LA JOLLA, Calif., Jan. 4, 2019 /PRNewswire/ -- Regulus Therapeutics
Inc. (Nasdaq: RGLS), a biopharmaceutical company focused on
the discovery and development of innovative medicines targeting
microRNAs, today announced the preliminary results of a planned
interim data analysis from the new mouse chronic toxicity study of
RGLS4326 in development for the treatment of Autosomal Dominant
Polycystic Kidney Disease, or ADPKD.
As previously reported by the Company in July 2018, and in consultation with FDA, the
Company voluntarily paused its ongoing Phase 1 Multiple Ascending
Dose ("MAD") study of RGLS4326 in healthy volunteers due to
unexpected observations in the 27-week mouse chronic toxicity
study. The Company terminated that mouse study prematurely at
week 14. The study was run in parallel to the Phase 1 program
to enable initiation of the Phase 2 program in ADPKD patients upon
completion of the Phase 1 MAD study. The observations from the
mouse chronic toxicity study were unexpected given the favorable
safety profile of RGLS4326 in previous 7-week non-GLP and GLP
toxicity studies in both mice and non-human primates required
for Phase 1 testing, which had no significant
findings across similar dose levels and frequencies.
Based upon the Company's investigation and the results announced
today, the Company believes the unexpected observations from the
previously terminated study were likely a result of technical
issues at the contract research organization ("CRO").
In September 2018, the Company
announced the initiation of a new 27-week mouse chronic toxicity
study, incorporating several changes intended to address the
unexpected observations in the previous mouse chronic toxicity
study. Certain key changes included the use of a different
CRO to conduct the study and the use of a new batch of
RGLS4326.
The planned interim analysis of this study after 13 weeks of
dosing has shown no adverse or other significant findings across
the range of doses tested and is intended to support re-initiation
of the Phase 1 MAD study after consultation with FDA.
RGLS4326 has also been generally well-tolerated in the Phase 1
Single Ascending Dose ("SAD") and MAD studies in human subjects to
date.
The Company plans to submit a comprehensive data package for
RGLS4326 to FDA that will include the results from the planned
13-week interim analysis of the ongoing repeat mouse chronic
toxicity study, as well as results from additional investigations,
analytical testing, additional data from the previously terminated
mouse chronic toxicity study, data from the completed Phase 1 SAD
study and data from the first cohort of the Phase 1 MAD
study. The Company anticipates engagement with FDA in the
coming weeks to discuss the resolution of the voluntary pause in
human dosing and the plan to resume the Phase 1 MAD
study.
"I am proud of the team at Regulus and the data package they
have assembled on RGLS4326," said Jay
Hagan, President and Chief Executive Officer of Regulus. "I
am pleased with the investigative work and encouraged by the
results of the planned interim analysis from this new mouse chronic
toxicity study. We look forward to engaging with FDA to discuss
this submission and the potential path forward to resuming the
clinical activities for this important program."
About Autosomal Dominant Polycystic Kidney Disease
(ADPKD)
ADPKD, caused by the mutations in the PKD1 or PKD2 genes, is
among the most common human monogenic disorders and a leading
genetic cause of end-stage renal disease. The clinical hallmark of
this disease is the development of multiple fluid filled cysts
primarily in the kidneys and to a lesser extent in the liver and
other organs. Excessive kidney tubule derived cyst cell
proliferation, a central pathological feature, fuels the expansion
of cysts, ultimately causing end-stage renal disease in
approximately 50% of ADPKD patients by age 60. Approximately 1 in
1,000 people bear a mutation in either PKD1 or PKD2 genes
worldwide.
About RGLS4326
RGLS4326 is a novel oligonucleotide designed to inhibit miR-17
and designed to preferentially target the kidney. Preclinical
studies with RGLS4326 have demonstrated direct regulation of PKD1
and PKD2 in human ADPKD cyst cells, a reduction in kidney cyst
formation, improved kidney weight/body weight ratio, decreased cyst
cell proliferation, and preserved kidney function in mouse models
of ADPKD.
About Regulus
Regulus Therapeutics Inc. (Nasdaq: RGLS) is a biopharmaceutical
company focused on the discovery and development of innovative
medicines targeting microRNAs. Regulus has leveraged its
oligonucleotide drug discovery and development expertise to develop
a pipeline complemented by a rich intellectual property estate in
the microRNA field. Regulus maintains its corporate
headquarters in La Jolla,
CA. For more information, please visit
http://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 the expected ability
of Regulus to undertake certain activities and accomplish certain
goals (including with respect to development and other activities
related to RGLS4326 and its ability to recommence human clinical
trials), the projected timeline of clinical development activities,
the anticipated engagement with the FDA regarding the
Regulus' RGLS4326 program and the timing thereof, and
expectations regarding future therapeutic and commercial potential
of Regulus' business plans, technologies and intellectual property
related to microRNA therapeutics and biomarkers 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 current shutdown of the U.S. Government, which may delay
or otherwise inhibit Regulus' ability to engage with FDA on matters
relating to RGLS4326; and 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 filings with the Securities and
Exchange Commission. 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.
View original content to download
multimedia:http://www.prnewswire.com/news-releases/regulus-announces-preliminary-results-of-planned-interim-data-analysis-of-rgls4326-in-new-mouse-chronic-toxicity-study-300773184.html
SOURCE Regulus Therapeutics Inc.