Safety and Efficacy of RT234 Vardenafil Inhalation Powder on Exercise Parameters in pulmonary Arterial Hypertension: Phase 2b, Dose-Escalation Study Design

Key assessments Primary efficacy endpoint •Change in peak VO2during CPET Secondary efficacy endpoints Effect on exercise capacity •Change in 6MWD measured during a 6MWT •Change in VE/VCO2slope •Change in end-tidal CO2apex response to exercise (highest level during CPET) •Change in duration of exercise during CPET Effect on exertional symptoms of PAH •Change in peak perceived dyspnea during CPET , assessed by Modified Borg DyspneaScale Score •Change in Patient Global Impression of Severity (PGI-S) for CPET •Change in PGI-S for 6MWT Exploratory endpoints •Pharmacokinetics •Exposure–response analysis Safety •Treatment-emergent adverse events •Vital signs •Physical examination •12-lead electrocardiogram Figure 2: Study design, CL202•Pulmonary arterial hypertension (PAH; Group 1 pulmonary hypertension) is a rare disease defined by abnormally high mean pulmonary arterial pressure (≥20 mmHg)1 •PAH is currently managed using chronic, scheduled treatments to improve exercise capacity and delay clinical worsening •Availability of an as-needed (PRN) treatment for rapid symptom resolution would further enhance patient quality of life •RT234 is an investigational drug/device combination of vardenafil hydrochloride and the novel Axial Oscillating Sphere (AOS™) dry powder inhaler BACKGROUND Safety and Efficacy of RT234 Vardenafil Inhalation Powder on Exercise Parameters in Pulmonary Arterial Hypertension: Phase 2b, Dose-Escalation Study Design Raymond L. Benza,1Veronica Franco,1Mandar A. Aras,2 Leslie Spikes,3Daniel Grinnan,4Carol Satler5 1The Ohio State University Wexner Medical Center, Columbus, OH, USA; 2University of California San Francisco, San Francisco, CA, USA; 3University of Kansas Medical Center, Kansas City, KS, USA; 4Virginia Commonwealth University School of Medicine, Richmond, VA, USA; 5Respira Therapeutics, Inc., Boston, MA, USA CONCLUSIONS •RT234 is a first-in-class treatment for exertional symptoms of PAH, addressing the unmet clinical need for a PRN treatment for this disease •If the CL202 trial is successful, it is anticipated that RT234 PRN therapy will provide acute improvements in VO2in patients with PAH •The results of this trial are expected to inform the design of Phase 3 trials of RT234 Poster presented at Pulmonary Hypertension Association (PHA 2022); June 9–12, 2022; Atlanta, GA, USA For more information, contact Dr Carol Satler([email protected]) Statistical analyses •The planned sample size is 40 patients, with a 20% dropout adjustment –The estimated power to detect a change in peak VO2of 1.5 mL O2kg-1min-1between baseline and post RT234 is ≥80% •The primary endpoint will be analyzedby 1-sample t-test (if peak VO2follows a normal distribution) or 1-sample Wilcoxon signed-rank test (if the normality assumption is rejected) •Hochberg step-up procedure will be used to account for multiplicity of secondary endpoint analyses •Safety data will be summarized descriptively OBJECTIVE METHODS •RT234 CL202 is a multicenter, open-label, dose-escalation, Phase 2b trial (NCT04266197) that will evaluate the efficacy and safety of RT234 as assessed by changes in peak oxygen consumption (VO2) by cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT) DISCLOSURES •R. L. Benza: Steering committee member for Abbott Laboratories, Cereno Scientific, Gossamer Bio, RespiraTherapeutics, and United Therapeutics; V. Franco: Ohio State University receives research support from Abbott Laboratories, AcceleronPharma, Cordella(Endotronix), RespiraTherapeutics, and United Therapeutics; M. A. Aras: None; L. Spikes: Principal investigator for trials sponsored by AcceleronPharma, Bayer, Gossamer Bio, Insmed, Merck & Co, RespiraTherapeutics, and United Therapeutics; D. Grinnan: Received grant support from and is on the grant review committee at Bayer,and received grant support from RespiraTherapeutics; C. Satler: Current employee of RespiraTherapeutics •This study is funded by RespiraTherapeutics, Inc. Medical writing assistance was provided by Elise Laming, PhD, of ProScribe –Envision Pharma Group, and was funded by RespiraTherapeutics, Inc. aPatients with PAH on stable, disease-specific PAH background therapy with limited exercise capacity. 6MWT , 6-minute walk test; CPET , cardiopulmonary exercise testing; DPI, dry powder inhaler; PAH, pulmonary arterial hypertension;PK, pharmacokinetic; SMC, Safety Monitoring Committee; VO2, oxygen consumption. Enrollment •Enrollmentbegan in September 2020 and the trial is expected to be completed in December 2023 •The trial will be conducted at 25–30 sites in the United States End of study Safety follow-up Screening Day -28 to Day -3 Day 1 Day 8 Day 15 Day 45 CPET (baseline) CPET 6MWT RT234 via DPI RT234 via DPI Enrolleda (N=40) 6MWT (baseline) Cohort 1 (N=20): RT234 0.5 mg SMC review of Cohort 1 safety, efficacy, and PK data Cohort 2 (N=20): RT234 1.0 mg Primary endpoint Change in peak VO2from Day 1 to Day 8 (15 min post dose) Prospective, multicenter, open-label, 2-cohort, dose-escalation, Phase 2b study Figure 1: The AOS DPI device used in RT234 (RespiraTherapeutics, Inc., Albuquerque, NM, USA) AOS, Axial Oscillating Sphere; DPI, dry powder inhaler. Key eligibility criteria Inclusion •Aged 18–80 years, inclusive •Right heart catheterization–confirmed PAH •On ≤2 stable oral and/or inhaled PAH-specific therapies •6-minute walk distance (6MWD) ≥50 m •CPET with minute ventilation/volume of exhaled CO2(VE/VCO2) slope ≥36 Exclusion •Baseline systemic hypotension (mean arterial pressure <50 mmHg or systolic blood pressure [SBP] <90 mmHg) •Uncontrolled hypertension (SBP >175 mmHg or sitting diastolic blood pressure >110 mmHg) •On parenteral PAH medication or riociguat •Current or previous left-sided heart disease and/or clinically significant cardiac disease Please scan code to view poster or visit https://bit.ly/3LjrMlQ REFERENCE 1.SimonneauG, et al. EurRespir J.2019;53:1801913.

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