Regulus Therapeutics Progresses to Phase 1b Cohort 4 in RGLS8429 Trial for ADPKD

SAN DIEGO, May 6, 2024 -- Regulus Therapeutics Inc. (Nasdaq: RGLS), a biopharmaceutical company dedicated to discovering and developing innovative medicines that target microRNAs, has started screening for the fourth cohort in its Phase 1b Multiple Ascending Dose (MAD) study of RGSL8429 for treating Autosomal Dominant Polycystic Kidney Disease (ADPKD). Following an extensive safety data review, this cohort will include up to 30 patients receiving a fixed dose of 300 mg of RGLS8429 every other week over three months.

CEO Jay Hagan expressed optimism about advancing to this final cohort after sharing positive data from the second cohort, reinforcing RGSL8429's potential efficacy in ADPKD. The open label, fixed-dose approach in this cohort aims to provide crucial insights and data that will inform the design of a potentially pivotal Phase 2 trial. Hagan anticipates additional updates, including topline data from the third cohort, by mid-year.

The Phase 1b MAD study is a rigorous, double-blind, placebo-controlled trial designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics (PK/PD) of RGLS8429 in adult ADPKD patients. The trial evaluates the drug's effects across three different weight-based doses and examines variables such as urinary polycystins PC1 and PC2, height-adjusted total kidney volume (htTKV), cyst architecture, and overall kidney function. PC1 and PC2, products of the PKD1 and PKD2 genes respectively, are inversely related to disease severity. The inclusion of the fourth cohort aims to further explore the impact on total kidney volume.

ADPKD, a prevalent monogenic disorder caused by mutations in PKD1 or PKD2 genes, leads to the development of numerous fluid-filled cysts primarily in the kidneys, and to a lesser extent in the liver and other organs. This excessive cyst cell proliferation ultimately results in end-stage renal disease in nearly half of ADPKD patients by age 60. In the United States, about 160,000 individuals are diagnosed with ADPKD, which has an estimated global prevalence of 4 to 7 million.

RGLS8429 represents a novel, next-generation oligonucleotide specifically designed to inhibit miR-17 and target the kidneys. Its administration in preclinical models has yielded significant improvements in kidney function, size, and other disease severity markers. The Phase 1 Single Ascending Dose (SAD) study, completed in September 2022, demonstrated a favorable safety and pharmacokinetic profile for RGLS8429, with no serious adverse events and approximately linear plasma exposure across the four doses tested. Topline data from the first cohort of the Phase 1b MAD study was released in September 2023, followed by data from the second cohort in March 2024. The third cohort, which completed enrollment in January 2024, involves patients receiving 3 mg/kg of RGLS8429 or placebo every other week for three months, with topline data expected in mid-2024.

Regulus Therapeutics, headquartered in San Diego, CA, is at the forefront of developing innovative microRNA-targeting medicines. Leveraging its expertise in oligonucleotide drug discovery and development, Regulus has built a robust pipeline supported by a strong intellectual property portfolio in the microRNA domain.

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