Regulus Therapeutics (RGLS) H.C. Wainwright 26th Annual Global Investment Conference 2024 summary

Clinical development updates

• Planning an end-of-Phase I FDA meeting by year-end to align on Phase II/III protocol for accelerated approval of RGLS8429.

• Phase Ib study showed a dose response with significant increases in Polycystin-1 and -2 at 3 mg/kg, supporting advancement to pivotal trials.

• GFR slope analysis across cohorts showed no impact over short treatment, as expected for the three-month dosing period.

• Pivotal trial will use height-adjusted total kidney volume as the primary endpoint, with a two-year dosing duration and interim unblinding at one year.

• Fourth cohort (300 mg fixed dose) data will be reported early next year, informing the pivotal trial design.

Regulatory and trial design

• FDA has indicated willingness to consider approval based on a single pivotal trial using height-adjusted total kidney volume for accelerated approval.

• Enrollment for the pivotal trial is expected to take about 15 months for 300 subjects, with trial initiation targeted for mid-next year.

• Post-marketing studies will confirm clinical benefit on GFR, following the model used in other renal diseases.

Market opportunity and competitive landscape

• Approximately 160,000 diagnosed ADPKD patients in the U.S., with about 100,000 in the moderate to severe category.

• Less than 10% of eligible patients currently receive tolvaptan, mainly due to tolerability issues and side effects.

• Tolvaptan will lose U.S. patent exclusivity next year; other late-stage competitors are limited, with Vertex in early development for a subset of patients.