"PH-ILD remains one of the most challenging forms of pulmonary hypertension to treat, given the heterogeneity of the disease and the fact that existing therapies are approved in limited geographies and poorly tolerated in patients with underlying lung disease," said Marc Humbert, MD, PhD, Professor of Respiratory Medicine at Université Paris-Saclay and Director of the French National Reference Center for Pulmonary Hypertension. "The PVR reduction observed in PHocus is remarkable and among the largest reported in a randomized controlled PH trial to date. The consistency of benefit across hemodynamic, functional, and cardiac biomarker endpoints makes these results even more impressive. Together, these results represent a clinically meaningful advancement in this field and highlight the potential of mosliciguat to address a longstanding gap in care for a patient population with high mortality and limited treatment options."

The PHocus study met its primary endpoint, demonstrating a clinically meaningful and statistically significant placebo-adjusted reduction in PVR of -56.3% (-51.3% mosliciguat vs. +6.6% placebo, p<0.0001) at Week 16. The study also met its secondary endpoints on a placebo-adjusted basis, demonstrating a clinically meaningful and statistically significant improvement in 6MWD of +35.2 meters (+20.3 mosliciguat vs. -14.9 placebo, p=0.0027) and a clinically meaningful and statistically significant reduction in NT-proBNP, a biomarker of cardiac strain, of -357.7 pg/mL (p=0.0002), corresponding to a -53.2% reduction from baseline at Week 16.

In a pre-specified exploratory analysis, treatment effects continued to strengthen through the end of the placebo-controlled period. By Week 24, the placebo-adjusted improvement in 6MWD reached +52.7 meters (nominal p<0.0001), while NT-proBNP showed a placebo-adjusted reduction of -487.1 pg/mL (-75.9%; nominal p<0.0001).

Mosliciguat was observed to be well tolerated, with a favorable safety profile and adverse events consistent with the underlying PH-ILD condition. Notably, the incidence of cough, a common tolerability concern with inhaled prostacyclins, was lower than placebo in patients receiving mosliciguat (12.1% for patients receiving mosliciguat vs. 18.2% for patients receiving placebo).

Mosliciguat is a potential first-in-class, once-daily, inhaled sGC activator with a differentiated mechanism of action designed to deliver targeted pulmonary vasodilation with limited systemic side effects for the treatment of PH-ILD. Mosliciguat targets sGC, a key enzyme in the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway that catalyzes cGMP production. Elevated cGMP levels are known to promote vasodilation and potentially contribute to anti-fibrotic effects, reduce inflammation and apoptosis, and reverse vascular remodeling. The PHocus results support mosliciguat's potential as an sGC activator, mechanistically distinct from sGC stimulators, to activate sGC independent of NO/heme status. This positions mosliciguat to address both oxidative-stress-associated diseases such as PH-ILD, where native sGC function is impaired, as well as diseases where native sGC remains responsive to NO/heme signaling.

PH is classified into five groups based on underlying causes, symptoms, and treatment approaches. Group 3 PH is a subtype of PH that arises from lung diseases, such as interstitial lung disease (ILD). ILD describes a large group of diseases that cause progressive damage to the lungs, making it difficult for patients to breathe. 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.

"PH-ILD is a disease as bad as some forms of cancer, with a median survival of just 1.5-2 years despite best-available standard of care. We wanted to see if we could make an impact in this terrible disease when we brought mosliciguat into Roivant. Our thesis was that the ATMOS study actually understated the potential of mosliciguat – and when dosed chronically, it would do considerably more. These PHocus results proved that out as clearly as we could have hoped: a profound 56.3% placebo-adjusted PVR reduction – the largest PVR reported in any controlled pulmonary hypertension trial of any group," said Mayukh Sukhatme, President and Chief Investment Officer at Roivant. "This data set puts mosliciguat in a league of its own on PVR reduction, 6MWD improvement, NT-proBNP % reduction, cough rate, and ease of use. It is a terrific example of the Roivant model working as planned: finding high-potential molecules and going after diseases where the patient needs are enormous and where the drug can truly shine."

"Our robust Phase 2 PHocus study results, in conjunction with mosliciguat’s inhaled, once-a-day administration and potential first-in-class sGC activator profile, strongly position it as a potential single agent treatment and combination therapy for patients with PH-ILD. Today, the treatment landscape is sparse, primarily consisting of formulations of inhaled treprostinil and their associated limitations, and off-label use of PDE5 inhibitors. With these results, mosliciguat has demonstrated that it may address many of these treatment gaps," said Drew Fromkin, Chief Executive Officer of Pulmovant. "We are truly grateful to the patients, investigators, and site teams who made this study possible. We are also pleased to announce that our Phase 3 PHrontier study for patients with PH-ILD has been initiated with the goal of rapidly bringing mosliciguat to patients battling PH-ILD."

The initiation of the Phase 3 PHrontier clinical trial of mosliciguat in PH-ILD, in tandem with the completion of our PHocus study, reflects the company’s commitment to expedite mosliciguat’s development and, upon approval, access to patients who are in need of effective treatment options.