SAN DIEGO, May 21, 2021 /PRNewswire/ -- Regulus
Therapeutics Inc. (Nasdaq: RGLS), a biopharmaceutical company
focused on the discovery and development of innovative medicines
targeting microRNAs (the "Company" or "Regulus"), today announced
an incremental update from the first cohort of patients with ADPKD
in its ongoing Phase 1b clinical
trial of RGLS4326. The study is evaluating the safety,
pharmacokinetics, and effects on pharmacodynamic biomarkers of
multiple doses of RGLS4326 in patients with ADPKD.
In the first cohort, nine patients were enrolled and received 1
mg/kg of RGLS4326 subcutaneously every other week for four doses.
The mean increase in polycystins 1 and 2 at the end of study
compared to baseline levels for all nine patients in the first
cohort were 58% (p=.0004) and 38% (p=.026) respectively. As
disclosed earlier, treatment with RGLS4326 was generally
well-tolerated with no serious adverse events reported. All
reported adverse events were mild and generally transient in
nature. Regulus believes these data demonstrate that
RGLS4326 engages the target miR-17 leading to increased expression
of the PKD1 and PKD2 genes and the resultant increases in
polycystins' levels. Levels of polycystin 1 (PC1) and
polycystin 2 (PC2) have previously been shown to inversely
correlate with disease severity and are believed to be directly
linked to the underlying genetic drivers of the disease.
As previously announced, these data will be presented at the
Oppenheimer Rare & Orphan Disease Summit today, Friday, May 21, 2021 at 11:35am ET. The presentation will be archived on
the Company's website. Additional data from this first cohort
will be presented at PKD Connect in June
2021, and an abstract will be submitted to the American
Society of Nephrology annual meeting in November 2021.
"We are very encouraged by these results and look forward to
data from the second cohort in the third quarter" said Jay Hagan, CEO of Regulus. "As previously
reported, the ninth and final patient was trending well at the end
of the dosing period and saw their polycystin levels continue to
rise until study completion, twenty-eight days after the last dose.
This pattern was generally consistent across the first cohort and
further enhanced the overall mean changes from baseline for both
biomarkers."
About RGLS4326 Phase 1b
The Phase 1b is an adaptive
design, open-label, multiple dose study in up to three cohorts of
patients with ADPKD. The study is designed to evaluate the
safety, pharmacokinetics, and changes in levels of PC1 and PC2 in
patients with ADPKD administered RGLS4326 every other week for a
total of four doses. To characterize the effect of RGLS4326
within each cohort, biomarker values at the end of study are
compared to baseline values using a two-sided paired t-test.
P-values less than 0.05 are considered statistically significant
with no adjustment for multiplicity. The dose level for the first
cohort is 1mg/kg of RGLS4326 and the dose level for the second
cohort is 0.3mg/kg. The third and final cohort will be dosed
at a level to be determined based on the results of the first two
cohorts.
For more information about the clinical trial design, please
visit www.clinicaltrials.gov (NCT04536688).
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, reduction of cyst growth in human
in vitro ADPKD models, and attenuation of cyst proliferation
and improvement of kidney function in mouse models of
ADPKD. The RGLS4326 IND is currently on a partial clinical
hold for treatment of extended duration by FDA until the
second set of requirements outlined by the agency have been
satisfactorily addressed. The Company will use information from the
Phase 1 clinical studies, including the first cohort of the Phase
1b study together with information
from the recently completed additional nonclinical studies
generated in 2020, in its plan to address the second set of
requirements outlined in the partial clinical hold letter to
support studies of extended duration. Regulus plans to discuss its
approach to addressing the remaining partial clinical hold
requirements with FDA in mid-2021. RGLS4326 has received
orphan drug designation from FDA in July
2020.
About ADPKD
ADPKD, caused by the mutations in the PKD1 or PKD2 genes, is
among the most common human monogenic disorders and a leading cause
of end-stage renal disease. The disease is characterized by the
development of multiple fluid filled cysts primarily in the
kidneys, and to a lesser extent in the liver and other organs.
Excessive kidney cyst cell proliferation, a central pathological
feature, ultimately leads to end-stage renal disease in
approximately 50% of ADPKD patients by age 60.
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 San Diego,
CA.
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 clinical
activities concerning the RGLS4326 program, including the
preliminary biomarker, pharmacokinetic and safety data resulting
from the first cohort of patients from the ongoing clinical study,
the sufficiency of the data required to recommence clinical studies
for extended duration dosing, the timing of the Company's
interactions with FDA regarding the clinical hold and the timing
and of other preclinical and clinical activities. 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, and feedback from the FDA. In
addition, while Regulus expects the COVID-19 pandemic to adversely
affect its business operations and financial results, the extent of
the impact on Regulus' ability to achieve its preclinical and
clinical development objectives and the value of and market for its
common stock, will depend on future developments that are highly
uncertain and cannot be predicted with confidence at this time,
such as the ultimate duration of the pandemic, travel restrictions,
quarantines, social distancing and business closure requirements in
the U.S. and in other countries, and the effectiveness of actions
taken globally to contain and treat the disease. These
and other risks 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.
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SOURCE Regulus Therapeutics Inc.