Regulus Provides Update on Road to the Clinic Strategy and Reports First Quarter 2013 Financial Results and Recent Highlights -Nominated RG-101 in HCV as First microRNA Candidate for Clinical Development- -Maintained Str

Regulus Provides Update on Road to the Clinic Strategy and Reports

First Quarter 2013 Financial Results and Recent Highlights

-Nominated RG-101 in HCV as First microRNA Candidate for Clinical Development-

-Maintained Strong Financial Position with Over $90 million in Cash-

May 14, 2013 - Regulus Therapeutics Inc. (NASDAQ:RGLS), a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs, today provided an update on its microRNA therapeutic

pipeline under the company s Road to the Clinic strategy and reported financial results for the quarter ended March 31, 2013.

Regulus Continues to Execute on Road to the Clinic Strategy:

RG-101 as First microRNA Candidate for Clinical Development

The nomination of RG-101 as our first

microRNA candidate for clinical development marks a tremendous milestone for Regulus and represents significant achievement of our initial goals under our Road to the Clinic strategy, said Kleanthis G. Xanthopoulos, Ph.D.,

President and CEO of Regulus. We continue to focus our efforts on preparing for a successful transition to a clinical-stage company and remain on track to nominate our second microRNA candidate for clinical development by the end of the year.

Our recent progress is encouraging and we look forward to realizing the potential that our microRNA technology may have in transforming the field of drug discovery.

Neil W. Gibson, Ph.D., Chief Scientific Officer, added, We believe that RG-101 is a novel, pan-genotypic agent that may play an important role in future HCV therapy. We are very encouraged by the

pre-clinical data seen to date, which includes activity against some of the known mutations that lead to resistance to the current HCV therapies and a favorable potency and PK

profile which supports a once a month dosing paradigm. We believe that RG-101 may be useful in difficult-to-treat HCV patients in combination with existing and emerging therapies and we look

forward to exploring its clinical utility.

Garry E. Menzel, Ph.D., Chief Operating Officer and Executive Vice President of Finance,

said, As we prepare for clinical activity with RG-101, Regulus continues to maintain a strong financial position with over $90 million in cash at quarter-end. We remain on track to achieve our stated goals of finishing 2013 with at least $60

million in cash, while maintaining a burn rate of approximately $30 million to $35 million.

First Quarter 2013 Financial Results & Highlights

Regulus reported a net loss of $7.2 million for the quarter ended March 31, 2013, compared to a net loss of $2.2 million for the quarter ended March 31, 2012. The quarter ended

March 31, 2013, included non-cash charges of $1.8 million from the change in value of the amended and restated convertible promissory note originally issued to GlaxoSmithKline in 2010, which was attributable to increases in value of the

underlying common stock of the Company since December 31, 2012. Basic and diluted net loss per share was $0.20 for the quarter ended March 31, 2013, compared to net loss per share of $13.06 for the quarter ended March 31, 2012. The

comparison of net loss per share for the periods presented is impacted by the initial public offering and concurrent common stock issuances in October 2012.

Regulus recognized revenue of $3.2 million for the quarter ended March 31, 2013, compared to $3.3 million for the quarter ended March 31, 2012. Revenue during these periods consisted

primarily of amortization of up-front payments received from our strategic alliances and collaborations, which is recognized over the estimated period of performance.

Research and development expenses were $6.9 million for the quarter ended March 31, 2013, compared to $4.6 million for the quarter ended March 31, 2012. The increase is attributable to an

expansion of our research and development team, expertise and capabilities, in addition to increasing pre-clinical study activities in the first quarter of 2013, compared to the same period in 2012.

General and administrative expenses were $1.9 million for the quarter ended March 31, 2013, compared to $0.9 million for the quarter ended

March 31, 2012. The increase is attributable to costs associated with increases related to additional personnel required to support the growth of the business, in addition to an increase in overall operating costs associated with being an

SEC registrant in the first quarter of 2013, compared to the same period in 2012.

As of March 31, 2013, Regulus had $90.7 million in cash, cash equivalents and short-term investments,

debt with a principal balance of $5.4 million and approximately 36 million shares of common stock outstanding. The Company expects its current cash position to be sufficient to fund operations into 2016 and to finish 2013 with at least

$60.0 million in cash, cash equivalents and short-term investments.

Conference Call & Webcast Information

Regulus will host a conference call and webcast at 5:00 p.m. Eastern Daylight Time today for an update on the Road to the Clinic Strategy and

to discuss its first quarter 2013 financial results and recent highlights. A live webcast of the call will be available online at www.regulusrx.com. A replay will also be available approximately one hour after completion of the call. To

access the replay, dial (855) 859-2056 (domestic) or (404) 537-3406 (international), passcode 59485223. The webcast and replay will be archived on the company s website following the call.

About the Road to the Clinic Strategy in 2013

Launched in February 2013, the Road to the Clinic Strategy outlines certain corporate goals that seek to advance our microRNA therapeutic pipeline toward the clinic this year. Specifically,

Regulus set the goal of nominating two microRNA candidates for clinical development in 2013. We announced the first candidate today as RG-101 for the treatment of HCV. The company also expects to file its first applications with regulatory

authorities in 2014, with the first being for RG-101 in early 2014. In order to achieve these stated goals and advance our programs toward clinical development, Regulus expects to maintain its strong financial position and end 2013 with at least $60

million in cash, cash equivalents and short-term investments.

Regulus Therapeutics Inc. (NASDAQ:RGLS) is a biopharmaceutical company leading the discovery and development of innovative medicines targeting microRNAs. Regulus is leveraging a mature therapeutic

platform based on technology that has been developed over 20 years. Regulus works with a broad network of academic collaborators and leverages the oligonucleotide drug discovery and development expertise of its founding companies, Alnylam

Pharmaceuticals and Isis Pharmaceuticals. Regulus has nominated RG-101 for the treatment of HCV as a candidate for clinical development and is advancing other microRNA therapeutics toward clinical development in several areas, including oncology,

fibrosis and metabolic diseases. Regulus has formed strategic alliances with AstraZeneca, GlaxoSmithKline and Sanofi and a research collaboration with Biogen Idec.

For more information, please visit http://www.regulusrx.com.

Statements contained in this press release regarding matters that are not historical facts are forward-looking

statements within the meaning of the Private Securities Litigation Reform Act

of 1995, including statements associated with financial estimates, the projected sufficiency of Regulus capital position for future periods, the expected ability of Regulus to undertake

certain activities and accomplish certain goals, the projected timeline of clinical development activities, and expectations regarding future therapeutic and commercial potential of Regulus business plans, technologies and intellectual

property related to microRNA therapeutics being discovered and developed by Regulus. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking

statements. Words such as believes, anticipates, plans, expects, intends, will, goal, potential and similar expressions are intended to identify

forward-looking statements. These forward-looking statements are based upon Regulus current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ

materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks associated with the process of discovering, developing and commercializing drugs that are

safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. These and other risks concerning Regulus financial position and programs are described in additional detail in Regulus

SEC filings. All forward-looking statements contained in this press release speak only as of the date on which they were made. Regulus undertakes no obligation to update such statements to reflect events that occur or circumstances that exist

after the date on which they were made.

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