ROIV Roivant Sciences Ltd

Pulmovant, a Roivant (Nasdaq: ROIV) company, today announced the presentation of data from the proof-of-concept Phase 1b ATMOS1 study during the ERS Congress in Vienna, Austria. ATMOS (NCT03754660) evaluated mosliciguat, a potential first-in-class, inhaled sGC activator with targeted delivery to the lungs and once-daily administration, in PH patients.

Mosliciguat has been extensively characterized across a robust Phase 1 program with 170 participants dosed to date, including patients with PH in the ATMOS study, and based these data has the potential to show differentiated efficacy, safety, and convenience. Mosliciguat’s target, sGC, is 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. This also allows mosliciguat to potentially retain efficacy in highly oxidative environments typical of PH, where stimulators are expected to lose efficacy given heme is oxidized or removed and NO levels are depleted.

“We believe mosliciguat can transform the lives of patients living with pulmonary hypertension, and I am excited to announce this potential first-in-class and best-in-category therapy. Mosliciguat has the incredibly rare advantage of potential differentiation across three separate key areas - efficacy, safety, and convenience in administration. We are impressed with the data generated so far, particularly the PVR results, and we believe its differentiated mechanism as an sGC activator can have maximal impact on PH-ILD patients, a large population with severe disease, high morbidity and mortality, and few treatment options,” said Matt Gline, Roivant’s Chief Executive Officer.

ATMOS was a non-randomized, open-label, dose escalation, proof-of-concept Phase 1b trial that assessed the efficacy, safety, tolerability, and pharmacokinetics of mosliciguat following single dose inhaled administration in participants aged between 18 and 80 years with World Health Organization (WHO) Group 1 PH (pulmonary arterial hypertension (PAH)) or Group 4 PH (chronic thromboembolic pulmonary hypertension (CTEPH)). Overall, 38 patients received mosliciguat in this study. In the per-protocol set of patients (N=20), mosliciguat 1.0, 2.0 and 4.0 mg doses led to mean peak percentage reductions in PVR from baseline of -25.9%, -38.1% and -36.3%, respectively, consistently exceeding the predefined ≥ -20% threshold for the primary outcome. The per-protocol analysis included the 20 patients who were nonresponsive to inhaled NO. Notably, a similar effect on PVR was observed in the pharmacodynamic analysis set (N=37), which included participants both responsive and non-responsive to inhaled NO, suggesting that mosliciguat’s novel mechanism of action may allow for broad activity across the spectrum of PH. Single dose administration via dry powder inhaler was well tolerated, with low rates of TEAEs observed.

Overall, in its Phase 1 development program in 170 healthy volunteers and PH patients, mosliciguat has shown a favorable safety profile, dose-dependent increases in cGMP, and a 40-hour half-life supporting convenient once-daily dosing. Mosliciguat is unique among inhaled PH therapies, requiring just one inhalation per day – all currently approved therapies require multiple inhalations, multiple times per day. Mosliciguat is formulated for delivery via DPI, providing greater convenience to patients compared to nebulizers required for many existing inhaled PH therapies. Direct delivery to the lungs also minimizes risk of serious adverse effects seen with systemic vasodilators, such as worsening of oxygenation status. In addition to greater efficacy as evidenced by PVR in ATMOS, a generally favorable safety profile and ease of administration support the potential differentiation for mosliciguat.

Pulmovant will advance the clinical program to assess mosliciguat in its global Phase 2 PHocus study in patients with PH-ILD, a subgroup of Group 3 PH. Approximately 120 patients will be enrolled in the study, which will start imminently. An estimated 200,000 patients across the U.S. and Europe are living with PH-ILD and have limited or no approved treatment options. The PH-ILD prevalence is meaningfully greater than that of PAH, representing an attractive commercial opportunity with limited competition and high unmet patient need.

“We have elected to initiate our global Phase 2 PHocus study in PH-ILD because of the lack of treatment options for patients coupled with the impressive Phase 1b results and strong biologic rationale,” noted Drew Fromkin, Pulmovant’s Chief Executive Officer. “PH-ILD is a devastating disease that is associated with high morbidity and mortality as well as poor quality of life. We are committed to making a significant difference for these patients and have assembled a stellar team, alongside our world-class investigators and advisors, to advance and optimize mosliciguat’s development.”

About Pulmonary Hypertension and Interstitial Lung Disease

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. The 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, 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 U.S. and Europe are living with PH-ILD, a subset of Group 3 PH, and have limited to no approved treatment options. Click here for more information.

About Pulmovant

Pulmovant is a clinical-stage biotechnology company developing innovative therapies for patients suffering from pulmonary diseases. Pulmovant’s first program, mosliciguat is designed to provide an effective, once-daily, inhaled treatment option for patients with pulmonary hypertension (PH). Mosliciguat is a novel, potential first-in-class, sGC activator with a differentiated mechanism that may have broad applicability across the PH spectrum.

For more information, please visit https://www.pulmovant.com.

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1 ATMOS, a Proof-of-Concept trial of inhaled mosliciguat in untreated PAH or CTEPH was presented during poster session (PS) 31, poster number PA5238, at the European Respiratory Society Congress on September 10, 2024, from 12:30 to 2:00 PM CET.