Regulus Therapeutics (RGLS) 2024 Wells Fargo Healthcare Conference summary

Program overview and clinical progress

• Lead program targets miR-17 for autosomal dominant polycystic kidney disease (ADPKD), currently in phase 1b with a fourth cohort nearing completion, focusing on a fixed dose for phase 2 readiness.

• ADPKD affects about 160,000 in the US, with 100,000 in the moderate to severe category; current treatment (tolvaptan) is used by less than 10% due to tolerability and safety issues.

• RGLS8429 has shown dose-dependent increases in polycystin levels and stabilization or reduction in kidney volume over a short treatment period, with statistical significance at higher doses.

• Cohort four uses a fixed dose in a prefilled syringe, aiming for safety, tolerability, and consistent biomarker response, with data expected early next year.

• Phase 2 could start mid-next year, with the pivotal trial planned as a global, 300-patient, one-year study for accelerated approval based on total kidney volume.

Disease landscape and unmet need

• ADPKD is an inherited disease, mostly due to PKD1 mutations, with a significant addressable population and limited treatment options.

• Tolvaptan, the only approved drug, has major tolerability issues (polyuria, liver toxicity), leading to low adherence and dose reductions.

• Market research shows high intent to prescribe a new therapy with similar efficacy but better safety and tolerability.

• Tolvaptan generated $1.3 billion in sales last year despite low utilization, indicating a large commercial opportunity.

Mechanism of action and clinical data

• miR-17 is upregulated in ADPKD, suppressing PKD1/2 gene expression; the therapy uses antisense oligonucleotides to inhibit miR-17, increasing polycystin and reducing cystogenesis.

• Clinical data show dose-dependent increases in polycystin and stabilization of kidney volume, with the most robust effects at 3 mg/kg.

• The fixed-dose cohort is open-label, designed to validate safety and efficacy for commercial use and home administration.