Regulus announces ‘positive’ results from Phase 1b MAD study of RGLS8429

Regulus Therapeutics announced positive topline results from the first cohort of patients in its Phase 1b MAD study of RGLS8429 for the treatment of ADPKD. In the first cohort, 12 subjects were randomized 3:1 to receive either 1 mg/kg of RGLS8429 or placebo every other week for three months. The study is designed to evaluate safety, pharmacokinetics, disease related urinary biomarkers, including urinary polycystin 1 and polycystin 2, height-adjusted total kidney volume, and novel cyst imaging biomarkers. PC1 and PC2 are the protein products of the PKD1 and PKD2 genes respectively and have been shown to inversely correlate with disease severity. RGLS8429 was well tolerated by all 9 subjects receiving active drug with no safety findings. Increases in both PC1 and PC2 biomarkers were observed. Statistically significant increases in mean PC1 levels were observed at Day 85 and Day 86 compared to baseline. Numeric increases in PC2 were observed during the treatment period, although not statistically significant. These data are consistent with what was observed with the company’s first-generation compound, RGLS4326, which showed a significant dose response between 0.3mg/kg and 1mg/kg of RGLS4326. Furthermore, the correlation between PK and urinary PC1 response at 1mg/kg is comparable between RGLS4326 and RGLS8429. Urinary polycystin exhibits an appropriate PK/PD correlation to potentially serve as a key pharmacodynamic biomarker for the Company’s program targeting miR-17 to treat ADPKD. Furthermore, the data suggest the opportunity to demonstrate increased urinary polycystin response at the higher doses being tested in subsequent cohorts in Phase 1b. Data from the second cohort, dosed at 2mg/kg, are anticipated in the first quarter of 2024.