Regulus Therapeutics Announces Results in Phase 1b Study for ADPKD Treatment

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 positive topline results from the third cohort of patients in its Phase 1b MAD study of RGLS8429 for the treatment of ADPKD.

The Phase 1b MAD study is a double-blind, placebo-controlled trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of RGLS8429 in adult patients with ADPKD. The study is evaluating RGLS8429 treatment across three different weight-based dose levels and one fixed dose level, including measuring changes in urinary polycystins 1 and 2 (PC1 and PC2), htTKV, cyst architecture, and overall kidney function. PC1 and PC2 are the protein products of the PKD1 and PKD2 genes and have been shown to inversely correlate with disease severity. Enrollment in the fourth cohort, which will include up to 30 patients, has been initiated and patients will receive an open label fixed dose of 300 mg of RGLS8429 every other week for three months. In addition to PC1 and PC2 and safety, imaging biomarkers will also be evaluated.

In the third cohort, 16 subjects were randomized 3:1 to receive either 3 mg/kg of RGLS8429 or placebo every other week for three months.

• RGLS8429 was well tolerated with no safety concerns
• Continued evidence of a mechanistic dose response was observed following completion of 3 mg/kg dose level based on urinary PC1 and PC2
• 3 mg/kg demonstrated more consistent increases in PC1 and PC2 across patients compared to earlier cohorts
• Percent change from baseline in PC1 and PC2 demonstrated a dose response across all doses tested, with statistical significance seen at 3 mg/kg compared to placebo
• Exploratory MRI imaging analysis suggested RGLS8429 reduced htTKV at 3 mg/kg after 3 months of dosing
• 70% of subjects demonstrated reductions in htTKV following completion of 3 mg/kg dose level

"We are pleased to see the consistent mechanistic response and reduction in htTKV at the 3mg/kg dose level of RGLS8429 along with an appropriate safety and tolerability profile," said Preston Klassen, M.D., President and Head of Research & Development.  "These data support our ongoing and final 300 mg fixed dose cohort in this Phase 1b trial. We believe the data from this study will form the basis for a potentially pivotal Phase 2/3 study of RGLS8429 under an Accelerated Approval regulatory pathway to be discussed with the FDA."

"Building on the positive results from our first two cohorts, these cohort 3 data, particularly the reduction in htTKV seen in the majority of patients, further strengthen our conviction in RGLS8429's ability to potentially address the underlying, genetic cause of ADPKD," said Jay Hagan, CEO of Regulus Therapeutics. "We anticipate requesting an End-of-Phase 1 meeting with the FDA in the fourth quarter of this year and look forward to providing a data update from the open-label fourth and final cohort of the Phase 1b MAD study by year-end."