8-K: Regulus Therapeutics Announces Positive Farabursen Data and FDA Agreement, Reports Year-End 2024 Financial Results

Regulus Therapeutics reported positive interim results from a Phase 1b trial of farabursen for ADPKD and alignment with the FDA on a Phase 3 trial design, along with its year-end 2024 financial results.

Summary

• Regulus Therapeutics announced 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).
• The company has reached an agreement with the FDA on key components of a Phase 3 single pivotal trial for potential Accelerated Approval.
• The interim analysis of the first 14 subjects in the fourth cohort showed continued evidence of a mechanistic dose response, with similar effects on polycystins 1 and 2 (PC1 and PC2) biomarkers to cohort 3.
• Data also suggested a reduction in htTKV growth rate after 3 months of treatment.
• As of December 31, 2024, Regulus had $75.8 million in cash, cash equivalents, and short-term investments, which is expected to fund operations into early 2026.
• Research and development expenses were $9.7 million for the fourth quarter of 2024 and $35.4 million for the year ended December 31, 2024.
• General and administrative expenses were $4.1 million for the fourth quarter of 2024 and $14.7 million for the year ended December 31, 2024.
• Net loss was $12.8 million, or $0.20 per share, for the fourth quarter of 2024 and $46.4 million, or $0.82 per share, for the year ended December 31, 2024.

Sentiment

Score: 7

Explanation: The document presents a generally positive outlook due to the positive clinical trial data and agreement with the FDA, but is tempered by the reported net losses and inherent risks in drug development.

Positives

• Positive topline data from the interim analysis of the fourth cohort in the Phase 1b MAD study of farabursen for ADPKD was reported.
• The company reached alignment with the FDA on key components of a Phase 3 trial design for farabursen.
• The company's cash runway is expected to extend into early 2026.

Negatives

• The company reported a net loss of $12.8 million, or $0.20 per share, for the fourth quarter of 2024.
• The company reported a net loss of $46.4 million, or $0.82 per share, for the year ended December 31, 2024.

Risks

• The approach to discover and develop drugs is novel and may not 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.
• The clinical development strategy may change.
• Preclinical and clinical studies may not be successful.
• There are risks related to regulatory review and approval.
• There are risks related to reliance on third-party collaborators and other third parties.
• There are risks related to intellectual property.
• There are risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics.
• Additional data may be negative.
• There are risks related to the ability to successfully secure and deploy capital.

Future Outlook

The company expects its cash runway to extend into early 2026 and looks forward to sharing topline data from all 26 subjects in cohort 4 in the coming weeks.

Management Comments

• 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 farabursens development for patients living with ADPKD, who currently have limited treatment options.

Industry Context

Regulus Therapeutics is focused on developing microRNA-targeting therapies, a relatively novel approach in the biopharmaceutical industry. The positive data and FDA agreement for farabursen position the company as a potential key player in the ADPKD treatment landscape, which currently has limited options.

Comparison to Industry Standards

• Regulus is developing Farabursen for ADPKD, a disease with limited treatment options, competing with companies like Otsuka Pharmaceutical, which markets Tolvaptan (Jynarque), a vasopressin V2 receptor antagonist.
• The agreement with the FDA on a Phase 3 trial design with a 12-month htTKV endpoint for potential Accelerated Approval is similar to strategies employed by other companies seeking expedited approval for rare disease treatments.
• The company's cash runway into early 2026 is a critical factor, as drug development is capital-intensive, and the company's financial position will be closely compared to peers in the biotechnology sector.

Stakeholder Impact

• Shareholders may react positively to the clinical trial progress and FDA agreement.
• Patients with ADPKD may benefit from the development of a new treatment option.
• Employees of Regulus Therapeutics may experience increased job security due to the company's progress.

Next Steps

• The company plans to share topline data from all 26 subjects in cohort 4 in the coming weeks.
• The company will proceed with the Phase 3 single pivotal trial for farabursen.

Key Dates