1.

The Study.

1.1

Company shall authorize specific assignments through the placement of a Work Order to Provider in the form set forth in Exhibit A hereto (“Work Order”) which shall describe (a) the Services to be performed, (b) any deliverables, (c) any special terms and conditions applicable to the Services, (d) an estimate of the total costs and payment schedule therefore, (e) the estimated delivery schedule for the provision of the Services, and (f) list any third parties authorized to communicate with Provider regarding the Services under the Work Order (each, a “Company Designee”).

1.2

Provider and Company shall execute a copy of each mutually acceptable Work Order.  In the event of a conflict between the terms contained in any Work Order and this Agreement, the terms of this Agreement shall control, unless specifically agreed upon to the contrary in the Work Order.  No obligation shall be incurred by either party unless a Work Order has been executed by the authorized agents of both parties.  

2.

Conduct of the Services.

2.1

Provider will maintain industry standards of professional conduct in the performance of the Services and each Study and in the preparation of all related reports.  Provider will adhere to all Applicable Law.  If applicable, Provider will perform the Services and each Study in compliance with the current good laboratory practices of the appropriate Government Authority.  For the purposes of this Agreement, “Applicable Law” shall mean all laws, statutes, ordinances, codes, rules and regulations which have been enacted by a Government Authority and are in force as of the Effective Date or come into force during the term of this Agreement, in each case to the extent that the same are applicable to the performance by the parties of their respective obligations under this Agreement.  “Government Authority” shall mean any supranational, national, regional, state

or local government, court, governmental agency, authority, board, bureau, instrumentality or regulatory body.

2.2

Provider will conduct the Study in accordance with the Work Order(s), which may be amended from time to time upon the mutual agreement of Provider and Company.  If an amendment requires additional or different work on the part of the Provider, Provider may agree to conduct such work and will be paid an amount mutually agreed to by the parties.  Provider agrees not to intentionally change or deviate in any material manner from the Work Orders without Company’s prior written approval.  Deviations from the Work Orders may be made in an emergency without Company’s approval, provided that Provider shall obtain Company’s prior written approval and that any deviation does not result in a substantial material cost increase or result in the Study not being conducted in accordance with Applicable Law.  

2.3

The parties acknowledge that during the course of performing the Study in accordance with the Work Orders, additional costs may be incurred by Provider as a result of procedural changes which do not amount to or require a change in the Work Orders, but which are deemed necessary by Provider to successfully perform said Study, and which could not be foreseen at the time of the preparation of the Work Orders.  If such procedural changes occur, Provider shall advise the Company prior to their implementation and solicit the Company’s prior written agreement as to the necessity and additional cost thereof.

2.4

After each Study has been completed, Provider may be requested by Company to provide additional consultation services concerning each Study.  Upon such a request by Company, Provider will provide the requested Services and will be paid an amount mutually agreed to by the parties.  These consultation Services will be subject to the provisions on Confidentiality and Data and Intellectual Property set forth in Sections 8 and 12, respectively.

3.

Study Material.  If applicable, Company or a Company Designee will provide Provider with sufficient amounts of all compounds, materials, or other substances meeting relevant specifications (“Test Materials”) with which to perform each Study, as well as such complete and accurate data as is reasonably necessary to apprise Provider of the stability, proper storage and safe handling requirements of the Test Materials, including a Material Safety Data Sheet (MSDS) or equivalent documentation.  Provider agrees that Test Materials shall be considered Confidential Information under Section 8 of this Agreement, and further agrees not to analyze or modify the Test Materials except as necessary to perform Services hereunder, with the prior written consent of Company.

4.

Personnel.  Provider will arrange for qualified personnel to support Provider’s obligations under this Agreement.  Provider represents that none of its employees who are to participate in a Study have been debarred and none of such employees are, to the best of Provider’s knowledge, under consideration to be debarred by the Food and Drug Administration from working in or providing services to any pharmaceutical or biotechnology company under the Generic Drug Enforcement Act of 1992, as amended or by any other Government Authority under any Applicable Law.  

5.

Inspections.  

5.1

Upon reasonable advance notice and not more than four (4) times per contract year, Provider will permit Company and/or its designated representatives, during normal business hours, to visit Provider’s facilities where any Study is taking place to monitor Provider’s performance of the Study.  Provider agrees to address, in writing, within thirty (30) days of the conclusion of Company’s audit of the facilities, any reasonably adverse findings made by Company pursuant to the audit.  The written report shall include an action plan for addressing the findings reasonably and a time line for the implementation of any corrective and preventative measures.  Provider shall permit, at the request of Company, a follow-up inspection to ensure that all corrective and preventative measures have been implemented.  Notwithstanding the foregoing, upon forty eight

(48) hours notice, Provider agrees to permit Company to visit the Provider for the express purpose of observing, dosing, and meeting with study directors and/or review study data on an unlimited basis as long as there is no conflicting audits or inspections being conducted during the requested time frame.  

5.2

Provider will notify Company as soon as practical in the event of any regulatory inspection of Provider’s facilities that directly impact a Study.  In the event of such an inspection by a regulatory or administrative agency, Provider will, to the extent permissible under Applicable Law, consult with and allow Company to be present at and to review and comment on any responses to such agency related to the inspection.  

6.

Records and Reports.

6.1

Provider will keep complete and accurate records of the status and progress of each Study, including any more specific requirements which may be set forth in any Work Orders.

6.2

Provider will furnish a report or data containing information specified in the Work Orders.  All reports will be prepared in the standard format of the Provider unless otherwise specified in the Work Orders or as otherwise agreed to by the parties.

6.3

All Study reports and any supporting documentation originating with Provider, in whatever form (e.g., laboratory notebooks, original data, tissues, slides, photographs, etc.) are and shall be the Company’s sole and exclusive property.  At Company’s cost and expense, if Company requires Company’s property to be held by Provider, Provider shall store Company’s property as agreed upon in the Work Orders.  Upon reasonable advance notice, Company’s representatives shall have reasonable access to such material, and shall have the right to obtain originals or certified legible photocopies, at the Company’s option, of the raw data and supporting documentation, at no additional expense.

7.

Compensation

7.1

Company will pay Provider as set forth in the Work Orders.  All invoices are due and payable thirty (30) days from invoice date and Company agrees to pay all invoices submitted.  Provider will invoice for amendments to a Study upon signature of such amendment by the Company.  

7.2

All applicable termination, delay or cancellation fees will be set forth in the Work Orders.

8.

Confidentiality.  

8.1

Definition.  Provider recognizes and acknowledges that certain information relating to the business of the Company or a Company Designee, including, without limitation, any clinical and product development plans, strategies, patent disclosures, patent applications, structures, models, techniques, know-how, trade secrets, processes, compositions, formulations, compounds and apparatus relating to the same and other proprietary information related to the current, future and proposed products and services of the Company or its subsidiaries or affiliates or a Company Designee disclosed by the Company, by a Company Designee or obtained by Provider through observation or examination of such information (collectively, “Confidential Information”) is the valuable property of the Company and/or the Company Designee.  Confidential Information also includes proprietary or confidential information of any third party who has disclosed such information to the Company in the course of the Company’s business. Both Parties have also entered into a Mutual Confidentiality Agreement dated 2-December-2013 which shall be adhered to according to the terms set for in that Agreement.

8.2

Nondisclosure of Confidential Information.  The Provider agrees that it will hold in strict confidence and not disclose to any third party any Confidential Information, except as approved in writing by the Company; provided, however, that the Provider shall not be obligated to treat as confidential, any Confidential Information that the Provider can prove through written documentation that (i) is known or made available to the public or otherwise is in the public domain at the time of disclosure by the Company or a Company Designee to Provider, (ii) becomes part of the public domain after disclosure by the Company to Provider by any means except through breach of this Agreement by the Provider, or by a third party under an obligation of confidentiality to the Company or a Company Designee, or (iii) has been otherwise known by the Provider prior to communication by the Company or a Company Designee to Provider of such information.  In the event a court or governmental agency legally compels the Provider to disclose Confidential Information, the Provider shall promptly inform the Company of the compelled disclosure, so that the Company or the Company Designee may seek a protective order or other remedy, and the Company agrees to cooperate with the Company in any proceeding to obtain a protective order or other remedy.  If, in the absence of a protective order or other remedy, Provider is nonetheless, in the opinion of Provider’s legal counsel, compelled to disclose Confidential Information, Provider may disclose only that portion of the Confidential Information that such counsel advises Provider is legally required to be disclosed.  In such an event, Provider shall give to the Company written notice of the Confidential Information to be disclosed as far in advance of its disclosure as is practicable and, upon the Company’s request, Provider shall use reasonable commercial efforts to obtain assurances that confidential treatment will be accorded to such information.

8.3

Limited Internal Disclosure.  The Provider agrees that any disclosure of Confidential Information will only be such as is necessary in connection with the conduct of the Services and will only be to the Provider’s employees who are bound by written agreements, at least as restrictive as this Agreement, with the Provider to maintain the Confidential Information in confidence.

8.4

Use of Confidential Information.  The Provider shall not use any Confidential Information provided to Provider for any reason or purpose other than for the intent of this Agreement and shall make no other use of the Confidential Information.

8.5

Notice of Certain Events.  The Provider will immediately notify the Company in the event of any loss or unauthorized disclosure of any Confidential Information.

8.6

No Reproduction of Confidential Information.  Confidential Information will not be reproduced in any form except as required to accomplish the intent of this Agreement.  Any reproduction of any Confidential Information will remain the property of the Company and will contain any and all confidential or proprietary notices or legends that appear on the original, unless otherwise authorized in writing by the Company.

8.7

Ownership.  As between the parties, all Confidential Information is the sole and exclusive property of the Company.  The Provider recognizes and agrees that nothing contained in this Agreement will be construed as granting any property rights, by license or otherwise, to the Provider to any Confidential Information disclosed under this Agreement, or to any invention or any patent, copyright, trademark, or other intellectual property right that has issued or that may issued, based on such Confidential Information.  The Provider will not make, have made, use or sell for any purpose any product or other item using, incorporating or derived from any Confidential Information.  The Company makes no warranty relating to the Confidential Information and the use to be made thereof by Provider and disclaims all warranties, express or implied, including the warranties of merchantability or fitness for a particular purpose.

8.8

Return of Materials.  Within sixty (60) days following the termination of this Agreement, or upon the Company’s written request, the Provider will promptly return to the Company all documents and other tangible materials representing any Confidential Information and all copies thereof and

all other property, materials or equipment that belong to the Company, its affiliates, subsidiaries, customers, prospects or suppliers, except for one archive copy which shall be retained by Provider to demonstrate compliance herein.  Provider further attests that all Provider employees and sub-contractors are held by confidentiality terms as strict as contained herein.

9.

Use of Names.   Neither party will use the other party’s name or the name of any employee of the other party in any advertising, packaging, promotional material, or any other publicity relating to this Agreement, without the prior written approval of the other party.  

10.

Warranties.  Provider represents and warrants that (i) the Services shall conform to the Work Order specifications and Applicable Law, (ii) without limiting the provisions of Section 4, Provider does not and will not use in any capacity the services of any person or entity debarred under the Generic Drug Enforcement Act of 1992, disqualified as a testing facility under CFR Part 58, Subpart K, or disqualified or restricted under 21 CFR 312.70, in connection with the Services, (iii) Provider and any employees of Provider are authorized to work and are not acting and will not act during the term of this Agreement in violation of the Immigration Reform and Control Act of 1986 and its amendments and the regulations promulgated thereunder, (iv) Provider has or will obtain appropriate agreements with its employees and others, including any permitted subcontractors, whose services it may require, sufficient to enable full compliance with all the provisions of this Agreement, particularly Sections 8 and 12, and (v) Provider has not undertaken and will not undertake any work with third parties which will conflict with the Services that Provider has performed or will perform for the Company.  

11.

Indemnities

11.1

Provider will defend, indemnify, save and hold harmless Company and its parent, subsidiaries, licensors and affiliates and their respective directors, officers, employees and agents (together, the “Company Indemnitees”) from and against any claims, demands, suits, actions, causes of action, losses, damages, fines and liabilities, including reasonable attorneys’ fees (“Claims”) arising out of or in connection with or attributable to Provider’s gross negligence or willful misconduct in performance of the Study, and will pay any costs and damages which, by final judgment, after exhaustion of all reasonable appeals, may be assessed against them, provided that Provider is given written notice of the Claims within five (5) days of the date of notice to Company and is given information, reasonable assistance, and sole authority to defend and/or settle the claim.

11.2

Company will defend, indemnify, save and hold harmless Provider and its parent, subsidiaries and affiliates and their respective directors, officers, employees and agents (together, the “Provider Indemnitees”) from and against any Claims arising out of or in connection with or attributable to any harmful or otherwise unsafe effect of the drug which is the subject of Services under this Agreement or any respective Work Order, the conduct of the clinical trial by Company which violates any applicable law, rule or regulation, Company’s gross negligence or willful misconduct in connection with this Agreement and will pay any costs and damages which, by final judgment, after exhaustion of all reasonable appeals, may be assessed against them, provided that Company is given written notice of the Claims within five (5) days of the date of notice to Provider and is given information, reasonable assistance and sole authority to defend and/or settle the claim.

12.

Data and Intellectual Property.  Any data, discoveries or inventions and other intellectual property rights, whether patentable or not, developed or generated pursuant to this Agreement which relate to any information or materials provided by Company or a Company Designee hereunder or otherwise arise from or are conceived and reduced to practice as a result of the performance of the Services, including without limitation new data, uses, processes or compositions relating to the information or materials provided hereunder shall be the exclusive property of Company.  Provider hereby assigns all of its right, title and interest in and to such data, discoveries, inventions and other intellectual property rights (including enforcement rights) to Company.  

Provider agrees to assist Company, at no additional cost, in securing for Company any patents, copyrights or other proprietary rights in such data, discoveries or inventions and other intellectual property rights, and to perform all acts that may be reasonably required to vest in Company all right, title and interest in such data, discoveries or inventions and other intellectual property rights.  Provider hereby designates Company as its agent for, and grants to Company a power of attorney, which power of attorney shall be deemed coupled with an interest, solely for the purpose of effecting the foregoing assignment from Provider to Company.

13.

Insurance.  Each party shall carry insurance sufficient to cover its interest or potential liabilities hereunder including, but not limited to worker’s compensation, if applicable, and comprehensive general liability.

14.

Force Majeure.  Except with respect to the payment of monies due hereunder, neither party shall be considered in default of the performance of any obligation hereunder to the extent that the performance of such obligation is prevented or delayed by fire, flood, earthquake, explosion, strike, acts of terrorism, war, insurrection, embargo, government requirement, civil or military authority, act of God, or any other event, occurrence or condition which is not caused, in whole or in part, by that party, and which is beyond the reasonable control of that party.

15.

Term and Termination.  

15.1

This Agreement will commence on the Effective Date and will continue for five (5) years from the Effective Date or until terminated by the parties as set forth below.

15.2

Company shall have the right to terminate an on-going Study at any time without cause upon thirty (30) days prior written notice to Provider.  In the event a Study is terminated without cause, Provider shall be paid for all related Services rendered through the effective date of termination, together with any additional expenses incurred in connection with the shutdown of the Study including without limitation any irrevocably committed costs.

15.3

Either party may terminate this Agreement upon sixty (60) days notice to the other party, provided that Provider completes all Studies in progress, and Company makes all payments due to Provider through the termination date as set forth in Section 16.2.  

15.4

Either party may terminate this agreement at any time upon thirty (30) days prior written notice to the other party, for material breach of this Agreement by the other party if such breach is not remedied to the non-breaching party’s reasonable satisfaction within the thirty (30) day notice period.

15.5

Upon termination, neither party will have any further obligations under this Agreement, except that (i) the liabilities accrued through the date of termination and (ii) the obligations which by their terms survive termination, including Sections 8 (Confidentiality) and 12 (Data and Intellectual Property) and the applicable record keeping, regulatory compliance, and indemnification provisions of this Agreement, shall survive termination.

16.

Dispute Resolution.

16.1

Each party agrees that the other party shall be entitled to equitable relief, including injunction and specific performance, in the event of any breach of the provisions of this Agreement, including without limitation breach of the confidentiality provisions hereunder.  Such remedies shall not be deemed to be the exclusive remedies for a breach of this Agreement, but shall be in addition to all other remedies available at law or equity.

16.2

The parties shall attempt, in good faith, to resolve through negotiations any controversy, claim, or dispute arising out of this Agreement.  In the event that negotiations are not successful, the controversy, claim, or dispute shall be submitted to third party mediation upon terms reasonably acceptable to the parties.  If such claim, controversy or dispute is not resolved through mediation, upon written demand of either party, the claim, controversy or dispute shall be submitted to arbitration.  Such arbitration shall take place in the jurisdiction in which the services are provided, and shall proceed in accordance with the laws of such jurisdiction and the Commercial Arbitration Rules of the American Arbitration Association or if the parties so elect, the Rules of the United Nations Commission on International Trade Law Model Law on International Commercial Arbitration.  A record and transcript of the proceedings shall be maintained.  Any award shall be made in writing and in reasonable detail, setting forth the findings of fact and conclusion of law supporting the award.  The determination of a majority of the panel of arbitrators shall be the decision of the arbitrators, which shall be binding regardless of whether one of the parties fails or refuses to participate in the arbitration.  The decision shall be enforceable by a court of law, provided that the decision is supported by substantial fact and is without material error of law.  All costs of such arbitration, except expert fees and attorneys’ fees, shall be shared equally by the parties.  In no event shall the liability of Provider for any breach of default hereunder exceed the amount of fees it has paid under the Work Order to which such breach or default relates. Neither party shall be entitled to claim consequential, indirect or special damages or loss of profit for any breach or default under this Agreement or any Work Order or any attachment hereto.

17.

Miscellaneous.  

17.1

Notices.  All notices from one party to the other will be in writing and will be delivered by addressing the same to the applicable address set forth below, or at such other address as either party may specify in writing to the other.  Notices shall be sent by overnight courier, certified mail, return receipt requested, or by other means of delivery requiring a written acknowledged receipt.  

Company Address:

Evoke Pharma, Inc.

505 Lomas Santa Fe Drive, Suite 270

Solana Beach, CA  92075

Attn: Matt D’Onofrio, EVP & Chief Business Officer

Provider Address:

Spaulding Clinical Research, LLC

525 South Silverbrook Drive

West Bend, WI 53095

Attn: Daniel Selness, GM & Sr. V.P. of Clinical Research

With a copy to:

Jason Baltz, Attorney at Law

4871 N. Sheffield Avenue

Whitefish Bay, WI 53217

17.2

Independent Contractor.  The business relationship of the Provider to the Company is that of an independent contractor and not of a partner, joint venturer, employer, employee or any other kind

of relationship.  Provider shall not have the authority under this Agreement to bind or obligate the Company and shall not represent that it has such authority.  Provider will be solely responsible for expenses and liabilities associated with the employment of its employees.

17.3

Assignment.  This Agreement, and the rights and obligations hereunder, may not be assigned or transferred by either party without the prior written consent of the other party, such consent not to be unreasonably withheld, except that the Company may assign this Agreement to an affiliated company or in connection with the merger, consolidation, license or sale of substantially all assets related to the Study.

17.4

Entire Agreement.  This Agreement, together with the Work Order(s), sets forth the entire agreement and understanding between the parties, superseding any and all previous statements, negotiations, documents agreements and understandings, whether oral or written, as to the subject matter of the Agreement.  No modification or waiver of the provisions of this Agreement or any Work Order shall be valid or binding on either party unless in writing and signed by both parties.  No waiver of any term, right or condition under this Agreement or any Work Order on any one occasion shall be construed or deemed to be a waiver or continuing waiver of any such term, right or condition on any subsequent occasion or a waiver of any other term, right or condition hereunder.

17.5

Severability.  In the event that any one or more of the provisions contained in this Agreement will, for any reason, be held to be invalid, illegal or unenforceable in any respect, that invalidity, illegality or unenforceability will not affect any other provisions of this Agreement, and all other provisions will remain in full force and effect.  If any provision of this Agreement is held to be excessively broad, it will be reformed and construed by limiting and reducing it so as to be enforceable to the maximum extent permitted by law.

17.6

Governing Law.  This Agreement shall be governed by, and construed in accordance with, the laws of the State of California, excluding those laws that direct the application of the laws of another jurisdiction.

17.7

No Public Announcement.  Neither party will disclose the name of the other party, the existence of this Agreement, or the subject matter hereof in any publicity, advertising or public announcement without the prior written consent of the other party.

17.8

Counterparts.  This Agreement may be executed in counterparts, which taken together shall constitute a single legal document.

Spaulding Clinical Research, LLC

Evoke Pharma, Inc.

By: /s/ Daniel Selness

By: /s/ Matt D’Onofrio

Name:  Daniel Selness

Name:  Matt D’Onofrio

Title:   GM & Sr. VP of Clinical Research

Title:  EVP & Chief Business Officer

Date:    29 Jan 2014

Date: 28 Jan 2014

1.

Work Order.  This document constitutes a “Work Order” under the Agreement and this Work Order and the services contemplated herein are subject in all respects to the terms and provisions of the Agreement.

2.

Services.

2.1

Time Line.  Tasks to be completed between ______________, and _________________ (the “Work Order Term”).

2.2

The provision of any additional Services by Provider to Company shall be mutually agreed in a Work Order signed by an authorized agent of Company and Provider.

3.

Fees.  

3.1

Company shall pay Provider ___________________________________.  Services provided shall not exceed a total of _______________ during the Work Order Term.  Payments of such fees shall be made in accordance with the provisions of the Agreement.  Such fees will be paid [insert payment schedule].

Provider

Evoke Pharma, Inc.

By:

By:

Name:

Name:  

Title:  

Title:  

Date:    

Date:

1)

Spaulding hereby agrees to perform for Sponsor the following services (as applicable) in connection with Protocol METO-IN-006:

i)

Spaulding will conduct the clinical research services pertaining to the Protocol; and

ii)

Spaulding will conduct the Biostatistics, Data Management and Medical Writing services pertaining to the Protocol

2)

To the extent that any of the services described in this Work Order are inconsistent with the services described in the MSA, this Work Order shall govern.  Attachment B will contain the scope of services for this project.  

EVOKE PHARMA, INC.

SPAULDING CLINICAL RESEARCH, LLC

By:

/s/ David A. Gonyer

By:

/s/ Daniel Selness

Name:

David A. Gonyer

Name:

Daniel Selness

Title:

President and CEO

Title:

Chief Strategy Officer

Date:

April 17, 2017

Date:

April 17, 2017

Attachments:

Attachment A:  Protocol (Incorporated by reference)

Attachment B:  Description of Services (As outlined in proposal)

Attachment B:  Study Budget and Payment Schedule (As outlined in proposal)

^*** Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted portions.

∎

∎

∎

∎

Prepared for:

Wayne Alves

∎

EVOKE Pharma, Inc.                    

∎

420 Stevens Avenue, Suite 370

∎

Solana Beach, CA 92075

∎

email: walves@evokepharma.com

∎

∎

∎

∎

Protocol #:

METO-IN-006

∎

∎

∎

∎

∎

∎

∎

Protocol Title:

A Four-Period, Four-Treatment, Four-Sequence Randomized Crossover Study of the Comparative Bioavailability of Metoclopramide After Nasal and Oral Administration to Healthy Volunteers Under Fasted Conditions

∎

∎

∎

∎

∎

∎

[name(s)]

∎

∎

∎

∎

∎

∎

Submitted by:

David Stark

∎

Director, Business Development

∎

Spaulding Clinical Research, LLC

∎

525 S. Silverbrook Drive

∎

West Bend, Wisconsin 53095

∎

Tel: 415-218-9646

∎

Email:  David.Stark@spauldingclinical.com

∎

∎

Date Submitted:

13 April 2017

∎

∎

∎

Budget Summary – 4 Period

Clinical Budget (excludes pass-throughs)

$[***]

Biometrics Budget (Data Management, Stats and CSR)

$[***]

Project Management

$[***]

TOTAL

$1,643,861.33

^***

Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted portions.

•

Spaulding Clinical Research operates a 200-bed clinical pharmacology unit which conducts all types of clinical pharmacology studies, from the most highly technical dose ranging studies down to bioavailability and bioequivalence studies.

o

With 96, Full 12-lead telemetry beds, Spaulding Clinical has the largest 12-lead ECG telemetry installation in the world.  This allows for the conduct of large TQT studies without having to split the cohorts, thus increasing delivery speed and passing on costing efficiencies to Sponsor.

•

The facility is paperless, using a fully integrated Phase I Electronic Data Capture system with bi-directional interfaces to clinical lab, bedside devices and ECG systems.

o

This allows Sponsors to continuously review their study data in real-time

o

Study managers can monitor study data remotely which can greatly reduce time out of the office, travel costs, and the overall burden of monitoring

o

Spaulding Clinical also has the ability to perform automatic data transfers to Sponsor Medidata Rave databases via an Interface

•

We also have a purpose built, state-of-the-Art, 12-bed, High-Visibility dedicated First-In-Man unit which is an exceptional place to execute FIM/SAD/MAD type trials.

Metric

2016

Study Enrollment

99.70%

Subject Retention

98.71%

PKs on time

97.40%

Drug dose on time

99.90%

•

True bi-directional interface support of HL7, CDISC LAB and other standards

•

Extensive cardiac integration with both telemetry and cardiograph ECG systems

•

Multi-site support that allows for deployment to the Cloud or to internal data centers

•

Barcode sample specimen management for protocol adherence

•

Bedside device integration that facilitates automatic data collection from medical devices

•

Support for traditional desktop and laptop computers in addition to mobile devices

•

The ability to communicate with potential study subjects with SMS (text messages)

•

Custom dashboards for monitors, PIs, or other staff for visualizations of study progress

Year

Retention Metrics

2015

98.20%

2014

97.85%

2013

98.71%

▪

The Study Coordinator and staff are responsible for the following:

▪

Ensure studies are conducted in accordance with the study protocol, Spaulding Clinical policies/procedures, GCP standards and specific Principal Investigator criteria in accordance with Sponsor expectations.

▪

Informing relevant personnel of any issues which may affect study performance (i.e. safety, training, enrollment, volunteer visit schedules)

▪

Operational conduct of the study, functioning as the primary Sponsor contact.

▪

Study specific training as needed

▪

Coordinating with the bioanalytical laboratory to ensure appropriate sample shipping handling/integrity

▪

Maintaining all study related logs and correspondence

▪

Regulatory documents

▪

IRB submission

▪

IRB approval received

▪

All regulatory documents filed within the Investigator Site File

1.

Provide an Overview of Clinical Pharmacology Services performed at your site.

2.

Please describe the Team typically assigned to conduct and report the study results.

3.

Do you have capability to allow Sponsor to review study data in real-time? Please describe.

4.

Please describe your experience with nasal spray products, including number of Bioavailability studies and Bioequivalence studies performed in the past year.

5.

Describe your pool of potential subjects and the typical time it would take to recruit 48 to 60 subjects.

6.

What is your subject retention rate?

7.

What percent of PK samples are typically drawn on time?

8.

Do you have genetic information in your potential subject database, specifically CYP4502D6, in order to select only subjects who are extensive metabolizers (i.e., no poor or ultra-extensive metabolizers)?

9.

Evoke wishes to be able to accommodate dosing for the pivotal study in a single cohort. Please describe the total number of subjects you can accommodate as a single cohort.

10.

Please describe how you will manage blood samples with the Bioanalytical Company selected in order to insure that fast and efficient PK results being available as soon as possible following final subject dosing.

11.

Please describe any data review meetings to be held at key milestones (e.g. Draft PK TLFs and Final PK TLFs).

12.

In the last 12 months have you been audited by the FDA? If yes, were any 483 deficiencies noted?

13.

Please provide 2 references for equivalent exposure or Bioequivalence studies performed in the 12 months.

^***

Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted portions.

Clinical Assumptions

Protocol Number

METO-IN-006

Date of Protocol

12-May-17

Phase

1

Study Population

Healthy Volunteers

Number of Sites

1

Approximate Start Date

May-17

Screen Failure Ratio

2:1

Total Number of Screened Subjects

[***]

Total Enrolled Subjects

[***]

^***

Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted portions.

General Biometrics Assumptions:

A project manager will be assigned to facilitate timelines, meetings and general communication.

A Data Review Meeting (DRM) will be held between the delivery of the draft PK TLFs and the final PK TLFs. Attendees will include the PM, sponsor, medical writer, PK Analyst, and statistician.

Spaulding Clinical standard templates will be utilized whenever applicable. This includes the Data Management Plan (DCM), Case Report Forms (CRFs), Statistical Analysis Plan (SAP), TLF Shells and Clinical Study Report (CSR).

Data Management Assumptions:

Number of Subjects Randomized

[***]

Number of Screen Failures

[***]

Unique CRF Pages per Subject

[***]

Total Number of CRF Pages per Subject

[***]

Number of Terms to be Coded Per Subject

[***]

Number of Edit Checks

[***]

Number of External Vendors

[***]

Number of Transfers (per vendor)

[***]

Number of Custom Reports

[***]

Statistical Analysis, Programming and PK Assumptions:

Randomization

Yes

Unblinding Envelops Provided

No

PK SAP

Yes

2 Drafts and a Final, includes TLF mocks

Number of SDTM Domains

24

1 Draft and a Final

SDTM Version

v3.2

Number of ADaM Datasets

10

1 Draft and a Final

ADaM Version

v1.0

Number of Analytes

1

Number of Unique Safety Tables

[***]

1 Draft and a Final

Number of Repeat Safety Tables

[***]

1 Draft and a Final

Number of Unique PK/PD Tables

[***]

1 Draft and a Final

Number of Repeat PK/PD Tables

[***]

1 Draft and a Final

Number of Unique Listings

[***]

1 Draft and a Final

Number of Repeat Listings

[***]

1 Draft and a Final

Number of Unique Figures

[***]

1 Draft and a Final

Number of Repeat Figures

[***]

1 Draft and a Final

SDTM Define.xml

Yes

1 Draft and a Final

ADaM Define.xml

Yes

1 Draft and a Final

Define.xml version

v2.0

Define.pdf

Yes

1 Draft and a Final

SDTM Reviewers' Guide

Yes

1 Draft and a Final

ADaM Reviewers' Guide

Yes

1 Draft and a Final

Medical Writing Assumptions:

Protocol

Yes

2 Drafts and a Final

CSR

Yes

Shell, 2 Drafts and a Final

Publishing

Yes

Full

^***

Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted portions.

Spaulding

Sponsor

Vendor

Comments

Study Start-Up

Synopsis Design and Development

X

Review of Sponsor developed draft Protocol

X

Informed Consent Design/Completion

X

Compilation of Regulatory Package & Submission to IRB

X

Clinical Conduct

Recruitment, Screening and Selection of Eligible Volunteers

X

Provides Investigational Supplies, Including Study Drug

X

Provide Marketed or Comparator Drug

X

Study Drug Disposal (e.g., Destruction, Return)

X

Execution of Clinical Conduct Aspects of Study

X

Perform Data Entry of CRFs/ Data Transfer

X

Clinical Monitoring Services

Provide Clinical Monitoring Services

X

Medical Monitoring Services

Provide Medical Monitoring Services

X

Bioanalvtical Services

Facilitate Receipt of PK Data Results from Outside Laboratory

X

ECG Analysis Reporting (TQT Studies)

ECG SAP (Statistical Analysis Plan)

To be Prepared/Contracted Separately by Dr. Jay Mason.

Expert Report

To be Prepared/Contracted Separately by Dr. Jay Mason.

Data Management*

Development of CRF/Data Collection Module

X

2 Drafts / 1 Final

Data Management Plan (DMP) Development and Maintenance

X

2 Drafts / 1 Final

Database Development, Testing and Validation

X

1 Database

Database Training

X

Up to 5 Users

Edit Check Writing, Programming, Testing and Validation

X

Data Validation and Query Management

X

Medical Coding (MeDRA and WHO-DRUG)**

X

Biometrics Project Management

X

Database Transfer

X

2 Interim and 1 Final

Third Party Vendor Transfers and Reconciliation

X

1 Source (PK)

PDF Bookmarked CRFs for early term subjects due to AE

X

eCRF Lock

X

Statistical Analysis and Programming - Safety

Protocol Review

X

Randomization*

X

Statistical Analysis Plan (SAP) w/table shells - Safety

X

2 Drafts / 1 Final

Listing Shells and Figure Shells Included in SAP - Safety

X

Statistical Programming - Tables

X

Validation and Production - Tables

X

Statistical Programming - Listings

X

Validation and Production - Listings

X

Statistical Programming - Figures

X

Validation and Production - Figures

X

SDTM Datasets & Define.xml

X

ADaM Datasets & Define.xml

X

Annotated (SDTM) eCRF

X

Other Requirements (see comments)

Spaulding

Sponsor

Vendor

Comments

Statistical Analysis and Programming - PK/PD*

Protocol Review

X

Statistical Analysis Plan (SAP) w/Table Shells - PK/PD

X

Listing Shells and Figure Shells Included in - PK/PD

X

Preliminary/Interim PK Analysis (at request of Sponsor)

WinNonLin Analysis

X

PK Data Review Meeting

X

Final PK Analysis

X

Preliminary/Interim PD Analysis (at request of Sponsor)

PD Data Review Meeting

X

Final PD Analysis

X

Statistical Programming - PK/PD Tables

X

Validation and Production - PK/PD Tables

X

Statistical Programming - PK/PD Listings

X

Validation and Production - PK/PD Listings

X

Statistical Programming - PK/PD Figures

X

Validation and Production - PK/PD Figures

X

Other requirement (see comments)

Medical Writing

Protocol Writing Services - Using Spaulding Template
(ICH-Compliant)

X

Clinical Summary Report (CSR) - Using Spaulding Template (ICH-Compliant)

X

Shell / 2 Drafts / 1 Final

Patient Narratives

Drafts

Final

Safety Only

Publishing

Loose Compile Appendices from our eTMF

Separate folders

PDF compilation of Appendices with hyper-links

Full CSR Publishing

X

*Assumes protocol requires only one Database Build, One Randomization Schedule, One set of TFLs programmed, etc. using Spaulding Standards

**Spaulding Clinical assumes Sponsor holds valid MedDRA and Uppsala Monitoring Center (for WHO-DRUG) Licenses

Sponsor Name: Evoke Pharma, Inc.
Protocol No: METO-IN-006

Protocol/Synopsis Date: 12 May 2017

Population: Healthy Volunteers

STATUS: Draft Budget

Date: 14-Jul--2017

Clinic Site: Spaulding Clinical Research

# of Subjects: [***]

Unit Charge

Frequency

Total per Subject

Recruiting & Screening

Informed Consent

[***]

[***]

[***]

[***]

[***]

Complete History (Incl. Concomitant Medication)

[***]

[***]

[***]

[***]

[***]

Physical Exam

[***]

[***]

[***]

[***]

[***]

Nasal Examination

[***]

[***]

[***]

[***]

[***]

ECG - 12 Lead

[***]

[***]

[***]

[***]

[***]

Laboratory Evaluation (CBC, Chem-20, U/A)

[***]

[***]

[***]

[***]

[***]

Pregnancy Test

[***]

[***]

[***]

[***]

[***]

Drug & Alcohol Screen

[***]

[***]

[***]

[***]

[***]

Serum Cotinine

[***]

[***]

[***]

[***]

[***]

Vital Signs

[***]

[***]

[***]

[***]

[***]

Height, Weight & BMI

[***]

[***]

[***]

[***]

[***]

Hepatitis B & C

[***]

[***]

[***]

[***]

[***]

HIV

[***]

[***]

[***]

[***]

[***]

Recruitment Fee

[***]

[***]

[***]

[***]

[***]

Screening Stipend

[***]

[***]

[***]

[***]

[***]

Screening Failures

[***]

[***]

[***]

[***]

[***]

Sub-Total

[***]

[***]

[***]

[***]

[***]

Confinement [***]

Drug & Alcohol Screen

[***]

[***]

[***]

[***]

[***]

Serum Cotinine Test

[***]

[***]

[***]

[***]

[***]

Concomitant Medication/Adverse Event Review

[***]

[***]

[***]

[***]

[***]

Pregnancy Test

[***]

[***]

[***]

[***]

[***]

Vital Signs

[***]

[***]

[***]

[***]

[***]

Laboratory Evaluation (CBC, Chem-20, U/A)

[***]

[***]

[***]

[***]

[***]

Nasal Examination

[***]

[***]

[***]

[***]

[***]

Clinic Bed

[***]

[***]

[***]

[***]

[***]

Medical and Nursing/Staffing Charge - Heavy Day

[***]

[***]

[***]

[***]

[***]

Supplies

[***]

[***]

[***]

[***]

[***]

Meals

[***]

[***]

[***]

[***]

[***]

PK Draws

[***]

[***]

[***]

[***]

[***]

Pharmacy Charge

[***]

[***]

[***]

[***]

[***]

Dosing Administration

[***]

[***]

[***]

[***]

[***]

Physical Exam - EOS

[***]

[***]

[***]

[***]

[***]

Nasal Examination - EOS

[***]

[***]

[***]

[***]

[***]

Laboratory Evaluation (CBC, Chem-20, U/A) - EOS

[***]

[***]

[***]

[***]

[***]

Safety ECG - EOS

[***]

[***]

[***]

[***]

[***]

Electronic Source Management

[***]

[***]

[***]

[***]

[***]

Sub-Total

[***]

Other Subject Charges

Administrative Overhead

[***]

Clerical

[***]

Volunteer Stipend

[***]

Sub-Total

[***]

Cost Per Completed Subject [***]

^***

Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted portions.

Other Study Charges

Alternate Stipends and Check-in Procedures
(# of subjects x # of cohorts)

[***]

[***]

[***]

[***]

[***]

Screening Charges for [***] Subjects

[***]

[***]

[***]

[***]

[***]

Dry Ice and Sample Shipment

[***]

[***]

[***]

[***]

[***]

Verified Clinical Trials (Subject Registry System)

[***]

[***]

[***]

[***]

[***]

Investigator Review/Signature of CSR

[***]

[***]

[***]

[***]

[***]

Study Data Transfers include QC & Query Resolution

[***]

[***]

[***]

[***]

[***]

Lab Data Transfers include QC & Query Resolution

[***]

[***]

[***]

[***]

[***]

ECG Data Transfers include QC & Query Resolution

[***]

[***]

[***]

[***]

[***]

IRB (Includes drafting ICF and compiling initial submission)

[***]

[***]

[***]

[***]

[***]

Sub-Total

[***]

[***]

[***]

[***]

[***]

Total Clinical Study Cost[***]

Pass Through Costs

Long-Term Storage of PK Samples $[***]/sample/month greater than 30 days LSO

IRB Modifications: $[***]/document

Advertising up to $[***]

Dry Ice and Sample Shipment costs above and beyond above charge

Study Data, ECG, or Lab Data transfer above and beyond above charge @ $[***]/transfer

Drug Procurement

Drug Destruction

Screen Failures in Excess of 2:1 Ratio will be billed at $[***]

Biometrics Budget

Data Management

Data Management Administration

[***]

[***]

[***]

[***]

[***]

Conduct and Maintenance

[***]

[***]

[***]

[***]

[***]

eCRF Development and Completion Guidelines

[***]

[***]

[***]

[***]

[***]

Database Development, Testing and Validation

[***]

[***]

[***]

[***]

[***]

Data Transfers (from external vendors)

[***]

[***]

[***]

[***]

[***]

Custom Reports (Dose Escalation Meetings)

[***]

[***]

[***]

[***]

[***]

Designing and Validating Paper Diary

[***]

[***]

[***]

[***]

[***]

Data Management Fees

[***]

[***]

[***]

[***]

[***]

Sub-Total

[***]

[***]

[***]

[***]

[***]

Statistical Analysis and Programming

Statistical Analysis, PK and Programming Administration

[***]

[***]

[***]

[***]

[***]

Randomization

[***]

[***]

[***]

[***]

[***]

Statistical Analysis Plan (SAP)

[***]

[***]

[***]

[***]

[***]

SDTM Programming

[***]

[***]

[***]

[***]

[***]

Analysis Programming (SDTM, ADaM, TLF - Safety/PK/PD)

[***]

[***]

[***]

[***]

[***]

Electronic Submission (eSUB)

[***]

[***]

[***]

[***]

[***]

Sub-Total

[***]

[***]

[***]

[***]

[***]

PK Analysis and Reporting

PK Administration

[***]

[***]

[***]

[***]

[***]

WinNonLin Analysis

[***]

[***]

[***]

[***]

[***]

Sub-Total

[***]

[***]

[***]

[***]

[***]

Medical Writing

Medical Writing Administration

[***]

[***]

[***]

[***]

[***]

Protocol

[***]

[***]

Clinical Study Report (CSR)

[***]

[***]

Publishing

[***]

[***]

Sub-Total

[***]

[***]

[***]

[***]

[***]

Total Biometrics Cost[***]

Project Management Cost[***]

TOTAL STUDY COST$ 1,643,861.33

^***

Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted portions.

[***]% of Study Total:$[***]

Due Upon [***]

[***]% of Study Total:$[***]

Due Upon [***]

[***]% of Study Total:$[***]

Due Upon [***]

[***]% of Study Total:$[***]

Due Upon [***]

[***]% of Study Total:$[***]

Due Upon [***]

[***]% of Study Total:$[***]

Due Upon [***]

[***]% of Study Total:$[***]

Due Upon [***]

Total Project Budget:$1,643,861.33

^***

Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted portions.