ELEVATE 2: Baseline Demographic Characteristics From the Phase IIB Study of the Efficacy and Safety of Two Doses of Rodatristat Ethyl When Added to Standard of Care for the Treatment of Pulmonary Arterial Hypertension

Background: Pulmonary arterial hypertension (PAH) is a rare progressive disease characterizedbyelevated resting mean pulmonary artery pressure and right ventricular hypertrophy. Platelet-derivedserotonin and serotonin produced in the lung induce excessive growth of pulmonary artery smoothmuscle cells and is associated with the development of PAH. Tryptophan Hydroxylase 1 (TPH1)isnecessary for serotonin synthesis and is overexpressed in pulmonary artery endothelial cells ofPAHpatients. Rodatristat ethyl is an investigational, orally administered prodrug for rodatristat, apotentTPH1 inhibitor, and potential first-in-class treatment for PAH. In the pulmonary vasculature,rodatristat may inhibit both receptor and serotonin transporter functions, with potential to reduceproliferation and contraction of pulmonary artery smooth muscle cells. Importantly, rodatristat ethyl wasdesigned tonot cross the blood brain barrier. Interim blinded baseline demographic data from theongoing Phase IIbstudy, ELEVATE 2 (NCT04712669), is summarized here in. Methods: ELEVATE 2 isa double blind, placebo-controlled study in which Group 1 PAH patients were randomized 1:1:1 toreceive placebo, 300 mg BID, or 600 mg BID of rodatristat ethyl in addition to standard of care (SOC)PAH treatment for a period of 24 weeks followed by an optional open-label extension (OLE). Theprimary end point is change in pulmonary vascular resistance (PVR) from baseline.The trial includedpatients age ≥18 years, functional class (FC) II-III, and six-minute walk distance(6MWD) between 100-550m and PVR of ≥350 dyn• sec•cm-5 at baseline. Results: Baseline characteristics are summarized inTable 1. At the time of this analysis, 90 patients wererandomized in the study; 37 patients completedthe main study, 35 enrolled in the OLE, and 6completed the first 24 weeks of the OLE. The mean agewas 53 years, 79% of the study population waswhite, and 76% of patients identified as female. Themean 6MWD was 420 m at baseline and 66% were classified as WHO FC II. Baseline pulmonaryvascular resistance was 668 dyn• sec•cm-5. Patients receiving three SOC drugs at randomizationrepresented 51% of the trial population and 29% were on a continuous infusion of a prostanoid.Conclusions: In this first report of ELEVATE 2, demographic data are broadly consistent with previouslyreported PAH clinical trial patient populations. Patients were stratified based on mono, dual, ortripleSOC therapies which could include a continuous infusion of a prostanoid.