Mechanistic dose response observed at a 2mg/kg
dose level based on urinary biomarker analyses
Encouraging exploratory results of
imaging-based biomarkers with greatest reductions in total kidney
volume seen in patients with the highest increases in PC1 and
PC2
Cohort 3 fully enrolled with data readout
anticipated in mid-2024; Cohort 4 screening to start in 2Q
2024
Company to hold conference call at
8:30am ET today
SAN
DIEGO, March 12, 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 second 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,
including measuring changes in urinary polycystins 1 and 2 (PC1 and
PC2), height-adjusted total kidney volume (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. The third cohort is
being dosed at 3mg/kg of RGLS8429 or placebo every other week for
three months. The Company recently added a fourth cohort for an
open label fixed dose of 300mg of RGLS8429 dosed every other week
for three months. Based on the results from this second cohort, the
Company plans to amend the protocol to increase the sample size to
up to 30 patients. In addition to PC1 and PC2 and safety, imaging
biomarkers will also be evaluated.
In the second cohort, 14 patients were randomized 3:1 to receive
either 2 mg/kg of RGLS8429 or placebo every other week for three
months.
- RGLS8429 was well tolerated with no safety findings of
concern.
- Clear evidence of a mechanistic dose response at a 2mg/kg dose
level based on urinary PC1 and PC2 polycystin levels was
observed.
- Urinary measurements of PC1 and PC2 demonstrated greater
biological activity of RGLS8429 at 2mg/kg compared to 1mg/kg and
placebo, which was most evident after 3 months of dosing.
- Exploratory results of imaging-based biomarkers were
encouraging with 3 patients with the highest increases in PC1 and
PC2 having reductions in htTKV >4%, with corresponding
reductions in total kidney cyst volume (TKCV).
These data suggest potential impact on htTKV and TKCV, which the
Company will further explore at higher doses in cohorts 3 and 4.
The ongoing Phase 1b study is
evaluating RGLS8429 dosing at 3 mg/kg in cohort 3 and will explore
a 300 mg fixed dose in cohort 4 that will provide higher exposure
in a larger number of patients based on anticipated body
weight.
"These results from cohort 2 are encouraging, with biomarker
data that demonstrate increased activity of RGLS8429 at 2 mg/kg,"
said Alan Yu, M.B., B.Chir, from the
University of Kansas Medical Center.
"Noting that several patients in this cohort who had the greatest
reductions in kidney volume also had the greatest increases in PC1
and PC2 is certainly intriguing, and I look forward to seeing
results from the higher doses planned in the study. As a physician
managing patients with ADPKD, the continued development of a
potential novel therapeutic is both important and welcome."
"We are pleased with the data we have seen in the second cohort,
in particular, the mechanistic dose response, as it continues to
validate RGLS8429's potential efficacy in ADPKD," said Preston Klassen, M.D., President and Head of
Research & Development of Regulus. "Based on these exciting
results from cohort 2, we plan to increase the sample size of the
cohort 4 fixed-dose open label enrollment up to 30 patients in
order to further examine potential impact on cystic volume in
patients with APDKD. The clear increases in polycystin levels we
saw in the second cohort were encouraging, in particular their
potential correlation with improvements in kidney volume and
function. We look forward to seeing the topline data from the third
cohort in the middle of this year."
"These data represent another important step on our way to
bringing a potential treatment to those living with ADPKD," said
Jay Hagan, CEO of Regulus. "RGLS8429
holds the potential to be able to address the underlying genetic
causes of the disease, and we look forward to the data from our
third and fourth cohorts to inform our potentially pivotal Phase 2
trial design. As always, I would like to thank the patients and
investigators participating in our past and ongoing studies as well
as our team who has worked so hard to bring us these data."
In addition, the Company recently held a Type D meeting with FDA
to discuss the accelerated approval pathway. The meeting was
constructive and confirms the potential for an accelerated approval
pathway based on a single Phase 2 study of RGLS8429 for the
treatment of ADPKD.
As of December 31, 2023, the
Company had cash and cash equivalents of approximately $23.8 million.
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 March 12, 2024, at 8:30 am Eastern
Time. To access the call, please dial (833) 816-1394 (domestic) or
(855) 669-9657 (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 (877) 344-7529 (domestic) or (412) 317-0088
(international), passcode ID 6852735. 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 robust data in preclinical models, where clear
improvements in kidney function, size, and other measures of
disease severity have been demonstrated along with a superior
pharmacologic profile in preclinical studies compared to Regulus'
first-generation compound, RGLS4326. 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 and is similar to
the PK data from the first-generation compound. In the Phase
1b MAD study Regulus announced both
top line data from the first cohort of patients, and completion of
enrollment for the second cohort of patients in September 2023. After review of all available
safety data, Regulus has advanced to the third cohort where dosing
has begun, and patients will receive 3 mg/kg of RGLS8429 or placebo
every other week for three months. Regulus announced completion of
enrollment in the third cohort in January 2024. Regulus
announced top line data from the second cohort of patients in
March 2024.
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 presentation 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, the expected timing
for initiating clinical studies, potentially achieving therapeutic
efficacy and the potential to address the underlying genetic causes
of ADPKD, the expected timing for reporting data, the timing and
future occurrence of other preclinical and clinical activities, the
potential accelerated approval pathway, and other statements
relating to future events or conditions. 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 approach we
are taking to discover and develop drugs is novel and may never
lead to marketable products, preliminary or initial results may not
be indicative of future results, 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 and in the endeavor of
building a business around such drugs, our need for additional
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, 2023. 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.