Regulus Therapeutics Inc. announced the preliminary results of a planned interim data analysis from the new mouse chronic toxicity study of RGLS4326 in development for the treatment of Autosomal Dominant Polycystic Kidney Disease, or ADPKD. As previously reported by the Company in July 2018, and in consultation with FDA, the Company voluntarily paused its ongoing Phase 1 Multiple Ascending Dose study of RGLS4326 in healthy volunteers due to unexpected observations in the 27-week mouse chronic toxicity study. The Company terminated that mouse study prematurely at week 14. The study was run in parallel to the Phase 1 program to enable initiation of the Phase 2 program in ADPKD patients upon completion of the Phase 1 MAD study. The observations from the mouse chronic toxicity study were unexpected given the favorable safety profile of RGLS4326 in previous 7-week non-GLP and GLP toxicity studies in both mice and non-human primates required for Phase 1 testing, which had no significant findings across similar dose levels and frequencies. Based upon the Company's investigation and the results announced now, the Company believes the unexpected observations from the previously terminated study were likely a result of technical issues at the contract research organization. In September 2018, the Company announced the initiation of a new 27-week mouse chronic toxicity study, incorporating several changes intended to address the unexpected observations in the previous mouse chronic toxicity study. Certain key changes included the use of a different CRO to conduct the study and the use of a new batch of RGLS4326. The planned interim analysis of this study after 13 weeks of dosing has shown no adverse or other significant findings across the range of doses tested and is intended to support re-initiation of the Phase 1 MAD study after consultation with FDA. RGLS4326 has also been generally well-tolerated in the Phase 1 Single Ascending Dose and MAD studies in human subjects to date. The Company plans to submit a comprehensive data package for RGLS4326 to FDA that will include the results from the planned 13-week interim analysis of the ongoing repeat mouse chronic toxicity study, as well as results from additional investigations, analytical testing, additional data from the previously terminated mouse chronic toxicity study, data from the completed Phase 1 SAD study and data from the first cohort of the Phase 1 MAD study. The Company anticipates engagement with FDA in the coming weeks to discuss the resolution of the voluntary pause in human dosing and the plan to resume the Phase 1 MAD study.