AMBIT BIOSCIENCES CORPORATION SECOND WARRANT AMENDMENT AGREEMENT

Exhibit 4.15

AMBIT BIOSCIENCES CORPORATION

SECOND WARRANT AMENDMENT AGREEMENT

This SECOND WARRANT AMENDMENT AGREEMENT (this “Amendment”) is made as of October 25, 2012, by and among AMBIT BIOSCIENCES CORPORATION, a Delaware corporation (the “Company”) and the other parties set forth on the signature pages hereto (the “Holders”), each of whom is a party to either (a) that certain Series D-2 and Series D-3 Preferred Stock and Warrant Purchase Agreement, dated May 9, 2011, by and among the Company and the individuals and entities listed on the Schedule of Purchasers attached thereto (as amended from time to time, the “Purchase Agreement”) or (b) that certain Subscription Agreement, dated May 17, 2011, by and among the Company, Ambit Biosciences (Canada) Corporation (“Ambit Canada”) and GrowthWorks Canadian Fund Ltd. (as amended from time to time, the “Subscription Agreement”).

RECITALS

WHEREAS, Section 12 of each of the warrants issued pursuant to the Purchase Agreement and the Subscription Agreement, as applicable, (collectively, the “Warrants”) provides that any term of the Warrants may be amended or waived with the written consent of the Company and the holders of at least 60% of the outstanding Shares, including Apposite Healthcare Fund LP (the “Requisite Purchasers”); and

WHEREAS, the undersigned constitute the Requisite Purchasers and desire to amend the Warrants as set forth herein.

AGREEMENT

NOW, THEREFORE, for good and valuable consideration, the sufficiency of which is hereby acknowledged, the parties hereto agree as follows:

1. Section 7 of each Warrant is hereby amended to add the following sentence as the last sentence of such Section 7:

“Notwithstanding Section 2(a), in the event the Holder, or any of its Affiliates (as defined in Article IV, Section E.4(n) of the Company’s Amended and Restated Certificate of Incorporation filed with the Secretary of State of the State of Delaware on or about October 26, 2012 (as amended from time to time, the “Charter”)) becomes a Non-participating Purchaser, Non-participating Holder, Non-participating Canadian Purchaser or Defaulting Preferred Holder (each as defined in the Charter), this Warrant shall immediately terminate.”

2. This Amendment may be executed in any number of counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument.

3. This Amendment shall be governed by and construed under the laws of the State of California, as applied to agreements among California residents entered into and to be performed entirely within California.

4. Except as specifically amended by this Amendment, all other terms and conditions of the Warrants shall remain in full force and effect in accordance with their terms without modification.

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2.

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]

IN WITNESS WHEREOF, the parties hereto have executed the Amendment as of the date set forth in the first paragraph hereof.

[Signature Page to Second Warrant Amendment Agreement]