SAN DIEGO, May 21, 2021 / PRNewswire / – Regulus Therapeutics, Inc. (Nasdaq: RGLS), a biopharmaceutical company specializing in the discovery and development of innovative drugs targeting microRNAs (the “Company” or “Regulus”), today announced an update incremental day of the first cohort of patients with ADPKD in its current phase 1b RGLS4326 clinical trial. The study evaluates the safety, pharmacokinetics, and pharmacodynamic biomarker effects of multiple doses of RGLS4326 in patients with ADPKD.
In the first cohort, nine patients were recruited and received 1 mg / kg RGLS4326 subcutaneously every two weeks for four doses. The mean increase in polycystins 1 and 2 at the end of the study from baseline for the nine patients in the first cohort was 58% (p = .0004) and 38% (p = .026) respectively . As previously stated, treatment with RGLS4326 was generally well tolerated and no serious adverse events were reported. All reported adverse events were mild and generally transient in nature. Regulus believes that these data demonstrate that RGLS4326 engages the miR-17 target, resulting in increased expression of the PKD1 and PKD2 genes and the resulting increases in polycystin levels. It was previously shown that the levels of polycystin 1 (PC1) and polycystin 2 (PC2) were inversely correlated with the severity of the disease and would be directly related to the genetic factors underlying the disease.
As previously announced, these data will be presented today at the Oppenheimer Rare & Orphan Disease Summit, Friday, May 21, 2021 at 11:35 a.m.ET. The presentation will be archived on the Company’s website. Additional data from this first cohort will be presented to PKD Connect at June 2021, and a summary will be submitted to the annual meeting of the American Society of Nephrology at November 2021.
“We are very encouraged by these results and look forward to the data from the second cohort in the third quarter,” said Jay Hagan, CEO of Regulus. “As previously reported, the ninth and final patient had a good trend at the end of the treatment period and saw his polycystine levels continue to rise until the end of the study, 28 days after the last dose. . This pattern was generally consistent in the first cohort. and further improved the overall mean changes from baseline for both biomarkers. “
About RGLS4326 phase 1b
The sentence 1b is an adaptive, open-label, multiple-dose study in up to three cohorts of patients with ADPKD. The study is designed to assess the safety, pharmacokinetics, and changes in PC1 and PC2 levels in patients with ADPKD administered RGLS4326 every two weeks for a total of four doses. To characterize the effect of RGLS4326 within each cohort, the biomarker values at the end of the study are compared to baseline values using a paired two-tailed t-test. P values less than 0.05 are considered statistically significant without adjustment for multiplicity. The dose level for the first cohort is 1 mg / kg RGLS4326 and the dose level for the second cohort is 0.3 mg / kg. The third and last cohort will be dosed at a level to be determined according to the results of the first two cohorts.
For more information on the clinical trial design, please visit www.clinicaltrials.gov (NCT04536688).
RGLS4326 is a novel oligonucleotide designed to inhibit miR-17 and designed to preferentially target the kidney. Preclinical studies with RGLS4326 demonstrated direct regulation Pkd1 and Pkd2, reduction in the growth of cysts in men in vitro ADPKD models and attenuation of cyst proliferation and improvement of renal function in mouse models of ADPKD. The RGLS4326 IND is currently on partial clinical hold for extended duration treatment by the FDA until the second set of requirements described by the agency have been satisfactorily met. The Company will use information from phase 1 clinical studies, including the first cohort of phase 1b study as well as information from additional recently completed non-clinical studies generated in 2020, in its plan to meet the second set of requirements outlined in the partial clinical suspension letter to support extended duration studies. Regulus plans to discuss its approach to meeting the remaining partial clinical suspension requirements with the FDA in mid-2021. RGLS4326 received orphan drug designation from the FDA in July 2020.
ADPKD, caused by mutations in the PKD1 or PKD2 genes, is among the most common human monogenic disorders and one of the main causes of end stage renal disease. The disease is characterized by the development of multiple fluid-filled cysts mainly in the kidneys and, to a lesser extent, in the liver and other organs. Excessive proliferation of renal cyst cells, a central pathologic feature, ultimately leads to end-stage renal failure in approximately 50% of patients with ADPKD by the age of 60 years.
Regulus Therapeutics Inc. (Nasdaq: RGLS) is a biopharmaceutical company focused on the discovery and development of innovative drugs targeting microRNAs. Regulus has leveraged its expertise in the discovery and development of oligonucleotide drugs to develop a pipeline complemented by a rich heritage of intellectual property in the field of microRNAs. Regulus is headquartered in San Diego, CALIFORNIA.
Statements in this press release regarding matters which are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements associated with clinical activities relating to the RGLS4326 program, including the preliminary biomarker, the pharmacokinetic and safety data resulting from the first cohort of patients in the current clinical study, the sufficiency of the data required to restart the clinical studies for a long-term dosage, the timing of the interactions of the company with the FDA regarding clinical suspension and timing and other preclinical and clinical activities. Since these statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied in these forward-looking statements. Words such as “believes”, “anticipates”, “plans”, “expects”, “intends”, “will”, “objective”, “potential” and similar expressions are intended to identify statements prospective. These forward-looking statements are based on Regulus’ current expectations and involve assumptions which may never materialize or prove to be incorrect. Actual results and timing of events could differ materially from those anticipated in these forward-looking statements due to various risks and uncertainties, which include, but are not limited to, risks associated with the process of drug discovery, development and commercialization. safe and effective for use as human therapeutics and in the effort to build a business around these drugs, and FDA reviews. Additionally, while Regulus expects the COVID-19 pandemic to adversely affect its business operations and financial results, the magnitude of the impact on Regulus’ ability to meet its preclinical and clinical development goals and the value and market of its common stock, is dependent on future developments which are very uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, distancing requirements social and business closure in the United States and other countries; and the effectiveness of global measures to contain and treat the disease. These and other risks are described in more detail in documents filed by Regulus with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. Regulus assumes no obligation to update these statements to reflect events that occur or circumstances that exist after the date on which they were made.
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