PKD1

Taylor Tieden for BioSpace At the heart of the acquisition is Regulus’ farabursen, an miRNA-targeting oligonucleotide in early-stage development for rare autosomal dominant polycystic kidney disease. Novartis is buying Regulus Therapeutics for $800 million upfront , beefing up its oligonucleotide pipeline with the San Diego biotech’s miRNA-targeting assets, according to a press announcement on Wednesday. Under the terms of the acquisition agreement, Novartis will procure all of Regulus’ shares for $7 a pop—a purchase price that represents a 108% premium to the biotech’s closing price on Tuesday. Novartis is also offering Regulus’ shareholders a $7-per-share contingent value right, payable after hitting certain milestones. All told, the acquisition could be worth $1.7 billion. Boards of directors of both companies have unanimously approved the transaction, which is expected to close in the back half of the year, pending customary closing conditions. The centerpiece of Wednesday’s merger is Regulus’ farabursen—its regulatory approval is the trigger for Novartis’ contingent value right offer—an oligonucleotide being developed for autosomal dominant polycystic kidney disease (ADPKD), a rare, hereditary condition that affects around 160,000 patients in the U.S., according to Regulus. The disease is caused by mutations in the Pkd1 or Pkd2 gene, leading to the accumulation of fluid-filled cysts in and across the kidneys and worsening kidney function over time. When left unchecked, ADPKD can lead to kidney failure and eventually death. According to Regulus, Pkd1 or Pkd2 mutations are tied to the upregulation of miR-17, a microRNA molecule that “ directly leads ” to suppression of certain genes, ultimately dampening the production of the proteins encoded by those genes, polycystin 1 (PC1) and 2 (PC2). Farabursen binds to miR-17 to disrupt this pathway to “correct the underlying pathology of ADPKD,” according to Regulus. Through this mechanism of action, farabursen can restore PC1 and PC2 levels, in turn reducing the growth of cysts. Farabursen is in a Phase Ib study that is expected to complete later this year. Aside from farabursen, Regulus is also advancing another nephrology asset and is working on a program for an undisclosed central nervous system indication. The Regulus move is in line with Novartis’ business development philosophy this year. During the pharma’s year-end report for 2024, CEO Vas Narasimhan told reporters the company would “continue our strategy to look for primarily bolt-on acquisitions that we think will bolster our growth in the 2030 and beyond period.” A few days later, Novartis put $3.1 billion on the line to acquire Anthos Therapeutics and its anticoagulant antibody abelacimab.

Positive Topline Data from the Fourth Cohort of Patients Consistent demonstration of polycystin (PC) biomarker impact confirming 300 mg fixed dose selection to achieve optimal kidney exposure Patients receiving 300 mg farabursen demonstrated a mean halting of height-adjusted total kidney volume (htTKV) growth over 4 months Exploratory analysis of patients from high-dose cohorts demonstrates statistical significance in htTKV change compared to a large cohort of historical placebo-treated patients, which meaningfully derisks the 12-month htTKV endpoint in the planned Phase 3 trial Company on track for initiation of Phase 3 single pivotal trial in third quarter 2025 SAN DIEGO, March 27, 2025 /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 positive topline results from all patients in the fourth cohort in its Phase 1b MAD study of farabursen for the treatment of ADPKD. The Phase 1b MAD study is a double-blind, placebo-controlled trial which evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of farabursen in adult patients with ADPKD. The study evaluated farabursen treatment for three months followed by one month of follow up across three weight-based dose levels (1, 2 and 3 mg/kg) and one fixed dose level (300 mg). Primary endpoints were changes in urinary PC1 and PC2, with an exploratory examination of change in htTKV growth rate. PC1 and PC2 are the protein products of the PKD1 and PKD2 genes and their levels have been shown to inversely correlate with disease severity; htTKV has been shown to inversely correlate with kidney function. In the fourth cohort, 26 subjects received a fixed dose of 300 mg of farabursen every other week for three months. Consistent with the previously announced interim analysis of efficacy data from the first 14 subjects of this fixed-dose cohort, the full cohort of 26 patients demonstrated similar mechanistic response based on urinary PC1 and PC2 levels as well as a mean halting of htTKV growth over the four-month study period. Cohort 4 data highlights: Increases in urinary PC1 and PC2 levels were similar to cohort 3 and reached a similar level of statistical significance compared to placebo (PC1 p=0.026; PC2 p=0.014). Mean htTKV growth rate over 4 months was 0.05% (SE -0.86% to +0.92%) while placebo subjects in the trial experienced a mean growth rate of 2.58% (SE +1.09% to +4.10%). Changes in htTKV were highly correlated with changes in renal cyst volume, suggesting farabursen directly impacts disease progression by limiting abnormal cyst growth. In an exploratory analysis, the combination of patients treated with 3 mg/kg or 300 mg fixed dose farabursen (n=35) were compared to a combined historical control group of placebo-treated patients from prior pivotal ADPKD trials (n=550). Farabursen-treated patients experienced mean reduction in htTKV growth rate (-0.14%) compared to a mean increase of (+1.87%) in placebo-treated patients (p=0.0056). Farabursen at 300 mg demonstrated a favorable safety and tolerability profile in this study, consistent with earlier cohorts. "We are pleased that the results of cohort 4 demonstrate a level of mechanistic response, as measured by urinary PC1 and PC2, that indicates maximal anti-miR-17 activity. Along with the observed favorable safety and tolerability profile, these results give us confidence that 300 mg provides optimal target exposure and is the appropriate dose to take forward into Phase 3," said Preston Klassen, M.D., President and Head of Research & Development of Regulus Therapeutics. "Even more encouraging is the repeated demonstration across multiple cohorts in the trial that, on average, growth of the kidney in ADPKD patients is halted after only a relatively short treatment period with farabursen. Based on exploratory analysis of Cohorts 3 & 4, which deliver overlapping drug exposures, we are confident that the htTKV effects seen with farabursen in this trial are clinically meaningful and provide important insight into the probability of success for the 12-month htTKV endpoint in the planned Phase 3 trial." "With full data from cohort 4 now analyzed, we are pleased with the positive results, in line with our expectations based on previous cohorts. These data suggest that farabursen has the potential to be an important addition to the limited therapeutic options for patients with ADPKD," said Jay Hagan, CEO of Regulus Therapeutics. "I would like to thank all the patients, physicians, and support staff who have been vital to the ongoing development of farabursen. We are excited to move forward with initiation of the pivotal Phase 3 trial later this year." In January, the Company announced that it held a meeting with U.S. Food and Drug Administration (FDA) and had confirmed alignment with the FDA on the acceptability of the program's CMC, non-clinical and clinical pharmacology plans and the key elements of a Phase 3 trial design as a single pivotal study, including a 12-month htTKV endpoint planned to support Accelerated Approval and a 24-month eGFR endpoint to support Full Approval. More information about the MAD clinical trial is available at clinicaltrials.gov (NCT05521191). About ADPKD Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in the PKD1 or PKD2 genes, is among the most common human monogenic disorders and a leading cause of end-stage renal disease. The disease is characterized by the development of multiple fluid filled cysts primarily in the kidneys, and to a lesser extent in the liver and other organs. Excessive kidney cyst cell proliferation, a central pathological feature, ultimately leads to end-stage renal disease in approximately 50% of ADPKD patients by age 60. Approximately 160,000 individuals are diagnosed with the disease in the United States alone, with an estimated global prevalence of 4 to 7 million. About Farabursen (RGLS8429) Farabursen is a novel, next generation oligonucleotide for the treatment of ADPKD designed to inhibit miR-17 and to preferentially target the kidney. Administration of farabursen has shown clear improvements in kidney function, size, and other measures of disease severity in preclinical models. Regulus announced completion of the Phase 1 SAD study in September 2022. The Phase 1 SAD study demonstrated that farabursen has a favorable safety and PK profile. Farabursen was well-tolerated with no serious adverse events reported and plasma exposure was approximately linear across the four doses tested. In the Phase 1b MAD study, Regulus announced topline data from the first cohort of patients in September 2023, from the second cohort of patients in March 2024, from the third cohort of patients in June 2024, and from the fourth cohort in March 2025. Patients in the fourth cohort received an open-label 300 mg fixed dose of farabursen which was administered every other week for three months. Review of complete safety data from all cohorts demonstrated that farabursen was well tolerated. 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 farabursen (RGLS8429) program, the potential that farabursen may be eligible for an Accelerated Approval pathway, predictions based on and future results and clinical outcomes suggested by the Cohort 4 data, our Phase 3 trial design including whether the selected fixed dose will be efficacious or whether the FDA will ultimately determine its components and the overall design to be acceptable and sufficient to serve as a single pivotal study, planned data announcements 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 "confident," "expectations," "on track," "plans," "probability," "potential," "suggest," 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: the risk that the approach we are taking to discover and develop drugs is novel and may never lead to marketable products; preliminary or topline results are based on a preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data related to the clinical trial and may not be indicative of future results; an Accelerated Approval pathway designation may not be received, or even if it is received, lead to a faster development, regulatory review or approval process, and does not increase the likelihood that farabursen will receive marketing approval; our clinical development strategy may change; the risk that future clinical studies may not be successful; risks related to regulatory review and approval; risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics; and the risk that additional data may be negative. 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 filed annual report on Form 10-K or subsequently filed quarterly report on Form 10-Q, available on the Company's website or at . 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. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Positive topline results from an interim analysis of the fourth cohort of patients in the Phase 1b multiple-ascending dose (MAD) clinical trial of farabursen (RGLS8429) for the treatment of autosomal dominant polycystic kidney disease (ADPKD) Agreement on key components of a Phase 3 single pivotal trial for potential Accelerated Approval with the U.S. Food and Drug Administration (FDA) SAN DIEGO, March 13, 2025 /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 reported financial results for the fourth quarter and year ended December 31, 2024, and provided a corporate update. "Following the rapid progress in 2024 advancing farabursen for ADPKD, we recently announced interim topline data from 14 subjects in the fourth cohort of patients in the Phase 1b MAD trial, where we continued to see an encouraging safety and tolerability profile and evidence of a mechanistic dose response through increases in polycystin biomarker levels as well as results suggesting a reduction on kidney volume (htTKV) growth rate," said Jay Hagan, CEO of Regulus. "Furthermore, we have reached alignment with FDA on the key components of the design of a Phase 3 single pivotal trial. The proposed pivotal trial includes an interim analysis to enable Accelerated Approval based on a 12-month htTKV endpoint to expedite farabursen's development for patients living with ADPKD, who currently have limited treatment options. We look forward to sharing topline data from all 26 subjects in cohort 4 in the coming weeks." Program Updates Farabursen for ADPKD: In January 2025, the Company shared positive topline data from an interim analysis of the fourth cohort of patients in the Phase 1b MAD study of farabursen for the treatment of ADPKD. In the fourth cohort, 26 subjects received a fixed dose of 300 mg of farabursen every other week for three months. The interim analysis of the first 14 subjects of the cohort showed continued evidence of a mechanistic dose response, with similar effects on polycystins 1 and 2 (PC1 and PC2) biomarkers to cohort 3 (dosed at 3 mg/kg), which is predicted to achieve optimal kidney exposure, resulting in miR-17 inhibition. Data also suggested a reduction in htTKV growth rate after 3 months of treatment. Complete safety data from all 26 subjects demonstrated farabursen was well-tolerated, with a profile similar to the previous cohorts. The Phase 1b MAD study is a double-blind, placebo-controlled trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of farabursen in adult patients with ADPKD. The study is evaluating farabursen treatment across three different weight-based dose levels and one fixed dose level, including measuring changes in urinary PC1 and PC2, htTKV, and overall kidney function. PC1 and PC2 are the protein products of the PKD1 and PKD2 genes and their levels have been shown to inversely correlate with disease severity. In December 2024, Regulus met with the FDA for an End-of-Phase 1 meeting where they reached alignment on the acceptability of the program's CMC, non-clinical and clinical pharmacology plans and key components of a Phase 3 trial design as a single pivotal study. Key components agreed upon in the meeting include a single active dose and placebo administered every other week in a 2:1 randomization scheme, a 12-month htTKV endpoint for potential Accelerated Approval and a 24-month eGFR endpoint for potential Full Approval and an acceptable safety database size. Financial Results Cash, Cash Equivalents and Short-term Investments: As of December 31, 2024, Regulus had $75.8 million in cash, cash equivalents and short-term investments. The Company expects its cash runway to extend into early 2026. Research and Development (R&D) Expenses: Research and development expenses were $9.7 million and $35.4 million for the fourth quarter and year ended December 31, 2024, respectively, compared to $5.8 million and $21.2 million for the same periods in 2023, respectively. General and Administrative (G&A) Expenses: General and administrative expenses were $4.1 million and $14.7 million for the fourth quarter and year ended December 31, 2024, respectively, compared to $2.5 million and $10.0 million for the same periods in 2023, respectively. Net Loss: Net loss was $12.8 million, or $0.20 per share (basic and diluted), and $46.4 million, or $0.82 per share (basic and diluted), for the fourth quarter and year ended December 31, 2024, compared to $8.1 million, or $0.40 per share (basic and diluted), and $30.0 million, or $1.58 per share (basic and diluted), for the same periods in 2023. About ADPKD Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in the PKD1 or PKD2 genes, is among the most common human monogenic disorders and a leading cause of end-stage renal disease. The disease is characterized by the development of multiple fluid filled cysts primarily in the kidneys, and to a lesser extent in the liver and other organs. Excessive kidney cyst cell proliferation, a central pathological feature, ultimately leads to end-stage renal disease in approximately 50% of ADPKD patients by age 60. Approximately 160,000 individuals are diagnosed with the disease in the United States alone, with an estimated global prevalence of 4 to 7 million. About Farabursen (RGLS8429) Farabursen is a novel, next generation oligonucleotide for the treatment of ADPKD designed to inhibit miR-17 and to preferentially target the kidney. Administration of farabursen has shown clear improvements in kidney function, size, and other measures of disease severity in preclinical models. Regulus announced completion of the Phase 1 SAD study in September 2022. The Phase 1 SAD study demonstrated that farabursen has a favorable safety and PK profile. Farabursen was well-tolerated with no serious adverse events reported and plasma exposure was approximately linear across the four doses tested. In the Phase 1b MAD study, Regulus announced topline data from the first cohort of patients in September 2023, from the second cohort of patients in March 2024, from the third cohort of patients in June 2024, and from the first 14 patients from the fourth cohort in January 2025. Patients in the fourth cohort received an open-label 300 mg fixed dose of farabursen which was administered every other week for three months. Review of complete safety data from all cohorts demonstrated that farabursen was well tolerated. 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 farabursen (RGLS8429) program and preclinical pipeline, the potential that farabursen may be eligible for an Accelerated Approval pathway, predictions based on and future results and outcomes suggested by the Cohort 4 data, our Phase 3 trial design including whether the FDA will ultimately determine its components and the overall design to be acceptable and sufficient to serve as a single pivotal study, planned data announcements, the timing and future occurrence of other preclinical and clinical activities, and the Company's expected cash runway. 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 "anticipates," "believes," "expects," "goal," "intends," "look forward to," "plans," "potential," "predict," "suggest," "will" 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: the risk that the approach we are taking to discover and develop drugs is novel and may never lead to marketable products; preliminary or topline results are based on a preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data related to the clinical trial and may not be indicative of future results; an Accelerated Approval pathway designation may not be received, or even if it is received, lead to a faster development, regulatory review or approval process, and does not increase the likelihood that farabursen will receive marketing approval; our clinical development strategy may change; the risk that preclinical and clinical studies may not be successful; risks related to regulatory review and approval; risks related to our reliance on third-party collaborators and other third parties; risks related to intellectual property; risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics; the risk that additional data may be negative; and risks related to our ability to successfully secure and deploy capital. 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 filed annual report on Form 10-K or subsequently filed quarterly report on Form 10-Q, available on the Company's website or at . 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. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED