Regulus Therapeutics Announces Successful Completion of Pre-IND Meeting with FDA for RGLS8429

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 that the Company has completed a pre-investigational new drug (Pre-IND) meeting with the U.S. Food and Drug Administration (FDA). The purpose of the meeting was to obtain input from the FDA on pre-clinical, clinical and regulatory matters pertaining to the Company’s next generation compound RGLS8429 as a potential treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD). The formal minutes from this meeting were received by the Company earlier this week.

The successful completion of this interaction with the FDA is an important milestone that provides regulatory clarity regarding Regulus’ planned Phase 1 trial design. The agency provided overall agreement with the trial design and length of the Phase 1 study, including the proposed starting dose for RGLS8429, as well as sufficiency of the non-clinical package, with no commentary regarding its first-generation compound, RGLS4326 and any additional filing requirements. Based on the minutes, the Company is on track to submit an IND application in the second quarter of 2022 to obtain clearance for initiation of the Phase 1 clinical trial.

The Phase 1 study will consist of two parts. Part 1 will consist of a single-ascending dose (SAD) study in healthy volunteers to assess safety and tolerability of RGLS8429 and characterize the pharmacokinetics of RGLS8429. A total of 32 subjects will be randomized to RGLS8429 or placebo into one of four sequential cohorts. The proposed doses for the four cohorts are 1 mg/kg, 2 mg/kg, 4 mg/kg, and 6 mg/kg. Part 2 will be a multiple ascending dose (MAD) study in adult patients with ADPKD to assess safety and tolerability of RGLS8429, to characterize the pharmacokinetics of RGLS8429, and to evaluate the dose response of RGLS8429 treatment on disease parameters in ADPKD patients including levels of the disease biomarker, polycystin, cystic kidney volume  (htTKV), and overall kidney function. A total of 36 subjects will be randomized to RGLS8429 or placebo into one of three sequential cohorts. The proposed doses for the three cohorts are 0.75 mg/kg, 1.5 mg/kg, and 3 mg/kg every other week for three months.

Regulus’ updated clinical plans agreed to with FDA include extending dosing to three months in each cohort of ADPKD patients, inclusion of measurements of changes in htTKV by Magnetic Resonance Imaging (MRI), and testing higher doses of RGLS8429 than were tested with the first-generation compound.  Height-adjusted total kidney volume (htTKV), a measure of cystic kidney volume, is a biomarker for disease severity and progression to kidney failure in patients with ADPKD. Increased htTKV has been found to occur prior to loss of kidney function, typically by years or decades, and retrospective evidence from published clinical studies has shown a correlation between reduction in TKV and reduction in the rate of decline in renal function.

“We are pleased with the clear and encouraging input we received from the FDA,” said Jay Hagan, President and Chief Executive Officer of Regulus Therapeutics. “The FDA’s feedback was informative and will be useful in finalizing the design of the Phase 1 study which now includes the opportunity to study the potential impact of our investigational product in patients longer. As we prepare for submission of the IND application, on track with our previous guidance, in the second quarter, we look forward to data from the healthy volunteer portion of the study in the second half of this year and data from patients with ADPKD in the first half of 2023.  We are pleased to have strengthened our balance sheet through the successful completion of a $34.6 million private placement in November which enables us to conduct this more robust clinical study design.”