor unless SynteractHCR does not wish to contract with that Sponsor-Designated Vendor based on commercially reasonable reasons (such as, but not limited to, the inability to agree with such Sponsor-Designated Vendor upon mutually acceptable terms after good-faith negotiations or a negative assessment in the reasonable exercise of SynteractHCR’s discretion of such Sponsor-Designated Vendor’s performance or abilities), in which case Sponsor may contract directly with such Sponsor-Designated Vendor and SynteractHCR shall, if retaining the management of such Sponsor-Designated Vendor, cooperate with such Sponsor-Designated Vendor and coordinate their efforts in the performance of the Services.  If SynteractHCR contracts with a Sponsor-Designated Vendor on behalf of Sponsor or facilitates Sponsor’s contracting with such Sponsor-Designated Vendor, then such Sponsor-Designated Vendor Contract shall include, without limitation, the Sponsor approved vendor budget and provisions addressing the specific duties and rights of the parties to the Sponsor-Designated Vendor Contract.  In no event will a Sponsor-Designated Vendor be construed to be an employee, agent, consultant, or representative of SynteractHCR, or be deemed to be a Subcontractor (as defined in Section 3.3).  Sponsor remains primarily responsible for the acts, omissions, performance (including willful misconduct) and ongoing quality of any Sponsor-Designated Vendor.

 

3.2          Clinical Trial Agreements.  If SynteractHCR will be negotiating the clinical trial agreement (“CTA”) and Study budget with the clinical investigational sites (“Sites”) on behalf of Sponsor, Sponsor will provide written approval on the Study specific CTA and budget templates to SynteractHCR for use during such negotiations.  Sponsor shall provide to SynteractHCR Sponsor’s negotiating parameters for CTA terms, subject budget amount, start-up and pass-through costs as the basis for negotiation with the Sites.  Any modification outside of such written parameters shall require approval of Sponsor.  In no event will a Site be construed to be an employee, subcontractor, agent, consultant, or representative of SynteractHCR, or be deemed to be a Subcontractor (as defined in Section 3.3).

 

3.3          Subcontracting.    With Sponsor’s prior written consent SynteractHCR may outsource the performance of certain Services under a specific Work Order to qualified third parties (“Subcontractor”), provided that (a) SynteractHCR notifies Sponsor of the proposed Subcontractor and identifies the specific Services to be performed by the Subcontractor,  (b) SynteractHCR ensures the Subcontractor has the requisite training, qualifications, experience, time and resources to perform, and ensures that the Subcontractor performs those  Services in a manner consistent with the terms and conditions of this Agreement, (c) SynteractHCR remains liable for the performance of the Subcontractor, and (d) SynteractHCR ensures that the Subcontractor has executed, prior to commencement of performance, an agreement containing provisions at least as stringent as the  obligations of, confidentiality, intellectual property, debarrment, patient privacy, financial disclosure and Applicable Laws (relative to Subcontractor’s performance of Services), set forth herein.  If SynteractHCR has an existing master agreement with a Subcontractor, which master agreement does not conform to Section 3.3(d) above, SynteractHCR shall include the missing provisions in a statement of work under such master agreement which shall be duly executed by the Subcontractor prior to commencement of performance.  In the event such additional provisions in the statement of work conflict with the existing master agreement and would be subordinate to

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

the terms of the existing master agreement, then the SynteractHCR shall amend the terms of the master agreement to allow the additional terms of the statement of work to control.

 

4.0          Payments.  The Parties agree that the fees and other reimbursements, including but not limited to pass-through expenses, that SynteractHCR will receive for performing the Services hereunder will be outlined in each Work Order and are subject to the following terms and conditions.

 

4.1          Compensation for Services.

 

a.     SynteractHCR Services.  In consideration for the Services rendered hereunder, Sponsor shall compensate SynteractHCR at the rate set forth in each Work Order, together with reimbursement for other out-of-pocket expenses (without mark-up) actually incurred on behalf of Sponsor and approved in advance by Sponsor.  SynteractHCR shall invoice Sponsor as set forth in each Work Order hereto.

 

b.             Sponsor-Designated Vendor Services.  In connection with the Services rendered hereunder by a Sponsor-Designated Vendor SynteractHCR shall invoice Sponsor *** for any of the following Sponsor-Designated Vendor fees, which fees were subject to Sponsor’s prior written approval pursuant to Section 3.1 above:  start-up fees, if applicable, fees for the service provided and any of their pre-approved out-of-pocket expenses (***) actually incurred as set forth in each Work Order hereto.  SynteractHCR shall provide regular and timely reports of the specific financial balances and timelines required under the Sponsor-Designated Vendor Contracts, and the amount and timing of the corresponding payments due from Sponsor, in order to timely meet the payment obligations under the Sponsor-Designated Vendor Contracts.  Sponsor agrees to provide the required funds to SynteractHCR in a timely manner for the Sponsor-Designated Vendor payment as specified in the Work Order or applicable Change in Scope.  On behalf of Sponsor, SynteractHCR will pay the Sponsor-Designated Vendor.  In no event will SynteractHCR be required to disburse payments to any Sponsor-Designated Vendor if Sponsor has not made sufficient advance funds available to SynteractHCR to cover such fees, unless SynteractHCR has failed to comply with the above requirements.  In the event that SynteractHCR has invoiced Sponsor in a timely manner and Sponsor has nevertheless failed to advance the funds sufficient to cover the Sponsor-Designated Vendor payments, and these payments are not in dispute by Sponsor, Sponsor will, as soon as practical upon receipt of SynteractHCR’s invoice, pay to SynteractHCR the additional amounts required consistent with the specific Sponsor Designated Vendor Contract for such payments., and, except for amounts in dispute, if Sponsor does not provide funds to SynteractHCR within ***  (***) business days of the Sponsor-Designated Vendor Contract payment term (or within forty-eight hours of Sponsor’s receipt of the SynteractHCR invoice, if later), Sponsor agrees to reimburse SynteractHCR for any interest, not to exceed *** %/month,  required by the Sponsor-Designated Vendor Contract to be paid by SynteractHCR to the Sponsor Designated Vendor to the extent attributable to Sponsor’s delay in payment of the Sponsor-Designated Vendor invoices.

 

c.             Site Payments.  If SynteractHCR is paying Sites on behalf of Sponsor as a pass-through expense, Sponsor will provide adequate funds to SynteractHCR in advance for Site payments in accordance with a schedule and budget that corresponds with the schedule and budget in the executed Site agreement, and according to any additional terms as may be mutually agreed upon in writing in advance between the Parties.  In no event will SynteractHCR be required to disburse payments to any Sites if Sponsor has not made sufficient advance funds available to SynteractHCR to cover such disbursements.  In the event the funds advanced by Sponsor pursuant to this Section are insufficient to cover such payments, Sponsor will upon receipt of SynteractHCR’s invoice pay to SynteractHCR the additional amounts required consistent with the budget for such payments.

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

d.             Subcontractor Payments.  SynteractHCR shall be solely responsible for all payments to Subcontractors for Services performed under this Agreement.  Separate and apart from other indemnification provided herein, SynteractHCR agrees to indemnify, hold harmless and defend Sponsor from any claims of failure to timely pay compensation to Subcontractors to the extent caused by SynteractHCR’s failure to timely submit payment to Subcontractors.

 

e.             Indemnification.  Separate and apart from other indemnification provided herein, Sponsor agrees to indemnify, hold harmless and defend SynteractHCR from any claims of failure to pay compensation by either Sponsor-Designated Vendor Services under Section 4.1 (b) or Sites under Section 4.1 (c) to the extent caused by Sponsor’s failure to timely submit payment to SynteractHCR invoice for Sponsor Designated Vendor or Site fees or pass-through expenses.

 

f.             The parties acknowledge and agree that the payments made under this Agreement represent the fair market value for the Services provided, and nothing in this Agreement incorporates or is intended to constitute, the solicitation, receipt or payment of any remuneration in return for referring an individual to Sponsor for the furnishing, or arranging for the furnishing, of any item or service for which payment may be made in whole or in part under a federal health care program, or in return for purchasing, leasing, ordering or arranging for or recommending purchasing, leasing or ordering any good, facility, service or item for which payment may be made in whole or in part under a federal health care program.

 

4.2          Invoices.

 

a.             SynteractHCR shall invoice the Sponsor on a monthly basis for Services provided or for Services determined by progress completion, including pass-through charges, in accordance with the project budget and schedule set forth in the applicable Work Order.    Unless amounts invoiced are subject to a valid dispute, payments for all invoices are due within *** (***) days of the date of receipt of invoice by Sponsor.  Interest will be charged at the rate of ***  percent (*** %) per month on undisputed amounts which remain unpaid after *** (***) days of receipt of the applicable invoice by Sponsor.  SynteractHCR retains the right to provide notice to terminate for material breach any Work Order when unpaid amounts outstanding greater than *** (***) days from invoice date, not subject to dispute, exceed the greater of (a) the amounts held on deposit, or (b) *** percent (*** %) of the total balance owed.

 

b.             In the event Sponsor deliberately suspends the execution of a Work Order for reasons not related to regulatory activity or for reasons outside of Sponsor’s reasonable control, for a period longer than *** (***) days (“On-Hold”) for reasons SynteractHCR is not liable for, Sponsor shall discontinue the Work Order or negotiate reasonable stand-by amounts during the On-Hold period.

 

c.             SynteractHCR shall be entitled to reasonable expenses incurred in its reasonable efforts to collect from Sponsor unpaid invoices on undisputed amounts overdue for more than *** (***) days including, without limitation, court costs and reasonable attorney’s fees.  In no event shall SynteractHCR be entitled to cease work under a Work Order based on disputed amounts.

 

d.             All invoices under this Agreement will be forwarded to Sponsor at *** with a copy to the Sponsor representative designated in the relevant Work Order.

 

4.4          Physician Payment Sunshine Act.  Sponsor shall retain the responsibility, if any, of reporting payments made to Health Care Institutions (HCI) and /or Health Care Professionals (HCP) as required in accordance with the Physician Payment Sunshine Act (the “PPSA”) or any other applicable national laws concerning payments to Health Care Institutions and/or Health Care Professionals.  On a periodic and mutually agreed basis to enable compliance with PPSA and using a mutually agreed upon format,

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

SynteractHCR will report to Sponsor the HCI and HCP payments administered on Sponsor’s behalf, including but not limited to information about the amount of payments, the dates on which payments were made, the forms of payment, and the nature of payments, as required for compliance with PPSA.

 

5.0                               Term and Termination

 

5.1          Term.  The term of this Agreement shall begin on the Effective Date and continue, for a period of three (3) years, unless sooner terminated as permitted herein.  In the event of termination of this Agreement, by either Party, the terms and conditions of this Agreement will continue to be applicable until the completion of the Services described in any outstanding, uncompleted Work Order(s) unless such termination includes appropriate termination of the Work Order(s).

 

5.2          Termination without Cause. This Agreement and/or any Work Order may be terminated by Sponsor for any reason and without cause by providing thirty (30) days written notice to SynteractHCR.

 

5.3          Transition, Effect of Termination.  In the event of termination by Sponsor under section 5.2, by or by either Party under section 5.4 or 5.5, the termination process and associated fee will be as follows:

 

a.                                      Sponsor and SynteractHCR will meet within *** (***) days of receipt of such termination notice by the other Party to develop a plan for closing down any Study which is the subject of any terminated Work Order, which will include transferring any remaining tasks or other responsibilities to Sponsor or its designee and using commercially reasonable efforts to minimize the cost of closing down.

 

b.                                      Except with respect to work done by SynteractHCR that is the subject of Sponsor’s termination under section 5.4 for breach by SynteractHCR, Sponsor will pay to SynteractHCR *** up to the date of receipt of notice of termination, and the *** incurred in the performance of Services under a Work Order prior to termination, the costs of all non-cancellable commitments reasonably made up to the date of notice of termination, as well as the *** reasonably incurred in the course of winding down or closing out the terminated Work Order according to the agreed-upon plan for closing down.  However, in no event shall the total amount of fees due under a Work Order exceed ***, unless mutually agreed to by the Parties and memorialized in a Change in Scope.  Any overpayments or advanced funds paid by Sponsor shall be refunded to Sponsor within *** (*** ) days of termination.

 

5.4                               Termination for Cause.  Either Party may terminate this Agreement and/or a Work Order for a material breach of the Agreement by the other Party effective on giving thirty (30) days prior written notice of termination if such breach is not cured within the thirty (30) day notice period. For the purposes of this Agreement, material breach shall include, but not be limited to, non-payment of undisputed amounts due to SynteractHCR hereunder.

 

5.5          Termination for Insolvency.  Either Party may terminate this Agreement and/or a Work Order hereunder, effective immediately upon written notice to the other Party, upon the other party filing a voluntary petition in bankruptcy or having an involuntary bankruptcy petition filed against it, which is not dismissed within thirty (30) days after its institution.

 

5.6          Termination for Other Reasons.  Either Party may terminate this Agreement and/or a Work Order hereunder, effective immediately upon written notice to the other Party, upon the happening of the following events: (i) if continuation of the Services would pose an undue risk to the health and/or well-being of a Study participant, or (ii) if any certificate, authorization, approval or exemption from a regulatory

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

authority required for the conduct of the Services is revoked, suspended, or expires without renewal, or (iii) if such party is of the reasonable opinion that the continuation of the Services would be in violation of applicable law.

 

5.7          Return of Sponsor funds.  Any overpayments or advanced funds paid by Sponsor shall be refunded to Sponsor within *** (***) days of termination or expiration of this Agreement.

 

5.8          Compensation for Premature Work Order Termination.  Pursuant to Article 5, if Sponsor terminates for any reason other than material breach of SynteractHCR pursuant to section 5.3 or insolvency of SynteractHCR pursuant to section 5.4, or if SynteractHCR terminates because of uncured material breach by Sponsor pursuant to section 5.3 or for Sponsor insolvency pursuant to section 5.4:

 

a.                                      a Work Order after commencement of a Study but prior to the agreed term of the Work Order, SynteractHCR is entitled to receive a compensation for *** properly incurred up to the date of notice of termination, non-cancellable reasonable expenses properly committed to prior to termination.  In no event shall the total amount of fees due under a Work Order exceed ***.

 

b.                                      a Work Order prior to the commencement of the Study SynteractHCR is entitled be reimbursed for all reasonable expenses properly incurred until the date of notice of termination.

 

6.0          Survival.   Expiration or termination of this Agreement or any applicable Work Order will not relieve the Parties of any obligation accruing prior to such expiration or termination.  In addition, Sections 4.0, 6.0, 7.0, 8.0, 9.0, 10.0, 11.0, 12.0, 13.0, 14.0, 15.0, 16.0, 17.0, 18.0 and 27.0 as well as any other sections which by their nature should survive, will survive expiration or termination of this Agreement indefinitely, or for the period of time noted in the specific clause.

 

7.0                               Representations and Warranties

 

7.1          Acknowledgments.  Sponsor acknowledges and agrees that the results of the Studies and Services performed hereunder are inherently uncertain and that, accordingly, there can be no assurance, representation or warranty by SynteractHCR that the drug, compound, device or other material which is the subject of a Study covered by this Agreement or any Work Order issued hereunder, either during the term of this Agreement or thereafter, will be successfully developed or, if so developed, will receive the required approval by the FDA or any other regulatory authority.

 

7.2          Mutual Representations.  Each of the Parties represents, warrants and covenants to the other that:

 

a.                                      it is a corporation duly incorporated, validly existing and in good standing;

 

b.                                      it has taken all necessary actions on its part to authorize the execution, delivery and performance of the obligations undertaken in this Agreement, and no other corporate actions are necessary with respect thereto;

 

c.                                       it is not a party to any agreement or understanding and knows of no law or regulation that would prohibit it from entering into and performing this Agreement;

 

d.                                      when executed and delivered by it, this Agreement will constitute a legal, valid and binding obligation of it, enforceable against it in accordance with this Agreement’s terms;

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

e.                                       it is duly licensed, authorized or qualified to do business and is in good standing in every jurisdiction in which a license, authorization or qualification is required for it to perform its obligations under this Agreement;

 

f.                                        it will perform its obligations hereunder in accordance with current industry standards, the terms of this Agreement and any Work Order issued hereunder;

 

g.                                       it will perform its obligations hereunder in accordance with all Applicable Law;

 

h.                                      to its knowledge, performance of its obligations hereunder will not infringe or violate the rights of any third party including but not limited to property, contractual, employment, trademark, trade secrets, copyright, patent, proprietary information and non-disclosure rights;

 

i.                                          it will not enter into any other agreements which would interfere with, delay or prevent performance of the obligations described herein; and

 

j.                                         it is aware, and will advise its respective employees who are informed of the matters that are subject of this Agreement, of restrictions imposed by the United States securities laws on the purchase or sale of securities by any person who has received material, non-public information from the issuer of such securities and on the communication of such information to any other person.

 

7.3                               Representations and Warranties of Sponsor.  Sponsor represents and warrants that:

 

a.                                      it has the right, title and interest in the Study Drug which is the subject of research covered by this Agreement or any Work Order (whether such right, title and interest is held solely by Sponsor or jointly with others);

 

b.                                      it has the legal right, authority and power to enter into this Agreement;

 

c.                                       it will obtain prior to commencement of the Study and maintain during the term of the Study all approvals and licenses necessary for the performance of the Study which is the subject of a Work Order issued hereunder; and

 

d.                                      If Sponsor requires SynteractHCR to use MedDRA or WHO Drug to code, analyze or report data for a Study, Sponsor represents and warrants that it has a current and valid license to use MedDRA and WHO Drug, as applicable.  If Sponsor does not currently have such licenses, it represents and warrants that such licenses will be in place prior to SynteractHCR’s delivery of data which is coded using such dictionaries. SynteractHCR will not be liable to Sponsor for use of data coded by SynteractHCR in accordance with a Work Order without proper licensing that is to be held by Sponsor, and Sponsor will hold SynteractHCR harmless and indemnify SynteractHCR for any claims where Sponsor has used the dictionaries without the proper licenses as required by Sponsor.

 

7.4                               Representations and Warranties of SynteractHCR.

 

a.                                      SynteractHCR represents and warrants that the personnel and Subcontractors assigned will have the proper skill, training, experience and resources to perform Services rendered under

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

this Agreement and any applicable Work Order.

 

b.                                      SynteractHCR further represents and warrants that it will cooperate with and make available to Sponsor or to the responsible regulatory authority relevant records, programs, and data as may be reasonably requested by Sponsor for purposes related to filing and prosecution of Sponsor’s related regulatory filings.

 

c.                                       SynteractHCR shall disclose to Sponsor any financial interest, other than the payment for Services agreed to hereunder, that SynteractHCR may have in Sponsor or any Study.

 

8.0                               Debarment Certification.

 

8.1          Debarment.  SynteractHCR certifies that it has not been debarred under Section 306 of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. §335a(a) or (b) and/or any equivalent local law or regulation or equivalent oversight body in a country other than the United States.  In the event that SynteractHCR becomes debarred, SynteractHCR agrees to notify Sponsor immediately.

 

8.2          Use of Debarred Individuals.  SynteractHCR certifies that it has not and will not use in any capacity the services of any individual, corporation, partnership, or association which has been debarred under Section 306 of the Federal Food, Drug and Cosmetic Act, 21 U.S.C §335a (a) or (b) and/or any equivalent local law or regulation or equivalent oversight body in a country other than the United States.  In the event that SynteractHCR becomes aware of or receives notice of the debarment of any individual, corporation, partnership, or association providing services to SynteractHCR, which relate to the Services being provided under this Agreement, SynteractHCR agrees to notify Sponsor immediately.

 

8.3          The obligation to notify Sponsor under this article 8.0 shall remain in force for one (1) year following expiration or termination of this Agreement.

 

9.0          Inspections.

 

9.1          Inspection by Sponsor.  During the term of this Agreement, SynteractHCR will permit employees of Sponsor or independent representatives of Sponsor who are not deemed by SynteractHCR, at its sole and reasonable discretion, competitors of SynteractHCR  to examine, at a reasonable time during normal business hours and subject to at least *** (***) business days prior written notice to SynteractHCR: (i) the facilities where the Services are being, will be or have been conducted, including sub-contractor(s); (ii) related Study documentation; and (iii) any other relevant information necessary or useful for Sponsor to confirm that the Services are being or will be or have been conducted in conformance with applicable standard operating procedures, the specific Work Orders, this Agreement and in compliance with Applicable Law.  SynteractHCR will provide copies of any materials reasonably requested by Sponsor during such inspection.  Sponsor shall have the right to conduct inspections for cause and to conduct co-monitoring without being restricted by the above prior notice and time requirements.  “To be considered a “competitor of SynteractHCR” for purposes of this Section, the third party must (a) provide the full range of services that SynteractHCR provides under this Agreement, (b) compete directly with SynteractHCR for projects and clients, (c) be comparable or greater in size to SynteractHCR, and (d) not be primarily focused on conducting auditing services”.

 

9.2          Inspection by Regulatory Authorities.  During the term of this Agreement, each Party will permit regulatory authorities to examine, (i) the facilities where the Services are being conducted; (ii) Study documentation; and (iii) any other relevant information, including information that may be designated by one or both of the Parties as confidential, reasonably necessary for regulatory authorities to confirm that the

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

Services are being conducted in compliance with Applicable Laws.  Each Party will immediately notify the other if any regulatory authority schedules, or without scheduling, begins an inspection that relates to the Services or the Parties’ respective obligations hereunder unless prohibited by law or regulation from providing such notification.  Sponsor shall, to the extent permitted by the regulatory authority, have the right to participate in such inspection or audit.  SynteractHCR shall provide Sponsor with any copies of any correspondence from the regulatory authority, and allow Sponsor to review and comment on any responses made by SynteractHCR.

 

10.0        Disposition of Computer Files and Study Materials.  SynteractHCR will employ commercially reasonable technologies and procedures for the safe, secure and accurate collection, processing, and storage to prevent the loss or alteration of Sponsor’s Study data, documentation, and correspondence.  Upon termination of this Agreement, SynteractHCR will archive Sponsor computer-stored files and Study materials according to SynteractHCR’s internal standard operating procedures.  Sponsor may communicate any special request for the disposition of materials in writing to SynteractHCR.  Sponsor will bear all additional costs incurred by SynteractHCR in complying with any such special written instructions furnished by Sponsor.  SynteractHCR will provide a written estimate to Sponsor, and Sponsor will provide written approval, of all such costs prior to any action by SynteractHCR.

 

11.0        Ownership of Data and Intellectual Property.

 

a.                                      All data generated or derived from a Study (including without limitation, written, printed, graphic, video and audio material, and information contained in any computer database or computer readable form) generated by SynteractHCR in the course of conducting the Services (the “Data”) will be Sponsor’s property.  Any copyrightable work created in connection with performance of the Services (“Copyrights”) will be considered work made for hire, whether published or unpublished, and all rights therein will be the property of Sponsor as employer, author and owner of copyright in such work.

 

b.                                      SynteractHCR understands and agrees that the underlying rights to the intellectual property and materials that are the subject of each Work Order, including, without limitation, all intellectual property rights in Sponsor’s drug candidates or products, any invention or discovery, including, without limitation, new uses, processes, formulations, therapeutic combinations, methods, information, improvements, innovations, suggestions, ideas, data (including Data), results and reports, whether patentable or not, related to the Study Drug or any Protocol or Sponsor Information (as defined below in section 12.1) or conceived or reduced to practice in the course of conducting the Services (“Inventions”) are owned by Sponsor.  SynteractHCR will not acquire any rights of any kind whatsoever with respect to Sponsor’s drug candidates or products as a result of conducting Services hereunder.  All rights to any know-how, trade secrets, developments, discoveries, and Inventions (whether or not patentable) conceived or reduced to practice in the performance of work conducted under this Agreement by SynteractHCR’s employees, or Subcontractors, either solely or jointly with employees, agents, consultants or other representatives of Sponsor or third parties (the “Intellectual Property”), will be owned solely by Sponsor.  For value received, SynteractHCR agrees to assign and hereby does assign to Sponsor all right, title, and interest in and to Intellectual Property.  SynteractHCR, Subcontractors and their respective employees will sign and deliver to Sponsor all writings and provide all such documents, instruments, applications, and assignments, and do all such things as may be necessary, useful or appropriate to vest in Sponsor all right, title and interest in and to such Intellectual Property.  SynteractHCR will promptly disclose to Sponsor any such Intellectual Property arising under this Agreement.  Sponsor may, in its sole discretion, file and prosecute in its

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

name and at its expense, patent applications on any patentable inventions within the Intellectual Property.  Upon the request of Sponsor, and at the sole expense of Sponsor, SynteractHCR will assist Sponsor in the preparation, filing and prosecution of such patent applications and will execute and deliver any and all instruments necessary to effectuate the ownership of such patent applications and to enable Sponsor to file and prosecute such patent applications in any country.  These obligations shall continue beyond the termination of this Agreement, and shall be binding on the SynteractHCR’s assignees, successors, administrators and other legal representatives.

 

c.                                       SynteractHCR reserves the rights to information, ideas, data, concepts, methods, techniques, computer technical expertise and software proprietary to SynteractHCR (“SynteractHCR Proprietary Property”) which were developed before or incidental to the completion of the Service or any other responsibilities under the Work Order, except to the extent that improvements or modifications include, incorporate or are based upon Sponsor’s information, and excluding Inventions.  Improvements or enhancements made to SynteractHCR’s Proprietary Property which are independently developed incidental to the provision of Services hereunder will remain the sole property of SynteractHCR.  Sponsor may use SynteractHCR Proprietary Property free of charge to access, use, analyze or reproduce all data, results, and Deliverables, including without limit for interpretation purposes, submissions to regulatory authorities or for any purposes that are appropriate within the scope of this Agreement.

 

12.0                        Confidential Information

 

12.1                        Sponsor Confidential Information.

 

a.                                      Sponsor may disclose confidential information to SynteractHCR during the course of this Agreement.  All information provided by or on behalf of Sponsor or data collected by SynteractHCR during the performance of the Services is deemed to be the confidential information of Sponsor and is hereinafter referred to as “Sponsor Information”.  SynteractHCR will keep Sponsor Information confidential in a secure location and exercise the same degree of care as it does for its own confidential information, and at least a reasonable degree of care.  SynteractHCR will not disclose Sponsor Information to any third party, and shall only disclose Sponsor Information to its employees and Subcontractors who have a need to know such Sponsor Information in order to perform the Services.  SynteractHCR shall not use, and shall ensure that its permitted employees and Subcontractors shall not use, such Sponsor Information for any purpose other than the performance of Services without the prior written consent of Sponsor.

 

b.                                      SynteractHCR will ensure that it and its employees and Subcontractors involved in the Services will comply with terms substantively similar to the confidentiality provisions of this Agreement.

 

c.                                       SynteractHCR will exercise due care to prevent the unauthorized disclosure and use of Sponsor Information associated with the Services.

 

d.                                      This confidentiality, nondisclosure and nonuse provision will not apply to Sponsor Information that SynteractHCR can demonstrate by competent evidence:

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

i.                  was known by SynteractHCR before initiation of the Services, as evidenced by written records;

 

ii.               was in the public domain at the initiation of the Services or subsequently became publicly available through no fault or action of SynteractHCR; or

 

iii.            was disclosed to SynteractHCR on a non-confidential basis by a third party authorized to so disclose it.

 

e.                                       In no event will either Party be prohibited from disclosing confidential information of the other Party to the extent required by law to be disclosed, provided that the disclosing Party provides the non-disclosing Party with written notice thereof unless prohibited by law or regulation from providing such notice, prior to disclosure, to the extent reasonably practicable, discloses only what is required to be disclosed by law or regulation, and, at the non-disclosing Party’s request and expense, cooperates with the non-disclosing Party’s efforts to obtain a protective order or other confidential treatment of the confidential information required to be disclosed.  Such disclosed information shall remain confidential to the extent it is not made publicly available by the manner in which disclosure is required by law to be made.

 

12.2                        SynteractHCR Confidential Information.  Sponsor agrees that all business processes, contract terms, prices, procedures, policies, methodologies, systems, computer programs, software, applications, databases, proposals and other documentation generally used by SynteractHCR and not developed solely for Sponsor and excluding all Sponsor Information are the exclusive proprietary and confidential property of SynteractHCR (hereinafter “SynteractHCR Information”). Sponsor agrees that all SynteractHCR Information, along with any improvement, alteration or enhancement made thereto during the course of the Services, will be the exclusive proprietary and confidential property of SynteractHCR, and will be subject to the same degree of protection as is required of SynteractHCR to protect Sponsor Information.

 

12.3                        Return or Destruction of Information.  At the conclusion of a Study, SynteractHCR will deliver to Sponsor all Sponsor Information in its possession unless Sponsor directs otherwise.  Upon the written request of the Sponsor, SynteractHCR shall either destroy or return to the Sponsor the Sponsor Information.  SynteractHCR shall use all reasonable efforts to destroy all notes, summaries, analyses and reports made by SynteractHCR’s employees and independent contractors containing such Sponsor Information; provided, however, that SynteractHCR shall be entitled to retain in confidence under this Agreement, including without limitation: (i) one (1) archived copy of Sponsor Information and all materials created by SynteractHCR and containing Sponsor Information, including without limitation notes and memoranda, solely for the purpose of administering SynteractHCR’s obligations under this Agreement; (ii) Sponsor Information contained in SynteractHCR’s electronic back-up files that are created in the normal course of business pursuant to SynteractHCR’s standard protocol for preserving its electronic records; and (iii) as required by Applicable Law.

 

12.4                        Third Party Confidential Information.

 

a.                                      Sponsor will need to disclose to SynteractHCR the confidential information of third parties, to which the following terms shall apply.  “Third Party Confidential Information” shall mean the *** including the accompanying script (“***”) developed by *** a Delaware corporation having offices at *** (“***”) and the *** (“***”) licensed from ***. The following terms shall apply to the *** (“*** Terms”):

 

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i.                        SynteractHCR (A) shall not disclose to any third party, or use any part or all of the *** other than as required to perform Services; (B) shall take all reasonable steps to prevent the unauthorized disclosure of the *** to any third party; (C) shall limit access to the *** only to those employees and Subcontractors who have a need to know in order to perform Services and who are bound by the terms of this Agreement; and (D) shall not remove or destroy any proprietary or confidentiality notice on the *** or related materials.

ii.               SynteractHCR shall use the *** solely and only to the extent necessary to perform Services and shall not use it for any other study.  SynteractHCR shall not (A) transfer, reveal, market, sell, offer for sale, lease, license, sublicense, loan, or otherwise provide the *** to any third party, whether or not such action is for commercial advantage, or (B) create derivative works of, use, copy, modify, distribute, authorize the use of, publish, publicly perform, physically, optically, or digitally transmit, or display the whole or any portion of the ***, except as specifically authorized herein.  SynteractHCR acknowledges and agrees that the use of the *** to manipulate, report, distribute, or otherwise use any data in violation of any law or of any terms or limitations imposed by this Agreement shall be a violation of this Agreement and shall automatically terminate the rights granted in these *** Terms.

iii.            This Agreement shall not transfer any title or ownership rights in the ***, including any intellectual property embodied therein or arising therefrom, which title and ownership rights shall at all times remain with ***.

iv.           Except for completed *** for individual patients which shall remain as part of the individual patient’s data for so long as such files are kept, upon termination or expiration of the Agreement, or earlier request of Sponsor, SynteractHCR shall return to Sponsor or destroy all copies of the *** and certify in writing that they have done so, that it has not retained any copies, and that it has deleted any copies from all computers under its control, provided, however, that SynteractHCR may retain one (1) copy of the *** for archival purposes, which shall remain subject to the terms of this Agreement.

v.              These obligations shall survive expiration or termination of the Agreement.  In the event the *** is or becomes available in the public domain through no fault of any party or third party, SynteractHCR shall have the same rights as a third party would have with respect to the ***.

vi.           In the event of a conflict between these Third *** Terms and this Agreement, these *** Terms shall be controlling with regard to the *** only.

 

b.                                      The following terms shall apply to the *** (“*** Terms”)”:  The *** shall be used solely for performing Services and shall not be used for any other subject, Study or purpose.  No right is granted to SynteractHCR to use or reproduce the *** beyond that required to perform Services.  All intellectual property rights in the ***, including without limit rights in trademarks, trade secrets and copyright, shall be and remain at all times with ***, ***, and SynteractHCR shall have no such rights, title or interest in or to the ***.  SynteractHCR shall not remove or destroy any proprietary notice, including without limit copyright or trademark symbols, on the *** or related materials.  ***, *** shall be acknowledged as the source of the *** in any publication which mentions the ***.

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

13.0                        Publication and Publicity.

 

13.1                        Publication.  Sponsor has the right to publish in any press or divulge at any meeting or symposia any report or result obtained from the Services.

 

13.2                        Publicity.  Except as is necessary to comply with applicable laws and regulations or to enforce their respective rights under this Agreement, or to a Party’s legal or financial advisors, and except as otherwise agreed to by the Parties in writing, the Parties shall keep the terms of this Agreement confidential.

 

Neither Party shall use, directly or by implication, the name of the other Party or any director, officer, employee or agent of the other Party or any adaptation thereof in connection with any products, publicity, promotion, advertising, or other public disclosure without the prior written approval of the other Party.

 

14.0                        Indemnification.

 

14.1                        Sponsor’s Agreement.  Sponsor shall indemnify, defend and hold harmless SynteractHCR and its employees, affiliates, directors, officers and agents (collectively, the “SynteractHCR Indemnitees”) from and against any and all damages, liabilities, losses, costs and expenses of any kind or nature whatsoever, including, without limitation, reasonable attorney’s fees, reasonable expert witness and court costs (collectively, “Claims”), incurred in connection with any claim, demand, action, or proceeding brought by a third party arising from (a) personal injury or death resulting or arising from any Study Drug  supplied by Sponsor and used according to the Protocol in a clinical trial, (b)  Sponsor’s or Sponsor-Designated Vendor’s negligence or willful misconduct in connection with the Services and other work conducted under this Agreement or (c) Sponsor’s breach of any obligations, representations or warranties under this Agreement; provided however, that Sponsor shall have no obligation of indemnity hereunder with respect to a Claim to the extent that such Claim arises from (i) the negligence or intentional misconduct on the part of SynteractHCR Indemnitees or its Subcontractors, (ii) a material breach of any of SynteractHCR’s obligations, representations or warranties under this Agreement, or (iii) failure of a SynteractHCR Indemnitees to comply with Applicable Law or the Protocol.

 

14.2                        SynteractHCR’s Agreement. SynteractHCR shall indemnify, defend, and hold harmless Sponsor and its employees, affiliates, directors, officers and agents (collectively, the “Sponsor Indemnitees”) from and against any and all Claims incurred in connection with any claim, demand, action, or proceeding brought by a third party arising from (a) the negligence or intentional misconduct on the part of any of the SynteractHCR Indemnitees, (b) a breach of any of SynteractHCR’s obligations, representations or warranties under this Agreement; or (c) the failure of a SynteractHCR Indemnitees to comply with Applicable Law or the Protocol; provided, however, that SynteractHCR shall have no obligation of indemnity hereunder with respect to any Claim to the extent that such Claim arises from (i) the negligence or intentional misconduct on the part of Sponsor or Sponsor-Designated Vendor(s), or (ii) a breach of any of Sponsor’s obligations under this Agreement.

 

14.3                        Indemnification Procedure.  Each Party’s agreement to indemnify, defend, and hold harmless the other Party and its respective indemnitees is conditioned upon the indemnified party:  (i) providing prompt written notice to the indemnifying party of any claim, demand, or action arising out of the indemnified activities after the indemnified party has knowledge of such claim, demand, or action; (ii) permitting the indemnifying party to assume full responsibility and authority to investigate, prepare for, settle, and defend against any such claim, demand, or action; (iii) assisting the indemnifying party, at the indemnifying party’s reasonable expense, in the investigation of, preparation for and defense of any such claim, demand, or action; and (iv) not compromising or settling such claim, demand, or action without the indemnifying party’s written consent.

 

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15.0                        Limitation of Liability.

 

15.1                        SynteractHCR assumes no responsibility for Sponsor’s use of the results of the Studies.

 

15.2                        The Parties total liability in any way related to the subject matter of this Agreement, and regardless of whether the claim for such damages is based on contract, tort or any other legal theory is limited and shall not exceed ***

 

15.3                        NEITHER SPONSOR NOR SYNTERACTHCR SHALL BE LIABLE TO THE OTHER FOR ANY LOST PROFITS OR PUNITIVE, CONSEQUENTIAL, INCIDENTAL, INDIRECT, EXEMPLARY OR SPECIAL DAMAGES (INCLUDING LOST REVENUES OR LOST PROFITS) IN CONNECTION WITH ANY CAUSE OF ACTION FOR BREACH OF THIS AGREEMENT.  THE FOREGOING DOES NOT LIMIT EITHER PARTY’S INDEMNIFICATION OBLIGATION WITH RESPECT TO THIRD PARTY CLAIMS.

 

16.0                        Insurance.

 

16.1                        Sponsor Insurance.  During the term of this Agreement, Sponsor shall maintain in full force and effect a policy or policies or self-insurance of:

 

a.                                      General Liability:  General liability insurance with limits of not less than *** (***) per occurrence and in the aggregate.  This general liability requirement may be satisfied through a combination of general liability and umbrella / excess liability policies;

 

f.                                        Products Liability:  Products liability insurance with limits of not less than *** (***) per occurrence and in the aggregate.

 

g.                                       Clinical Trials Insurance:  Clinical trials insurance in compliance with local compulsory requirements.

 

h.                                      Sponsor shall add SynteractHCR as an additional insured under its Products Liability and Clinical Trials insurance, which coverage shall not include coverage for claims arising out of the negligence or intentional misconduct of Synteract HCR.

 

16.2                        SynteractHCR Insurance.  SynteractHCR shall at all times during the term of this Agreement, provide and maintain at its own expense, the following types of insurance:

 

a.                                      Professional Liability: Professional Liability insurance covering all professional acts, errors and omissions in an amount of not less than *** (***) per occurrence and in the aggregate.  The Professional Liability insurance policy shall exist as a means of curing financial harm incurred by Sponsor or a third party.

 

b.                                      General Liability: Commercial General Liability insurance against claims for bodily injury and property damage in an amount of not less than *** (***) in the aggregate.

 

c.                                       Workers Compensation: Amounts in accordance with applicable law.

 

d.                                      SynteractHCR shall add Sponsor as an additional insured under SynteractHCR’s Products Liability and Clinical Trials insurance policy to cover claims against Sponsor for bodily

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

injury arising out of the negligence or intentional misconduct of SynteractHCR in the implementation and management of clinical Studies involving administration of the Study Drug to a patient.

 

16.3                        General Terms.

 

a.                                      All policies shall be issued by one or more insurance companies rated A- VII or better by the BEST Rating guide or its equivalent.

 

b.                                      Such insurance may be provided on a claims-made basis (with the exception of workers compensation and employers’ liability), however, such insurance shall have a retroactive date at least as early as the date that any work will be performed pursuant to the Agreement, and shall be maintained for a period (or shall have an extended reporting period) of at least *** (***) years after the termination of this Agreement.

 

c.                                       In the event that such policies are cancelled, terminated or altered, the insured Party shall endeavor to provide at least *** (***) days prior written notice to the other Party.

 

d.                                      Each Party shall upon request provide the other Party with a Certificate(s) of Insurance reflecting such endorsement(s) or evidence of specific policy language granting such coverage.

 

e.                                       It is agreed and understood that the above limits are minimum required amounts and are not limitations of liability.

 

17.0                        Independent Contractor.  SynteractHCR and Sponsor are independent contractors.  Nothing in this Agreement will be construed to create the relationship of partners, joint venturers, or employer and employee between Sponsor and SynteractHCR or SynteractHCR’s employees or Subcontractors.  Neither Party, nor its employees, or independent contractors will have authority to act on behalf of or bind the other Party in any manner whatsoever unless otherwise authorized in this Agreement or a specific Work Order or in a separate writing signed by both Parties.

 

18.0                        Employment.  During the term of this Agreement and for *** (***) months after the expiration or termination of this Agreement, the Parties agree that neither Party shall solicit for employment or hire any employee or independent contractor of the other Party without that Party’s prior written consent.  For avoidance of doubt, responding to a public announcement of an open position that was posted by the Sponsor or SynteractHCR or introduction by a third party recruiter shall not be considered solicitation and there shall be no prohibition against hiring such employee.

 

19.0                        Notices. Any notice or other communication required or permitted by this Agreement to be given to a Party shall be in writing in English and shall be deemed given if delivered personally or when delivered by commercial messenger or courier service, or mailed by U.S. registered or certified mail (return receipt requested) or its foreign equivalent, to the Party at the Party’s address written below.  If sent by mail, the notice delivery will be deemed effective three (3) business days after mailing in accordance with this Section.

 

	
If   to Sponsor:
    	
 
    	
If   to SynteractHCR:
    

 

	
Insmed   Incorporated
    	
 
    	
SynteractHCR, Inc.
    
	
10   Finderne Avenue
    	
 
    	
5759   Fleet Street
    

 

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Building   10, Suite F
    	
 
    	
Suite 100
    
	
Bridgewater,   NJ 08807-3365
    	
 
    	
Carlsbad,   CA 92008
    
	
Attn:   General Counsel
    	
 
    	
Attn:   Contract Services
    
	
 
    	
 
    	
Fax:   ***
    

 

Each Party may change its address and/or contact person for such notices and communications by written notice to the other Party in accordance with this Section.

 

20.0                        Force Majeure.  If the performance of this Agreement by SynteractHCR or Sponsor is prevented, restricted, interfered with or delayed (either totally or in part) by reason of any cause beyond the control of the Parties (including, but not limited to, acts of God, explosion, disease, weather, war, insurrection, terrorism, civil strike, riots or extensive power failure), the Party so affected will, upon giving notice to the other Party as soon as is practical, be excused from such performance to the extent of such prevention, restriction, interference or delay, provided that the affected Party will use reasonable efforts to avoid or remove such causes of non-performance and will continue performance whenever such causes are removed.

 

21.0                        Severability.  If any of the provisions or a portion of any provision of this Agreement is held to be invalid, illegal or unenforceable by a court of competent jurisdiction, the validity and enforceability of the enforceable portion of any such provision and/or the remaining provisions will not be affected thereby.  The Parties agree that they will negotiate in good faith to replace any provision hereof so held invalid, illegal or unenforceable with a valid provision, which is similar as possible in substance to the invalid, illegal or unenforceable provision.

 

22.0                        Assignment.  Sponsor may assign its rights and obligations under this Agreement (a) to an Affiliate, or (b) in conjunction with a sale or transfer of the business or assets to which this Agreement relates (whether by stock purchase, asset purchase, merger or otherwise), and SynteractHCR may make assignment(s) to financial institutions or other lenders solely of the right to payments due to SynteractHCR hereunder; otherwise, this Agreement may not be assigned in whole or in part by either Party except with the prior written consent of the other Party.  Any assignment not in compliance with this Section will be null, void and of no effect.  This Agreement will be binding upon and inure to the benefit of each Party’s permitted assigns and successors-in-interest.  No assignment will relieve either Party of the performance of any accrued obligation that such Party may then have under this Agreement.

 

23.0                        Waiver.  No waiver of any term, provision or condition of this Agreement (whether by conduct or otherwise) in any one or more instances will be deemed to be construed as a further or continuing waiver of such term, provision or condition or of any other term, provision or condition of this Agreement.

 

24.0                        Entire Agreement.  This Agreement, including all Work Orders attached hereto contains the full understanding of the Parties with respect to the Services and supersedes all previous written or oral representations, agreements and understandings between the Parties concerning the subject matter hereof. This Agreement will not be modified in any way except in writing and signed by a duly authorized representative of Sponsor and an authorized officer of SynteractHCR.

 

25.0                        English Language.  The Parties hereto confirm that this Agreement as well as any other documents relating hereto, including notices, and excluding any document required by law to be in another language, have been and shall be drawn up in the American English language only.

 

26.0                        Headings.  This Agreement contains headings only for convenience and the headings do not constitute or form a part of this Agreement and should not be used in the construction of this Agreement.

 

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27.0                        Dispute Resolution.  In the event that any dispute arises relating to this Agreement, the Parties shall promptly meet and attempt to resolve such dispute through good faith discussions.  If the Parties are unable to resolve any dispute to their mutual satisfaction within *** (***) days after the dispute arose, and do not agree to extend the time for resolution of the issue, then the Parties shall escalate such dispute to the Chief Executive Officer of Sponsor and the Chief Executive Officer of SynteractHCR for resolution.  The two CEOs will use reasonable efforts to attempt to resolve the dispute through good faith negotiations by telephone or in person as may be agreed.  In the event the dispute is not resolved through negotiation within *** (***) days after the dispute arose, and the Parties do not agree to extend the time, the parties will submit to confidential, non-binding mediation before a mutually acceptable mediator.  Each Party will designate at least one corporate officer with full authority to resolve the dispute that will attend and participate in the mediation.  If the dispute remains unresolved *** (***) days after the dispute arose, and the Parties do not agree to extend the time for mediation, then each Party will be free to pursue any available remedy at law or in equity.  Each Party will bear its own legal fees and any costs incurred under this Section.

 

28.0                        Governing Law.   This Agreement will be governed by, and construed and enforced in accordance with the laws of New York and will be binding upon the parties hereto in the United States and worldwide, without regard to the conflicts of law provisions.  Any dispute arising out of this Agreement shall be submitted exclusively to the competent courts of New York County, New York without restricting any rights of appeal.

 

29.0                        Work with Competitors.  During the term of this Agreement, SynteractHCR may contract for work with competitors of the Sponsor or other groups, however, SynteractHCR affirms that it does not have and shall not enter into an agreement which would restrict its ability to fulfill this Agreement.  SynteractHCR agrees that in fulfilling contracts with others, it shall not use or disclose any confidential or proprietary information of Sponsor as set forth in Section 12.0.

 

30.0                        Counterparts.  This Agreement shall become binding when any one or more counterparts hereof, individually or taken together, shall bear the signatures of both Parties.  This Agreement may be executed by facsimile or exchange of PDF copies, and in two or more counterparts, each of which will be deemed an original document, and all of which, together with this writing, will be deemed one instrument.

 

IN WITNESS WHEREOF, the Parties have caused this Agreement to be executed by their duly authorized representatives as of the Effective Date.

 

	
SynteractHCR, Inc.
    	
 
    	
Insmed   Incorporated
    
	
 
    	
 
    	
 
    
	
/s/   Stewart Bieler
    	
 
    	
/s/   Gina Eagle
    
	
Name:   
    	
Stewart   Bieler
    	
 
    	
Name:   
    	
Gina   Eagle, MD
    
	
Title:   
    	
CAO
    	
 
    	
Title:   
    	
VP,   Clinical Operations
    
	
Date:   
    	
August 27,   2014
    	
 
    	
Date:   
    	
September 16,   2014
    

 

18

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

APPENDIX A — FORM OF WORK ORDER

 

Insmed Incorporated -  SynteractHCR, Inc.

Work Order 1

 

<List Services> Services for:

 

<Study Title> <Protocol >

 

Table of Contents

 

	
1
    	
Incorporation
    	
22
    
	
2
    	
Statement of Services (Add Services to Table)
    	
22
    
	
3
    	
Project Specifications (List Project Specifications)
    	
22
    
	
4
    	
Miscellaneous
    	
22
    
	
4.1
    	
Backup and   Security
    	
22
    
	
4.2
    	
Language
    	
22
    
	
5
    	
Project Costs
    	
23
    
	
5.1
    	
Assumptions (List Project Assumptions)
    	
23
    
	
5.2
    	
Cost Estimates
    	
23
    
	
5.3
    	
Pass-Through   Costs
    	
24
    
	
5.4
    	
Payment Terms
    	
24
    
	
5.5
    	
Overscope
    	
25
    
	
5.6
    	
Invoices and   Payment Correspondence
    	
25
    

 

19

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

20

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

21

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

INSMED INCORPORATED — SYNTERACTHCR

 

WORK ORDER X

 

COMPREHENSIVE SERVICES

 

1                      Incorporation

 

This Work Order X is made and entered on <Day, Month, Year> (“Effective Date”) between Insmed Incorporated (“Sponsor”) and SynteractHCR, Inc. (“SynteractHCR”).  Unless specifically stated otherwise in this Work Order X, the Master Agreement for Services, signed on <Date> between Sponsor and SynteractHCR shall govern the provision of services set forth in this Work Order X for comprehensive clinical trial services in support of Sponsor’s protocol <Protocol >.

 

2                      Statement of Services (Add Services to Table)

 

The table below describes the activities (“Services”) that would be performed for this study as detailed in this Work Order X.  This Work Order X with any incorporated Work Order Amendments will collectively hereinafter be referred to as the “Project”.

 

X= primary responsibility; (X) = secondary responsibility

 

	
Activity
    	
 
    	
Sponsor
    	
 
    	
Synteract
   HCR
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    

 

3                      Project Specifications (List Project Specifications)

 

4                      Miscellaneous

 

Backup and Security

 

SynteractHCR performs incremental *** backups *** server locations, ***.  The *** backups are retained for a *** period.  Every week, a full backup is written to media and stored off-site for a *** retention period at ***.  All backups are verified and logged by the Global Systems staff.  Quarterly tapes are stored offsite at *** for *** years.  Offsite data is available within a few hours of requesting the data from ***.

 

All clinical data is stored ***  No clinical data are stored on local workstations.  Access to the clinical data files is restricted based on directory permission levels that are determined by job function.  Databases are password protected, and only SynteractHCR authorized personnel have access.  No clinical data will be altered or updated without going through the proper application interface.  ***

 

All connections to SynteractHCR’s secure web portal, used for document viewing, downloading, and Argus are encrypted using ***  Published applications, like *** and *** are secured via our

 

22

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

***.  A secure FTP server is available for uploading files to the SynteractHCR network.  SynteractHCR utilizes *** for securing e-mail communication if requested by Sponsor.

 

Language

 

It is assumed that all deliverables will be provided in English for this study.

 

5                      Project Costs

 

Assumptions  (List Project Assumptions)

 

Number of Enrolled Patients

Number of Screened Patients

Number of Sites

Project Duration (Months)

Clinical Operations (Months)

Patient Enrollment Duration

Patient Treatment/Follow-up Duration

Patient Enrollment/Treatment Duration (Months)

Number of Unique CRF Pages

Number of CRF pages/patient

Total Number of CRF Pages

Number of Edit Checks

Number of queries per patient

Number of coded items/patient

Number of Analysis Datasets

Number of Tables

Number of Figures

Number of Listings

Number of ADaM Datasets

Number of SDTM Domains

Number of TDM Datasets

 

The following assumptions have also been made in determining the cost estimates:

 

1.                    (List General Assumptions for the Project)

 

Cost Estimates

 

With the exception of flat rate items, SynteractHCR will only charge for actual time spent per task and will not exceed the project study maximum without an approved change order.  Site Visits are listed in the budget on a per visit cost basis, however these tasks will be invoiced on an hourly basis based on the actual work performed.

 

23

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

 

TIME AND MATERIALS - <Data Collection System>

 

	
ACTIVITY
    	
 
    	
RATE
    	
 
    	
UNIT
    	
 
    	
EST. REQ.
    	
 
    	
ESTIMATED CHARGE
    	
 
    
	
Clinical Operations
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Clinical Operations Subtotal
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Safety Surveillance
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Safety Surveillance Subtotal
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Data Management
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Data Management Subtotal
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Biostatistics & Medical   Writing
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Biostatistics & Medical   Writing Subtotal
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Project Management
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Project Management Subtotal
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Study Total
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    

 

Rates stated in this Work Order are current through ***.  As of January 1st of each year starting in *** SynteractHCR’s activity rates will increase in accordance with the latest ***.

 

Pass-Through Costs

 

<List anticipated expenses> expenses are considered study-related pass-through costs and are not included in the above cost estimates.  ***

 

Estimated pass-through costs have been provided in the table below:

 

	
Item
    	
 
    	
Number
    	
 
    	
Unit
    	
 
    	
Cost Per
   Unit
    	
 
    	
Total
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Total
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    

 

Payment Terms

 

An advance of *** ($XXXX) of the Cost Estimate ($XXXX) is due upon signing this Work Order X.  Sponsor will then be invoiced monthly for actual work performed.  Flat-rate items will be billed upon completion of the deliverable or monthly as indicated in the Cost Estimates provided above.  At the completion of the project, if payments received by SynteractHCR exceed the cost of the work completed, SynteractHCR will reimburse Sponsor for the amount overpaid.

 

24

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

Sponsor’s payment of SynteractHCR’s invoices shall in no way be conditioned or delayed pending Sponsor’s receipt of payment from any third party.  Additionally, SynteractHCR shall be entitled to expenses incurred in its efforts to collect unpaid invoices from Sponsor, if necessary, including, without limitation, court costs and reasonable attorney’s fees.

 

Overscope

 

If, in the opinion of SynteractHCR, and mutually agreed to by Sponsor, the scope of the work exceeds what is described in this Work Order X, the nature, time, and cost of work over scope will be documented in a change order and provided to Sponsor.   A Work Order Amendment will be generated by SynteractHCR to reflect these changes and will be reviewed, mutually agreed to, and signed by SynteractHCR and Sponsor.  If the scope of Services in a Work Order Amendment causes the total Project cost estimate to increase, SynteractHCR, at its discretion, reserves the right to request from Sponsor an additional advance to be payable to SynteractHCR. The advance held by SynteractHCR for the Project will not exceed ***.

 

Invoices and Payment Correspondence

 

SynteractHCR will send invoices via US Mail and email> to the following mailing address and Email:

 

Insmed Incorporated

10 Finderne Avenue

Building 10

Bridgewater, NJ 08807-3365

Attn:       Accounts Payable

Phone:   ***

Email:  ***

 

With an email copy to:

 

*** at ***

 

Phone or email correspondence in regard to payment inquiries should be addressed to the following individuals:

 

	
If   to Sponsor:
    	
If   to SynteractHCR:
    
	
 
    	
 
    
	
Insmed   Incorporated
    	
SynteractHCR, Inc.
    
	
10   Finderne Avenue
    	
5759   Fleet Street
    
	
Building   10
    	
Suite 100
    
	
Bridgewater,   NJ 08807-3365
    	
Carlsbad,   CA 92008
    
	
Attn:
    	
Attn:   Accounts Receivable
    
	
Phone:   ***
    	
Phone:   ***
    
	
Email:   ***
    	
Email:   ***
    

 

Each Party may change its address and/or contact person for such notices and communications by written notice to the other party in accordance with this Section.

 

To pay an invoice via wire transfer, Sponsor will use the following information to process the payment:

 

25

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

Account Name:  SynteractHCR, Inc.

Bank Name:  ***

Bank Address: ***

Account Number:  ***

Routing Number:  ***

 

For invoices paid via wire transfer or ACH, Sponsor will send a remittance of the payment to Accounts Receivable at *** or fax number ***.

 

IN WITNESS WHEREOF, the parties have caused this Work Order to be executed by duly authorized representatives as of the Work Order X Effective Date.

 

	
SynteractHCR, Inc.
    	
 
    	
Insmed   Incorporated
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
Name:
    	
 
    	
Name:
    
	
Title:
    	
 
    	
Title:
    

 

26Exhibit 10.30

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
 
    	
Work Order 1
    	
 
    	
INS-212
    

 

Insmed Incorporated  -  SynteractHCR, Inc.

 

Work Order 1

 

Comprehensive Services for:

 

Protocol INS-212: A Randomized, Open-Label, Multicenter Study of Liposomal Amikacin for Inhalation (LAI) in Adult Patients with Nontuberculous Mycobacterial (NTM) lung infections caused by Mycobacterium avium complex (MAC) that are refractory to treatment

 

Table of Contents

 

	
1
    	
Incorporation
    	
2
    
	
2
    	
Statement of Services
    	
2
    
	
3
    	
Project Specifications
    	
8
    
	
4
    	
Miscellaneous
    	
19
    
	
4.1
    	
Backup and Security
    	
19
    
	
4.2
    	
Language
    	
19
    
	
5
    	
Project Costs
    	
20
    
	
5.1
    	
Assumptions
    	
20
    
	
5.2
    	
Summary Cost Estimates
    	
27
    
	
5.3
    	
Pass-Through Costs
    	
28
    
	
5.4
    	
Payment Terms
    	
29
    
	
5.5
    	
Change in Scope
    	
30
    
	
5.6
    	
Invoices and Payment Correspondence
    	
30
    
	
Attachment 1: Detailed   Budget
    	
32
    
				

 

1

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
 
    	
Work Order 1
    	
 
    	
INS-212
    

 

INSMED INCORPORATED — SYNTERACTHCR

 

WORK ORDER 1

 

COMPREHENSIVE SERVICES

 

1                      Incorporation

 

This Work Order 1 is made and entered on 24 December 2014 (“Effective Date”) between Insmed Incorporated (“Sponsor”) and SynteractHCR, Inc. (“SynteractHCR”). Unless specifically stated otherwise in this Work Order 1, the Master Agreement for Services, signed on 27 August 2014 between Sponsor and SynteractHCR shall govern the provision of services set forth in this Work Order 1 for comprehensive clinical trial services in support of Sponsor’s protocol INS-212.

 

2                      Statement of Services

 

The table below describes the activities (“Services”) that would be performed for this study as detailed in this Work Order 1. This Work Order 1 with any incorporated Work Order Amendments will collectively hereinafter be referred to as the “Project”.

 

	
Sponsor: Insmed
    	
 
    	
Study ID:    INS-212
    

 

Services Checklist & Transfer of Obligations

X=Responsibility (Primary); (X)=Responsibility (Secondary); A=Approve; R=Review; NA=Not Applicable

 

	
Activity
    	
 
    	
Sponsor
    	
 
    	
SynteractHCR
    	
 
    	
Comments
    
	
REGULATORY   ***
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Investigational New Drug (IND) Preparation/   Submission (***)
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
IND Ongoing Maintenance (***)
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Annual Update/Report to the IND (***) 
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Annual Update/Report to the IND — Preparation of   the T/L/Fs  (***) 
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
New Drug Application (NDA) or Biologics License   Application (BLA) Preparation/Submission (***)
    	
 
    	
NA
    	
 
    	
NA
    	
 
    	
 
    
	
Drug Submission Application (***)
    	
 
    	
NA
    	
 
    	
NA
    	
 
    	
 
    
	
Document Submission to Regulatory Authority (***)
    	
 
    	
 
    	
 
    	
X
    	
 
    	
CTA and Clinical Trial Site Information Form   (CTSIF) which includes REB approval
    
	
REGULATORY   ***
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Obtain a *** Clinical Trials (*** Database Number
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Application for Clinical Trial Authorization (CTA)   Preparation/Submission
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    

 

2

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
 
    	
Work Order 1
    	
 
    	
INS-212
    

 

 

	
Sponsor: Insmed
    	
 
    	
Study ID:    INS-212
    

 

Services Checklist & Transfer of Obligations

X=Responsibility (Primary); (X)=Responsibility (Secondary); A=Approve; R=Review; NA=Not Applicable

 

	
Activity
    	
 
    	
Sponsor
    	
 
    	
SynteractHCR
    	
 
    	
Comments
    
	
Investigational Medicinal Product Dossier (IMPD)   Preparation/Submission
    	
 
    	
X
    	
 
    	
X
    	
 
    	
CRO will review and submit
    
	
Application for Ethics Committee (EC) Approval   Preparation/Submission
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Qualified Person (QP) Release 
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Investigational Drug Import Licensure
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Investigational Drug Export Licensure 
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Local Warehouse(s)
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Clinical Trial Insurance (Provide/Arrange For)
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
REGULATORY   (for ***)
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Ethics Committee Submission
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Regulatory Authority Notification (TGA)
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
PROJECT START-UP/INITIATION: Assume CRO SOPs to be used
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Protocol Development
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Protocol Amendment(s) Development 
    	
 
    	
A
    	
 
    	
X
    	
 
    	
To be costed if applicable
    
	
Protocol Review
    	
 
    	
X
    	
 
    	
R
    	
 
    	
 
    
	
Protocol Amendment(s) Review & Approval
    	
 
    	
A
    	
 
    	
 
    	
 
    	
 
    
	
Protocol/Protocol Amendment(s)   Printing/Distribution
    	
 
    	
 
    	
 
    	
X
    	
 
    	
To be costed if applicable
    
	
Investigator Drug Brochure (IDB) Development
    	
 
    	
X
    	
 
    	
R
    	
 
    	
 
    
	
IDB Printing/Distribution
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Model Informed Consent Form (ICF) Development
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Model ICF Review
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Model ICF Distribution
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Country-Specific ICF (***)
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Country-Specific ICF Distribution (***
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Case Report Form (CRF) Screens Development
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
CRF Printing/Shipping
    	
 
    	
 
    	
 
    	
NA
    	
 
    	
 
    
	
CRF Review
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
CRF Completion Guidelines
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Translation of Study Documents
    	
 
    	
 
    	
 
    	
X
    	
 
    	
SynteractHCR will manage translation vendor
    
	
Site Feasibility/Report
    	
 
    	
R
    	
 
    	
X
    	
 
    	
 
    
	
Site Identification/Selection
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Document Submission to Appropriate Review   Committee (i.e., IRB/EC)
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Regulatory/Essential Document Collection/Review
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    

 

3

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
 
    	
Work Order 1
    	
 
    	
INS-212
    

 

 

	
Sponsor: Insmed
    	
 
    	
Study ID:    INS-212
    

 

Services Checklist & Transfer of Obligations

X=Responsibility (Primary); (X)=Responsibility (Secondary); A=Approve; R=Review; NA=Not Applicable

 

	
Activity
    	
 
    	
Sponsor
    	
 
    	
SynteractHCR
    	
 
    	
Comments
    
	
Regulatory/Essential Document Maintenance (Ongoing   Collection/Review)
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Trial Master File (TMF) Set-up/Maintenance
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Site Regulatory Binder/Study Procedures Manual
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Other Study Documents/Tools
    	
 
    	
R
    	
 
    	
X
    	
 
    	
 
    
	
Investigator (Site) Agreements/Contracts
    	
 
    	
A
    	
 
    	
X
    	
 
    	
SynteractHCR will sign site contracts after   Sponsor review/approval
    
	
Investigator Fee Negotiation
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Investigator Fee Payment/Tracking
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Investigator’s Meeting (Organization/Conduct)
    	
 
    	
 
    	
 
    	
X
    	
 
    	
3 IMs, SynteractHCR will manage meeting planning   vendor
    
	
Prepare Investigator’s Meeting Binders
    	
 
    	
R
    	
 
    	
X
    	
 
    	
 
    
	
Investigator’s Meeting (Attend/Participate)
    	
 
    	
X
    	
 
    	
X
    	
 
    	
 
    
	
Aggregate spend/Sunshine Data Reporting
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
CLINICAL MONITORING Assume CRO SOPs to be used
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Monitoring Plan
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Pre-Study Qualification Visits
    	
 
    	
 
    	
 
    	
X
    	
 
    	
On site or via telephone
    
	
Site Initiation Visits
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Interim Monitoring Visits
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Site Close-out Visits
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Monitoring Visit Reports/Follow-up Letters
    	
 
    	
R
    	
 
    	
X
    	
 
    	
 
    
	
Site Management/Contact
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Query Resolution 
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Study Drug Management   (Storage/Distribution/Destruction)
    	
 
    	
 
    	
 
    	
X
    	
 
    	
Site level
    
	
Nebulizer and cleaning supplies Management   (Storage/Distribution/Return/Destruction)
    	
 
    	
 
    	
 
    	
X
    	
 
    	
Site level
    
	
MEDICAL MONITORING
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Medical Monitoring/Support to Project Team/Sites
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
After-Hours Medical Coverage
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Review of AE Coding
    	
 
    	
A
    	
 
    	
 
    	
 
    	
 
    
	
Review of SAE Coding
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Medical Review of Routine Laboratory Reports
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Review (Medical) of Data Listings
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Review (Medical) of CRFs
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Review (Medical) of Routine ECG Reports
    	
 
    	
NA
    	
 
    	
 
    	
 
    	
 
    

 

4

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
 
    	
Work Order 1
    	
 
    	
INS-212
    

 

	
Sponsor: Insmed
    	
 
    	
Study ID:    INS-212
    

 

Services Checklist & Transfer of Obligations

X=Responsibility (Primary); (X)=Responsibility (Secondary); A=Approve; R=Review; NA=Not Applicable

 

	
Activity
    	
 
    	
Sponsor
    	
 
    	
SynteractHCR
    	
 
    	
Comments
    
	
Safety Management Plan
    	
 
    	
X
    	
 
    	
 
    	
 
    	
3rd party vendor
    
	
SAE Receipt/Review 
    	
 
    	
X
    	
 
    	
 
    	
 
    	
3rd party vendor
    
	
SAE Documentation (SAE Narrative Form)
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Collection of Safety Data (SAE Data) 
    	
 
    	
X
    	
 
    	
X
    	
 
    	
Work with 3rd party vendor to obtain   information from sites
    
	
Preparation of *** Form (Safety Reports) North   America
    	
 
    	
X
    	
 
    	
 
    	
 
    	
3rd party vendor
    
	
Preparation of *** Form (Suspected Unexpected   Serious Adverse Reactions [SUSARs] Reports) (***)
    	
 
    	
X
    	
 
    	
 
    	
 
    	
3rd party vendor
    
	
Safety Reporting to Health/Regulatory Authorities 
    	
 
    	
X
    	
 
    	
 
    	
 
    	
3rd party vendor
    
	
SUSARs Reporting to Competent Authorities (***)
    	
 
    	
X
    	
 
    	
 
    	
 
    	
3rd party vendor
    
	
Electronic Reporting of SUSARs to (***) (***)
    	
 
    	
X
    	
 
    	
 
    	
 
    	
3rd party vendor
    
	
Preparation/Submission of Registration Package for   Electronic Reporting of SUSARs (***)
    	
 
    	
X
    	
 
    	
 
    	
 
    	
3rd party vendor
    
	
Notify Sites of SAEs/Distribute Safety Reports
    	
 
    	
X
    	
 
    	
 
    	
 
    	
3rd party vendor will provide   notifications, per ***
    
	
Notify Sites and ECs of SAEs and SUSARs/   Distribute Safety Reports (***)
    	
 
    	
X
    	
 
    	
 
    	
 
    	
3rd party vendor will provide   notifications, per ***
    
	
SAE Reconciliation 
    	
 
    	
 
    	
 
    	
(X)
    	
 
    	
CRO to assume collaboration with 3rd party vendor for SAE   reconciliation
    
	
DATA MANAGEMENT: Assume CRO SOPs to be used
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Data Management Plan 
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Data Edit Specifications
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Data Listings
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Annotated CRF
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Database Development/Set-up/Programming 
    	
 
    	
A
    	
 
    	
X
    	
 
    	
***
    
	
Electronic Data Capture (EDC)
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Electronic Data Capture (EDC) Training 
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
EDC Helpdesk 
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
CRF Processing, Tracking, and Receipting
    	
 
    	
NA
    	
 
    	
NA
    	
 
    	
 
    
	
Data Entry/Verification
    	
 
    	
NA
    	
 
    	
NA
    	
 
    	
 
    
	
Queries Generation/Resolution
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Coding Dictionaries (***)
    	
 
    	
X
    	
 
    	
X
    	
 
    	
 
    

 

5

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
 
    	
Work Order 1
    	
 
    	
INS-212
    

 

	
Sponsor: Insmed
    	
 
    	
Study ID:    INS-212
    

 

Services Checklist & Transfer of Obligations

X=Responsibility (Primary); (X)=Responsibility (Secondary); A=Approve; R=Review; NA=Not Applicable

 

	
Activity
    	
 
    	
Sponsor
    	
 
    	
SynteractHCR
    	
 
    	
Comments
    
	
Medical Coding (AEs; medical histories; concomitant   drugs)
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
SAE Reconciliation
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Receipt of Local Lab Data (Paper)
    	
 
    	
NA
    	
 
    	
NA
    	
 
    	
 
    
	
Receipt of Vendor Electronic Data (Central   Laboratory, Electrocardiogram, etc.)
    	
 
    	
 
    	
 
    	
X
    	
 
    	
Needs to be reconciliation of this data too.
    
	
Define Critical Variables 
    	
 
    	
NA
    	
 
    	
NA
    	
 
    	
 
    
	
Critical Variable Audit 
    	
 
    	
NA
    	
 
    	
NA
    	
 
    	
 
    
	
Final Database QC Audit 
    	
 
    	
NA
    	
 
    	
NA
    	
 
    	
 
    
	
Interim Data Transfer(s)
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Final Database Closure/Transfer
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Archive CRFs and Database of Record
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Planning & Coordination
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Routine Status Reports
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Create and transfer CDISC compliant datasets   (SDTM)
    	
 
    	
A
    	
 
    	
X
    	
 
    	
Quarterly SDTM transfers to sponsor, SDTM   reviewers guide at end of study
    
	
BIOSTATISTICAL SERVICES Assume CRO SOPs to be used
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Develop Randomization Code
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Statistical Analysis Plan (SAP)
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
T/L/Fs
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Dry Runs
    	
 
    	
 
    	
 
    	
X
    	
 
    	
*** dry runs prior to first interim analysis
    
	
Interim Statistical Analysis/Summary
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Statistical Analysis
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Final Summary T/L/Fs
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Final Statistical Report 
    	
 
    	
NA
    	
 
    	
NA
    	
 
    	
 
    
	
Analysis Datasets Transfers (ADaM)
    	
 
    	
A
    	
 
    	
X
    	
 
    	
ADaM reviewers guide at end of study
    
	
DSMB TLFs 
    	
 
    	
 
    	
 
    	
X
    	
 
    	
SynteractHCR statistician attendance (via   teleconference) at DSMB meetings
    
	
DSMB Plan
    	
 
    	
 
    	
 
    	
X
    	
 
    	
Analysis plan for DSMB
    
	
Population PK Analysis
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
MEDICAL WRITING Assume CRO SOPs to be used
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Patient Narratives (for Study Report)
    	
 
    	
X
    	
 
    	
 
    	
 
    	
Provided by ***
    
	
CSR with appendices
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Activation of Hyperlinks
    	
 
    	
 
    	
 
    	
X
    	
 
    	
Assumes *** links per TLF, section   cross-references, external links
    

 

6

 

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
 
    	
Work Order 1
    	
 
    	
INS-212
    

 

	
Sponsor: Insmed
    	
 
    	
Study ID:    INS-212
    

 

Services Checklist & Transfer of Obligations

X=Responsibility (Primary); (X)=Responsibility (Secondary); A=Approve; R=Review; NA=Not Applicable

 

	
Activity
    	
 
    	
Sponsor
    	
 
    	
SynteractHCR
    	
 
    	
Comments
    
	
Final Integrated Study Report
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Subject Profiles
    	
 
    	
A
    	
 
    	
X
    	
 
    	
SynteractHCR will provide patient profiles via   ***.
    
	
Manuscript
    	
 
    	
NA
    	
 
    	
NA
    	
 
    	
 
    
	
Preparation of Periodic and Annual Safety ***
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Submission of Periodic and Annual Safety Reports   to the Health/Competent Authorities and Ethics Committees (ECs) (***)
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
IWRS
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
IWRS for randomization, tracking enrollment and   drug supplies, nebulizers and cleaning supplies
    	
 
    	
 
    	
 
    	
 
    	
 
    	
TBD
    
	
Drug Supply, Nebulizer and Cleaning Supplies Management   — tracking through IWRS
    	
 
    	
 
    	
 
    	
 
    	
 
    	
TBD
    
	
QUALITY ASSURANCE (QA)
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
GCP/ICH Site Audits
    	
 
    	
X
    	
 
    	
X
    	
 
    	
Assumes ***% of sites may require a GCP audit
    
	
Vendor Audits
    	
 
    	
X
    	
 
    	
X
    	
 
    	
Vendor audits may occur for those sponsor   designated vendors that SynteractHCR will hold the contract for
    
	
PROJECT MANAGEMENT Assume CRO SOPs to be used
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Project Management
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Project Management Plan 
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Project Set-up/Maintenance
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Face-to-Face Meeting(s) 
    	
 
    	
X
    	
 
    	
X
    	
 
    	
*** per year, per sponsor, Global PM, Global CL,   regional PMs
    
	
Team Teleconference(s) (Frequency: weekly)
    	
 
    	
X
    	
 
    	
X
    	
 
    	
 
    
	
Enrollment Updates/Project Status Reports
    	
 
    	
A
    	
 
    	
X
    	
 
    	
Posted on project website
    
	
Project Newsletters 
    	
 
    	
NA
    	
 
    	
NA
    	
 
    	
Regular, frequent eBlasts
    
	
Trial Master File (TMF) Reconciliation
    	
 
    	
A
    	
 
    	
X
    	
 
    	
 
    
	
Training of Project Team
    	
 
    	
X
    	
 
    	
X
    	
 
    	
 
    
	
Vendor Management
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
SUB-CONTRACTING SERVICES
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Central IRB Selection
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Drug Packaging/Labeling/Depot
    	
 
    	
X
    	
 
    	
 
    	
 
    	
 
    
	
Central Laboratory (Select/Contract)
    	
 
    	
 
    	
 
    	
X
    	
 
    	
 
    
	
Vendor Management
    	
 
    	
A
    	
 
    	
X
    	
 
    	
Includes contracting and payment administration
    

 

7

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
 
    	
Work Order 1
    	
 
    	
INS-212
    

 

3                      Project Specifications

 

Global Project Management

 

SynteractHCR manages all projects according to a Project Team approach. The SynteractHCR Global Program Manager will have the primary responsibility of communication with Sponsor for overall project information for the duration of the project. However, Sponsor is welcome to contact any team members as needed. This includes daily, weekly and monthly updates to keep core team members current on all project activities.

 

Project meetings will be conducted on a routine basis. During each meeting, critical issues, unexpected problems and trends are identified and discussed. In addition, milestones are set and reviewed and timelines for all departments working on the project are discussed. Any deviations in project deadlines, expenses and action items are examined with respect to the impact on all departments. Additionally, the team members will “trouble-shoot” problems and solutions before milestones or deadlines are jeopardized. Meeting minutes will be distributed to all team members.

 

Secure Web-Access

 

SynteractHCR will provide secure, web-based access via browser-enabled computers for Sponsor and the rest of the project team to project information such as:

 

·                  Enrollment Status Reports

·                  Regulatory Document status

·                  Monitoring Schedule and report status

·                  CRF, data clarification status, and other data management reports

·                  Project Timelines

 

Specific information to be provided on the website would be determined in conjunction with Sponsor.

 

Vendor Contracts and Management

 

On behalf of Sponsor, SynteractHCR will execute contracts with Sponsor-designated vendors. These vendors may also require audits by SynteractHCR to be compliant with SOPs. SynteractHCR will administer vendor payments for Sponsor.

 

Regulatory Submissions Across Regions

 

SynteractHCR will provide Sponsor with list(s) of required documentation in order to submit to appropriate regulatory authorities in the regions selected for this study.

 

IMPD Review/CTA Submission to Regulatory Authorities

 

SynteractHCR will provide review of IMPD for CTA submission ***. Submissions to Central Regulatory Authorities, as well as to the local authorities and ECs, have been included. Costs associated with amendments are not included in this work order.

 

CTA submission *** to Health Authorities

 

SynteractHCR will prepare the CTA for submission ***. Sponsor will provide the the Quality Overall Summary (QOS). After approval of the CTA by ***, SynteractHCR will prepare the Clinical Trial Site Information Form (CTSIF) for each participating site. Costs have not been included for CTA amendments.

 

8

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

Submissions in Australia

 

SynteractHCR will submit to the Ethics Committee. Therapeutics Goods Administration (TGA) will be notified once approval has been provided.

 

Project Start-Up Activities

 

Protocol and Investigators Brochure Development

 

Sponsor will prepare the protocol and Investigators Brochure (IB) and incorporate any revisions to the protocol and IB which may occur during the project. SynteractHCR in conjunction with Sponsor will ensure that all revisions of the IB have been submitted to the site and are in the Investigator files.

 

Investigator Selection

 

SynteractHCR will perform site identification and will obtain a Non-Disclosure Agreement in a form approved by sponsor, complete a phone questionnaire (if needed) for the site. SynteractHCR will perform a Site Qualification Visit at the site and document the visit in a Site Qualification Visit report. Sponsor will make the final decision on site selection for the project.

 

Negotiation of Clinical Trial Agreements and Site Budgets

 

A Clinical Trial Agreement is defined as any agreement between SynteractHCR or Sponsor and a clinical site, site personnel, Investigator, or site ancillary service provider, in order to perform clinical research for the study. Sponsor will review and approve the SynteractHCR clinical trial agreement, site budget and letter of indemnification templates. SynteractHCR will negotiate the clinical trial agreement and budget to reach mutually agreeable final and fully executed Clinical Trial Agreements and site budgets. Sponsor will provide to SynteractHCR the site budget negotiation parameters for study budget items, such as start-up, scheduled visits, unscheduled visits, screen failure and pass-through fees. After execution of this Work Order, Sponsor and SynteractHCR will develop a mutually agreed upon “Contracts Program Plan” that sets forth the escalation, communication, and approval processes for all Clinical Trial Agreements and their respective components.

 

In addition, SynteractHCR will facilitate the negotiation of the site letter of indemnification, which will be executed by the Sponsor and site. The negotiation and execution shall follow the process as specifically set forth in the Contracts Program Plan for the site letter of indemnification.

 

SynteractHCR will administer site payments on behalf of Sponsor as a pass-through expense. SynteractHCR will invoice Sponsor for the site payment amount (and any applicable bank wire transfer fees) on a monthly basis and will be due upon receipt. Once the site payment amount is received and processed, SynteractHCR will remit payment on behalf of Sponsor to the sites. SynteractHCR will track the site payments administered by SynteractHCR on behalf of Sponsor.

 

Project Meetings

 

Project Kick-off Meeting

 

SynteractHCR will attend a Project Kick-off Meeting with Sponsor. The agenda for the Kick-off Meeting will be planned jointly by SynteractHCR and Sponsor. SynteractHCR will determine with Sponsor the required project team members for attendance.

 

Investigators Meetings

 

SynteractHCR will plan and conduct regional Investigators Meetings in conjunction with Sponsor. SynteractHCR will be responsible for planning meeting logistics. Each Investigators Meeting will include a CRA training meeting. The agenda for the Investigators Meetings will be planned jointly by SynteractHCR and Sponsor.

 

9

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

Teleconferences

 

SynteractHCR will conduct regular team teleconferences, both internally and with Sponsor. Minutes for Sponsor teleconferences will be provided by SynteractHCR.

 

Face-to-Face Meetings

 

Per Sponsor request, SynteractHCR will attend face-to-face status update meetings at Sponsor offices in New Jersey, US. The Global Project Manager, Global Clinical Lead, and regional Project Managers will attend in person. Additional team attendees may participate via teleconference.

 

Regulatory Documents

 

SynteractHCR will prepare the template patient Informed Consent Form (ICF). SynteractHCR will ensure that the ICF meets the minimum requirements as outlined by the US Code of Federal Regulations and ICH guidelines where applicable. SynteractHCR will develop draft Protected Health Information (PHI) language to be incorporated into the ICF, or as a standalone authorization form for use with this project.

 

SynteractHCR will be responsible for the initial collection and review of all regulatory documents, such as IRB approvals, Informed Consent Documents, and financial disclosure statements, from the site to ensure compliance with appropriate regulations and ICH/ GCP Guidelines. SynteractHCR will assist the sites with obtaining IRB approval. Regulatory documents will be sent to Sponsor for full approval. Sponsor will forward all fully approved regulatory packages to SynteractHCR for Central files. SynteractHCR will maintain the Central files for the project and the project sites. SynteractHCR will track and collect regulatory documents after the receipt of the initial regulatory package.

 

Set up Project Tracking System

 

SynteractHCR will track regulatory documents, site visits and reports as well as project team contact information within its Clinical Trials Management system.

 

Study Reference Manual

 

SynteractHCR will prepare a Study Reference Manual. The Study Reference Manual will consist of key project instructions for project specific procedures, and items such as, adverse experience reporting, key contacts and project supply ordering. SynteractHCR will prepare the CRF completion instructions in conjunction with Sponsor. Sponsor will provide review and feedback prior to finalization.

 

Site Qualification & Initiation Visits

 

Site Qualification Visit

 

SynteractHCR will qualify the investigational sites and project investigators. The Site Qualification Visit may be performed in conjunction with Sponsor at Sponsor’s option. SynteractHCR may qualify sites via telephone if they have been previously qualified and/or participated in a trial with Sponsor or SynteractHCR within the past 12 months. SynteractHCR will communicate to Sponsor any concerns regarding the site’s ability to conduct the project. Sponsor will make the final decision on site selection.

 

Site Initiation Visit

 

SynteractHCR will conduct Site Initiation Visits (SIV) at the sites. The SIVs may be performed in conjunction with Sponsor at Sponsor’s option. The SIV will include a review of the protocol and project procedures, case report form (CRF) completion, investigator obligations, laboratory specimen collection and handling. SynteractHCR will confirm that proper source documentation is in place in addition to receipt/storage of project drug if available during the scheduled visit.

 

10

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

The Site Initiation Visits will be documented in a monitoring visit report and follow-up letter to the site. The visit report will be drafted within *** working days from the last day of the visit.

 

On-Site Monitoring

 

Monitoring Plan

 

SynteractHCR will develop a monitoring plan for review and approval by Sponsor. The monitoring plan will address the proposed monitoring schedule for each region. The monitoring plan will also describe source document verification (SDV) and any other monitoring conventions. SynteractHCR will provide Curricula Vitae (CVs) of prospective project monitors to Sponsor for review prior to project assignment. Every effort will be made to assign project monitor(s) in close proximity to the selected project sites to reduce travel time and cost.

 

Site Monitoring Visits

 

Monitoring frequency may be adjusted as necessary on a site-by-site basis, based on patient enrollment, monitoring requirements prior to the interim database lock, or specific site issues. Sponsor would be involved in monitoring frequency discussions, if any adjustments are necessary.

 

During on-site monitoring visits SynteractHCR will perform the following tasks to monitor compliance with GCP and appropriate federal regulations and Sponsor requirements as stated in the monitoring plan:

 

·                  Perform ***% review of all signed ICFs and PHI authorizations or local privacy laws;

·                  Review and verify ***% of available source documentation on all CRFs;

·                  Review all clinical data at the site for legibility, completeness, and consistency within the CRF set;

·                  Instruct clinical site staff to supply missing data, complete data corrections, and clarify CRF information;

·                  Check data clarifications against source documents to confirm that all clarifications accurately reflect the source documents;

·                  Monitor IP and nebulizer accountability, including the reconciliation of inventory;

·                  Review required clinical site regulatory documentation, and provide updates to Sponsor;

·                  Document deficiencies and follow-up until they are corrected by the clinical site staff;

·                  Train site personnel as required.

 

SynteractHCR will monitor to verify that the clinical site staff perform the following tasks:

 

·                  CRF completion and Data Corrections;

·                  Provision of source documents at each site visit;

·                  CRF corrections as necessary during each monitoring visit or prior to the next scheduled monitoring visit.

 

The monitoring visits will be documented in a monitoring visit report and follow-up letter to the sites.

 

Close-Out Visits

 

SynteractHCR will conduct one project closeout visit at each of the clinical sites. While conducting this visit, SynteractHCR will perform the following tasks:

 

·                  Final IP, nebulizer, and supply accountability review and authorize final project supply returns to Sponsor;

·                  Reconcile the site regulatory binder including the IRB final report;

 

11

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

·                  Required data reconciliation;

·                  Review investigator’s adherence to record retention responsibilities and preparation of project records; and

·                  Collect and dispose of unused project supplies in a manner agreed upon with Sponsor.

 

Site Visit Reports

 

Site visit reports will be drafted within the time frame agreed upon in the monitoring plan. Upon completion of a draft visit report, the report will be forwarded to SynteractHCR and Sponsor for review and comment. Revisions and comments will be returned to the appropriate monitor for incorporation into the final report. The final report will be forwarded to Sponsor within *** of finalization. Any urgent project issues will be communicated to Sponsor immediately.

 

Clinical Lead

 

SynteractHCR will utilize a Global Clinical Lead, approved by Sponsor, to oversee the clinical aspects of the entire project. Additionally, there will be regional Clinical Lead(s) in Europe and regional Clinical Lead(s) in the US, all approved by Sponsor. SynteractHCR will require any non-employee Global Clinical Lead and regional Clinical Leads agree to execute an agreement to comply with the terms of the MSA prior to commencing services, and will ensure their compliance with the Sponsor-SynteractHCR MSA terms. SynteractHCR will remain responsible for their performance.

 

The SynteractHCR Clinical Lead assumes responsibility for the coordination of the CRA team and monitoring of daily activities to ensure the successful completion of clinical trials. The Clinical Lead participates in the planning, implementation, and management of clinical trials in compliance with federal regulations, ICH Guidelines, Good Clinical Practices (GCPs) and standard operating procedures (SOPs). Specific lead activities include designating site assignments and ensuring CRA resources are continuously adequate; tracking and reviewing monitoring visit reports and ensuring standards for monitoring and reporting are met; facilitating communication and standardization of monitoring procedures by providing a leadership role at CRA teleconferences; preparing materials and minutes for CRA teleconferences, meetings, and training seminars; and coordination of project specific training and other requirements for internal and external staff. The clinical lead develops and/or contributes to the development of clinical documents such as Study Manuals, CRF Completion Guidelines, Monitoring Plans and other project specific tools as required and may perform the on-site monitoring of clinical studies.

 

Site Management and Communication

 

The SynteractHCR project monitor will be the primary point of contact with the sites, and will be in contact with the site on a regular basis. SynteractHCR will document relevant correspondence with clinical site and Sponsor. SynteractHCR will keep Sponsor informed of all project issues on an ongoing basis throughout the project. Original copies of telephone reports and other written clinical site correspondence will be provided to Sponsor at the conclusion of the project as part of the central file transfer. Proper documentation within the regulatory files and IRB of all serious adverse events (SAEs) will be confirmed during the monitoring visits.

 

Site Audits

 

SynteractHCR and/or Sponsor may conduct clinical site audits at selected clinical sites according to their respective SOPs. Sponsor may accompany SynteractHCR during their audits. Sponsor will work with SynteractHCR to determine the sites to be audited. SynteractHCR will provide an audit report to Sponsor within *** business days.

 

12

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

Vendor Audits

 

SynteractHCR and/or Sponsor may conduct audits for selected vendors (e.g., sponsor-designated vendors) according to their respective SOPs. Sponsor may accompany SynteractHCR during their audits. These audits may be conducted on site at a vendor location or via the internet. SynteractHCR will provide an audit report to Sponsor within *** business days.

 

Investigational Product (IP) Management

 

IP Shipments

 

Sponsor will be responsible for supplying, packaging, labeling, and distributing the IP to the project sites. During the course of routine site management, SynteractHCR will be responsible for requesting additional IP shipments as necessary and returning any unused IP at the project conclusion to Sponsor. Project supplies that remain on site at the conclusion of the project will either be destroyed or returned to Sponsor as requested. SynteractHCR will ensure that all proper documentation is filed appropriately in the investigator’s project files. This includes IP receipt, inventory, accountability and return.

 

Nebulizer and Cleaning Supply Management

 

Nebulizer and Cleaning Supply Shipments

 

Sponsor will be responsible for supplying, packaging, labeling, and distributing the nebulizers and cleaning supplies to the project sites.  During the course of routine site management, SynteractHCR will be responsible for requesting additional nebulizers and cleaning supply shipments as necessary and returning all used and any unused nebulizers and cleaning supplies at the project conclusion to Sponsor. SynteractHCR will ensure that all proper documentation is filed appropriately in the investigator’s project files. This includes nebulizer and cleaning supply receipt, inventory, accountability and return.

 

Interactive Web-Response System (IWRS)

 

Specific transfer of obligations for IWRS services are to be determined; costs for IWRS support will be included in a Change in Scope.

 

Data Management

 

Accuracy and timeliness are of the highest priority in SynteractHCR’s management of clinical data. Once entered, data are stored in a SAS database from which all reporting and data analyses are done. Quality control checks are built in every step of the way to ensure complete accuracy. An experienced data manager will be assigned to the project and will be responsible for all activities leading to a clean database.

 

Data Management Plan

 

The SynteractHCR data manager will develop a data management plan, incorporating input from Sponsor, addressing the following:

 

·                  Overview of the data entry and data management process for the project

·                  Special handling procedures

·                  Edit check plan

·                  Database close procedures

·                  Data back-up processes

·                  Any other project-specific processes or issues.

 

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This data management plan will be sent to Sponsor for review and approval prior to implementation.

 

***

 

Electronic Case Report Forms

 

SynteractHCR will develop the Pre-build worksheet. The design will be reviewed from a data management perspective and suggestions will be made regarding consistency and the ability to collect the data accurately and in a manner that will facilitate analysis.

 

eCRF Completion Guidelines

 

SynteractHCR Data Manager will prepare eCRF Completion Guidelines. This document contains a general overview of the database, data entry guidelines, general site requirements and expectations, completion instructions for all of the eCRFs, and any specific instructions.

 

Start-up Activities

 

SynteractHCR will set up a database for this project using the ***. (“***”) *** system for electronic data capture at the project sites. The SynteractHCR team will work with the team at Sponsor to determine goals and project requirements.

 

Start-up activities include (in conjunction with Sponsor as appropriate):

 

·                  Design project workflow and training documentation.

·                  Design roles and responsibilities matrix.

·                  Prepare appropriate materials necessary to train Sponsor and project site personnel at the start-up meetings.

·                  Implementation of automated data edit checks (browser-side and server-side).

·                  Validate configured system.

·                  Devise system management and database strategy, which includes security, storage, back-ups, recovery, and server connectivity.

 

Database Creation

 

SynteractHCR will provide the *** database build. A new Sponsor -SynteractHCR URL hosted securely by *** will be created for Sponsor for the performance of studies performed in collaboration with SynteractHCR. SynteractHCR will provide a Core Configuration model from which Sponsor may customize for their unique project requirements. In order to identify potential errors in data entry, SynteractHCR will provide a list of validation checks. Upon approval of the Edit Check Document, the edit checks and custom functions will be programmed to help identify any errors in data entry.

 

*** ***. *** was developed with ease-of-use as a fundamental design principal providing ‘point and click’ functionality to end users. All modules and tools within *** are deployed securely over the Internet and require no special skills to operate the system.

 

License Grant and Use

 

Subject to this Agreement and Sponsor’s payment of the applicable Applications Services Fees (including License Fees), SynteractHCR (“SynteractHCR”) hereby grants Sponsor, during the term set forth in the applicable Statement of Work/Sales Order, a non-exclusive, limited, non-transferable license to remotely access and use the object code version of the *** software applications and documentation (collectively, the *** Applications) only for Sponsor’s internal business purposes for conducting the clinical trial project identified in the applicable Statement of Work. Only Sponsor’s employees and contractors conducting the clinical trial project (the “Authorized Users”) may access the *** Applications on behalf of Sponsor. Sponsor shall use the *** Applications only for lawful

 

14

 

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INS-212
    

 

purposes and in accordance with this Agreement. All rights not expressly granted under this Agreement are reserved to *** (“***”).

 

Restrictions Applicable to *** Applications:

 

Sponsor acknowledges that the *** Applications that will be made available to Sponsor by SynteractHCR on a hosted basis is proprietary to *** and that *** owns all right, title and interest in the *** Applications, including, but not limited to, any derivative works, modifications, updates and enhancements. The *** Applications and all materials relating thereto are confidential and proprietary to *** and Sponsor and its Authorized Users shall protect and treat such as confidential using the same care as required under the Agreement with respect to SynteractHCR’s confidential information, but no less than reasonable care. Sponsor understands and agrees that the *** Applications may only be used by Sponsor and its Authorized Users in accordance with the license grant set forth above and that Sponsor will not (1) modify, copy, reverse engineer or create derivative works of the *** Applications; (2) use the *** Applications to provide hosting, service bureau, time sharing, outsourcing or other services to third parties; (3) resell, lease, license, sublicense or time-share the *** Applications to third parties or otherwise permit the use of or access to the *** Applications by any third party, (4) transfer an existing clinical trial to a third party that is either a competitor of *** or doesn’t implement the *** Applications to support the balance of such clinical trial; (5) remove or alter any proprietary rights notices affixed to or contained within the *** Applications; or (6) use the *** Applications to build a competitive product or service or to perform clinical trial studies for any third party(ies) or input data from any clinical trial project of any third party(ies). Sponsor shall not disclose the *** Applications to third-parties or use such *** Applications for any purposes whatsoever other than in accordance with this Agreement and agrees that it will not engage in, and may be held liable for any unauthorized use, copying or disclosure of the *** Applications. The parties agree that *** is a direct and intended third party beneficiary to this Agreement and shall have the right to enforce the license restrictions and confidentiality obligations contained herein.

 

Access from Any Browser on Any Computer

 

*** is designed to enhance the role of the entire project team, anywhere in the world, on any computer, through any browser. The *** system user interface requires only an HTML 4.01 Transitional compliant browser such as Internet Explorer, Netscape, or Safari to be accessed. This standard is now adopted by virtually all current browsers (and is overseen by the W3C consortium). All platforms and browsers that fulfill this requirement can be used to access any *** module. This architectural feature ensures the maximum amount of flexibility for user adoption at all levels, as well as eliminating reliance on any current Sponsor technology which may be superseded or amended (e.g. Windows XP SP2, Internet Explorer 8, etc.). All data processing, including edit checks and derivations, are conducted on the server side. The zero Sponsor approach applies equally to the project build tools as well as the data entry and cleaning functions. At no time is any data being processed or stored on the Sponsor platform. Similarly, any identifiers such as standard cookies or session cookies (which may be hijacked or decrypted) are not used. This eliminates any concerning factors surrounding validation and firewall issues in the deployment of ***.

 

One login, One password, One URL

 

While many systems have been designed as an EDC front-end to the CDMS (Clinical Data Management System) back-end database, *** ***. The *** system uses a single integrated database to manage one or more project environments. The development, production and a virtually unlimited number of test and or training environments can be managed centrally within the application, with ***, eliminating the need for the definition and maintenance of complex multi-database, multi application configurations.

 

15

 

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Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

Lab Administrative Module

 

*** provides robust lab data management which includes multivariable dependent reference ranges (e.g. gender, age, fasting status, analyte effective dates), central lab data import, and site maintenance of local lab ranges. Some additional lab management features include two-way unit conversions that accommodate percent to absolute and absolute to percent, auto prompting for clinical significance when required, on CRF display of appropriate lab ranges, and auto fill/automatic updates to all lab values upon lab configuration changes.

 

Local Lab Capabilities: *** includes the ability to manage multiple local labs for each investigational site. Local lab ranges can be administered by the site or centrally by a user with the appropriate level of permissions. Local lab ranges can be dependent upon parameters based on any data point entered on the eCRF (i.e. gender, fasting status), as well as, effective dates. Non-numeric data including code lists and out of limits of detection results (e.g. < .001%), can still be interpreted by ***and have range checks applied against them. In situations where sites may not have access to local lab ranges, they can enter their data and substitute reference or text book ranges. Labs and local ranges that are entered for one project can be leveraged in subsequent studies eliminating the need for redundant efforts in lab setup.

 

Site Training

 

Prior to receiving access to ***, each site user must complete the required training provided by *** and also by SynteractHCR. *** training will be completed using their on-line eLearning tool. The SynteractHCR data manager will set up each user so that the eLearning module can be completed. Additionally, SynteractHCR will provide project-specific training to site personnel by WebEx, if requested by Sponsor. All training will be documented and retained in the project files.

 

Data Processing

 

Sites will enter data, which will be followed by CRA source document verification and review of the data. A data management review of the data will also be performed, which will include the execution of some post-entry logical edit checks.

 

Data Management Review

 

SynteractHCR’s data management personnel will run crosschecks and review data as needed. Queries will be provided to the sites. This process will be performed as needed, providing there is new data to be processed.

 

Adverse Event and Medications Coding

 

SynteractHCR will use ***’s *** *** for all coding activities. SynteractHCR will code adverse events and medical history terms using ***. Concomitant medications will be coded using WHO-Drug. Appropriate codes will be agreed upon with Sponsor and SynteractHCR will generate coding reports for review and approval by the Sponsor designee. Sponsor will be provided with all current mappings and provided adjustments, as necessary. SynteractHCR and Sponsor will agree on the frequency that these mappings will be generated and reviewed.

 

Sponsor and SynteractHCR hold current *** licenses. Validation of licenses may be requested by the MSSO (Maintenance and Support Services Organization) for *** and by the UMC (Uppsala Monitoring Centre) for ***.

 

Integrated Review (***)

 

SynteractHCR will provide *** whereby Sponsor personnel can review data over the private website. *** is a clinical data review, reporting, multi-dimensional analysis, graphical and statistical modeling tool. It facilitates the creation of graphical profiles, tabular profiles, as well as data browsing without

 

16

 

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Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

the need for custom programming. The following reports are standard *** reports and will be provided in MS Excel format:

 

·                  Graphic patient profile containing AE, CM, vitals, demography and lab

·                  AE listing

·                  CM listing

·                  DM listing

·                  Term listing

·                  Vitals listing

·                  Labs listing

·                  Patient profile containing all patient data

 

Biostatistics

 

Programming and statistical analysis are done using *** software (currently version ***). As with data management, quality control checks are built into the programming and data analysis process to ensure the accurate reporting of data.

 

Analysis Plan

 

SynteractHCR will prepare an analysis plan including definition of endpoints to be analyzed, statistical methodology, rules for data handling, requirements for dry runs, and design of tables, figures, and listings (TFLs) for all data displays. The analysis plan will also incorporate the DSMB analyses. Sponsor will review the analysis plan and provide consolidated comments prior to finalization by SynteractHCR.

 

Patient Randomization

 

A randomization schedule will be developed by SynteractHCR using *** (currently version ***) *** and will be incorporated into the randomization IWR system. The randomization code will be developed by the project Statistician and finalized and QC’d by an independent unblinded statistician.

 

Statistical Analysis

 

A Statistician will perform the statistical analysis. Statistical analysis includes time for review of relevant project documentation including the SAP, programming of primary and secondary efficacy analyses, statistical oversight of the project (where applicable), and Senior Level Review of deliverables.

 

Programming/Validation

 

After approval of the analysis plan, programmers will develop the programs to generate the TFLs using SAS according to the agreed analysis plan.

 

The programmer will verify the accuracy of his/her own work, but all outputs will be independently verified for accuracy and consistency by a second individual. This validation will be carried out by a combination of independent programming, cross-checking, and verification against CRFs. Quality assurance documentation will be maintained, including samples of each output, the *** program used to produce it, and the quality assurance checks performed.

 

Dry Runs

 

Draft TLFs (dry runs) will be generated by SynteractHCR prior to the interim database lock for Sponsor’s review and query of data as appropriate. Each set of draft TLFs will be QC’d by SynteractHCR before sending to Sponsor for review.

 

17

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

*** Programming

 

SynteractHCR will create *** datasets per SynteractHCR’s standard processes for creating *** datasets. SynteractHCR will provide *** format.

 

Blankcrf.pdf

 

SynteractHCR will create the annotated CRF (blankcrf.pdf) after the modeling of SDTM begins and will complete these items when the database is closed and all programming and quality control procedures have been completed.

 

*** Programming

 

SynteractHCR will create *** analysis datasets per SynteractHCR’s standard processes for creating *** datasets. *** datasets will be used exclusively as the source data for *** datasets. SynteractHCR will provide *** datasets in *** format.

 

Define.xmls

 

SynteractHCR will create the Define.xmls after the modeling *** begins and will complete these deliverables when the database is closed and all programming and quality control procedures have been completed.

 

CDISC Reviewer’s Guides

 

Per Sponsor’s request, SynteractHCR will prepare a Reviewer’s Guide ***. These guides will contain a brief summary of notes or unusual issues regarding the final data that is not included in the define.***. The guides will be delivered to Sponsor at the end of the study.

 

DSMB Meetings

 

SynteractHCR will prepare the tables and listings for the DSMB data review meetings. The Project Biostatistician will also attend the meetings via teleconference.

 

Clinical Study Report

 

A final clinical study report will be developed that includes a complete description of the clinical and statistical aspects of the trial. The SynteractHCR medical writer will work with Sponsor to develop a clinical study report in a format that is compliant with FDA and ICH Guidelines. SynteractHCR can also provide a standardized ICH compliant CSR template.

 

An initial draft of the report includes a description of all study methodology and presentation of results based on final tables, listings, and figures. The draft report will undergo statistical and quality review by SynteractHCR prior to distribution. A draft clinical study report is typically generated within four to six weeks after final tables, listings, and graphs are received or generated and approved by Sponsor. The cost of this report includes up *** revisions of the report, and inclusion of up to *** narratives of serious adverse events, deaths, or discontinuations due to adverse events (combined). Cost estimates assume the CSR conforms to standard metrics detailed in the assumptions table.

 

For each revision cycle, SynteractHCR will circulate the draft report for review to Sponsor; consolidated comments/changes will be provided to SynteractHCR, and the report will be revised by SynteractHCR accordingly for either the next review or final approval by Sponsor. If requested by Sponsor, SynteractHCR can perform a *** QC review of the report prior to finalization. Estimates for a *** QC review are not included in this proposal and can be provided upon request.

 

Compiling the Final Clinical Study Report and Appendices for Regulatory Submission

 

SynteractHCR will compile (publish or PDF) the final clinical study report and all supporting documentation referenced in the CSR for regulatory submission. Required documentation will be

 

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Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

provided by SynteractHCR (if available) and Sponsor. A final project signature page is also required to begin compiling.

 

The compiled granular CSR consists of the main body (sections 1,3-15), Synopsis (Section 2), and Appendix 16 (each appendix in 16.1, 16.2 and 16.3 as separate granules).

 

The main body granule of the CSR will have a bookmarked and hyperlinked Table of Contents. TFLs and section cross-references will be hyperlinked within the CSR.

 

4                      Miscellaneous

 

4.1            Backup and Security

 

SynteractHCR performs incremental *** backups *** are retained for a *** period. ***, a full backup is written to media and stored off-site for a *** retention period at ***. All backups are verified and logged by the Global Systems staff. Quarterly tapes are stored offsite at *** for ***. Offsite data is available within a few hours of requesting the data from ***.

 

Clinical data is generally stored on SynteractHCR network servers unless otherwise specified (e.g., third party hosting that is contractually specified). No clinical data are stored on local workstations. Access to the clinical data files is restricted based on directory permission levels that are determined by job function. *** No clinical data will be altered or updated without going through the proper application interface. Anti-virus scan software programs are in place to detect and prevent corruption of data due to computer viruses. All server-side application files are stored in a secured, dedicated network directory.

 

All connections to SynteractHCR’s secure web site, used for document viewing, downloading, and Argus are encrypted using ***. Published applications, like *** and ***, are secured via our ***. A *** is available for uploading files to the SynteractHCR network. SynteractHCR utilizes *** for securing e-mail communication if requested by Sponsor.

 

4.2            Language

 

All deliverables will be provided in English for this study.

 

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Insmed Incorporated —   SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

5                      Project Costs

 

5.1            Assumptions

 

	
Project Assumptions
    	
 
    	
 
    	
 
    
	
General Study Information
    	
 
    	
 
    	
 
    
	
Number   of Screened Patients
    	
 
    	
***
    	
 
    
	
Total   Number of Enrolled Patients
    	
 
    	
***
    	
 
    
	
Projected Number of Enrolled Patients ***
    	
 
    	
***
    	
 
    
	
Projected Number of Enrolled Patients in ***
    	
 
    	
***
    	
 
    
	
Projected Number of Enrolled Patients in ***
    	
 
    	
***
    	
 
    
	
Total   Number of Sites
    	
 
    	
***
    	
 
    
	
Number of Sites — ***
    	
 
    	
***
    	
 
    
	
Number of Sites — ***
    	
 
    	
***
    	
 
    
	
Number of Sites — ***
    	
 
    	
***
    	
 
    
	
Number of Sites — ***
    	
 
    	
***
    	
 
    
	
Number of Sites — ***
    	
 
    	
***
    	
 
    
	
Number of Sites — ***
    	
 
    	
***
    	
 
    
	
Number of Sites — ***
    	
 
    	
***
    	
 
    
	
Number of Sites — ***
    	
 
    	
***
    	
 
    
	
Number of Sites — ***
    	
 
    	
***
    	
 
    
	
Number of Sites — ***
    	
 
    	
***
    	
 
    
	
Number of Sites — ***
    	
 
    	
***
    	
 
    
	
Number of Sites — ***
    	
 
    	
***
    	
 
    
	
Project   Duration (Months)
    	
 
    	
***
    	
 
    
	
Clinical   Operations (Months)
    	
 
    	
***
    	
 
    
	
Patient Enrollment Duration (Months)
    	
 
    	
***
    	
 
    
	
Patient Randomized Open-Label Treatment Duration   (Months)
    	
 
    	
***
    	
 
    
	
Patient Off-Treatment Duration (Months)
    	
 
    	
***
    	
 
    
	
Project Meetings
    	
 
    	
 
    	
 
    
	
Kick-Off   Meeting at Sponsor office in ***
    	
 
    	
***
    	
 
    
	
Investigator   Meetings assumes *** in each region (***)
    	
 
    	
***
    	
 
    
	
Number of Days per Meeting   (Including CRA Training Meeting)
    	
 
    	
***
    	
 
    
	
*** Meeting: Global Project Manager, Global   Clinical Lead, *** Clinical Lead, *** Project Manager, *** Project Manager,   CRA team, Lead Data Manager, IWRS Manager
    	
 
    	
 
    	
 
    

 

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Insmed Incorporated —   SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

	
Project Assumptions
    	
 
    	
 
    	
 
    
	
*** Meeting: Global Project Manager, Global   Clinical Lead, *** Clinical Leads, ***, ***, and ***s Project Manager, CRA   team, Lead Data Manager, IWRS Manager
    	
 
    	
 
    	
 
    
	
*** Meeting: Global Project Manager, Global   Clinical Lead, *** Clinical Lead, *** and *** Project Manager, CRA team, Lead   Data Manager, IWRS Manager
    	
 
    	
 
    	
 
    
	
Number   of Face-to-Face Meetings *** per year per   Sponsor
    	
 
    	
***
    	
 
    
	
Number   of Team Teleconferences with Sponsor
    	
 
    	
***
    	
 
    
	
Data Management
    	
 
    	
 
    	
 
    
	
Number   of Unique CRF Pages
    	
 
    	
***
    	
 
    
	
Number   of CRF Pages per Screened Patient per Sponsor
    	
 
    	
***
    	
 
    
	
Number   of CRF Pages per Completed Patient
    	
 
    	
***
    	
 
    
	
Total   Number of CRF Pages
    	
 
    	
***
    	
 
    
	
Number   of Edit Checks
    	
 
    	
***
    	
 
    
	
Number   of Queries per Patient
    	
 
    	
***
    	
 
    
	
Number   of Complex BOXI Reports
    	
 
    	
***
    	
 
    
	
Number   of Non-Complex BOXI Reports
    	
 
    	
***
    	
 
    
	
Site Identification
    	
 
    	
 
    	
 
    
	
Site   ID Duration (Months)
    	
 
    	
***
    	
 
    
	
Number   of Sites Contacted with Survey/Questionnaire
    	
 
    	
***
    	
 
    
	
Number   of Sites for Debarment Verification
    	
 
    	
***
    	
 
    
	
Number   of Countries
    	
 
    	
***
    	
 
    
	
Site Contracts
    	
 
    	
 
    	
 
    
	
Total   Estimated Number of Site Contracts
    	
 
    	
 
    	
 
    
	
Number of Contracts per Site — ***
    	
 
    	
***
    	
 
    
	
Number of Contracts per Site — ***
    	
 
    	
***
    	
 
    
	
Number of Contracts per Site — ***
    	
 
    	
***
    	
 
    
	
Number of Contracts per Site — ***
    	
 
    	
***
    	
 
    
	
Number of Contracts per Site — ***
    	
 
    	
***
    	
 
    
	
Number of Contracts per Site — ***
    	
 
    	
***
    	
 
    
	
Number of Contracts per Site — ***
    	
 
    	
***
    	
 
    
	
Number of Contracts per Site — ***
    	
 
    	
***
    	
 
    
	
Number of Contracts per Site — ***
    	
 
    	
***
    	
 
    
	
Number of Contracts per Site — ***
    	
 
    	
***
    	
 
    
	
Number of Contracts per Site — ***
    	
 
    	
***
    	
 
    
	
Number of Contracts per Site — ***
    	
 
    	
***
    	
 
    
	
costs for additional sworn translations are not included
    	
 
    	
 
    	
 
    

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed Incorporated —   SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

	
Project Assumptions
    	
 
    	
 
    	
 
    
	
Clinical Operations
    	
 
    	
 
    	
 
    
	
Total   Number of Clinical Leads
    	
 
    	
***
    	
 
    
	
Global Clinical Lead
    	
 
    	
***
    	
 
    
	
Regional Clinical Leads — ***
    	
 
    	
***
    	
 
    
	
Regional Clinical Lead — ***
    	
 
    	
***
    	
 
    

 

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[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed Incorporated —   SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

	
Project Assumptions
    	
 
    	
 
    	
 
    
	
Total   Number of Regional CRAs
    	
 
    	
***
    	
 
    
	
Number of CRAs — ***
    	
 
    	
***
    	
 
    
	
Number of CRAs — ***
    	
 
    	
***
    	
 
    
	
Number of CRAs — ***
    	
 
    	
***
    	
 
    
	
Number   of Qualification Visits — ***

average *** day travel, *** day on site, *** day   preparation/follow-up/report-writing
    	
 
    	
***
    	
 
    
	
Number   of Qualification Visits — ***

average *** day travel, *** day on site, *** day   preparation/follow-up/report-writing
    	
 
    	
***
    	
 
    
	
Number   of Qualification Visits — ***

average *** day travel, *** day on site, *** day   preparation/follow-up/report-writing
    	
 
    	
***
    	
 
    
	
Number   of Telephone Qualification Visits — ***
    	
 
    	
***
    	
 
    
	
Number   of Initiation Visits — ***

average *** day travel, *** day on site, *** day   preparation/follow-up/report-writing
    	
 
    	
***
    	
 
    
	
Number   of Initiation Visits — ***

average *** day travel, *** day on site, *** day   preparation/follow-up/report-writing
    	
 
    	
***
    	
 
    
	
Number   of Initiation Visits — ***

average *** day travel, *** day on site, *** day   preparation/follow-up/report-writing
    	
 
    	
***
    	
 
    
	
Number   of Monitoring Visits/Site — ***

average *** day travel, *** day on site, *** day   preparation/follow-up/report-writing
    	
 
    	
***
    	
 
    
	
Number   of Monitoring Visits/Site — ***

average *** day travel, *** day on site, *** day   preparation/follow-up/report-writing
    	
 
    	
***
    	
 
    
	
Number   of Monitoring Visits/Site — ***

average *** day travel, *** day on site, *** day   preparation/follow-up/report-writing
    	
 
    	
***
    	
 
    
	
Total   Number of Monitoring Visits — ***
    	
 
    	
***
    	
 
    
	
Total   Number of Monitoring Visits — ***
    	
 
    	
***
    	
 
    

 

23

 

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Insmed Incorporated —   SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

	
Project Assumptions
    	
 
    	
 
    	
 
    
	
Total   Number of Monitoring Visits — ***
    	
 
    	
***
    	
 
    
	
Additional   Days on Site — ***
    	
 
    	
***
    	
 
    
	
Additional   Days on Site — ***
    	
 
    	
***
    	
 
    
	
Additional   Days on Site — ***
    	
 
    	
***
    	
 
    
	
Number   of Study Close-out Visits — ***

average *** days travel, *** day on site, *** days   preparation/follow-up/report-writing
    	
 
    	
***
    	
 
    
	
Number   of Study Close-out Visits — ***

average *** day travel, *** day on site, *** day   preparation/follow-up/report-writing
    	
 
    	
***
    	
 
    
	
Number   of Study Close-out Visits — ***

average *** day travel, *** day on site, *** day   preparation/follow-up/report-writing
    	
 
    	
***
    	
 
    
	
Q.A. Audits
    	
 
    	
 
    	
 
    
	
Number   of Site Audits — ***
    	
 
    	
***
    	
 
    
	
Number   of Site Audits — ***
    	
 
    	
***
    	
 
    
	
Number   of Site Audits — ***
    	
 
    	
***
    	
 
    
	
Number   of Vendor Audits — ***
    	
 
    	
***
    	
 
    
	
Number   of Vendor Audits — ***
    	
 
    	
***
    	
 
    
	
Number   of Vendor Audits — ***
    	
 
    	
***
    	
 
    
	
Medical Safety
    	
 
    	
 
    	
 
    
	
Number   of SAEs
    	
 
    	
***
    	
 
    
	
Number   of Coded Items per Patient
    	
 
    	
***
    	
 
    
	
Biostatistics
    	
 
    	
 
    	
 
    
	
Number   of Outside Data Vendors
    	
 
    	
***
    	
 
    
	
Number   of Outside Vendor Data Transfers (Monthly)
    	
 
    	
***
    	
 
    
	
Number   of Unique Efficacy Tables
    	
 
    	
***
    	
 
    
	
Number   of Unique Safety Tables
    	
 
    	
***
    	
 
    
	
Number   of Repeat Tables
    	
 
    	
***
    	
 
    
	
Number   of DSMB Tables
    	
 
    	
***
    	
 
    
	
Number   of Annual Report Tables
    	
 
    	
***
    	
 
    
	
Number   of Unique Graphs
    	
 
    	
***
    	
 
    
	
Number   of Repeat Graphs
    	
 
    	
***
    	
 
    
	
Number   of DSMB Graphs
    	
 
    	
***
    	
 
    
	
Number   of Listings
    	
 
    	
***
    	
 
    

 

24

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed Incorporated —   SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

	
Project Assumptions
    	
 
    	
 
    	
 
    
	
Number   of DSMB Listings
    	
 
    	
***
    	
 
    
	
Number   of Annual Report Listings
    	
 
    	
***
    	
 
    
	
Number   of *** Datasets
    	
 
    	
***
    	
 
    
	
Number   of *** Domains
    	
 
    	
***
    	
 
    
	
Number   of *** Datasets
    	
 
    	
***
    	
 
    
	
Number   of Interim Analyses
    	
 
    	
***
    	
 
    
	
Number   of DSMB Meetings
    	
 
    	
***
    	
 
    
	
Number   of Transfers of SDTMs to Sponsor
    	
 
    	
***
    	
 
    
	
Number   of Annual Reports
    	
 
    	
***
    	
 
    

 

The following assumptions have also been made in determining the cost estimates:

 

1.              All assumptions are based on the draft protocol and schedule of events dated *** and are subject to change based on the final protocol and/or amendments.

2.              Costs are included for SynteractHCR to perform activities in the regions and service areas and with the vendors as detailed in this Work Order. Activities requested by Sponsor not included in this Work Order will be included in a Change in Scope.

3.              All deliverables and project materials will be in English (this includes all documents provided to SynteractHCR). If translations are needed, translation activities will be handled by a third party vendor and SynteractHCR.

4.              All SynteractHCR activities will be conducted according to SynteractHCR SOPs.

5.              SynteractHCR templates will be used for all appropriate project documents.

6.              Sponsor will retain responsibility for any other activities that are not referenced in this proposal.

7.              Estimates assume four rounds of revisions for project documents requiring review/approval by Sponsor. All Sponsor comments/changes will be collated and provided to SynteractHCR in one document.

8.              SynteractHCR may perform site and vendor audits; exact sites/locations will be determined by SynteractHCR and Sponsor and costs may be adjusted accordingly.

9.              Site CDAs and contracts will be between SynteractHCR and the sites, after Sponsor has reviewed and approved.

10.       Sponsor and SynteractHCR hold a current *** license and a current *** license.

11.       Data for screen failure patients will be entered into *** on eCRFs by site personnel.

12.       *** training will be web-based.

13.       Costs include Sponsor User Acceptance Testing (UAT) of the clinical database.

14.       Web Access includes access to the reports portion of the project web page and *** for eight Sponsor personnel. Additional users will incur additional costs.

15.       All Central Laboratory results will be provided to SynteractHCR as electronic data transfers.

16.       Costs have been included for central laboratory data to be integrated into *** via *** Web Services.

17.       Costs do not include database migrations.

18.       SynteractHCR will receive and reconcile PK header information on a monthly basis for this study.

19.       DM site payment report programming assumes monthly site payments.

20.       For the interim analyses, SynteractHCR will provide a subset of the final tables, listings and figures.

21.       The database will be locked for the *** of primary endpoints. For the DSMB analyses and the ***, the tables, listings, and figures will be run on dirty data (a database soft-lock will not occur prior to the analyses).

 

25

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed Incorporated —   SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

22.       SynteractHCR will provide *** datasets, *** datasets, *** and user guides.

23.       Sponsor (or designee) will provide SynteractHCR with the final patient SAE narratives for inclusion in the final study report. The SynteractHCR medical writer will not revise or re-format the patient SAE narratives.

24.       Non-SAE narratives are generally written and included in the CSR for patients with AEs that lead to discontinuation of the study and/or study drug, or for AEs of special interest. Depending on the number and complexity of these narratives, additional time may be required to produce and QC. This is usually determined during CSR development.

25.       The compiled CSR will have a hyperlinked and bookmarked Table of Contents. Collection and filing of CSR appendix documents will be completed per ICH guidelines.

26.       Project Management costs include Sponsor meeting attendance, managing team meetings and conference calls and providing meeting minutes, vendor management, and overall project administration tasks.

27.       Project Administration includes the creation and maintenance of the clinical document database, maintenance of regulatory documents, review and processing of expense reports, generation of regular reports, and processing of site and vendor payments.

28.       If reasonably requested by Sponsor, periodic face to face internal management meetings between SynteractHCR and ***, US SynteractHCR and EU SynteractHCR, and SynteractHCR and Insmed may occur during the life of the study. Sponsor will be billed for pass-through travel costs if applicable.

 

26

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

5.2            Summary Cost Estimates

 

With the exception of flat rate/unit items listed in the detailed budget, SynteractHCR will only charge for actual time spent per task. SynteractHCR will not exceed the project study maximum without an approved change order. A detailed budget table is provided in Attachment 1, Detailed Budget.

 

ACTIVITY

 

	
 
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***
    	
 
    
	
Clinical Operations 
    	
 
    	
$
    	
***
    	
 
    	
$
    	
***
    	
 
    	
$
    	
***
    	
 
    
	
Site/Vendor Audits
    	
 
    	
$
    	
***
    	
 
    	
$
    	
***
    	
 
    	
$
    	
***
    	
 
    
	
Regulatory Affairs
    	
 
    	
$
    	
***
    	
 
    	
$
    	
***
    	
 
    	
$
    	
***
    	
 
    
	
Interactive Web Response System (IWRS) - Central   Randomization/ Inventory Management
    	
 
    	
 
    	
 
    	
***
    	
 
    	
 
    	
 
    
	
Data Management
    	
 
    	
 
    	
 
    	
$
    	
***
    	
 
    	
 
    	
 
    
	
Biostatistics
    	
 
    	
 
    	
 
    	
$
    	
***
    	
 
    	
 
    	
 
    
	
Medical Writing
    	
 
    	
 
    	
 
    	
$
    	
***
    	
 
    	
 
    	
 
    
	
Project Management
    	
 
    	
$
    	
***
    	
 
    	
$
    	
***
    	
 
    	
$
    	
***
    	
 
    
	
Sub-Totals
    	
 
    	
$
    	
***
    	
 
    	
$
    	
***
    	
 
    	
$
    	
***
    	
 
    
	
Study Total
    	
 
    	
 
    	
 
    	
$
    	
***
    	
 
    	
 
    	
 
    
	
***% discount on invoicing
    	
 
    	
 
    	
 
    	
$
    	
***
    	
 
    	
 
    	
 
    
	
Estimated Study Total
    	
 
    	
 
    	
 
    	
$
    	
***
    	
 
    	
 
    	
 
    

 

Rates stated in this Work Order are current through ***. As of *** of each year starting in ***, SynteractHCR’s activity rates will increase or decrease in accordance with the most recent ***, and the percent increase or decrease will not exceed the percent increase or decrease corresponding to the median compensation rates for the functions listed in the budget for a similarly sized study in the prior 1-year period. SynteractHCR will notify Sponsor of the proposed increase at least *** (***) days in advance of such increase.  SynteractHCR and Sponsor shall negotiate in good faith any disagreement as to the appropriate percent increase, and Sponsor may terminate this Work Order upon *** (***) days notice.

 

The costs for services provided by resources in the *** and *** and presented in this Work Order are based on an identified fixed exchange rate dated *** using *** between *** and *** and *** and ***, (“Base Rate: *** = ***, *** = ***”). If the exchange value of the *** rises or falls by ***% or more from the Base Rate during the course of the project, the costs *** and ***-resourced services shall be adjusted accordingly.

 

The above-referenced ***% discount on invoicing will be applied only if the *** project (or a similar study or group of studies with a service value of $*** using SynteractHCR standard rates) is contracted in conjunction (i.e., within *** months of work order execution) with the INS-212 project. The discount will be applied to both projects as a bottom line discount on monthly invoices, and no other additional discounts will apply to these projects.

 

If the *** study (or a similar study or group of studies with a service value of $*** using SynteractHCR standard rates) is not contracted and initiated with SynteractHCR, Sponsor will refund the sum total of the ***% applied discount to SynteractHCR within *** months of INS-212 work order execution.

 

27

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

5.3            Pass-Through Costs

 

Travel-related expenses, mailing/courier costs, translation costs, IRB/EC and other regulatory submission fees, site fees, patient recruitment/retention fees, Investigator Meeting planning fees, laboratory fees, and miscellaneous project expenses (e.g., binders, folders, tabs, labels, packaging materials, printing)  are considered project-related pass-through costs and are not included in the above cost estimates. These costs would be invoiced directly to Sponsor without markup. Additional pass-through expenses that are not listed in the table below will require pre-approval from Sponsor before incurring and invoicing.

 

SynteractHCR assumes that Sponsor’s teleconference number(s) will be used for regular project team calls, otherwise SynteractHCR will pass through conference call costs directly to Sponsor.

 

International wire fees for site/vendor payments will be passed through to Sponsor.

 

*** pass-through costs are estimates and subject to change.

 

Prices quoted in the proposal are net and excluding any applicable VAT.

 

Estimated pass-through costs have been provided in the table below; these estimates will be passed through at no mark-up to Sponsor based on the actual costs. SynteractHCR will not exceed the estimated pass-through budget maximum without an approved change order.

 

	
Item
    	
 
    	
Number
    	
 
    	
Unit
    	
 
    	
Cost Per
   Unit
    	
 
    	
Total
    
	
Travel
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Travel   (*** Visits)
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    
	
Travel   (*** Visits)
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    
	
Travel   (*** Visits — Air, etc.)
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    
	
Travel   (*** Visits — Local)
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    
	
Meeting   Travel — ***
    	
 
    	
***
    	
 
    	
meeting
    	
 
    	
***
    	
 
    	
***
    
	
Meeting   Travel — ***
    	
 
    	
***
    	
 
    	
meeting
    	
 
    	
***
    	
 
    	
***
    
	
Meeting   Travel — ***
    	
 
    	
***
    	
 
    	
meeting
    	
 
    	
***
    	
 
    	
***
    
	
Ad   hoc Visit Travel — ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    
	
Site   Audit Travel - ***
    	
 
    	
***
    	
 
    	
audit
    	
 
    	
***
    	
 
    	
***
    
	
Site   Audit Travel - ***
    	
 
    	
***
    	
 
    	
audit
    	
 
    	
***
    	
 
    	
***
    
	
Site   Audit Travel - ***
    	
 
    	
***
    	
 
    	
audit
    	
 
    	
***
    	
 
    	
***
    
	
Vendor   Audit Travel - ***
    	
 
    	
***
    	
 
    	
audit
    	
 
    	
***
    	
 
    	
***
    
	
Vendor   Audit Travel - ***
    	
 
    	
***
    	
 
    	
audit
    	
 
    	
***
    	
 
    	
***
    
	
Vendor   Audit Travel - ***
    	
 
    	
***
    	
 
    	
audit
    	
 
    	
***
    	
 
    	
***
    
	
Regulatory/EC/IRB Fees
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Central   IRB Fees ***
    	
 
    	
***
    	
 
    	
study
    	
 
    	
***
    	
 
    	
***
    
	
Local   and Central EC Fees ***
    	
 
    	
***
    	
 
    	
study
    	
 
    	
***
    	
 
    	
***
    
	
Fees   for Central Authority Notification - ***
    	
 
    	
***
    	
 
    	
country
    	
 
    	
***
    	
 
    	
***
    

 

28

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

	
Item
    	
 
    	
Number
    	
 
    	
Unit
    	
 
    	
Cost Per
   Unit
    	
 
    	
Total
    
	
Regulatory/EC   Submission Fees ***
    	
 
    	
***
    	
 
    	
study
    	
 
    	
***
    	
 
    	
***
    
	
Regulatory   Fees ***
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
***
    
	
Other
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Protocol   and ICF Printing
    	
 
    	
***
    	
 
    	
*** sites
    	
 
    	
***
    	
 
    	
***
    
	
Shipping
    	
 
    	
***
    	
 
    	
month
    	
 
    	
***
    	
 
    	
***
    
	
Miscellaneous   Project Expenses
    	
 
    	
***
    	
 
    	
month
    	
 
    	
***
    	
 
    	
***
    
	
Legal   Representation - ***
    	
 
    	
***
    	
 
    	
study
    	
 
    	
 
    	
 
    	
***
    
	
Investigator   Fees — ***
    	
 
    	
***
    	
 
    	
patient
    	
 
    	
***
    	
 
    	
***
    
	
Investigator   Fees — ***
    	
 
    	
***
    	
 
    	
patient
    	
 
    	
 
    	
 
    	
***
    
	
Investigator   Fees — ***
    	
 
    	
***
    	
 
    	
patient
    	
 
    	
 
    	
 
    	
***
    
	
Site   Start-up Fees — ***
    	
 
    	
***
    	
 
    	
site
    	
 
    	
***
    	
 
    	
***
    
	
Site   Start-up Fees — ***
    	
 
    	
***
    	
 
    	
site
    	
 
    	
 
    	
 
    	
***
    
	
Site   Start-up Fees — ***
    	
 
    	
***
    	
 
    	
site
    	
 
    	
 
    	
 
    	
***
    
	
Trial   Insurance
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
***
    
	
Central   Laboratory (***)
    	
 
    	
***
    	
 
    	
laboratory
    	
 
    	
***
    	
 
    	
***
    
	
Regional   Laboratories (***)
    	
 
    	
***
    	
 
    	
laboratory
    	
 
    	
 
    	
 
    	
***
    
	
Investigator   Meeting — ***
    	
 
    	
***
    	
 
    	
meeting
    	
 
    	
***
    	
 
    	
***
    
	
Investigator   Meeting — ***
    	
 
    	
***
    	
 
    	
meeting
    	
 
    	
***
    	
 
    	
***
    
	
Investigator   Meeting — ***
    	
 
    	
***
    	
 
    	
meeting
    	
 
    	
***
    	
 
    	
***
    
	
Translation   Vendor (estimate)
    	
 
    	
***
    	
 
    	
language
    	
 
    	
***
    	
 
    	
***
    
	
***:   Professional Service Fee including New URL
    	
 
    	
***
    	
 
    	
study
    	
 
    	
***
    	
 
    	
***
    
	
***   Applications Service Fee (Hosting) for Rave
    	
 
    	
***
    	
 
    	
month
    	
 
    	
***
    	
 
    	
***
    
	
Total
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
$
    	
***
    

 

5.4            Payment Terms

 

An advance of $*** (***% of the Cost Estimate after discount, less the $*** advance from the Letter of Intent) is due (i) *** and (ii) ***. Sponsor will then be invoiced *** for actual work performed. The total advance provided ($***+$***) of $*** (the “Advance”) will be adjusted on *** basis, beginning *** from the signing of this Work Order 1 until all payments have been made/credited under this Work Order 1, such that the Advance will equal ***% of the remaining Cost Estimate, after discount, that remains following payments made during the prior year.  The dollar amount of the Advance that exceeds ***% of the remaining Cost Estimate shall be, at Sponsor’s option, refunded to Sponsor within *** (***) days or credited against any outstanding invoice(s) and then any subsequent invoice(s) until expended.  Flat-rate/unit items will be billed upon completion of the deliverable or *** as indicated in

 

29

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

the detailed cost estimates provided in Attachment 1, Detailed Budget. At the completion of the project, if payments received by SynteractHCR exceed the cost of the work completed, SynteractHCR will reimburse Sponsor for the amount overpaid within *** (***) days.

 

Additionally, prior to the payment of sites, Sponsor and SynteractHCR will agree upon the site/investigator grant schedule and budget that corresponds with the schedule and budget in the executed Site Agreement and Sponsor will provide adequate funds to SynteractHCR in advance for site payments. All payments from SynteractHCR to investigators will be made from funds provided in advance by Sponsor. SynteractHCR will make payment to sites upon presentation of an invoice at the frequency detailed within the site agreement.

 

5.5            Change in Scope

 

If, in the opinion of SynteractHCR, and mutually agreed to by Sponsor, the scope of the work exceeds, or is reduced from, what is described in this Work Order 1, the nature, time, and cost of work over or under scope will be documented in a change order and provided to Sponsor. A Work Order Amendment will be generated by SynteractHCR to reflect these changes and will be reviewed, mutually agreed to, and signed by SynteractHCR and Sponsor. If the scope of Services in a Work Order Amendment causes the total Project cost estimate to increase, SynteractHCR, at its discretion, reserves the right to request from Sponsor an additional advance in proportion to that provided for in section 5.4 above to be payable to SynteractHCR. If the scope of Services in a Work Order Amendment causes the total Project cost estimate to decrease, Sponsor, at its discretion, reserves the right to request from SynteractHCR refund of the Advance in proportion to that provided for in section 5.4 above to be payable to Sponsor.

 

5.6            Invoices and Payment Correspondence

 

SynteractHCR will send invoices via US Mail and email to the following mailing address and email:

 

Insmed Incorporated

10 Finderne Avenue

Building 10

Bridgewater, NJ 08807-3365

Attn: Accounts Payable

Phone: ***

Email:  ***

With an email copy to:

***

 

Phone or email correspondence in regard to payment inquiries should be addressed to the following individuals:

 

	
If   to Sponsor:
    	
If   to SynteractHCR:
    
	
Insmed   Incorporated
    	
SynteractHCR, Inc
    
	
10   Finderne Avenue
    	
5759   Fleet Street
    
	
Building   10
    	
Suite 100
    
	
Bridgewater,   NJ 08807-3365
    	
Carlsbad,   CA 92008
    
	
Attn:   Accounts Payable
    	
Attn:   Accounts Receivable
    
	
Phone:   ***
    	
Phone:   ***
    
	
Email:   ***
    	
Email:   ***
    

 

30

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

Each Party may change its address and/or contact person for such notices and communications by written notice to the other party in accordance with this Section.

 

To pay an invoice via wire transfer, Sponsor will use the following information to process the payment:

 

Account Name:  SynteractHCR, Inc.

Bank Name:  ***

Account Number:  ***

Routing Number:  ***

 

For invoices paid via wire transfer or ACH, Sponsor will send a remittance of the payment to Accounts Receivable at *** or fax number ***.

 

IN WITNESS WHEREOF, the parties have caused this Work Order to be executed by duly authorized representatives as of the Work Order 1 Effective Date.

 

	
SynteractHCR, Inc.
    	
 
    	
Insmed   Incorporated
    
	
 
    	
 
    	
 
    
	
/s/   Stewart Bieler***
    	
 
    	
/s/   Peggy Berry
    
	
 
    	
 
    	
 
    
	
Name:   ***Stewart Bieler
    	
 
    	
Name:   Peggy Berry
    
	
 
    	
 
    	
 
    
	
Title:   ***CAO
    	
 
    	
Title:   VP, Regulatory Affairs
    
	
 
    	
 
    	
 
    

 

31

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

ATTACHMENT 1: DETAILED BUDGET

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

	
ACTIVITY
    	
 
    	
RATE
    	
 
    	
UNIT
    	
 
    	
EST.
   REQ.
    	
 
    	
ESTIMATED
   CHARGE
    	
 
    	
COMMENTS
    
	
Clinical Operations
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Feasibility   ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Feasibility   ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Assumes   *** countries
    
	
Site   Identification — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Assumes   ID/screening of *** sites
    
	
Site   Identification - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Assumes   ID/screening of *** sites
    
	
Site   Identification - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Assumes   ID/screening of *** sites
    
	
Site   Qualification Visits — Telephone — ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Telephone   qualifications in lieu of a site qualification visit for sites that have been   used (or qualified) within the past *** months, assumes *** sites
    
	
Site   Qualification Visits - ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Visits   will be billed upon completed visit unit.
    
	
Site   Qualification Visits - *** — Telephone
    	
 
    	
 
    	
 
    	
visit
    	
 
    	
 
    	
 
    	
***
    	
 
    	
No   telephone qualification visits anticipated in ***
    
	
Site   Qualification Visits - ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Visits   will be billed upon completed visit unit.
    
	
Site   Qualification Visits - *** — Telephone
    	
 
    	
 
    	
 
    	
visit
    	
 
    	
 
    	
 
    	
***
    	
 
    	
No   telephone qualification visits anticipated in ***
    
	
Site   Qualification Visits - ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Visits   will be billed upon completed visit unit.
    
	
Site   Initiation Visits — ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Visits   will be billed upon completed visit unit.
    
	
Site   Initiation Visits — ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Visits   will be billed upon completed visit unit.
    
	
Site   Initiation Visits - ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Visits   will be billed upon completed visit unit.
    

 

32

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

	
ACTIVITY
    	
 
    	
RATE
    	
 
    	
UNIT
    	
 
    	
EST.
   REQ.
    	
 
    	
ESTIMATED
   CHARGE
    	
 
    	
COMMENTS
    
	
Investigators   Meeting — *** Attendees
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Attendance   of CRAs at *** meeting, regional CL at *** and *** meetings, and global PM,   *** PM, Lead DM, and IWRS at three, average *** d per attendee per meeting
    
	
Investigators   Meeting - *** Attendees
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Attendance   of CRAs, regional CLs, regional PM at *** meeting, and global CL at ***
    
	
Investigators   Meeting - *** Attendees
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Attendance   of CRAs at *** meeting and *** Project Manager at three
    
	
Study   Document Development — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Includes   review of global monitoring plan and other documents
    
	
Study   Document Development - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Includes   development of ICF templates, global monitoring plan and other documents
    
	
Study   Document Development - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Informed   consent development
    
	
Budgets/Contracts:   3rd Party Vendors
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
For   sponsor-designated third party vendors
    
	
Site   Budgets/Contracts — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   and *** sites, SynteractHCR will negotiate and will hold contracts directly   with sites on Insmed’s behalf. SynteractHCR will negotiate Indemnification   agreements between sites and Sponsor. SynteractHCR will develop master budgets   for each country listed in this Work Order 1.
    
	
Site   Budgets/Contracts- ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   sites, SynteractHCR will negotiate and will hold contracts directly with   sites on Insmed’s behalf. SynteractHCR will negotiate Indemnification   agreements between sites and Sponsor. SynteractHCR will develop master   budgets for each country listed in this Work Order 1.
    

 

33

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

	
ACTIVITY
    	
 
    	
RATE
    	
 
    	
UNIT
    	
 
    	
EST.
   REQ.
    	
 
    	
ESTIMATED
   CHARGE
    	
 
    	
COMMENTS
    
	
Site   Budgets/Contracts - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   sites, SynteractHCR will negotiate and will hold contracts directly with   sites on Insmed’s behalf. SynteractHCR will negotiate Indemnification   agreements between sites and Sponsor. SynteractHCR will develop master   budgets for each country listed in this Work Order 1.
    
	
Study   Start-up- ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
project   team familiarization and training for *** team members
    
	
Study   Start-up - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
project   team familiarization and training for *** team members
    
	
Regulatory   Document Collection — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Regulatory   Document Collection — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Regulatory   Document Collection — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
TMF   Set-up and Maintenance — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Regional   site files and TMF
    
	
TMF   Set-up and Maintenance — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Regional   site files and Master TMF for project
    
	
TMF   Set-up — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Regional   TMF (set-up only)
    
	
Study   Monitoring — Interim Monitoring Visits — ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Visits   will be billed upon completed visit unit.
    
	
Study   Monitoring — Additional Days On Site — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
To   be used in conjunction with an existing visit if more time on-site is   required
    
	
Study   Monitoring — Interim Monitoring Visits - ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Visits   will be billed upon completed visit unit.
    
	
Study   Monitoring — Additional Days on Site — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
To   be used in conjunction with an existing visit if more time on-site is   required
    
	
Study   Monitoring — Interim Monitoring Visits — ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Visits   will be billed upon completed visit unit.
    

 

34

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

	
ACTIVITY
    	
 
    	
RATE
    	
 
    	
UNIT
    	
 
    	
EST.
   REQ.
    	
 
    	
ESTIMATED
   CHARGE
    	
 
    	
COMMENTS
    
	
Study   Monitoring — Additional Days On Site — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
To   be used in conjunction with an existing visit if more time on-site is   required
    
	
Clinical   Operations Lead — Regional (***)
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Clinical   oversight of *** and ***, approximately *** FTE
    
	
Clinical   Operations Leads — Regional (***)
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Clinical   oversight of ***, approximately *** FTE
    
	
Clinical   Operations Lead — Global (***)
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Global   clinical oversight, approximately *** FTE
    
	
Site   Management — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Contact   with sites, respond to site questions, reminder calls to push recruitment,   reminder calls to get data in the eCRF/answer queries, request updated study   documents, address any issue with supplies, team calls, etc.
    
	
Site   Management — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Contact   with sites, respond to site questions, reminder calls to push recruitment,   reminder calls to get data in the eCRF/answer queries, request updated study   documents, address any issue with supplies, team calls, etc.
    
	
Site   Management - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Contact   with sites, respond to site questions, reminder calls to push recruitment,   reminder calls to get data in the eCRF/answer queries, request updated study   documents, address any issue with supplies, team calls, etc.
    
	
Study   Close-Out Visits — ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Visits   will be billed upon completed visit unit.
    
	
Study   Close-Out Visits — ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Visits   will be billed upon completed visit unit.
    
	
Study   Close-Out visits - ***
    	
 
    	
***
    	
 
    	
visit
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Visits   will be billed upon completed visit unit.
    
	
Clinical Operations Subtotal
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
***
    	
 
    	
 
    
	
Quality Assurance
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Site   Audit — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Time   includes prep, travel, on-site audit, and report-writing/follow-up for ***   site audits
    

 

35

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

	
ACTIVITY
    	
 
    	
RATE
    	
 
    	
UNIT
    	
 
    	
EST.
   REQ.
    	
 
    	
ESTIMATED
   CHARGE
    	
 
    	
COMMENTS
    
	
Site   Audit — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Time   includes prep, travel, on-site audit, and report-writing/follow-up for ***   site audits
    
	
Site   Audit — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Time   includes prep, travel, on-site audit, and report-writing/follow-up for ***   site audits
    
	
Vendor   Audit — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Vendor   audits (sponsor-designated vendors)
    
	
Vendor   Audit — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Vendor   audits (sponsor-designated vendors)
    
	
Vendor   Audit — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Vendor   audits (sponsor-designated vendors)
    
	
Quality Assurance Subtotal
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
***
    	
 
    	
 
    
	
Regulatory Affairs
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
IMPD   Review
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Regulatory   Submissions - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Submissions   to central and local authorities/ECs
    
	
Regulatory   Submissions - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Submissions   to EC and TGA
    
	
Regulatory   Submissions - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
CTA   preparation and publishing for ***, plus Clinical Trial Site Information   Form (CTSIF) submissions
    
	
Regulatory   Document Management
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Handling   of insurance, translations, label review
    
	
Regulatory   Correspondence
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Communication   with authorities
    
	
Regulatory   Document Preparation - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
CTA   preparation for ***
    
	
Regulatory   Consulting - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Regulatory   Lead for ***
    
	
Legal   Representation - ***
    	
 
    	
***
    	
 
    	
project
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   will act as the local sponsor in ***
    
	
Regulatory Affairs Subtotal
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
***
    	
 
    	
 
    
	
Interactive Web Response System (IWRS) - Central   Randomization/Inventory Management
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    

 

36

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

	
ACTIVITY
    	
 
    	
RATE
    	
 
    	
UNIT
    	
 
    	
EST.
   REQ.
    	
 
    	
ESTIMATED
   CHARGE
    	
 
    	
COMMENTS
    
	
IWRS   Development, Testing and Implementation
    	
 
    	
***
    	
 
    	
day
    	
 
    	
 
    	
 
    	
***
    	
 
    	
Randomization   and inventory management via IWRS
    
	
IWRS   Study Maintenance, Site Support, and DCF processing
    	
 
    	
***
    	
 
    	
month
    	
 
    	
 
    	
 
    	
***
    	
 
    	
Enrollment/treatment/follow-up   period
    
	
24   hour Technical Support
    	
 
    	
***
    	
 
    	
month
    	
 
    	
 
    	
 
    	
***
    	
 
    	
International   support
    
	
Interactive Web Response System (IWRS) - Central   Randomization/Inventory Management
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
***
    	
 
    	
 
    
	
Data Management
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
CRF   Completion Guidelines
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Clinical   Database Design
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   database
    
	
DM   Programming
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
DM   SAS programming for reports outside of *** (e.g. site payment reports, coding   reports), also includes programming to set up patient profiles in ***
    
	
Site   Training/Documentation
    	
 
    	
***
    	
 
    	
site
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Database   Management (Reports/Meetings)
    	
 
    	
***
    	
 
    	
month
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Data   Management Plan
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
includes   defining data handling processes and writing of edit specifications
    
	
Data   Management
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Assumes   data management involvement over *** months of study (clinical duration)
    
	
Local   Lab Reference Ranges
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
No   normal ranges needed for these lab results
    
	
***   Set-up & Training
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Web   Access Set-up
    	
 
    	
***
    	
 
    	
user
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Project   website
    
	
Monthly   Web Access
    	
 
    	
***
    	
 
    	
month
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
User   Administration Support
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
For   *** users, including site personnel, CRAs, Sponsor, safety vendor
    

 

37

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

	
ACTIVITY
    	
 
    	
RATE
    	
 
    	
UNIT
    	
 
    	
EST.
   REQ.
    	
 
    	
ESTIMATED
   CHARGE
    	
 
    	
COMMENTS
    
	
Medical   Terminology Coding
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Assumes   *** coded terms per patient
    
	
Data Management Subtotal
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
***
    	
 
    	
 
    
	
Biostatistics
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Statistical   Writing: Protocol Review
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Analysis   Plan
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Statistical   analysis plan to include appendix for DSMB analysis plan, includes mock TFLs
    
	
Randomization   Schedule
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Programming   / Validation
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Standard   TFL programming, includes programming and QC for DSMBs, annual reports,   interim analyses, and final analysis
    
	
Statistical   Programming
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Efficacy   table programming, includes more complicated programming and QC for DSMBs,   annual reports, interim analyses, and final analysis
    
	
CDISC   Specifications — Reviewer’s Guides
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   Reviewer’s Guide and *** Reviewer’s guide
    
	
CDISC-***   Dataset Programming
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   *** datasets
    
	
CDISC-***   Dataset Programming
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   *** datasets; includes *** transfers of *** per sponsor request
    
	
CDISC-***   Dataset Programming
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   *** datasets
    
	
CDISC   aCRF: blankcrf.pdf
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
CDISC   Define.xml (SDTM and ADaM)
    	
 
    	
***
    	
 
    	
xml
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Data   Transfers (from 3rd party vendors)
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   transfers from *** data vendors
    

 

38

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

	
ACTIVITY
    	
 
    	
RATE
    	
 
    	
UNIT
    	
 
    	
EST.
   REQ.
    	
 
    	
ESTIMATED
   CHARGE
    	
 
    	
COMMENTS
    
	
Statistical   Analysis
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Includes   time for project statistician to attend regular team meetings as needed, DSMB   meetings via teleconference, and ad hoc face-to-face meetings; also includes   interim and final statistical analyses
    
	
Statistical   Review of the CSR
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Biostatistics Subtotal
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
***
    	
 
    	
 
    
	
Medical Writing
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Protocol   Review/Writing
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
 
    	
 
    	
 
    
	
Clinical   Study Report (CSR)
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Assumes   *** major round of reviews, *** minor round
    
	
Clinical   Writing General — Informed Consent Template Review
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Review   of ICF template
    
	
CSR   Compilation and Activation of Hyperlinks
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Compilation   of appendices to the CSR, activation of hyperlinks (e.g., TFLs)
    
	
Medical Writing Subtotal
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
***
    	
 
    	
 
    
	
Project Management
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Project   Administration — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Includes   project support, teleconference/minutes, assistance with status reports, and   payment administration (sites, vendors) for ***
    
	
Project   Administration- ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Includes   project support, assistance with status reports, and payment administration   (sites, vendors) for ***
    
	
Project   Administration - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Includes   project support for Australia
    
	
Project   Management — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   project management, vendor management
    
	
Project   Management — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   project management
    

 

39

 

[*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.  EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK ****, HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.]

 

	
Insmed   Incorporated — SynteractHCR
    	
Work Order 1
    	
INS-212
    

 

TIME AND MATERIALS/UNIT COST HYBRID BUDGET: INS-212

 

	
ACTIVITY
    	
 
    	
RATE
    	
 
    	
UNIT
    	
 
    	
EST.
   REQ.
    	
 
    	
ESTIMATED
   CHARGE
    	
 
    	
COMMENTS
    
	
Project   Management - ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
***   project management
    
	
Global   Project Management
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Global   Project Director to oversee all global aspects of the project
    
	
Project   Archival
    	
 
    	
***
    	
 
    	
project
    	
 
    	
***
    	
 
    	
***
    	
 
    	
 
    
	
Project   Meetings — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Face-to-face   meetings (e.g., kick-off meeting, sponsor meetings, ad hoc site visits) for   *** team members
    
	
Project   Meetings — ***
    	
 
    	
***
    	
 
    	
day
    	
 
    	
***
    	
 
    	
***
    	
 
    	
Face-to-face   meetings for *** Project Manager, assumes attendance at *** F2F meetings
    
	
Project Management Subtotal
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
***
    	
 
    	
 
    
	
SynteractHCR Study Total
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
***
    	
 
    	
 
    
	
discount on invoicing
    	
 
    	
***
    	
%
    	
 
    	
 
    	
 
    	
 
    	
***
    	
 
    	
 
    
	
SynteractHCR Study Total After Discount
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
***
    	
 
    	
 
    

 

40

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00241-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00241-of-00352.parquet"}]]