Our Science

About Mosliciguat

Pulmovant’s first investigational product is mosliciguat, a soluble guanylate cyclase (sGC) activator. It has the potential to be first-in-class and to have a differentiated mechanism of action (MOA). Mosliciguat’s MOA is thought to drive vasodilation^1,2, including in conditions characterized by increased lung tissue hypoxia and oxidative stress^3,4 and may have anti-inflammatory⁵ and anti-fibrotic properties⁶. 

What is sGC?

sGC is a key enzyme in the nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) signaling pathway that helps maintain vascular homeostasis^3,4.  

NO binds the prosthetic heme group of sGC, catalyzing cGMP production, which literature suggests leads to:  

• Increased vasodilation^1,3
• Reduced inflammation and apoptosis^5,7
• Reduced platelet aggregation⁵
• Reverse vascular remodeling^6,7
• Anti-proliferative effects⁹
• Anti-fibrotic effects^7,8

PH and lung disease conditions can have dysfunctional sGC activity¹⁰.

Mosliciguat, an sGC activator, aims to restore sGC function, even in conditions of oxidative stress seen in PH-ILD.

• PH and lung disease conditions lead to oxidative stress, which results in less NO and less of the reduced (native) form of sGC and more of the other pathologic variants, such as oxidized and heme-free sGC (Apo) forms^4,7,9.
• Mosliciguat, an sGC activator, aims to restore and improve catalytic function of sGC, even the pathological oxidized and heme-free sGC (Apo) variants^1,3,4.
• sGC activators mimic NO-bound heme, and therefore are NO-independent and heme-independent^1,3,4. This property may allow activators to preserve more sGC enzymatic activity in PH and ILD disease conditions of oxidative stress where there is less NO and less heme^1,3.