Positive Preclinical Profile of RG-101, a GalNAc-conjugated anti-miR Targeting microRNA-122, Supports Clinical Development for

Positive Preclinical Profile of RG-101, a GalNAc-conjugated anti-miR Targeting
     microRNA-122, Supports Clinical Development for the Treatment of HCV

- Late-Breaking Poster to be Presented at AASLD -

- Regulatory Application for RG-101 to be Filed in the Near Term: Clinical
Studies in Man Expected to Commence in Early 2014 -

PR Newswire

LA JOLLA, Calif., Nov. 4, 2013

LA JOLLA, Calif., Nov. 4, 2013 /PRNewswire/ -- Regulus Therapeutics Inc.
(NASDAQ: RGLS), a biopharmaceutical company leading the discovery and
development of innovative medicines targeting microRNAs, today announced that
data demonstrating the positive preclinical profile of RG-101 will be
presented in a late-breaking poster session at the 64th Annual Meeting of the
American Association for the Study of Liver Disease (AASLD) being held in
Washington, D.C. on Monday, November 4, 2013 from 8:00 a.m. Eastern Standard
Time (EST) to 5:30 p.m. EST. The poster is available on the Company's website
at http://www.regulusrx.com.

"RG-101 utilizes a unique mechanism of action by targeting microRNA-122, a
liver-specific host factor for stability, replication and translation of HCV.
We believe that therapies that target host-encoded factors essential for HCV
replication may act as attractive combination agents because they may
demonstrate activity across all HCV genotypes and may have a high barrier to
resistance," said Neil W. Gibson, Ph.D., Chief Scientific Officer of Regulus.
"We continue to be encouraged by the preclinical data seen to date and believe
that RG-101 has the potential to be a best-in-class host factor agent. In the
near term, we expect to file our application with regulatory authorities and
look forward to commencing clinical trials in man in early 2014."

Late-Breaking Poster on RG-101 – Monday, November 4, 2013, 8:00 a.m. EST –
5:30 p.m. EST

-RG-101, a GalNAc-conjugated anti-miR Employing a Unique Mechanism of Action
by Targeting Host Factor MicroRNA-122 (miR-122), Demonstrates Potent Activity
and Reduction of HCV in Preclinical Studies-

In the late-breaking poster, Regulus will present positive data from completed
preclinical studies evaluating RG-101 for in vitro and in vivo potency,
pharmacokinetic/pharmacodynamics, toxicology and safety pharmacology and
inhibition of HCV replication.

Potency and Pharmacokinetics/Pharmacodynamics of RG-101

Pharmacologic potency of RG-101 was significantly enhanced by approximately 20
fold in vivo in both mice and non-human primates, relative to the unconjugated
oligonucleotide of RG-101 (RG-101-N). RG-101 is rapidly taken up in the liver
and metabolized to the active oligonucleotide, which has an approximately 14
day tissue half-life. Additionally, potency as measured by AldoA (a miR-122
target gene) de-repression in the liver is achieved at significantly lower
liver concentrations of oligonucleotide following efficacious doses of RG-101
of 1mg/kg-10mg/kg, compared to similar doses of RG-101-N. In addition to the
potency studies, Regulus tested the efficacy of RG-101 to reduce HCV viral
load titer in a human chimeric liver mouse model infected with HCV, as these
mice are estimated to contain greater than 80 percent human hepatocytes.
Genotype 1a HCV infected mice were subcutaneously administered a single dose
of RG-101 at 3 mg/kg, 10mg/kg or 30 mg/kg and monitored for up to 36 days. Up
to a 2 log reduction in HCV viral load titer was observed, which is similar to
that observed for oral direct-acting antivirals as monotherapy in this mouse
model. Additionally, the duration of action observed for RG-101 supports the
potential for a once-a-month dosing regimen.

Regulus believes these preclinical data will assist the Company in determining
the most efficacious dose of RG-101, including optimal dosing frequency, for
clinical studies in man.

Toxicology and Safety Pharmacology of RG-101

RG-101 has demonstrated an excellent preclinical safety profile to date, with
no findings observed up to 450 mg/kg in mice and 45 mg/kg in non-human
primates. AldoA levels in non-human primates were maximally elevated at 1
mg/kg. These data demonstrate that RG-101 is safe and well tolerated with a
high therapeutic index. Additionally, these data provide support that the
chemistry and conjugation approach for RG-101 may mitigate the potential for
pro-inflammatory effects.

Currently, additional preclinical toxicology and safety pharmacology studies
are ongoing in which multiple doses of RG-101 are being evaluated.

About RG-101 for the Treatment of HCV

RG-101 is a key program in Regulus' 'Road to the Clinic' Strategy for 2013, in
which the Company expects to nominate two microRNA candidates for clinical
development, be positioned to file its first applications with regulatory
authorities by the first half of 2014 and maintain a strong year-end cash
position to support these goals. RG-101 was the first microRNA candidate
nominated for clinical development under this strategy.

microRNA-122 (miR-122) is the most abundant microRNA in hepatocytes and is a
critical host factor for survival and replication of all know HCV genotypes.
RG-101 is a novel anti-miR-122 oligonucleotide therapeutic that is effectively
targeted to hepatocytes for the treatment of HCV through conjugation to
GalNAc, a carbohydrate-based chemistry approach for asialoglycoprotein
receptor-mediated delivery of oligonucleotides to hepatocyte cells of the
liver. Utilizing the GalNAc conjugate chemistry has significantly improved the
potency of the active oligonucleotide of RG-101 by achieving targeted delivery
of the oligonucleotide to the infected hepatocytes. Given its attractive
properties and positive preclinical profile seen to date, Regulus believes
that RG-101 may be an attractive agent to add to existing HCV therapeutic
regimens. The Company plans to develop RG-101 as a key component of an HCV
combination regimen for patients who have failed, or are intolerant of, the
current standard of care and specific patient populations such as HCV/HIV
co-infection. In the near term, Regulus expects to submit an application with
regulatory authorities and to commence clinical studies in man in early 2014.

About Regulus

Regulus Therapeutics Inc. (NASDAQ:RGLS) is a biopharmaceutical company leading
the discovery and development of innovative medicines targeting
microRNAs.Regulus is uniquely positioned to leverage a mature therapeutic
platform that harnesses the oligonucleotide drug discovery and development
expertise of Alnylam Pharmaceuticals, Inc. and Isis Pharmaceuticals, Inc.,
which founded the company. Regulus has a well-balanced microRNA therapeutic
pipeline entering clinical development, an emerging microRNA biomarkers
platform to support its therapeutic programs, and a rich intellectual property
estate to retain its leadership in the microRNA field. Regulus intends to
focus its proprietary efforts on developing microRNA therapeutics for oncology
indications and orphan diseases and is currently advancing several programs
toward clinical development in oncology, fibrosis and metabolic diseases.
Regulus is also developing RG-101, a GalNAc-conjugated anti-miR targeting
microRNA-122, for the treatment of chronic hepatitis C virus infection.
Regulus' commitment to innovation and its leadership in the microRNA field
have enabled the formation of strategic alliances with AstraZeneca,
GlaxoSmithKline and Sanofi. In addition, Regulus has formed a research
collaboration with Biogen Idec around its emerging microRNA biomarkers

For more information, please visithttp://www.regulusrx.com.

Forward-Looking Statements

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 Regulus' expectations regarding future therapeutic and
commercial potential of Regulus' business plans, including the belief that
RG-101 is the best-in-class anti-HCV host factor agent and its expectations
regarding future clinical studies, and 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' 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.

SOURCE Regulus Therapeutics Inc.

Website: http://www.regulusrx.com
Contact: Amy Conrad, Director, Investor Relations and Corporate
Communications, aconrad@regulusrx.com, 858-202-6321; or Media: Liz Bryan,
Spectrum Science, lbryan@spectrumscience.com, 202-955-6222 x2526
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