-Company will advance RGLS8429 supported by strong preclinical data and superior pharmacologic profile as compared to first-generation RGLS4326-

-Validating sections of IND-enabling toxicity studies for RGLS8429 have been completed, with IND submission and Phase 1 initiation expected in Q2 2022-

-Based on discussions with the US Food and Drug Administration, and data from the second cohort of patients in Phase 1b trial, first-generation RGLS4326 will not be further advanced based on likely limitations on dose and duration of therapy-

SAN DIEGO, CA, USA I October 12, 2021 I 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 prioritization of its promising, next-generation candidate, RGLS8429, for the treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD). The Company recently completed the dosing period of the in-life portion of the IND-enabling toxicity studies for RGLS8429; anticipates submitting an Investigational New Drug application (IND); and subject to U.S. Food and Drug Administration (FDA) clearance, initiating a phase 1 study in the second quarter of 2022.

Based on discussions with FDA and data from the second cohort of patients in the Phase 1b trial of first-generation RGLS4326 in ADPKD, the Company believes that a strategic prioritization of RGLS8429 represents a more judicious use of its resources, rather than continuing the development of RGLS4326 based on likely limitations on dose and duration of therapy.

“In light of our discussions with FDA and early analysis of data from the second cohort of our Phase 1b trial in ADPKD, we have determined that advancing our next-generation compound RGLS8429 is more compelling than further development of RGLS4326,” commented Jay Hagan, CEO of Regulus. “The extensive work and investment we have made in RGLS4326 will directly inform the advancement of RGLS8429, and we believe will make this transition both expeditious and productive. This prioritization of RGLS8429 is supported both by robust data in preclinical models, where we have seen clear improvements in kidney function, size, and other measures of disease severity, as well as the compound’s superior pharmacologic profile.”

With the completion of the dosing phase of the IND-enabling toxicity studies, the Company believes RGLS8429 has demonstrated a superior profile, including absence of the off-target CNS effects that were seen with RGLS4326 at the top doses tested in chronic preclinical toxicology studies as well as equal potency to RGLS4326 for its molecular target (miR-17) in both in-vitro and in-vivo efficacy studies. The Company expects to have a pre-IND meeting with the FDA for RGLS8429 later this year and is on track for an IND submission and, subject to FDA clearance of the IND, initiation of a Phase 1 clinical study in the second quarter of 2022. Leveraging the learnings from the first-generation compound, coupled with the superior pharmacological profile of RGLS8429 in animal models, the Company’s Phase 1 plans include a single dose escalation study in healthy volunteers to enable a multi-dose escalation study in ADPKD patients around the dose levels where robust clinical biomarker effects were demonstrated with RGLS4326. The Company anticipates reporting top-line biomarker data in the first cohort of RGLS8429 treated patients in early 2023.

About Regulus

Regulus Therapeutics Inc. (Nasdaq: RGLS) is a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs. Regulus has leveraged its oligonucleotide drug discovery and development expertise to develop a pipeline complemented by a rich intellectual property estate in the microRNA field. Regulus maintains its corporate headquarters in San Diego, CA.

SOURCE: Regulus Therapeutics