Regulus Therapeutics Completes Enrollment in Phase 1b Trial of RGLS8429 for ADPKD

Regulus Therapeutics Inc. (Nasdaq: RGLS), a San Diego-based biopharmaceutical company, has successfully completed the enrollment of 26 patients in the fourth cohort of its Phase 1b MAD study evaluating RGLS8429 for treating autosomal dominant polycystic kidney disease (ADPKD). This marks a significant milestone for the company as it advances towards the culmination of its Phase 1b study.

The company's CEO, Jay Hagan, highlighted the promising nature of the study's results thus far, with all three prior cohorts showing a mechanistic dose response through increased urinary polycystins (PC1 and PC2). Preliminary imaging analysis further indicated reductions in height-adjusted total kidney volume (htTKV), a crucial metric that will also be assessed in the fourth cohort and the anticipated Phase 3 trial. Hagan confirmed the company's plans to meet with the FDA by the end of 2024 to discuss the end of Phase 1 and to share topline data from the fourth cohort in early 2025.

The Phase 1b MAD study is a comprehensive, double-blind, placebo-controlled, and weight-based dosing trial, combined with an open-label fixed dose trial. It aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RGLS8429 in adult patients with ADPKD. The study assesses RGLS8429 across three different weight-based dose levels and one fixed dose level. It measures changes in urinary polycystins PC1 and PC2, htTKV, cyst architecture, and overall kidney function. PC1 and PC2 are protein products of the PKD1 and PKD2 genes, which inversely correlate with disease severity. Patients in the fourth cohort receive a fixed dose of 300 mg of RGLS8429 every other week for three months.

ADPKD is a common monogenic disorder caused by mutations in the PKD1 or PKD2 genes, and it is a leading cause of end-stage renal disease. This disease is distinguished by the formation of multiple fluid-filled cysts in the kidneys, with secondary involvement of the liver and other organs. The excessive proliferation of kidney cyst cells, a central pathological aspect of ADPKD, typically leads to end-stage renal disease in about half of the patients by age 60. In the United States, approximately 160,000 individuals are diagnosed with ADPKD, with global prevalence estimated between 4 to 7 million.

RGLS8429 is a next-generation oligonucleotide aimed at treating ADPKD by inhibiting miR-17 and preferentially targeting the kidney. Preclinical models have shown that RGLS8429 administration leads to significant improvements in kidney function, size, and other disease severity metrics. Regulus concluded the Phase 1 SAD study in September 2022, which demonstrated that RGLS8429 has a favorable safety and pharmacokinetic profile. The drug was well-tolerated with no serious adverse events reported, and plasma exposure was approximately linear across the four doses tested. The company has sequentially released topline data from the first three cohorts between September 2023 and June 2024, culminating in the completion of the fourth cohort's enrollment in October 2024.

Regulus Therapeutics Inc. focuses on discovering and developing innovative medicines that target microRNAs, leveraging its expertise in oligonucleotide drug discovery and development. The company is headquartered in San Diego, CA.