Phase 3, Open-Label Multicenter Study of Sotatercept in Japanese Participants With Pulmonary Arterial Hypertension (copy) | JACC: Asia

0:00Hello, my name is Yoon Shenzhou. I'm a professor and chief over the heart, lung, and the rest of the center, at the Sichuan Provincial People's Hospital. Today, I'm honored to present an article from Jack Asher entitled Open Label Multi-Santer Study of Sultatecept in Japanese participants with pulmonary artery hypertension, led by Professor Hiromi Matsubara and the colleagues from the Clinical Research Institute at Okayama Medical Center. Pulmonary artery hypertension, or PAH, is a less limiting disease, characterized by progressive increases in pulmonary muscular resistance, rising right ventricular afterload, and the eventual red heart failure. For decades, PAH therapy has largely been extrapolated from systemic hypertension, with a predominant focus on vasodilation. This approach is effective

1:06in systemic hypertension, where a disease is driven by functional dysregulation of vascular tone. PAH, however, is fundamentally different. PAH is not simply a disease of elevated pressure, but a disease of progressive pulmonary vascular remodeling, and docellular dysfunction, excessive cellular proliferation, and resistance to aptosis. Progressive releases that distal pulmonary vascular, creating a lottery fixed increase in pulmonary vascular resistance, that vasodilators alone cannot reverse. Although current PAH therapy has improved the symptoms, and the exercise capacity, long-term outcomes remain suboptimal. Importantly, the benefits may not be driven primarily by vasodilation, but rather by modest anti-proliferative effects on the pulmonary vascular. Against this backdrop,

2:10PAH treatment is shifting from vasodilation toward disease modification. Central to this shift is the BMP-TGF-Bate signaling axis. So, to accept, on active receptor type 2A-FC-fueling protein, targets this pathway by restoring anti-proliferative signaling and the pulmonary vascular hemostasis, rather than inducing acute vasodilation. This started by mass borrower and colleagues provides critical regional evidence supporting this approach. In the Japanese cohort, with lost standing disease and intensive background therapy, so touch-cept produce consistent improvements across hemodynamic, functional, and biomarker domains, with a safety profile consistent with prior global experience. In summary, this study feels an important regional evidence gap, and reinforces a broader

3:14paradigm shift in PAH management, from treating pressure to correcting vascular pathology. So touch-cept represents a mechanistically distinct addition to current therapy and may meaningfully alter the disease trajectory of PAH in Asia and beyond. Thank you for listening.