Core Viewpoint - Regulus (RGLS) has been upgraded to a Zacks Rank 2 (Buy), indicating a positive outlook on its earnings estimates, which is a significant factor influencing stock prices [1][3]. Earnings Estimates and Stock Price Impact - The Zacks rating system is based on changes in earnings estimates, which are strongly correlated with near-term stock price movements [4][6]. - Institutional investors often rely on earnings estimates to determine the fair value of stocks, leading to buying or selling actions that affect stock prices [4]. Regulus Earnings Outlook - For the fiscal year ending December 2025, Regulus is expected to report earnings of -$1.38 per share, reflecting a 68.3% decrease from the previous year [8]. - Despite the negative earnings outlook, analysts have raised their estimates for Regulus, with a 0.2% increase in the Zacks Consensus Estimate over the past three months [8]. Zacks Rank System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with a strong historical performance, particularly for Zacks Rank 1 stocks, which have averaged a +25% annual return since 1988 [7]. - Regulus's upgrade to Zacks Rank 2 places it in the top 20% of Zacks-covered stocks, suggesting potential for market-beating returns in the near term [10].

Financial Overview - The company has received a total of $530.1 million from equity and convertible debt securities, $101.8 million from collaborations, and $19.8 million from a Term Loan as of December 31, 2024[30]. - As of December 31, 2024, the company had cash, cash equivalents, and short-term investments totaling $75.8 million[30]. - The net loss for the year ended December 31, 2024, was $46.4 million, compared to a net loss of $30.0 million for the year ended December 31, 2023, with an accumulated deficit of $559.6 million[192]. - The company has incurred losses in each year since its inception in September 2007, and it does not anticipate generating revenues from product sales for the foreseeable future[191][196]. - The company may need to raise additional capital to fund operations, and if unable to do so, it may have to significantly delay or discontinue development of future product candidates[186][190]. - The company relies primarily on equity and/or debt financings for funding, which may create challenges if there is volatility in the equity markets[188]. Product Development - The product candidate farabursen is in Phase 1b clinical development for the treatment of autosomal dominant polycystic kidney disease (ADPKD) and has shown improvements in kidney function in preclinical models[31]. - In September 2023, positive top-line data was announced from the first cohort of farabursen-treated ADPKD patients, with no safety concerns reported[36]. - In March 2024, positive topline results were reported from the second cohort, showing greater biological activity at a 2 mg/kg dose compared to lower doses[37]. - The third cohort results in June 2024 indicated consistent increases in urinary PC1 and PC2 levels at the 3 mg/kg dose[39]. - An End of Phase 1 meeting with the FDA in December 2024 supported the potential for an accelerated approval pathway based on a single pivotal Phase 3 study of farabursen[41]. - The company announced the discontinuation of RGLS4326 development in October 2021, shifting focus to farabursen targeting miR-17[151]. - The FDA granted Orphan Drug Designation to farabursen for the treatment of ADPKD in June 2022, with potential for additional designations for other candidates[172]. - The company may seek accelerated approval for farabursen based on a single pivotal Phase 3 study, but there is no assurance that the FDA will agree to this pathway[165][167]. Regulatory Environment - The FDA review process for NDAs typically takes 10 months for standard applications and 6 months for priority applications, but may be extended[90]. - The FDA may require post-marketing clinical trials to further assess drug safety and effectiveness after initial approval[95]. - Orphan drug designation can provide exclusivity for 7 years if the product receives the first FDA approval for a rare disease[97]. - The FDA has expedited development pathways such as Fast Track and Breakthrough Therapy designations to accelerate the approval process for serious conditions[98]. - The Fast Track program expedites the development of drugs for serious conditions, allowing for rolling review of NDA sections as they are completed[99]. - Breakthrough Therapy designation provides intensive guidance on drug development, starting as early as Phase 1, for drugs showing substantial improvement over existing therapies[100]. - Accelerated Approval allows drugs to be approved based on surrogate endpoints, with post-marketing studies required to confirm clinical benefits[101]. - Priority Review is granted to products that offer significant improvements in treatment where no satisfactory alternatives exist, facilitating faster evaluation by the FDA[102]. Competition and Market Landscape - The biotechnology and pharmaceutical industries are characterized by intense competition, with the company facing potential competition from larger, better-funded pharmaceutical companies[74]. - Otsuka Pharmaceutical Co., Ltd. received FDA approval in 2018 for Jynarque® to slow kidney function decline in adults at risk of rapidly-progressing ADPKD[75]. - Vertex completed IND-enabling studies of VX-407 in 2024 for a specific PKD1 mutation and is recruiting for a Phase 1 clinical trial[75]. - PYC Therapeutics announced regulatory clearance to initiate a Phase 1 study of PYC-003 in February 2025 targeting the PKD1 gene[75]. - Competitors have greater financial resources and expertise in R&D, which may lead to resource concentration through collaborations and M&A[76]. - The commercial potential may be reduced if competitors develop safer, more effective, or less expensive products[77]. Intellectual Property - The company has a portfolio of approximately 145 U.S. and foreign patents and patent applications related to microRNA drug products, with expected patent protection expiration between 2025 and 2045[53]. - The company has exclusive rights to approximately 150 patents and patent applications related to microRNA and microRNA drug products, with key chemical modifications expected to expire in 2027 and 2029[58]. - Intellectual property protection is critical, as failure to secure patents or protect trade secrets may hinder competitive positioning in the market[216]. - The lifespan of patents is limited, and once expired, the company may face competition from generic medications, affecting revenue potential[220]. - The company may encounter significant challenges in protecting intellectual property rights in foreign markets, which could adversely affect business operations[222]. Clinical Trials and Risks - The company faces significant risks if preclinical and clinical studies of product candidates do not yield successful results[146]. - The marketability of product candidates may suffer if adequate coverage and reimbursement are not provided by government and third-party payors[127]. - The company is subject to various regulations governing clinical trials and commercial sales in different jurisdictions[128]. - The company experienced delays in clinical trials, including a voluntary pause in the Phase 1 MAD trial for RGLS4326 due to unexpected toxicity observations in a mouse study[151]. - Clinical trial delays could shorten exclusive commercialization rights and allow competitors to enter the market earlier, impacting revenue generation[155]. - Adverse effects observed in clinical trials could lead to interruptions, delays, or denials of regulatory approval, significantly affecting commercialization efforts[156][157]. - The company faces risks related to the interpretation of clinical data, which may differ from regulatory authorities, impacting the approval and commercialization of product candidates[163]. - The outcome of clinical trials is uncertain, and interim results may not predict final outcomes, which could materially affect business prospects[159][162]. Operational Challenges - Manufacturing is contracted out to third parties, and the company does not own or operate manufacturing facilities[71]. - The company depends on third-party manufacturers for producing preclinical and clinical product candidates, which introduces risks related to supply chain disruptions and regulatory compliance[204]. - Limited sources of supply for drug substances may cause delays in developing and commercializing product candidates if disruptions occur[207]. - Manufacturing issues could lead to increased costs and delays in regulatory approvals, impacting the commercialization timeline[210]. - The company relies on CROs and clinical trial sites for conducting clinical trials, and any unsatisfactory performance could harm business prospects[212]. Employee and Organizational Structure - As of December 31, 2024, the company had 34 full-time employees, with 25 engaged in research and development[134]. - The company focuses on microRNA technology for drug development, which is a novel approach with no prior regulatory approvals for therapeutics targeting microRNAs[142]. - The success of the company's business depends on the ability to identify, develop, and commercialize microRNA therapeutics[145]. - The company relies on third-party collaborations for the development and commercialization of certain microRNA product candidates, which may limit control over development processes[199]. - There is a risk that third-party collaborators may not meet deadlines or perform satisfactorily, potentially delaying product development and revenue generation[201].

Financial Performance - Regulus reported a net loss of $12.8 million, or $0.20 per share, for Q4 2024, compared to a net loss of $8.1 million, or $0.40 per share, in Q4 2023[8] - Total operating expenses for the year ended December 31, 2024, were $50.0 million, compared to $31.1 million in 2023[15] - General and administrative expenses for Q4 2024 were $4.1 million, up from $2.5 million in Q4 2023[7] Research and Development - Research and development expenses increased to $9.7 million for Q4 2024, up from $5.8 million in Q4 2023, and totaled $35.4 million for the year, compared to $21.2 million in 2023[6] - The Phase 1b MAD trial of farabursen for ADPKD showed a reduction in kidney volume growth rate, with 26 subjects receiving a fixed dose of 300 mg every other week for three months[3] - The interim analysis of the fourth cohort indicated a mechanistic dose response with increases in polycystin biomarker levels[2] Cash and Assets - As of December 31, 2024, Regulus had $75.8 million in cash, cash equivalents, and short-term investments, with an expected cash runway extending into early 2026[6] - The company reported total assets of $84.2 million as of December 31, 2024, compared to $30.8 million in 2023[15] Regulatory and Market Information - The FDA has agreed on key components for a Phase 3 pivotal trial, including a 12-month htTKV endpoint for potential Accelerated Approval[5] - Approximately 160,000 individuals are diagnosed with ADPKD in the United States, with a global prevalence estimated at 4 to 7 million[9]

Core Insights - Regulus Therapeutics Inc. reported positive topline results from an interim analysis of the fourth cohort in the Phase 1b multiple-ascending dose clinical trial of farabursen for treating autosomal dominant polycystic kidney disease (ADPKD) [1][2] - The company has reached an agreement with the FDA on key components for a Phase 3 single pivotal trial, which may allow for Accelerated Approval based on a 12-month htTKV endpoint [2][5] Program Updates - The interim analysis involved 14 subjects from the fourth cohort, showing a favorable safety and tolerability profile, with evidence of a mechanistic dose response and a suggested reduction in kidney volume growth rate [2][3] - In the fourth cohort, 26 subjects received a fixed dose of 300 mg of farabursen every other week for three months, with results indicating similar effects on polycystin biomarkers compared to previous cohorts [3][4] - The Phase 1b MAD study is designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of farabursen in adult patients with ADPKD [4] Financial Results - As of December 31, 2024, the company had $75.8 million in cash, cash equivalents, and short-term investments, with an expected cash runway extending into early 2026 [6] - Research and development expenses for Q4 2024 were $9.7 million, compared to $5.8 million in Q4 2023, while total R&D expenses for the year were $35.4 million, up from $21.2 million in 2023 [6] - General and administrative expenses for Q4 2024 were $4.1 million, compared to $2.5 million in Q4 2023, with total G&A expenses for the year at $14.7 million, up from $10.0 million in 2023 [7] - The net loss for Q4 2024 was $12.8 million, or $0.20 per share, compared to a net loss of $8.1 million, or $0.40 per share, in Q4 2023 [8][14] About ADPKD - Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder leading to end-stage renal disease, characterized by the development of multiple cysts in the kidneys [9] - Approximately 160,000 individuals are diagnosed with ADPKD in the U.S., with a global prevalence estimated between 4 to 7 million [9] About Farabursen - Farabursen (RGLS8429) is a novel oligonucleotide designed to inhibit miR-17 and target the kidney, showing improvements in kidney function and size in preclinical models [10] - The Phase 1 studies have demonstrated that farabursen is well-tolerated with no serious adverse events reported [10] About Regulus - Regulus Therapeutics Inc. focuses on discovering and developing innovative medicines targeting microRNAs, with a strong intellectual property portfolio in the microRNA field [11]

Core Insights - Regulus Therapeutics Inc. announced positive clinical and regulatory updates from its ADPKD program, including favorable topline results from an interim analysis of the fourth cohort of its Phase 1b Multiple Ascending Dose (MAD) study of farabursen (RGLS8429) [1][4] - The company successfully held an End-of-Phase 1 meeting with the FDA, achieving alignment on key components for a Phase 3 pivotal trial aimed at potential Accelerated Approval [1][4] Clinical Trial Details - The Phase 1b MAD study is a double-blind, placebo-controlled trial assessing the safety, tolerability, pharmacokinetics, and pharmacodynamics of farabursen in adult patients with ADPKD [2] - The fourth cohort involved 26 subjects receiving a fixed dose of 300 mg of farabursen every other week for three months, showing a mechanistic dose response and a reduction in height-adjusted total kidney volume (htTKV) growth rate [3][5] - Safety data from all subjects indicated that farabursen was well tolerated [3][9] Regulatory Progress - The End-of-Phase 1 meeting with the FDA confirmed the acceptability of the program's chemistry, manufacturing, and controls (CMC), non-clinical, and clinical pharmacology plans [4] - The trial design for the Phase 3 study includes a 12-month htTKV endpoint for potential Accelerated Approval and a 24-month eGFR endpoint for potential Full Approval [5][6] Biomarker and Efficacy Insights - Exploratory results indicated a notable impact on urinary polycystin levels and htTKV growth rate, consistent across different imaging classes and PKD1 mutations [5][6] - The data suggest a high probability of success in meeting or exceeding targeted htTKV efficacy thresholds [5] Company Overview - Regulus Therapeutics Inc. focuses on developing innovative medicines targeting microRNAs, with a strong pipeline and intellectual property in the microRNA field [10] - The company is headquartered in San Diego, CA, and is publicly traded on Nasdaq under the ticker RGLS [10]

Core Points - Regulus Therapeutics Inc. is participating in two upcoming investor conferences: Evercore 7th Annual HealthCONx Conference on December 3, 2024, and Piper Sandler 36th Annual Healthcare Conference on December 4, 2024 [1] - The live events and replays will be available on the company's investor relations website for 90 days following the presentations [1] Company Overview - Regulus Therapeutics Inc. is a biopharmaceutical company focused on discovering and developing innovative medicines that target microRNAs [2] - The company has developed a pipeline supported by a strong intellectual property portfolio in the microRNA field and is headquartered in San Diego, CA [2]

Core Insights - Regulus Therapeutics has completed enrollment in the fourth cohort of the Phase 1b multiple-ascending dose clinical trial for RGLS8429, targeting autosomal dominant polycystic kidney disease (ADPKD) [1][3] - The company plans to present topline data from this cohort in early 2025, following positive results from earlier cohorts [2][4] - As of September 30, 2024, Regulus reported $87.3 million in cash and equivalents, providing a cash runway into the first half of 2026 [1][8] Program Updates - The fourth cohort of the Phase 1b MAD study involves patients receiving a 300 mg fixed dose of RGLS8429 every other week for three months [3] - Previous cohorts demonstrated a mechanistic dose response, with increases in urinary polycystins and reductions in height-adjusted total kidney volume (htTKV) [4][5] - An End-of-Phase 1 meeting with the FDA is anticipated by the end of 2024 [4] Corporate Highlights - Regulus presented a late-breaking poster at ASN Kidney Week, showcasing data from the first three cohorts, which indicated dose-responsive activity of RGLS8429 [5] - The company has entered into a Patent & Technology License Agreement with The University of Texas at Southwestern Medical Center, acquiring rights to jointly-owned patent rights targeting miR-17 for ADPKD treatment [7] Financial Results - For the third quarter of 2024, research and development expenses were $11.3 million, up from $5.5 million in the same period of 2023 [8][9] - General and administrative expenses increased to $3.9 million from $2.6 million year-over-year [9] - The net loss for the third quarter was $14.1 million, compared to $7.8 million in the same quarter of 2023 [10][16]

Announced positive topline data from the third cohort of patients in the Phase 1b MAD study of RGLS8429 in autosomal dominant polycystic kidney disease (ADPKD) On track for an End-Of-Phase 1 meeting by year-end Appointed Rekha Garg, M.D., M.S., to Chief Medical Officer Ended second quarter 2024 with cash, cash equivalents, and investments of $95.9 million; Cash runway into H1 2026 SAN DIEGO, Aug. 8, 2024 /PRNewswire/ -- Regulus Therapeutics Inc. (Nasdaq: RGLS), a biopharmaceutical company focused on the dis ...

SAN DIEGO, Aug. 6, 2024 /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 that members of the management team will present at the Canaccord Genuity 44th Annual Growth Conference on Tuesday, August 13th at 8:30 a.m. ET. A replay of the live presentation will be available under "Events and Presentations" through the investor relations section of ...

SAN DIEGO, July 9, 2024 /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 that the Company will participate in the following investor conferences: 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 ...