Mechanism of Action

In rat models of PAH, a sotatercept analog:

• Reduced expression of proinflammatory markers at the pulmonary arterial wall,
• Reduced leukocyte recruitment,
• Inhibited proliferation of endothelial and smooth muscle cells, and
• Promoted apoptosis in diseased vasculature.

These cellular changes were associated with thinner vessel walls, reversed arterial and RV remodeling, and improved hemodynamics.

---

In PAH clinical studies, WINREVAIR decreased PVR
and reversed RV remodeling

---

WINREVAIR is a novel PAH treatment that targets the activin signaling pathway

---

Treat PAH differently by adding a first in-class activin signaling inhibitor—target a key
pathway underlying PAH and prescribe WINREVAIR for your patients on stable
background therapy^1-11,14

---

ActRIIA = activin receptor type IIA; BMPRII = bone morphogenetic protein receptor type II; NO-sGC-cGMP = nitro oxide-soluable guanylate cyclase-cyclic guanosine monophosphate; PDE5i = phosphodieterase 5 inhibitor; sGC = soluble guanylate cyclase; TGF-β = transforming growth factor β.

[SSI PLACEHOLDER]

Lorem ipsum dolor sit amet, consectetur adipiscing elit. Vestibulum in nu Ila odio. Donec vitae libero hendrerit, tincidunt erat a, aliquam arcu. Proin vel dictum risus. Nunc aliquam pellentesque magna, ut dignissim mi viverra sed. Nunc eget dolor quis erat rhoncus varius ut vel urna. Etiam commodo odio felis, nee mattis ex lobortis quis. Nulla eleifend eleifendjusto. Phasellus varius tempor lacinia. Suspendisse lacus ante, consequat nee orci et, congue dictum lectus. Phasellus lectus nisi, maximus ac sem ut, varius blandit sapien. Nam efficitur sapien sed dui mattis, nee varius elit egestas. Mauris commodo nee neque sit amet sodales.

Ut congue imperdiet diam, non faucibus sapien finibus non. Maecenas lacus mi, sodales non convallis non, malesuada at mi. Maecenas risus eras, luctus eget dapibus quis, semper vel massa. Phasellus euismod tortor id tortor interdum maxim us. Etiam sodales erat sit amet quam sollicitudin hendrerit. Sed sollicitudin lectus ut mi lobortis, vel efficitur arcu ullamcorper. Nam aliquam eget ligula sit amet feugiat. Sed vulputate, arcu et cursus ultrices, velit nisl feugiat mauris, ut eleifend ante dolor vitae massa. Praesent lacinia purus leo, quis porta ipsum commodo in. Donec pretium leo ante, id faucibus purus bibendum id. Donec iaculis augue augue, aliquet pulvinar mi vehicula in. Pellentesque habitant morbi tristique senectus et netus et malesuada fames ac turpis egestas. Phasellus enim massa, tempor non elit congue, rutrum rhoncus nulla. Donec finibus eu ipsum vitae porttitor. Vestibulum tincidunt tincidunt quam, id lobortis eras luctus ac. Pellentesque faucibus lacus vel elit viverra fringilla.

1. Hoeper MM, Badesch DB, Ghofrani HA, et al; STELLAR Trial Investigators. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388(16):1478-1490. 2. Treposuvi. Summary of Product Characteristics. AOP Orphan Ltd; 2024. 3. Adempas. Summary of Product Characteristics. Bayer AG; 2023. 4. Ventavis. Summary of Product Characteristics. Bayer AG; 2023. 5. Adcirca. Summary of Product Characteristics. Eli Lilly Nederland BV; 2024. 6. Volibris. Summary of Product Characteristics. GlaxoSmithKline (Ireland) Limited; 2024. 7. Opsumit. Summary of Product Characteristics. Janssen-Cilag International NV; 2023. 8. Tracleer. Summary of Product Characteristics. Janssen-Cilag International NV; 2024. 9. Uptravi. Summary of Product Characteristics. Janssen-Cilag International NV; 2024. 10. Flolan. Summary of product characteristics, labelling and package leaflet. EMA; 2012. 11. Revatio. Summary of Product Characteristics. Upjohn EESV; 2024. 12. Humbert M, McLaughlin V, Gibbs SR, et al. Sotatercept for the treatment of pulmonary arterial hypertension. N Engl J Med. 2021;384:1204-1215. 13. Hassoun PM. Pulmonary arterial hypertension. N Engl J Med. 2021;385(25):2361-2376. 14. Humbert M, Kovacs G, Hoeper MM, et al; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022;43(38):3618-3731.