SAN DIEGO, May 6, 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, after review of all available safety data, the Company initiated screening in the of the fourth cohort of patients in the Phase 1b MAD study of RGSL8429 for the treatment of ADPKD. Patients in the fourth cohort will receive an open label fixed dose of 300 mg of RGLS8429 every other week for three months. The study protocol has been amended to include up to 30 subjects in the fourth cohort in order to further examine potential impact on total kidney volume in patients with APDKD.

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"After sharing positive topline data from cohort 2 that further validates RGLS8429's potential efficacy in ADPKD, we are moving to the fourth and final cohort of the Phase 1b MAD study," said Jay Hagan, CEO of Regulus Therapeutics. "This open label, fixed dose cohort will provide essential insight and data as we begin to think about study design for our potentially pivotal Phase 2 trial. Our team is looking forward to sharing further updates as they become available, including topline data from the third cohort in the middle of this year."

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 will evaluate RGLS8429 treatment across three different weight-based dose levels, including measuring changes in urinary polycystins 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 respectively and have been shown to inversely correlate with disease severity. The Company amended the protocol to include a fourth cohort of up to 30 subjects who will receive a fixed dose of 300 mg of RGLS8429 administered every other week for three months.

More information about the MAD clinical trial is available at clinicaltrials.gov (NCT05521191).

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 both topline data from the first cohort of patients in September 2023 and from the second cohort of patients in March 2024. Regulus announced completion of enrollment in the third cohort in January 2024 with patients receiving 3 mg/kg of RGLS8429 or placebo every other week for three months. Topline data from the third cohort is anticipated in mid-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 clinical translation for ADPKD patients, the expected timing for reporting topline data, the timing and future occurrence of other preclinical and clinical activities and the expected length of our cash runway. 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, and the risk additional toxicology data may be negative and 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' most recently filed quarterly report on Form 10-Q. 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.

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