Benzinga | May 21, 2021 08:11AM EDT

Regulus Therapeutics Announces Incremental Update Of Autosomal Dominant Polycystic Kidney Disease (ADPKD) Program

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 an incremental update from the first cohort of patients with ADPKD in its ongoing Phase 1b clinical trial of RGLS4326. The study is evaluating the safety, pharmacokinetics, and effects on pharmacodynamic biomarkers of multiple doses of RGLS4326 in patients with ADPKD.

In the first cohort, nine patients were enrolled and received 1 mg/kg of RGLS4326 subcutaneously every other week for four doses. The mean increase in polycystins 1 and 2 at the end of study compared to baseline levels for all nine patients in the first cohort were 58% (p=.0004) and 38% (p=.026) respectively. As disclosed earlier, treatment with RGLS4326 was generally well-tolerated with no serious adverse events reported. All reported adverse events were mild and generally transient in nature. Regulus believes these data demonstrate that RGLS4326 engages the target miR-17 leading to increased expression of the PKD1 and PKD2 genes and the resultant increases in polycystins' levels. Levels of polycystin 1 (PC1) and polycystin 2 (PC2) have previously been shown to inversely correlate with disease severity and are believed to be directly linked to the underlying genetic drivers of the disease.

As previously announced, these data will be presented at the Oppenheimer Rare & Orphan Disease Summit today, Friday, May 21, 2021 at 11:35am ET. The presentation will be archived on the Company's website. Additional data from this first cohort will be presented at PKD Connect in June 2021, and an abstract will be submitted to the American Society of Nephrology annual meeting in November 2021.

"We are very encouraged by these results and look forward to data from the second cohort in the third quarter" said Jay Hagan, CEO of Regulus. "As previously reported, the ninth and final patient was trending well at the end of the dosing period and saw their polycystin levels continue to rise until study completion, twenty-eight days after the last dose. This pattern was generally consistent across the first cohort and further enhanced the overall mean changes from baseline for both biomarkers."

About RGLS4326 Phase 1b

The Phase 1b is an adaptive design, open-label, multiple dose study in up to three cohorts of patients with ADPKD. The study is designed to evaluate the safety, pharmacokinetics, and changes in levels of PC1 and PC2 in patients with ADPKD administered RGLS4326 every other week for a total of four doses. To characterize the effect of RGLS4326 within each cohort, biomarker values at the end of study are compared to baseline values using a two-sided paired t-test. P-values less than 0.05 are considered statistically significant with no adjustment for multiplicity. The dose level for the first cohort is 1mg/kg of RGLS4326 and the dose level for the second cohort is 0.3mg/kg. The third and final cohort will be dosed at a level to be determined based on the results of the first two cohorts.

For more information about the clinical trial design, please visit www.clinicaltrials.gov (NCT04536688).

About RGLS4326