Pulmovant presents positive proof-of-concept data from the Phase 1b ATMOS study of Mosliciguat in Pulmonary Hypertension at European Respiratory Society Congress

Rhea-AI Summary

Pulmovant, a Roivant company, presented positive proof-of-concept data from the Phase 1b ATMOS study of Mosliciguat in Pulmonary Hypertension at the European Respiratory Society Congress. Mosliciguat, a potential first-in-class, inhaled soluble Guanylate Cyclase (sGC) activator, showed promising results:

- Single dose led to sustained, clinically meaningful mean peak reduction in pulmonary vascular resistance (PVR) of up to 38%
- Once-daily dosing via dry powder inhaler was well tolerated
- Low rates of treatment-emergent adverse events observed

The global Phase 2 'PHocus' study in ~120 patients with PH associated with interstitial lung disease (PH-ILD) is set to begin soon. PH-ILD affects ~200,000 patients in the U.S. and Europe, with treatment options.

Positive

• Mosliciguat showed a mean peak reduction in pulmonary vascular resistance (PVR) of up to 38% in PH patients
• Once-daily dosing via dry powder inhaler was well tolerated with low rates of treatment-emergent adverse events
• Mosliciguat demonstrated a favorable safety profile in 170 participants across its Phase 1 development program
• The drug has a 40-hour half-life, supporting convenient once-daily dosing
• Mosliciguat's unique formulation requires just one inhalation per day, unlike currently approved therapies
• Direct delivery to the lungs minimizes risk of serious adverse effects seen with systemic vasodilators

Negative

• The study was non-randomized and open-label, which may introduce bias in the results
• The Phase 1b ATMOS study had a relatively small sample size of 38 patients
• Efficacy and safety in larger populations and long-term use still need to be established in further clinical trials

Medical Research Analyst

The Phase 1b ATMOS study results for mosliciguat in pulmonary hypertension (PH) are highly promising. The 38% peak reduction in pulmonary vascular resistance (PVR) is impressive, potentially setting a new benchmark in PH treatment efficacy. The drug's novel mechanism as an sGC activator, functioning independently of heme and NO, could offer a significant advantage in oxidative environments typical of PH. The favorable safety profile and once-daily dosing via dry powder inhaler further enhance its potential. The upcoming Phase 2 PHocus study focusing on PH-ILD, a condition affecting ~200,000 patients in the U.S. and Europe with treatment options, represents a substantial market opportunity. However, it's important to note that these are early-stage results and further studies are needed to confirm long-term efficacy and safety.

Financial Analyst

Pulmovant's mosliciguat shows significant potential in the pulmonary hypertension market. The addressable market of ~200,000 PH-ILD patients in the U.S. and Europe presents a substantial commercial opportunity. Given the lack of approved treatments for PH-ILD, successful development could lead to rapid market penetration and potentially high pricing power. The once-daily dosing and dry powder inhaler formulation could provide a competitive edge over existing therapies. However, investors should consider that the drug is still in early stages, with the Phase 2 trial yet to begin. While promising, there's still a long road to potential approval and commercialization. The positive data could potentially increase Roivant's (NASDAQ: ROIV) valuation, but this is contingent on continued successful development and eventual market entry.

Oncology Doctor

As an oncology specialist, I'm intrigued by mosliciguat's potential in treating pulmonary hypertension associated with interstitial lung disease (PH-ILD). Many cancer treatments, particularly radiation therapy to the chest, can lead to ILD as a side effect, which can progress to PH-ILD. The 38% reduction in PVR is impressive and could significantly improve outcomes for these patients. The once-daily dosing via dry powder inhaler could enhance patient compliance, a important factor in managing chronic conditions. Moreover, the drug's mechanism as an sGC activator, independent of heme and NO, could be particularly beneficial in the oxidative environment often seen in post-cancer treatment lung conditions. However, we need to see results from larger, longer-term studies to fully understand its efficacy and safety profile in this specific patient population.

• Mosliciguat is a potential first-in-class, inhaled soluble Guanylate Cyclase (sGC) activator with targeted delivery to the lungs via once-daily administration, which may have broad applicability across the spectrum of pulmonary hypertension (PH)
• In the Phase 1b ATMOS study, presented today at the European Respiratory Society (ERS) Congress, a single dose of inhaled mosliciguat in PH patients (N=38) led to sustained, clinically meaningful mean peak reduction in pulmonary vascular resistance (PVR) of up to 38%, one of the highest reductions seen in PH trials to date
• Once-daily dosing via dry powder inhaler (DPI) was well tolerated, with low rates of treatment-emergent adverse events (TEAEs)
• The global Phase 2 “PHocus” study of mosliciguat in ~120 patients with PH associated with interstitial lung disease (PH-ILD) is expected to begin imminently. PH-ILD affects ~200,000 patients in the U.S. and Europe, a prevalence that is meaningfully greater than that of pulmonary arterial hypertension (PAH), with limited to no treatment options

WALTHAM, Mass., Sept. 10, 2024 (GLOBE NEWSWIRE) -- 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.

© 2024 Pulmovant, Inc. All Rights Reserved. All trademarks are the property of their respective owners.

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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.

FAQ

What were the key results of the Phase 1b ATMOS study for Mosliciguat (ROIV)?

The Phase 1b ATMOS study showed that Mosliciguat led to a mean peak reduction in pulmonary vascular resistance (PVR) of up to 38% in pulmonary hypertension patients. The drug was well-tolerated with once-daily dosing via dry powder inhaler and demonstrated low rates of treatment-emergent adverse events.

What is the target population for Mosliciguat's (ROIV) upcoming Phase 2 PHocus study?

The upcoming global Phase 2 PHocus study will target approximately 120 patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). This condition affects about 200,000 patients in the U.S. and Europe and has treatment options.

How does Mosliciguat (ROIV) differ from other pulmonary hypertension treatments?

Mosliciguat is a potential first-in-class, inhaled soluble Guanylate Cyclase (sGC) activator that works independently of heme and nitric oxide. It requires only one inhalation per day, unlike current therapies that need multiple daily doses. Its direct lung delivery may also minimize systemic side effects associated with other vasodilators.

What is the market potential for Mosliciguat (ROIV) in treating PH-ILD?

PH-ILD affects approximately 200,000 patients in the U.S. and Europe, which is a larger patient population than pulmonary arterial hypertension (PAH). With treatment options currently available, Mosliciguat represents a potentially significant commercial opportunity in an area of high unmet medical need.