Acute Hemodynamic Improvement in Chronic Pulmonary Arterial Hypertension on Dual Therapy Following RT234-PAH Inhalation.

A. Keogh1, N. Dwyer2, E. Kotlyar1, D. Kaye3, M. Maurer4, J. Weers4, and E. Parsley4 Acute hemodynamic improvement in chronic pulmonary arterial hypertension on dual therapy following RT234 inhalation 1.St. Vincent’s Hospital, Sydney, NSW , Australia 2.Royal Hobart Hospital, Tasmania, Australia 3.The Alfred Hospital, Melbourne, VIC, Australia 4.RespiraTherapeutics, Inc., Burlingame, CA, USA Conflict of Interest Disclosure §The RT234-CL201 study was funded by RespiraTherapeutics, Inc. §The institutions of Anne Keogh, Nathan Dwyer, Eugene Kotlyar, and David Kaye received payment for the conduct of the trial. §Jeffry Weers, Mari Maurer, and Edward Parsley were employees or consultants of Respira, and received compensation in the form of salary, benefits, stock options or consulting fees. §Jeffry Weers is a co-inventor on two patent applications related to RT234 A PRN inhaled treatment designed to acutely improve symptoms and exercise capacity RT234-CL201 Baseline Demographics Study Design •Hemodynamic, dose escalation study in 15 PAH patients, 3 dose cohorts of 5 subjects each •Two-part study: Part A and Part B •Part A: Receive 2 doses while undergoing a Right Heart Catherization procedure (Day 1) •Part B: 6MWT post dose at highest tolerated dose achieved in Part A (Day 15) Category Value Age (Years ±SD) 54 ±14 Range 22 to 80 Sex (n) Female (11) Race (n) White (11) 6MWD (m) 426 ±129 FC (n) II (8); III (5); IV (1) mPAP(mmHg) 46 ±15 PCWP (mmHg) 12 ±3 PVR (dyn.sec.cm-5) 584 ±345 PDE5i (n) Sildenafil 5 Tadalafil 9 ERA (n) Macitentan 10 Bosentan 2 Ambrisentan 2 RT234-CL201 Hemodynamics Study Inhaled vs. Oral: Comparable pulmonary hemodynamics at 1/33rdthe dose *Measurements at peak effect in PVR (30 min); 95% CI determined using Hodges-Lehman point estimates Source (oral vardenafil):Ghofraniet al.: J Am Coll Cardiol. 2004; 6: 1488. RT234 acutely improves cardiac output over 2 h (cycle ergometry) Acute Improvements in 6MWD (Part B) §Represents results for PAH patients with a baseline 6MWD < 450 m §Increases in mean 6MWD is observed for RT234 in the presence of therapeutic levels of PDE5i/ERA dual therapy §Unlike treprostinil, significant increases in 6MWD are observed after administration of a single dose (36 m vs. 6 m) PDE5i / ERA TRIUMPH (McLaughlin, 2010) Inhaled Treprostinil + monotherapyRT234 Single dose of RT234 is well tolerated on top of maintenance therapies Conclusions §The RT234-CL201 study validated that the RT234 drug product has the critical design features of an as-needed vasodilator - A rapid onset of action within 5 minutes of administration; acute improvements in exercise tolerance of 35 m - A duration of action of at least one to two hours post-administration - Minimal local and systemic safety and tolerability issues when administered in addition to maintenance therapies - Noninvasive delivery system with administration over < 1 minute §The results of the study indicate that RT234 has a safety and efficacy profile suitable for continued clinical development as an as-needed vasodilator Questions?

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