{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:46:50Z","timestamp":1792007210464,"version":"4.4.0"},"reference-count":32,"publisher":"BMJ","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","award":["No award\/grant number"],"award-info":[{"award-number":["No award\/grant number"]}],"id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pulmovant, Inc.","award":["No award\/grant number"],"award-info":[{"award-number":["No award\/grant number"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"accepted":{"date-parts":[[2026,6,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Mosliciguat, a soluble guanylate cyclase (sGC) activator, is designed for lung-targeted delivery via dry powder inhalation. Nitric oxide (NO) binds sGC\u2019s prosthetic heme group, catalysing cyclic guanosine monophosphate (cGMP) production, resulting in increased vasodilation, reduced inflammation\/apoptosis, reverse vascular remodelling and antifibrotic effects. sGC is redox sensitive, losing heme in pulmonary hypertension (PH) oxidative stress conditions. Mosliciguat\u2019s novel \u2018activator\u2019 mechanism directly binds the sGC heme-binding pocket to induce cGMP, allowing it to target NO-insensitive heme-free sGC, potentially rescuing additional enzymatic activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A Proof-of-Concept Trial of Inhaled Mosliciguat, a First-in-Class Soluble Guanylate Cyclase Activator (ATMOS; non-randomised, open-label phase 1b trial) assessed single-dose escalation of mosliciguat in participants with pulmonary arterial hypertension or chronic thromboembolic PH. 38 participants received mosliciguat. The per protocol set (PPS, n=20) included NO-non-responsive participants with baseline pulmonary vascular resistance (PVR) \u22655 Wood units (n=4\/dose). The pharmacodynamic set (PDS, n=37) included NO-responsive participants. Five PPS participants underwent a \u226524-hour washout from background therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the PPS, doses of 0.24, 0.48, 1.0, 2.0 and 4.0\u2009mg resulted in mean peak per cent PVR reductions from baseline (95%\u2009CI) of 21.0% (31.6% to 10.4%), 16.1% (32.8% to \u22120.7%), 25.9% (60.3% to \u22128.4%), 38.1% (55.9% to 20.3%) and 36.3% (48.3% to 24.4%), respectively, and generally persisted over the 3-hour observation period. Similar effects were seen in the PDS. The majority of adverse events were mild; most frequently reported were headache (n=3\/38; 7.9%), decreased oxygen saturation and fatigue (n=2\/38; 5.3% each). No safety-relevant changes were seen in systemic vascular resistance or blood pressure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Mosliciguat demonstrated a favourable safety profile and sustained, clinically meaningful reductions in PVR in participants with PH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03754660\">NCT03754660<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  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