Letter Agreement, dated May 8, 2018, by and between the Registrant and AstraZeneca AB

AstraZeneca R&D Gothenburg ∙ SE-431 83 Mölndal ∙ Sweden

T: +46 31 776 10 00 ∙ F: +46 31 776 37 00 ∙ astrazenenca.com

Visitors: Pepparedsleden 1 ∙ Mölndal

Mr. Joseph Hagan

President and Chief Executive Officer

Regulus Therapeutics Inc.

10614 Science Center Dr.

San Diego, CA 92121

Confidential

May 8, 2018

Dear Mr. Hagan:

AstraZeneca requests to extend the Collaboration and License Agreement termination effective date by an additional twelve (12) months to allow AstraZeneca to complete all activities involving AZD4076. By the end of this 12-month extension, AstraZeneca and Regulus will complete the transfer activities contemplated by the agreement.

The new termination effective date pursuant to the extension will be June 8, 2019. Kindly confirm your acceptance of this extension by your signature below.

Sincerely,

/s/ Regina Frische-Danielson

__________________________

Regina Fritsch-Danielson, PhD

Vice President and Head of CVRM, Innovate Medicines and Early Development

ACCEPTED AND AGREED:

Regulus Therapeutics Inc.

/s/ Joseph Hagan

____________________________

By: Joseph Hagan

President and CEO