Regulus Therapeutics Announces Strategic Prioritization of RGLS8429, its Next-Generation Candidate for the Treatment of Autosomal Dominant Polycystic Kidney Disease

-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-

-Company to hold conference call at 5:00 p.m. EDT today-

News provided by

Regulus Therapeutics Inc.

Oct 12, 2021, 16:05 ET

SAN DIEGO, Oct. 12, 2021 /PRNewswire/ -- 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.

Conference Call Information
The Company will host a conference call and live audio webcast on Tuesday, October 12, 2021 at 5:00 p.m. Eastern Daylight Time. To access the call, please dial (877) 257-8599 (domestic) or (970) 315-0459 (international) and refer to conference ID 7733988. To access the telephone replay of the call, dial (855) 859-2056 (domestic) or (404) 537-3406 (international), passcode ID 7733988. The webcast and telephone replay will be archived on the Company's website at www.regulusrx.com following the call.

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.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements associated with the Company's RGLS8429 program, including the potential sufficiency of the preclinical data required to support clinical studies, the expected timing for submitting an IND and initiating a Phase 1 clinical study, the expected timing for reporting topline data, and the timing and future occurrence of other preclinical and clinical activities. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "intends," "will," "goal," "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Regulus' current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and in the endeavor of building a business around such drugs, and the risk additional toxicology data may be negative. In addition, while Regulus expects the COVID-19 pandemic to adversely affect its business operations and financial results, the extent of the impact on Regulus' ability to achieve its preclinical and clinical development objectives and the value of and market for its common stock, will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements in the U.S. and in other countries, and the effectiveness of actions taken globally to contain and treat the disease. These and other risks are described in additional detail in Regulus' filings with the Securities and Exchange Commission, including under the "Risk Factors" heading of Regulus most recently quarterly report on Form 10-Q. All forward-looking statements contained in this press release speak only as of the date on which they were made. Regulus undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

SOURCE Regulus Therapeutics Inc.