exh_415.htm

Exhibit 4.15

THE SYMBOL “[****]” DENOTES PLACES WHERE PORTIONS OF THIS DOCUMENT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT. SUCH MATERIAL HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.

Amendment #4 to Clinical Services Agreement

Sponsor’s study drug RHB-104

This Change Order 4 (“Change Order”) to the Clinical Services Agreement signed 15 June 2011 (“Clinical Services Agreement”), is by and among:

(1) RedHill Biopharma Ltd., having its principle place of business at 21 Ha’arba’a St., Tel Aviv 64739, Israel (hereafter “SPONSOR”);

(2) 7810962 Canada Inc., a Canadian corporation, having its principal office at 245 Victoria Ave, Suite 100, Montreal, Quebec, H3Z 2M6, Canada (hereinafter "MANAGER");

Is hereby made effective as of September 11, 2014 (“Effective Date”) and the parties hereby agree as follows:

1. Amendment # 4 to Clinical Services Agreement.

This Amendment constitutes an amendment to the Clinical Services Agreement pursuant to section 3.0 therein. As such, this Amendment is subject in all respects to the terms and provisions of the Clinical Services Agreement.

2. Scope of Work

In addition to the Services to be provided in the above-referenced Clinical Services Agreement, Manager will cause inVentiv Health Clinical to perform additional Services for Client’s study drug RHB-104, in accordance with the Summary of Changes attached hereto and incorporated herein as Exhibit A.

3. Compensation

[****]

Payment due to inVentiv Health Clinical for the Services provided under this Change Order shall be made pursuant to the Agreement and the revised unit Payment Schedule attached hereto and incorporated herein as Exhibit B.

4. Project Period

The term of this Amendment shall commence on the date of its execution and shall continue until the Services as described in the Clinical Services Agreement are completed, unless this Amendment or corresponding Clinical Services Agreement are terminated early in accordance with the Clinical Services Agreement.

By their signatures below, the parties hereto agree to the terms of this Change Order and represent that they are authorized to enter into this Amendment on behalf of their respective companies.

ACCEPTED AND AGREED TO:

RedHill Biopharma Ltd.		For 7810962 Canada Inc.

/s/ Dror Ben-Asher		/s/ Alain Guimond PhD
Name: Dror Ben-Asher		Name: Alain Guimond PhD
Title: CEO		Title: Senior Director of R&D

Date:	01 Dec 2014	Date	01 Dec 2014

RedHill Biopharma Ltd.

/s/ Ori Shilo
Name: Ori Shilo
Title: Deputy CEO Finance & Operations

Date:	01 Dec 2014

Exhibit A Summary of Changes

Study Assumption Changes

Changes to the parameters and assumptions for the study are defined below. Unless otherwise noted, activities will be performed according to the original contract.

Change Order 4 for 7810962 Canada Inc. /RedHill Biopharma Ltd.

Overview of major level changes

Category	Contract	Start Up Work in [**] and [**]	Rationale for change
# of countries	[****]	[****]	Added [**] and [**]
# of sites	[****]	[****]	[****]
# of PSVs	[****]	[****]	[****]

1.1	Revised Costs

Costs for this study are presented below in two categories, pass-through costs and professional fees.

1.1.1

Pass-Through Costs

Pass-through costs are in US dollars and include those expenses listed below. inVentiv Health Clinical will invoice Client for actual costs in these areas, it being understood that any pass-through costs in excess of the amounts set out below will require the Client’s prior written approval. inVentiv Health Clinical will use its best efforts to keep actual costs to reasonable levels through adherence to inVentiv Health Clinical’s travel policy and prudent negotiation with outside providers. Pass-through costs are presented in the table below:

Task	Current (USD)	Start Up Work in [**] and [**]	Assumption Changes influencing the change in the budget	Additional comments
Site Visit Travel	[****]	[****]	[****]
Investigators' Meeting Organisation	[****]	[****]	No change.
Kick-off Meeting Travel/Attendance	[****]	[****]	No change.
Shipping/Photocopying	[****]	[****]	No change
Translation	[****]	[****]	No change

Task

Current

(USD)

Start Up Work in [****] and [****]

Assumption Changes influencing the change in the budget

Additional comments

Regulatory Fees	[****]	[****]	No change
Ethics Committee Fees	[****]	[****]	No change
EDC Studies/3G Cards	[****]	[****]	No change
DSMB member fees	[****]	[****]	No change
EDC Fees (Oracle)	[****]	[****]	No Change
CRA Face to Face Meeting Travel expenses	[****]	[****]	No change
Pass Through Costs	[****]	[****]

1.1.2

Investigator Grants Costs

Investigator Grants	Current (NA USD)	NA (USD)	Assumption Changes influencing the change in the budget	Additional Comments
Investigator Grants	$ [****]	$ [****]	No Change	Estimate only. Will be paid based on actual costs as approved by the Client.

1.1.3

Professional Fees

Based on the parameters and assumptions outlined in the original proposal, inVentiv Health Clinical fees are categorised by major activity in the table below and in USD:

Task	Current (US Dollars)	Start Up Work in [**] and [**]	Change	Assumption Changes influencing the change in the budget	Additional comments
Pre-study Activities
Case Report Form Preparation/Review	[****]	[****]	[****]	[****]	[****]
Data Management Plan Preparation/Review	[****]	[****]		[****]
Informed Consent Preparation/Review	[****]	[****]	[****]	[****]	[****]

Task

Current

(US Dollars)

Start Up Work

in [****] and [****]

Change

Assumption Changes

influencing the change

in the budget

Additional comments

IRB/Ethics Committee Interactions	[****]	[****]		No change
Investigators' Meetings	[****]	[****]	[****]	[****]	[****]
Investigator Site Contract	[****]	[****]	[****]	[****]	[****]
Investigator Recruitment	[****]	[****]	[****]	[****]	[****]
Project Feasibility	[****]	[****]	[****]	[****]	[****]
Project Plan Preparation/Review	[****]	[****]	[****]	[****]	[****]
Protocol Preparation/Review	[****]	[****]	[****]	[****]	[****]

Task

Current

(US Dollars)

Start Up Work

in [****] and [****]

Change

Assumption Changes

influencing the change

in the budget

Additional comments

Randomization Schedule Preparation	[****]	[****]		No change
Study-Specific Form Preparation	[****]	[****]		No change
Training - Project-Specific	[****]	[****]	[****]	[****]	[****]
Translations	[****]	[****]		No change
PROMIS	[****]	[****]	[****]	[****]	[****]
Monitoring/Site Management
Data Clean-up	[****]	[****]		[****]
Investigator Grant Administration	[****]	[****]		[****]	[****]
Laboratory Report Review	[****]	[****]		[****]
Serious/Significant Adverse Event Management	[****]	[****]		[****]
Site Management	[****]	[****]		[****]
Remote Monitoring of Site Data	[****]	[****]		[****]
Site Visits - Pre-study Visits	[****]	[****]	[****]	[****]	[****]
Site Visits - Initiation Visits	[****]	[****]		[****]	[****]

Task

Current

(US Dollars)

Start Up Work

in [****] and [****]

Change

Assumption Changes

influencing the change

in the budget

Additional comments

Site Visits - Routine Visits conducted on site	[****]	[****]		[****]	[****]
Site Visits - Close-out Visits at each site at Study End	[****]	[****]		[****]	[****]
Study Master File/Project File Set-up and Maintenance	[****]	[****]		[****]	[****]
Patient/Site Recruitment	[****]	[****]		[****]
Client/CRO meeting	[****]	[****]		[****]
Regulatory
Regulatory Documentation Preparation/Review	[****]	[****]	[****]	[****]	[****]
Project Management /Project Tracking
Financial Project Management	[****]	[****]		[****]
Project Management	[****]	[****]	[****]	[****]	[****]

Task

Current

(US Dollars)

Start Up Work

in [****] and [****]

Change

Assumption Changes

influencing the change

in the budget

Additional comments

Project Tracking / Communications	[****]	[****]	[****]
Vendor Management	[****]	[****]	[****]	[****]
Data Management
Database Archiving	[****]	[****]	[****]
Data Cleanup (DM)	[****]	[****]	[****]
Data Management: Database Quality Control Inspection	[****]	[****]	[****]
Database Design	[****]	[****]	[****]	[****]
Dictionary Coding	[****]	[****]	[****]
Edit Check Programming	[****]	[****]	[****]
Electronic Data Import	[****]	[****]	[****]
Case Report Form Data/Document Transfers	[****]	[****]	[****]
EDC Fees	[****]	[****]	[****]
Statistical Analysis and Table Generation
Electronic Data Transfer	[****]	[****]	[****]
Interim Analysis/Report Preparation and Review	[****]	[****]	[****]
Statistical Analysis Plan Preparation/Review	[****]	[****]	[****]
Table Generation	[****]	[****]	[****]
Table/Listings Review	[****]	[****]	[****]

Task

Current

(US Dollars)

Start Up Work

in [****] and [****]

Change

Assumption Changes

influencing the change

in the budget

Additional comments

Clinical Study Report
Clinical Study Report Preparation/Review	[****]	[****]		[****]
Team Meetings
Project Team Meetings - Internal Meetings	[****]	[****]	[****]	[****]	[****]
Project Team Meetings - Client Teleconferences	[****]	[****]		[****]
Project Team Meetings - Kick-off Meeting	[****]	[****]		[****]
Total Direct Costs	[****]	[****]

Total Costs

Category	Total Costs($)
Category	Current Contract (USD)	Change in Scope # 4 (USD)	Revised Total (USD)
Pass-Through Costs	[****]	[****]	[****]
Investigator Grants Costs	[****]		[****]
Professional Fees	[****]	[****]	[****]
Discount	[****]	[****]	[****]
Revised Professional Fees	[****]	[****]	[****]
Grand Total	[****]	[****]	[****]

Exhibit B Payment Schedule

1. PAYMENT TERMS

A. Service Fees:

[****]

2. Pass Through Costs:

(a)

CO#2: [****] of the average estimated expenses as set forth in the Expenses Estimate (exclusive of funds for investigator grants), totaling [****], will be due and payable upon execution of this Agreement. Prepayment for Out of Pocket Expenses (to be drawn down once paid and replenished once 75% depleted). This process to continue until the end of the study.

(a)

CO#3: [****] of the average estimated expenses as set forth in the Expenses Estimate (exclusive of funds for investigator grants), totaling [****], will be due and payable upon execution of this Agreement. Prepayment for Out of Pocket Expenses (to be drawn down once paid and replenished once 75% depleted). This process to continue until the end of the study.

(b)	CO#4: This is a one time payment of [****] (exclusive of funds for investigator grants), that will be due and payable upon execution of this Agreement.

(c)	Actual pass-through expenses, as provided in the expenses estimate, will be billed as incurred by inVentiv Health Clinical

(d)	Any unused funds will be returned within ninety (90) days from the date of the final reconciliation

3. Investigator Grants:

(a)

[****]

(b)	inVentiv Health Clinical will submit invoices in advance for estimated amounts to be paid to investigators during the next quarter to ensure that adequate funds are available to pay investigator grants

(c)	inVentiv Health Clinical will not make payments to investigators without having sufficient funds available in advance.

(d)	Any unused funds will be returned within ninety (90) days from the date of the final reconciliation

4. Payment Conditions:

(a)	For all Services, pass through expenses and investigator grants invoiced, payments are due net thirty (30) days from invoice date as set forth in Terms, Item 2 of the Agreement. In the event of a dispute, all undisputed portions of the invoice(s) are due within the above stated terms

(b)	Payments shall be made in the currency identified above and shall be made free of any applicable local withholding taxes, charges or remittance fees. Invoices will be inclusive of applicable taxes as determined by local laws and regulations

(c)	inVentiv Health Clinical reserves the right to charge interest against any unpaid overdue balance at the rate of [****]

(d)	All services and pass-through payments should be sent via wire or ACH

(e)	All services and pass-through payments should be sent via wire or ACH