Benzinga | Jun 25, 2021 07:07AM EDT

Regulus Therapeutics To Present Additional Data From Autosomal Dominant Polycystic Kidney Disease Program At PKD Connect 2021 At 2-3 p.m. CDT.

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 the presentation of additional data from the first cohort of patients in the Company's Phase 1b clinical trial of RGLS4326 for the treatment of autosomal dominant polycystic kidney disease (ADPKD), as well as new preclinical data from relevant animal models of the disease. The E-poster presentation, titled "Preclinical Evaluation and Results from the First Cohort of Phase 1b Clinical Trial of RGLS4326 for the Treatment of Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)," is available to attendees of the PKD Connect Conference 2021, on Friday, June 25, from 2-3 p.m. CDT.

The poster presents results from the Company's ongoing Phase 1b study evaluating the safety, pharmacokinetics, and effects on pharmacodynamic biomarkers of multiple doses of RGLS4326 in patients with ADPKD. The data demonstrate clinical proof of mechanism by showing target engagement in the kidneys through a statistically significant increase in urinary biomarkers PC1 and PC2, validating miR-17 as a target for ADPKD treatment. Levels of PC1 and PC2 have previously been shown to be inversely correlated with disease severity. RGLS4326 was well-tolerated with no serious adverse events. The poster also describes new data from relevant preclinical models showing treatment with RGLS4326 results in increased gene and polycystin levels in vitro. In addition, improvements in key disease markers including serum creatinine and BUN were demonstrated in the Pkd1(F/RC) mouse model that harbors Pkd1 mutation equivalent to human ADPKD.

"These exciting results lend further support to the therapeutic potential of RGLS4326 in ADPKD and also bring us a step closer to our mission to improve the lives of patients suffering from this disease," commented Jay Hagan, President and Chief Executive Officer of Regulus. "The data from the first cohort of patients in this clinical study suggest that further increases in polycystin levels may be achievable with longer term and, potentially, less frequent, dosing and reinforce our belief that RGLS4326 represents an innovative approach to the treatment of underlying genetic drivers of ADPKD."

Clinical study details:

RGLS4326 is currently being evaluated in a Phase 1b, multicenter, open-label, adaptive design dose-ranging study to evaluate its safety, tolerability, pharmacokinetics and pharmacodynamics in patients with ADPKD. In the first cohort of the Phase 1b study, nine patients were enrolled and received 4 doses of 1 mg/kg of RGLS4326 administered every other week.

Clinical study results:

* The data demonstrate clinical proof of mechanism by showing target engagement in the kidneys through statistically significant increases in urinary biomarkers, PC1 and PC2, at study completion compared to baseline.

* In addition, one patient with pre-study levels uNGAL almost twice the upper limit of normal saw their uNGAL levels drop into the normal range during the course of the study.

* Administration of RGLS4326 was well-tolerated with no serious adverse events.

The study is continuing to enroll patients with ADPKD in additional cohorts to evaluate different doses of RGLS4326. The second cohort of patients are receiving a dose of 0.3mg/kg administered every other week and is nearing completion of enrollment.

Preclinical study details:

Pkd1(RC/-) cells were treated with either vehicle, control or RGL4326 for 2 days prior to measuring changes in Pkd1 and Pkd2 genes, and for 3 days prior to measuring changes in PC1 and PC2 proteins. In addition, Pkd1(F/RC) mice were dosed with either a control or RGLS4326 for four doses prior to assessment of efficacy.

Preclinical study results

* RGLS4326 treatment led to increased Pkd1 and Pkd2 gene expression (>100% increase) and increased levels of their encoded proteins PC1 and PC2 (~50% increase) in Pkd1(RC/-) cells in vitro.

* RGLS4326 treatment demonstrated improvement in key efficacy parameters including kidney-weight-to-body-weight ratio (~75% decrease), serum creatinine (~50% decrease) and BUN (~60% decrease) in Pkd1(F/RC) mice compared to control.

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).