RTN-001

A next-generation PDE-5 inhibitor in development for hypertension

RTN-001

RTN-001 is a next-generation, once-daily, oral, small molecule PDE-5 inhibitor designed to lower blood pressure by potentiating endogenous nitric oxide levels and signaling, thus favoring the restoration of vascular homeostasis.

Unlike first-generation PDE-5 inhibitors, RTN-001 was engineered to enable more effective distribution into cardiovascular smooth muscle tissues and potentiate nitric oxide signaling through its key intracellular secondary messenger, cGMP, within the arterial smooth muscle cell.

Clinical experience to date

RTN-001 has been evaluated in a clinical development program of nine completed trials, a total of 265 subjects were enrolled of whom 243 received RTN-001. The trials included two randomized, placebo-controlled Phase 2 pilot trials in adults with hypertension receiving up to four concomitant antihypertensive medications.

In the two Phase 2 pilot trials, RTN-001 achieved clinically meaningful placebo-adjusted reductions in systolic and diastolic blood pressure in patients with hypertension, and reductions in both peripheral and central blood pressure were also observed at trough. RTN-001 was generally well tolerated, with no drug-related serious adverse events reported. The observed adverse event profile was consistent with the established PDE-5 inhibitor class.

Ongoing Phase 2b trial

We have initiated a randomized, multicenter, double-blind, placebo-controlled Phase 2b dose-ranging trial in adults with uncontrolled hypertension.

Active Phase 2 Study (NCT07142356)

Population
Adults with uncontrolled hypertension receiving two to five concomitant antihypertensive medications
Sites
30+ clinical sites across the United States
Design
Four cohorts receiving placebo or one of three doses of the modified release formulation of RTN-001, once daily for 12 weeks
Primary endpoint
Change from baseline in peripheral office-seated systolic blood pressure at week 4 compared to placebo
Key secondary endpoints
Mean change from baseline in 24-hour ambulatory blood pressure monitoring, and mean change in central blood pressure compared to placebo

The trial also includes pharmacokinetic and safety assessments to characterize drug exposure, support dose selection and evaluate the overall safety and tolerability profile of RTN-001. We believe this trial will enable and inform our planned Phase 3 clinical trial.

Phase 2b trial schema: 2-week run-in, then 12-week treatment with RTN-001 15 mg, 30 mg, or 45 mg QD or placebo, followed by post-treatment follow-up.