Topline data from an interim analysis of the
fourth cohort of its Phase 1b
Multiple-Ascending Dose (MAD) clinical trial showed continued
mechanistic dose response
Exploratory results of imaging-based
biomarkers continued to show reduction in height-adjusted total
kidney volume (htTKV) growth rate
Successful End-of-Phase 1 meeting with the
U.S. Food and Drug Administration (FDA) with agreement on key
components of a Phase 3 single pivotal trial for potential
Accelerated Approval
Company to hold conference call at
8:30 a.m. ET today
SAN
DIEGO, Jan. 29,
2025 /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 clinical and
regulatory updates from its ADPKD program. The update
includes positive topline results from an interim analysis of the
fourth cohort of its Phase 1b
Multiple Ascending Dose (MAD) study of farabursen (RGLS8429) for
the treatment of ADPKD and an overview on its recent successful
End-of Phase 1 meeting with the FDA.
The Phase 1b MAD study is a
double-blind, placebo-controlled trial evaluating the safety,
tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of
farabursen in adult patients with ADPKD. The study is evaluating
farabursen 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, and overall
kidney function. PC1 and PC2 are the protein products of the PKD1
and PKD2 genes and their levels have been shown to inversely
correlate with disease severity.
In the fourth cohort, 26 subjects received a fixed dose of 300
mg of farabursen every other week for three months. An interim
analysis of efficacy data from the first 14 subjects of the cohort
demonstrated continued evidence of a mechanistic dose response
based on urinary PC1 and PC2 levels as well as a notable reduction
in htTKV growth rate. In addition, review of complete safety data
from all 26 subjects demonstrated farabursen was well
tolerated.
Cohort 4 data highlights:
- Effects on polycystin biomarker levels were similar to cohort 3
at 3 mg/kg which is predicted to achieve optimal kidney exposure
and resulting miR-17 inhibition
- Exploratory results continue to suggest a notable impact on
htTKV growth rate after 3 months of treatment
- htTKV results are consistent across Mayo Imaging Class and PKD1
truncating vs non-truncating mutations
- Exploratory conditional probability analyses suggest high
probability of success to meet or exceed targeted htTKV efficacy
threshold
- Safety and tolerability profile is encouraging and consistent
with earlier cohorts
In December 2024, the Company met
with the FDA for an End-of-Phase 1 meeting. Alignment with the FDA
was achieved regarding the acceptability of the program's CMC,
non-clinical and clinical pharmacology plans and key components of
a Phase 3 trial design as a single pivotal study, including:
- A single active dose and placebo administered every other week
in a 2:1 randomization scheme
- Key inclusion/exclusion criteria for the trial population
- A 12-month htTKV endpoint for potential Accelerated Approval
and a 24-month eGFR endpoint for potential Full Approval
- An acceptable safety database size
"These trial results extend our understanding of the potential
benefits and advantages to Regulus' approach in this area of high
unmet medical need," said Preston
Klassen, M.D., President and Head of Research &
Development of Regulus. "Additionally, the data highlight that
farabursen appears to be well tolerated, reinforcing its potential
as a safe option in the treatment of ADPKD."
"The results from Cohort 4 are very promising, further
validating the impact of farabursen on urinary exosomal polycystin
levels and suggesting an opportunity to beneficially impact kidney
volume growth rate, as we have now observed notable improvements
across multiple treatment cohorts," said Alan Yu, M.D., University of Kansas Medical
Center. "As Regulus moves into a pivotal study of farabursen, those
patients living with ADPKD are one step closer to a potentially
safer and more tolerable treatment option."
"Following a productive End-of-Phase 1 meeting with the FDA in
December along with the interim results announced today, we are
encouraged by the feedback from the agency and are excited about
the path forward for farabursen in ADPKD," said Jay Hagan, CEO of Regulus. "The positive results
announced today underscore our conviction in the potential of
farabursen in ADPKD and we look forward to advancing this program
into a pivotal study later this year."
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 Wednesday, January
29 at 8:30 am Eastern Time. To access the call, please
dial (833) 816-1394 (domestic) or (412) 317-0487
(international). To access the telephone replay of the call,
dial (877) 344-7529 (domestic) or (412) 317-0088 (international),
passcode ID 1454429. 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 farabursen (RGLS8429)
Farabursen is a novel, next generation oligonucleotide for the
treatment of ADPKD designed to inhibit miR-17 and to preferentially
target the kidney. Administration of farabursen 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 farabursen has a favorable
safety and PK profile. Farabursen 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, from the third cohort
of patients in June 2024, and from the first 14 patients from
the fourth cohort in January 2025.
Patients in the fourth cohort received an open-label 300 mg fixed
dose of farabursen which was administered every other week for
three months. Review of complete safety data from all cohorts
demonstrated that farabursen was well tolerated.
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
farabursen (RGLS8429) program and preclinical pipeline, the
potential that farabursen may be eligible for an Accelerated
Approval pathway, predictions based on and future results and
outcomes suggested by the Cohort 4 data, our Phase 3 trial design
including whether the FDA will ultimately determine its components
and the overall design to be acceptable and sufficient to serve as
a single pivotal study, the advancing of farabursen into a pivotal
study later this year, farabursen potentially being a safe and
effective treatment option for ADPKD, 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 "anticipates,"
"believes," "expects," "goal," "intends," "look forward to,"
"plans," "potential," "predict," "suggest," "will" 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; 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; an Accelerated Approval
pathway designation may not be received, or even if it is received,
lead to a faster development, regulatory review or approval
process, and does not increase the likelihood that farabursen 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
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 September 30, 2024,
available on the Company's website or at www.sec.gov. 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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