Regulus Therapeutics Inc. is a clinical-stage biopharmaceutical company focused on discovering and developing first-in-class drugs targeting micro RNAs to treat diseases with significant unmet medical need. The company was formed in 2007 when Alnylam Pharmaceuticals, Inc. and Ionis Pharmaceuticals, Inc. contributed significant intellectual property, know-how and financial and human capital to pursue the development of drugs targeting micro RNAs.
Business Overview
Regulus is currently focused on orphan kidney diseases where micro RNA genetic drivers are implicated and there are clear unmet medical needs. The company's lead product candidate, RGLS8429, an anti-miR oligonucleotide targeting miR-17 for the treatment of autosomal dominant polycystic kidney disease (ADPKD), is in Phase 1b clinical development. In June 2022, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to RGLS8429 for the treatment of ADPKD.
In addition to this program, Regulus continues to advance and expand its internal discovery pipeline to identify potential product candidates. The company has assembled significant expertise in the micro RNA field, including expertise in micro RNA biology and oligonucleotide chemistry, a broad intellectual property estate, relationships with key opinion leaders and a disciplined drug discovery and development process.
Financials
From inception through March 31, 2023, Regulus has received $530.1 million from the sale of its equity and convertible debt securities, $101.8 million from collaborations, principally from upfront payments, research funding and preclinical and clinical milestones, and $19.8 million in net proceeds from its Term Loan. As of March 31, 2023, the company had cash, cash equivalents and investments of $107.7 million.
For the full year 2022, Regulus reported an annual net loss of $30.0 million, with no revenue generated. The company's annual operating cash flow was negative $26.8 million, and its annual free cash flow was negative $27.4 million.
In the first quarter of 2023, Regulus reported a net loss of $8.5 million, with no revenue generated. The company's operating cash flow was negative $8.7 million, and its free cash flow was negative $8.7 million during the quarter.
Recent Developments
Regulus' lead program, RGLS8429, is being evaluated in a Phase 1b multiple-ascending dose (MAD) study in adult patients with ADPKD. In the first cohort of the MAD study, RGLS8429 was well-tolerated and demonstrated increases in both polycystin-1 (PC1) and polycystin-2 (PC2) biomarkers, which are key disease markers in ADPKD. The company has since advanced the study to higher dose cohorts and is evaluating the impact of RGLS8429 on imaging-based biomarkers of kidney disease progression.
In March 2023, Regulus announced positive topline results from the second cohort of the Phase 1b MAD study, which showed greater biological activity of RGLS8429 at the 2 mg/kg dose level compared to the 1 mg/kg dose and placebo. Exploratory results also suggested potential impacts on height-adjusted total kidney volume (htTKV) and total kidney cyst volume (TKCV), which the company plans to further evaluate in the ongoing study.
Regulus is also conducting a chronic mouse toxicology study for RGLS8429 to support potential accelerated approval pathways. In December 2022, the company held a constructive Type D meeting with the FDA to discuss the accelerated approval pathway for RGLS8429 in ADPKD, which confirmed the potential for this regulatory approach based on a single pivotal Phase 2 study.
Beyond RGLS8429, Regulus' preclinical pipeline focuses on dysregulated micro RNAs implicated in diseases of high unmet medical need where the company can effectively deliver to the target tissue or organ, such as the liver, kidney and central nervous system. The company is also investigating target organ-selective delivery strategies to enhance the therapeutic potential of its micro RNA modulators.
Risks and Challenges
Regulus faces several key risks in its business, including the novel and unproven nature of its micro RNA technology, the challenges of successfully developing and commercializing product candidates, potential safety and efficacy issues with its product candidates, the need for additional capital to fund its operations, and intense competition in the biotechnology and pharmaceutical industries.
Outlook
Despite these risks, Regulus remains committed to advancing its micro RNA-based therapeutic approach and addressing significant unmet medical needs in areas such as ADPKD. The company's progress with RGLS8429 and the potential for an accelerated approval pathway provide cautious optimism, though the path to commercialization remains uncertain. Investors will closely monitor Regulus' ability to navigate the challenges of micro RNA drug development and deliver on its promising pipeline.