Exhibit 4.4

Confidential

THE SYMBOL “[****]” DENOTES PLACES WHERE CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THE EXHIBIT BECAUSE IT IS BOTH (i) NOT MATERIAL, AND (ii) WOULD LIKELY CAUSE COMPETITIVE HARM TO THE COMPANY IF PUBLICLY DISCLOSED

AMENDMENT NO. 1 TO AGREEMENT

This Amendment No.1 to Agreement is made as of February  26, 2018  (the “ Amendment Effective Date ”) by and between RedHill Biopharma Ltd. (“ RedHill ”) and Salix Pharmaceuticals, Inc. (“ Salix ”).

WITNESETH

WHEREAS, RedHill and Salix have entered into that certain Agreement dated February 27, 2014 (the “ Agreement ”); and

WHEREAS, [****] and the Parties desire to amend the Agreement to reflect certain changes to the Agreement;

NOW, THEREFORE , in consideration of the mutual promises and covenants set forth herein, the Parties hereby agree as follows:

1.           All terms not otherwise defined herein shall have the meaning ascribed thereto in the Agreement, unless the context requires otherwise.

2.           RedHill hereby [****] of the Agreement pursuant to [****] and the Parties agree that the Agreement shall be [****].

3.           In consideration for the covenants, agreements and undertakings made herein, the receipt and sufficiency of which is hereby acknowledged, RedHill (for itself and each of its successors, assigns, parents, subsidiaries, affiliates, attorneys, agents, employees, directors, officers, representatives, or any persons or entities acting on its behalf) hereby releases and discharges Salix from and against any and all claims, liabilities or damages, whether known or unknown, whether present or future, that RedHill had, has or may have against Salix, and hereby waives any right RedHill may have [****],  in each case, relating to or arising out of any [****] of the Agreement, from the beginning of time through the Amendment Effective Date.

4.           Other than with respect to the releases expressly detailed in Section 3 of this Amendment, nothing herein shall prejudice any rights and remedies conferred [****] in accordance with its terms following the Amendment Effective Date.

5.           In accordance with Section 13.7 of the Agreement, the Agreement is hereby amended as follows:

5.1.         Article 1 is hereby amended to include the following definitions:

“ Commercially Reasonable Efforts ” shall mean, with respect to the efforts and resources to be expended by a Party with respect to any objective or activity under this Agreement, [****] .

“ Development Plan ”  shall mean the development plan prepared by Salix setting out Salix’s plan to Develop [****] , as such plan may be amended from time to time by Salix [****] , which development plan (and any amendments thereto) shall be provided to RedHill promptly upon completion and, in the case of the initial Development Plan, no later than [****] following the Amendment Effective Date.”

5.2.      Article 3.7.2 is hereby deleted in its entirety and replaced with the following:

“3.7.2     Without limiting the provisions of Section 3.7.1, the Parties acknowledge and agree that, other than as set out in Sections 5.4 and 12.3, Salix has no obligation to Develop or Commercialize any Licensed Product or any obligation to satisfy the conditions to the milestone payments set forth in Section 6.2 or to achieve any particular level of additional consideration or other payments (or additional consideration or other payments payable to Redhill under Section 6.3).”

5.3.      Article 5 is hereby amended by the addition of the following after Section 5.3:

“5.4 Development Diligence . Salix shall use Commercially Reasonable Efforts to pursue the Development of [****] in accordance with the Development Plan.”

5.4.      Section 6.3.1(c) is hereby amended by replacing [****].

5.5.      Section 7.1.1(c) is hereby deleted in its entirety and replaced with the following:

“(c) RedHill shall have the right to be actively involved in the maintenance of Licensed RedHill Patents and License RedHill Know-how. Salix shall provide RedHill with copies of all relevant documentation so that RedHill will be informed of the continuing preparation, filing, prosecution and maintenance of the Licensed RedHill Patents and may comment upon such documentation sufficiently in advance of any filing deadline. Salix shall consider in good faith any comments received from RedHill; provided, however, that if RedHill has not commented upon such documentation in a reasonable time for Salix to sufficiently consider RedHill’s comments prior to a deadline with the relevant government patent office, or Salix must act to preserve the Licensed RedHill Patents, Salix will be free to act without consideration of RedHill’s comments, if any. Salix shall keep RedHill fully informed with respect to any communications with any relevant governmental offices and (i) within [****] of Salix’s receipt thereof, provide to RedHill any written correspondence from any governmental office, and (ii) no later than [****] prior to the submission thereof provide to RedHill any proposed written correspondence to any governmental office, including copies of any and all underlying data to accompany any such correspondence. Salix shall consider in good faith any written comments received from RedHill with respect to such

correspondence prior to its submission; provided, however, that if RedHill has not commented upon such correspondence in a reasonable time for Salix to sufficiently consider RedHill’s comments prior to a deadline with respect to such correspondence, Salix will be free to act without consideration of RedHill’s comments, if any. Without derogating from the foregoing, at any time that Salix is not Developing [****] or the Development Plan does not contemplate the Development of [****] , Salix shall act in accordance with all comments provided by RedHill in connection with preparation, filing, prosecution and maintenance of the Licensed RedHill Patents, including in preparing any proposed written correspondence to any governmental office and otherwise act in accordance with RedHill’s patent and regulatory strategy as notified timely to Salix’s patent counsel in writing, in each case, unless Salix has a documented and compelling reason not to do so. All of the obligations of Salix set out in this Section 7.1.1(c) shall be subject to (and limited by) its obligations under Applicable Law and under its contractual commitments with any Third Party, including, but not limited to, its obligations of confidentiality and non-disclosure existing as of the Amendment Effective Date.”

5.6.      Section 12.3 is hereby deleted in its entirety and replaced with the following:

“12.3      Additional Termination Rights by RedHill.

12.3.1     In the event that Salix should, at any time during the period beginning [****] following the Effective Date and ending on the date [****] , not then be using Commercially Reasonable Efforts to pursue the Development of [****] in accordance with the Development Plan, then RedHill shall be entitled to give Salix notice requiring Salix to commence or resume using Commercially Reasonable Efforts to Develop [****] in accordance with the Development Plan and stating RedHill’s intention to terminate this Agreement if Salix fails to do so. For the avoidance of doubt, RedHill shall be entitled to give such notice more than once, but any such notice may be given only during the period beginning [****] and ending on the date on which [****] . If Salix fails to commence or resume using Commercially Reasonable Efforts to Develop [****] , and give notice of such commencement or resumption to RedHill, within [****] after its receipt of such notice (or, if relevant Development activities cannot reasonably be commenced or resumed within such [****] period, if Salix does not commence actions to commence or resume relevant Development activities, and give notice of such commencement to RedHill, within [****] period and thereafter diligently continue such actions or if in any event Salix has not commenced or resumed relevant Development activities, and given notice of such commencement or resumption to RedHill, within [****] after its receipt of such notice), then RedHill shall be entitled, by notice to Salix and without prejudice to any other rights conferred on RedHill by this Agreement and in addition to any other remedies available to RedHill at law or in equity, to terminate this Agreement forthwith.

12.3.2 Without derogating from the foregoing, in the event that Salix shall fail, for any reason,  and even if having used Commercially Reasonable Efforts to do so, to (i)   [****] (ii) [****] (as may be extended on mutual agreement of the Parties), then RedHill shall be entitled to give Salix notice requiring Salix to [****] and stating RedHill’s intention to terminate this Agreement if Salix fails to do so. For the avoidance of doubt, RedHill shall be entitled to give such notice more than once (but not for the same event resulting in Salix’ failure to comply with such matters), but any such notice may be given only during (and with respect to events occurring during) the period beginning on the Amendment Effective Date and ending on the date on which [****] . If Salix fails to [****] , in each case, within [****] after its receipt of such notice, then this Agreement shall terminate forthwith.  Such right of termination shall be RedHill’s sole remedy with respect to the breaches described in this Section 12.3.2.

6.           Except as specifically amended herein, the provisions of the Agreement shall continue in full force and effect.

[ signature page follows ]

IN WITNESS WHEREOF , the Parties have executed this Amendment as of the date first above written.

ANNEX A

[****]

Exhibit 4.6

Confidential

THE SYMBOL “[****]” DENOTES PLACES WHERE CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THE EXHIBIT BECAUSE IT IS BOTH (i) NOT MATERIAL, AND (ii) WOULD LIKELY CAUSE COMPETITIVE HARM TO THE COMPANY IF PUBLICLY DISCLOSED

Amendment #1  

To

EXCLUSIVE LICENSE AGREEMENT

Apogee Biotechnology Corporation

and

RedHill Biopharma Ltd

This Amendment is entered into effective as of the date of the last signature below (the "Effective Date") by and between RedHill Biopharma Ltd ("RedHill") and Apogee Biotechnology Corporation ("Apogee") to amend the terms of that Exclusive License Agreement entered into by the parties effective March 30, 2015 ("Agreement").

NOW, THEREFORE, the mutual covenants set forth herein, the parties agree to amend the terms of the Agreement as follows:

1.           Clause 6.2.1 is hereby modified to: [****] days following the earlier of (i) approval for the first Phase II clinical trial protocol submitted to the US FDA by or on behalf of RedHill and (ii) [****]: Two Million US Dollars ($2,000,000).

2.           All other terms of the Agreement are unchanged and remain in full force and effect.

WHEREFORE, the parties hereunto have caused this Amendment to be executed by their duly authorized representatives as of the date of the last party to sign to be effective and in agreement.

Exhibit 4.9

Confidential

THE SYMBOL “[****]” DENOTES PLACES WHERE CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THE EXHIBIT BECAUSE IT IS BOTH (i) NOT MATERIAL, AND (ii) WOULD LIKELY CAUSE COMPETITIVE HARM TO THE COMPANY IF PUBLICLY DISCLOSED

Amendment #4

To

EXCLUSIVE LICENSE AGREEMENT

Apogee Biotechnology Corporation

and

RedHill Biopharma Ltd

This Amendment is entered into effective as of the date of the last signature below (the “Effective Date”) by and between RedHill Biopharma Ltd (“RedHill”) and Apogee Biotechnology Corporation (“Apogee”) to amend the terms of that Exclusive License Agreement entered into by the parties effective March 30, 2015 (“Agreement”).

NOW, THEREFORE, the mutual covenants set forth herein, the parties agree to amend the terms of the Agreement as follows:

1.     Clause 6.2.1 is hereby modified to: [****] days following [****]: One Million US Dollars ($1,000,000). Additionally, [****] days following[****]: Five hundred thousand US Dollars ($500,000).

2.     Clause 6.3.1.1 is hereby modified to: A Royalty equal to [****].

3.     Clause 6.3.1.2 is hereby modified to: A Royalty equal to [****].

4.     Clause 6.3.2.1 is hereby modified to: A Royalty equal to [****].

5.     Clause 6.3.2.2 is hereby modified to: A Royalty equal to [****].

6.     Clause 6.3.3 is hereby modified to: A royalty equal to [****].

All other terms of the Agreement are unchanged and remain in full force and effect.

WHEREFORE, the parties hereunto have caused this Amendment to be executed by their duly authorized representatives as of the date of the last party to sign to be effective and in agreement.

Exhibit 4.12

Confidential

THE SYMBOL “[****]” DENOTES PLACES WHERE CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THE EXHIBIT BECAUSE IT IS BOTH (i) NOT MATERIAL, AND (ii) WOULD LIKELY CAUSE COMPETITIVE HARM TO THE COMPANY IF PUBLICLY DISCLOSED

AMENDMENT NO. 1 TO EXCLUSIVE COMMERCIALIZATION AGREEMENT

This Amendment No.1 to Exclusive Commercialization Agreement is made effective as of August 24, 2018 by and between RedHill Biopharma Ltd. (“ RedHill ”) and Concordia Pharmaceuticals Inc., by way of its Barbados branch (“ Concordia ”).

WITNESETH

WHEREAS, Concordia and RedHill entered into an Exclusive Commercialization Agreement dated December 30, 2016 (the “ Main Agreement ”);

WHEREAS, Concordia and RedHill desire to amend the Main Agreement;

NOW, THEREFORE , in consideration of the mutual promises and covenants set forth herein, the Parties hereby agree as follows:

1.           All terms not otherwise defined herein shall have the meaning ascribed thereto in the Main Agreement, unless the context requires otherwise.

2.           In accordance with Section 20.6 of the Main Agreement, the Main Agreement is amended as follows:

2.1.         Section 1.4 of the Main Agreement is hereby amended effective October 1, 2018 by the deletion of the second sentence thereof so that Section 1.4 in its entirety is as follows:

“1.4        “ Applicable Percentage ” means [****] ”

2.2.         The following provision shall be added to the Main Agreement as a new Section 9.6:

“Concordia shall pay RedHill two (2) one-time payments as follows: (i) $[****] to be paid on or before [****]; and (ii) $ [****] for [****] to be paid on or before [****].  In consideration for [****] RedHill: (i) has provided  [****]; and (ii) continue, until September 30, 2018,  Promotion and commercialization of the Product for the Field of Use (with the number of representatives throughout geographical territories)  substantially similar to that provided through the first half of 2018; subject, inter alia ,  to reassignment and prompt replacement of representatives and other ordinary course and commercially reasonable changes in the geographical territories.

2.3.         The following provision shall be added to the Main Agreement as the last sentence of Section 9.2:

“All amounts paid or payable by Concordia to RedHill pursuant to the applicable Quarterly Report shall, absent fraud or manifest error, be considered final and binding and shall not be subject to dispute or adjustment.”

3.           Except as specifically amended herein, the provisions of the Main Agreement shall continue in full force and effect.

4.           This Amendment No. 1 may be executed in any number of counterparts, each of which shall be deemed an original, but all of which shall constitute one and the same instrument.

IN WITNESS WHEREOF , the parties have executed this Amendment as of the date first above written.

THE SYMBOL “[****]” DENOTES PLACES WHERE CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THE EXHIBIT BECAUSE IT IS BOTH (i) NOT MATERIAL, AND (ii) WOULD LIKELY CAUSE COMPETITIVE HARM TO THE COMPANY IF PUBLICLY DISCLOSED

AMENDMENT TO EXCLUSIVE LICENSE AGREEMENT

This Amendment to the Exclusive License Agreement (the "Amendment') is entered into as of September 7, 2018 (the "Amendment Effective Date") by and between Entera Health, Inc., an Iowa Corporation, having an address at 2425 SE Oak Tree Court, Ankeny,  Iowa 50021 (the ''Licensor''), and RedHill Biopharma, Inc. a Delaware corporation, having an address at 8045 Arco Corporate Drive, Suite 120, Raleigh, North Carolina 27617, along with all Affiliates thereof (as defined in that certain Exclusive License Agreement dated as of April 4, 2017 between the parties hereto (the "Agreement")) ("Licensee") . Unless otherwise specifically defined in this Amendment, any term used in this Amendment which is defined in the Agreement shall have the meaning assigned to it in the Agreement.

WHEREAS, on August 16, 2018, [****] of the Agreement; and

WHEREAS, pursuant to Section 17.4 of the Agreement, Licensor may [****]; and

WHEREAS, the Licensee [****].

NOW, THEREFORE, in consideration of the premises and of the mutual covenants above, and for good and valuable consideration, the adequacy and sufficiency of which is hereby acknowledged, the parties agree as follows:

l.     Replacement of Section 1.6 :  The Agreement is hereby amended and modified by deleting Section 1.6 in its entirety and replacing such deleted section with a new Section 1.6 as set forth below:

1.6         "Contract   Year" shall mean: (a) until October 1, 2018, a period of twelve (12) successive months commencing on the RedHill Launch Date (as defined below); and (b) from and after October 1, 2018, each period of twelve (12) successive months.

2.     Addition of New Section 4.4 :  The Agreement is hereby amended and modified by adding a new Section 4.4 to the Agreement, as set forth below:

4.4         Licensee hereby agrees that the minimum amount of Licensed Product that Licensee shall purchase from Licensor in any one order shall comprise a [****] of Licensed Product, containing 30 sachets per box.

3.     Addition of New Section 4.5 : The Agreement is hereby amended and modified by adding a new Section 4.5 to the Agreement, as set forth below:

4.5         Licensee hereby agrees that, once per month, personnel of Licensee chosen at the full and sole discretion of the Licensee and who are intimately involved and familiar with Licensee's sales and commercialization efforts with respect to Licensed Product shall be available for, and participate in, monthly update teleconference calls, with personnel of Licensor. During such calls, Licensee personnel shall provide, within reason, monthly updates of sales efforts, progress, trends, forecasts, and the like, with respect to Licensed Product, and shall answer all questions reasonably related thereto submitted or asked by Licensor. The information and updates provided by Licensee shall include, without limitation, information and updates concerning the numbers of open territories, total prescriptions, new prescriptions, calls made, and sample calls made, in furtherance of the commercialization and sales activities for the Licensed Product. Licensee personnel shall participate on such calls for a duration reasonably requested by Licensor, up to one hour per monthly call. For the avoidance of any doubt, any and all operational decisions regarding the Licensed Product remain at the full and sole discretion of the Licensee and Licensor shall not intervene or attempt to intervene, in such decisions in any manner whatsoever.

4.     Replacement of Section 17.4 : The Agreement is hereby amended and modified by deleting Section 17.4 in its entirety and replacing such deleted section with a new Section 17.4 as set forth below:

17.4 Either of Licensor or Licensee may terminate this Agreement if Licensee fails to meet the Minimum Net Sales target in any Contract Year provided the terminating party delivers termination notice to the other party within [****] from the date Licensee notifies Licensor of an applicable failure. Either Licensor or Licensee may terminate this Agreement in the event of each and every such failure, and any failure to provide notice of termination within the timelines stipulated above in respect of any particular failure shall not preclude either party from later terminating such Agreement in respect of a later failure. Either Licensor or Licensee shall also be entitled to terminate this Agreement at any time, upon [****] prior written notice to the other party provided Licensor delivers termination notice to Licensee within [****] from the date Licensee provides the reports detailed below evidencing a failure to meet the sales targets provided below, if Licensee fails to meet any one or more of the following sales targets applicable to any one or more of the time periods as set forth below:

(a)   [****] of Licensed Product during [****].

(b)   [****] of Licensed Product during [****].

(c)   [****] of Licensed Product [****].

(d)   [****] of Licensed Product [****].

Termination of this Agreement shall constitute the only remedy Licensor is entitled to for such commercial failures described in this Section 17.4, with no further liability by Licensee whatsoever in  connection with such commercial failures.

Without limiting any other obligation of Licensee in this Agreement, Licensee shall provide reports of all

sales of Licensed Product made during each calendar quarter sufficient to enable Licensor to determine whether Licensee has met the foregoing sales milestones within [****] during the Contract Term.

5.     Replacement of Section 17.8 (a) : The Agreement is hereby amended and modified by deleting Section 17.8(a) in its entirety and replacing such deleted section with a new Section 17.8(a) as set forth below:

(a)          Within  [****] before the Expiration Date or within [****] after the Termination Date, Licensee shall provide Licensor with a statement indicating the number and description of Licensed Products which it has on hand as of the date of expiration or termination and the amount of such inventory necessary to fill Licensee's existing customer orders with such documentation provided to Licensor. Licensee shall have the right to sell Licensed Products it has on hand to fulfill Licensee's existing customer orders, as aforesaid, under the License, subject to payment of Royalties. Furthermore, Licensee shall have the option, exercisable upon notice to Licensor within [****]following the date of expiration or termination, to require Licensor to repurchase from Licensee all such remaining Licensed Products (or the part thereof that is not needed to fulfill Licensee's existing customer orders, as aforesaid) that are in a sellable condition, meaning that all such Licensed Products: (i) are undamaged, unopened, unadulterated, unmodified, and in substantially identical condition as when such Licensed Products arrived at the Licensee's facilities; and (b) have at least [****] remaining shelf-life, at the price paid by Licensee. In the event that any such remaining Licensed Products bear, incorporate, or embody any trademarks or other intellectual property rights of Licensee, Licensee hereby grants a perpetual, irrevocable, non-exclusive, worldwide, royalty-free, fully paid up, assignable, sublicensable license to Licensor to undertake any and all actions, including, without limitation, to sell and offer to sell such remaining Licensed Products bearing or incorporating such Licensee intellectual property rights, with respect to such remaining Licensed Products solely to the extent reasonably necessary, convenient, or advisable to enable Licensor to undertake any and all sales and commercialization activities for such remaining Licensed Products.

6.    Entire Agreement: This Amendment, together with the Agreement, constitutes the entire agreement between the parties with respect to the subject matter of the Agreement, as amended by this Amendment. The Agreement, together with this Amendment supersedes all prior agreements, whether written or oral, with respect to the subject matter of the Agreement, as amended, provided that nothing herein shall affect the Supply Agreement or any other document or instrument referenced in the Agreement, except as modified herein. Each party confirms that it is not relying on any representations, warranties or covenants of the other party except as specifically set out in the Agreement as amended. The parties hereby agree that subject to the modifications specifically stated in this Amendment, all terms and conditions of the Agreement shall remain in full force and effect. This Amendment shall be governed by the same choice of law and subject to the same venue and dispute resolution provisions as set forth in the Agreement.

[Signature Page Next Page]

IN WITNESS WHEREOF, the parties have entered into this Amendment to the Exclusive License Agreement as of the Amendment Effective Date by their duly authorized representatives.