Continued mechanistic dose response observed
following completion of 3 mg/kg dose level based on urinary
biomarker analyses
Percent change from baseline in PC1 and PC2
demonstrated a dose response across all doses tested, with
statistical significance seen at 3 mg/kg compared to
placebo
Exploratory imaging analyses indicated
reduction in total kidney volume in 70% of patients dosed with 3
mg/kg
Fourth cohort enrollment
underway
Company to hold conference call at
8:30am ET today
SAN
DIEGO, June 24, 2024 /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
positive topline results from the third cohort of patients in its
Phase 1b MAD study of RGLS8429 for
the treatment of ADPKD.
The Phase 1b MAD study is a
double-blind, placebo-controlled trial evaluating the safety,
tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of
RGLS8429 in adult patients with ADPKD. The study is evaluating
RGLS8429 treatment across three different weight-based dose levels
and one fixed dose level, including measuring changes in urinary
polycystins 1 and 2 (PC1 and PC2), htTKV, cyst architecture, and
overall kidney function. PC1 and PC2 are the protein products of
the PKD1 and PKD2 genes and have been shown to inversely correlate
with disease severity. Enrollment in the fourth cohort, which will
include up to 30 patients, has been initiated and patients will
receive an open label fixed dose of 300 mg of RGLS8429 every other
week for three months. In addition to PC1 and PC2 and safety,
imaging biomarkers will also be evaluated.
In the third cohort, 16 subjects were randomized 3:1 to receive
either 3 mg/kg of RGLS8429 or placebo every other week for three
months.
- RGLS8429 was well tolerated with no safety concerns
- Continued evidence of a mechanistic dose response was observed
following completion of 3 mg/kg dose level based on urinary PC1 and
PC2
- 3 mg/kg demonstrated more consistent increases in PC1 and PC2
across patients compared to earlier cohorts
- Percent change from baseline in PC1 and PC2 demonstrated a dose
response across all doses tested, with statistical significance
seen at 3 mg/kg compared to placebo
- Exploratory MRI imaging analysis suggested RGLS8429 reduced
htTKV at 3 mg/kg after 3 months of dosing
- 70% of subjects demonstrated reductions in htTKV following
completion of 3 mg/kg dose level
"We are pleased to see the consistent mechanistic response and
reduction in htTKV at the 3mg/kg dose level of RGLS8429 along with
an appropriate safety and tolerability profile," said Preston Klassen, M.D., President and Head of
Research & Development. "These data support our ongoing
and final 300 mg fixed dose cohort in this Phase 1b trial. We believe the data from this study
will form the basis for a potentially pivotal Phase 2/3 study of
RGLS8429 under an Accelerated Approval regulatory pathway to be
discussed with the FDA."
"Building on the positive results from our first two cohorts,
these cohort 3 data, particularly the reduction in htTKV seen in
the majority of patients, further strengthen our conviction in
RGLS8429's ability to potentially address the underlying, genetic
cause of ADPKD," said Jay Hagan, CEO
of Regulus Therapeutics. "We anticipate requesting an End-of-Phase
1 meeting with the FDA in the fourth quarter of this year and look
forward to providing a data update from the open-label fourth and
final cohort of the Phase 1b MAD
study by year-end."
More information about the MAD clinical trial is available at
clinicaltrials.gov (NCT05521191).
Conference Call Information
The Company will host a
conference call and live audio webcast on June 24,
2024, at 8:30am Eastern Time. To access the call, please
dial 1-833-816-1394 (domestic) or 1-412-317-0487
(international). The live webcast can be found under "Events
and Presentations" through the investor relations section of the
Company's website. To access the telephone replay of the call, dial
1-877-344-7529 (domestic) or 1-412-317-0088 (international),
passcode ID 6325389. The webcast and telephone replay will be
archived on the Company's website at
www.regulusrx.com following the call.
About ADPKD
Autosomal dominant polycystic kidney
disease (ADPKD), caused by 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. Approximately
160,000 individuals are diagnosed with the disease in the United States alone, with an estimated
global prevalence of 4 to 7 million.
About RGLS8429
RGLS8429 is a novel, next generation
oligonucleotide for the treatment of ADPKD designed to inhibit
miR-17 and to preferentially target the kidney. Administration of
RGLS8429 has shown clear improvements in kidney function, size, and
other measures of disease severity in preclinical models. Regulus
announced completion of the Phase 1 SAD study in September 2022. The Phase 1 SAD study
demonstrated that RGLS8429 has a favorable safety and PK profile.
RGLS8429 was well-tolerated with no serious adverse events reported
and plasma exposure was approximately linear across the four doses
tested. In the Phase 1b MAD study
Regulus announced topline data from the first cohort of patients in
September 2023, from the second
cohort of patients in March 2024 and
from the third cohort of patients in June
2024. Regulus initiated enrollment in the fourth cohort of
patients in May 2024. Patients in the
fourth cohort will receive an open label, 300 mg fixed dose of
RGLS8429 administered every other week for three months.
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 Company's RGLS8429 program and preclinical
pipeline, the potential that RGLS8429 may be eligible for an
Accelerated Approval pathway, the expected timing for reporting
topline data, and the timing and future occurrence 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, the risk that the
approach we are taking to discover and develop drugs is novel and
may never lead to marketable products, that preliminary or topline
results are based on a preliminary analysis of key efficacy and
safety data, and such data may change following a more
comprehensive review of the data related to the clinical trial and
may not be indicative of future results, the FDA has not designated
RGLS8429 for an Accelerated Approval pathway and such designation
may not lead to a faster development, regulatory review or approval
process and does not increase the likelihood that RGLS8429 will
receive marketing approval, the risk that preclinical and clinical
studies may not be successful, risks related to regulatory review
and approval, risks related to our reliance on third-party
collaborators and other third parties, risks related to
intellectual property, risks associated with the process of
discovering, developing and commercializing drugs that are safe and
effective for use as human therapeutics, the risk that additional
toxicology data may be negative, and risks related to our ability
to successfully secure and deploy capital. These and other risks
are described in additional detail in Regulus' filings with the
Securities and Exchange Commission, including under the "Risk
Factors" heading of Regulus' quarterly report on Form 10-Q for the
quarter ended March 31, 2024. 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.