Pulmovant, a clinical-stage biotechnology company and Roivant subsidiary, announced the publication of Phase 1 pharmacokinetics data for mosliciguat, a potential first-in-class inhaled soluble guanylate cyclase (sGC) activator designed for pulmonary hypertension treatment. The peer-reviewed manuscript, titled "Pharmacokinetics and Lung Deposition After Administration of Inhaled Mosliciguat (BAY 1237592): Results from Randomized Phase I Studies in Healthy Men," was published in Clinical Pharmacokinetics.
Favorable Pharmacokinetic Profile Supports Once-Daily Dosing
The published data from three Phase 1 studies in healthy male volunteers demonstrate that inhaled mosliciguat has a longer half-life compared to oral and intravenous administration, supporting further evaluation of once-daily dosing. The studies characterized the pharmacokinetic profile of mosliciguat after inhalation using a low-resistance device in a lactose carrier-based dry powder formulation.
"Mosliciguat is the first sGC activator designed for dry powder inhalation, and these PK results from completed studies indicate that mosliciguat achieves measurable, effective systemic exposure via inhalation with no evidence of serious side effects reported to date," said Ubaldo Martin M.D., FCCP, Pulmovant's Senior Vice President and Head of Clinical Development.
Safety Profile and Lung-Targeted Delivery
In all three Phase 1 studies, mosliciguat was well tolerated without major systemic effects on heart rate or blood pressure. The data suggest a long residence time in the lungs and a slow, continuous release of mosliciguat into the systemic circulation, providing evidence that mosliciguat at the tested doses is appropriate for further evaluation as an inhaled therapy.
Mechanism of Action and Clinical Development
Mosliciguat targets sGC, a key enzyme in the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway that catalyzes cGMP production leading to increased vasodilation, reduced inflammation and apoptosis, reverse vascular remodeling, and anti-fibrotic effects. Unlike sGC stimulators, which require reduced heme and NO to exert their effect on sGC, mosliciguat is an sGC activator that works independently of heme and NO.
The safety and efficacy of mosliciguat in adult patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD) are currently being evaluated in the Phase 2 PHocus study (NCT06635850).
Addressing Significant Unmet Medical Need
Pulmonary hypertension is a progressive and debilitating condition characterized by high blood pressure in the blood vessels of the lungs, forcing the heart to work harder to pump blood through the lungs and leading to symptoms such as shortness of breath, fatigue, chest pain, and dizziness. Group 3 PH is a subtype that arises from lung diseases, such as interstitial lung disease (ILD), which describes a large group of diseases that cause progressive damage to the lungs.
Up to 200,000 patients across the U.S. and Europe are living with PH-ILD, a subset of Group 3 PH, and have limited or no approved treatment options. Martin emphasized that PH-ILD is "a severe disease with high morbidity and mortality and limited treatment options."
