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 vasodilation1, including in conditions characterized by increased lung tissue hypoxia and oxidative stress and may have anti-inflammatory2 and anti-fibrotic properties3.
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.
NO binds the prosthetic heme group of sGC, catalyzing cGMP production, which leads to:1-5
- Increased vasodilation
- Reduced inflammation and apoptosis
- Reduced platelet aggregation
- Reverse vascular remodeling
- Anti-proliferative effects
- Anti-fibrotic effects
PH and lung disease conditions can have reduced sGC activity.
Mosliciguat, an sGC activator, aims to restore sGC function, even in conditions of oxidative stress seen in PH-ILD.
Mosliciguat's potential to be a safe and effective treatment option is supported by early clinical data and strong biological rationale for pulmonary vasodilation to treat Group 3 PH patients. The inhaled delivery of the drug targets the lungs directly and is intended to improve therapeutic potential while minimizing systemic side effects.
70 million people live with pulmonary hypertension
What is Pulmonary Hypertension?
Pulmonary hypertension (PH) is a progressive and debilitating condition characterized by high blood pressure in the blood vessels of the lungs. This elevated pressure forces the heart to work harder to pump blood through the lungs, leading to symptoms such as shortness of breath, fatigue, chest pain, and dizziness.6 The World Health Organization (WHO) has classified PH into five groups based on their underlying causes, symptoms, and treatment approaches. Group 3 PH is a subtype of PH that arises from lung diseases and is the second most common form of PH.
Interstitial lung disease (ILD) describes a large group of diseases that causes progressive damage of the lungs, making it difficult for patients to breathe.
In the US and EU, up to 200,000 patients are living with pulmonary hypertension associated with interstitial lung disease (PH-ILD), a subset of Group 3 PH, and have limited to no approved treatment options.7-8 Current available treatment options require multiple doses per day and can be difficult for patients to adhere to.
Mosliciguat aims to provide an effective, once-daily, inhaled treatment option with a favorable tolerability and safety profile to patients with high unmet need and limited to no approved treatment options.
Sources:
1. Stasch, JP. Circulation. 2011. Volume: 123, Issue: 20, Pages: 2263-2273
2. Mauersberger, C et al. Nature Cardiovascular Research. 2022. Volume 1, Pages 1174–1186
3. Dumitrascu, R et al. Circulation. 2006. Volume 113, Number 2
4. Sandner, P et al. Respir Med. 2017. Jan:122 Suppl 1:S1-S9
5. Bayer HealthCare. Respiratory Medicine. 2017. Volume 122, Supplement 1, Pages S1-S9
6. Rich, S et al. Lancet Respir Med. 2018. Volume 6, Issue 8
7. Raghu, G et al. Eur Respir J. 2015; 46:1113-1130
8. Sathananthan, M et al. Chest. 2023. Volume 165, Issue 2