EXHIBIT 4.9





AMENDMENT #2







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 TO THE MASTER SERVICE AGREEMENT
FOR REDHILL

BIOPHARMA LTD.’S RHB R&D PROGRAM










|BY AND BETWEEN: | RedHill Biopharma Ltd., with principle place of business at21 Ha’arba’a St. Tel-Aviv 64739, Israel(herein referred to as the “Client”),                                                                                                                                                          
|--------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
|                |                                                                                                                                                                                                                                                                                                  
|AND:            | 7810962 Canada Inc (doing Business under the name “InSymbiosis”), a body politic and corporate, duly incorporated according to the laws of Canada and with principle place of business at 245 Victoria Ave, Suite 100, Montreal, Quebec, H3Z 2M6, Canada, (herein referred to as the “Provider”),



The Client and the Provider are, in this
Agreement, sometimes individually referred to as “Party” and collectively as the “Parties”.



WHEREASon 28
April 2011,the Client and the Provider entered into a Master Service Agreement in relation to the Client’s RHB R&D
Program (the “MSA”);



WHEREASWHEREAS
the MSA was scheduled to terminate on April 28, 2013 and the parties hereby agree to formally extend the term of the MSA until
on April 28, 2015 (the "Extended Period"); and



WHEREASthe Parties
have agreed to certain terms and conditions, the whole as is fully set forth below.



NOW, THEREFORE, THE PARTIES HERETO AGREE
AS FOLLOWS:



| | 1. | Unless specifically set out otherwise in this agreement (the “AMENDMENT AGREEMENT”),
the terms of the MSA shall continue to apply.
| | -- | ----------------------------------------------------------------------------------------------------------------------------------



| | 2. | The parties hereby agree to formally extend the term of the MSA until April 28, 2015.
| | -- | -------------------------------------------------------------------------------------



| | 3. | The parties hereby agree that as per Section 7l of the MSA, [****] will replace [****] as clinical
project manager.
| | -- | -------------------------------------------------------------------------------------------------------------------



7810962 Canada Inc











| | 2 | 
| | - | 



| | 4. | During the term of the Agreement, PROVIDER will charge CLIENT a monthly project management fee
of $US[****]. This monthly project management fee will be payable each quarter, in advance, upon lawful invoice to be provided by
the PROVIDER to the CLIENT within 21 days of the beginning of the relevant quarter according to the following payment schedule:
| | -- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------



| | · | [****]
| | - | ------



IN WITNESS WHEREOF,
the parties hereto have executed this Amendment Agreement as of the date first herein above mentioned.



REDHILL BIOPHARMA
Ltd.



|/s/ Dror Ben-Asher |                | /s/Ori Shilo      
|------------------ | -------------- | ------------------
|Per:               | Dror Ben-Asher |                   
|Title:             | CEO            |                   
|Date: May 29, 2013 |                | Date: May 29, 2013



PARTY OF THE FIRST PART



7810962 Canada
Inc.



|/s/ Alain Guimond  |                            
|------------------ | ---------------------------
|Per:               | Alain Guimond              
|Title:             | Senior Director of Research
|Date: May 29, 2013 |                            



7810962 Canada Inc











| | 3 | 
| | - | 



PARTY OF THE SECOND PART



7810962 Canada Inc