Chronic thromboembolic pulmonary hypertension

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 dateOnce-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. _______________________________ 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.

Mosliciguat, a potential first-in-class and best-in-category inhaled soluble Guanylate Cyclase (sGC) activator with targeted delivery to the lungs and once-daily administration, is being developed for pulmonary hypertension associated with interstitial lung disease (PH-ILD), which affects ~200,000 patients in the U.S. and Europe; PH-ILD prevalence is meaningfully greater than that of pulmonary arterial hypertension (PAH) with limited to no treatment optionsIn the Phase 1b ATMOS study, presented today at the European Respiratory Society (ERS) Congress, a single dose of inhaled mosliciguat in pulmonary hypertension (PH) patients (N=38) led to sustained, clinically meaningful mean-max reductions in pulmonary vascular resistance (PVR) of up to ~38%, one of the highest reductions seen in PH trials to dateOnce-daily dosing via dry powder inhaler (DPI) was generally well-tolerated, with low rates of treatment-emergent adverse events (TEAEs)The global Phase 2 “PHocus” study of mosliciguat in ~120 patients with PH-ILD is expected to begin imminently BASEL, Switzerland and LONDON and NEW YORK, Sept. 10, 2024 (GLOBE NEWSWIRE) -- Roivant (Nasdaq: ROIV) today announced its previously undisclosed pipeline program mosliciguat, a potential first-in-class, inhaled, once-daily sGC activator with targeted delivery to the lungs via dry powder inhaler, at Pulmovant. Pulmovant presented data from the proof-of-concept Phase 1b ATMOS study during the ERS Congress in Vienna, Austria. “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. “Along with the positive Graves’ data announcement at Immunovant yesterday, we feel incredibly fortunate to announce another exciting clinical update this week. As promised, we are continuing to expand our existing pipeline and remain laser-focused on clinical execution, with a number of important study readouts and milestones expected in the coming months.” Mosliciguat has been extensively characterized across a robust Phase 1 program with 170 participants dosed to date, including in the ATMOS study, and based on data from these studies has the potential to show differentiation in 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. 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-max peak reductions in PVR from baseline of -25.9%, -38.1% and -36.3%, respectively, consistently exceeding the predefined ≥ -20% threshold for the primary outcome. 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. Data from 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 ERS Congress today. 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 dosing. Mosliciguat is unique among inhaled PH therapies, requiring just one puff once per day to deliver its potential best-in-category PVR reductions – all currently approved therapies require multiple puffs, 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. Roivant created Pulmovant, a wholly-owned Roivant subsidiary, to in-license from Bayer exclusive worldwide rights to develop and commercialize mosliciguat. Bayer received an upfront cash payment of ~$14.0 million, with up to an additional $280 million agreed upon for future development, regulatory and commercial milestone payments, as well as tiered high-single digit sales-based royalties. Investor Call A conference call and webcast will be held at 8:00 AM EDT on Tuesday, September 10, 2024, to discuss these updates. Please register here for the event. The live webcast will also be available under the Events & Presentations section of Roivant's website. A replay of the event and presentation will be available immediately following the event. About Roivant Roivant is a commercial-stage biopharmaceutical company that aims to improve the lives of patients by accelerating the development and commercialization of medicines that matter. Today, Roivant’s pipeline includes VTAMA, a novel topical approved for the treatment of psoriasis and in development for the treatment of atopic dermatitis; IMVT-1402 and batoclimab, fully human monoclonal antibodies targeting the neonatal Fc receptor (“FcRn”) in development across several IgG-mediated autoimmune indications; and brepocitinib, a potent small molecule inhibitor of TYK2 and JAK1 for the treatment of dermatomyositis and non-infectious uveitis, in addition to other clinical stage molecules. We advance our pipeline by creating nimble subsidiaries or “Vants” to develop and commercialize our medicines and technologies. Beyond therapeutics, Roivant also incubates discovery-stage companies and health technology startups complementary to its biopharmaceutical business. For more information, www.roivant.com. Roivant Forward-Looking Statements This press release contains forward-looking statements. Statements in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), which are usually identified by the use of words such as “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intends,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “would” and variations of such words or similar expressions. The words may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act. Our forward-looking statements include, but are not limited to, statements regarding our or our management team’s expectations, hopes, beliefs, intentions or strategies regarding the future, and statements that are not historical facts, including statements about potential share repurchases, the clinical and therapeutic potential of our products and product candidates, the availability and success of topline results from our ongoing clinical trials and any commercial potential of our products and product candidates. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. Although we believe that our plans, intentions, expectations and strategies as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, those risks set forth in the Risk Factors section of our filings with the U.S. Securities and Exchange Commission. Moreover, we operate in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of our management as of the date of this press release and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Contacts:InvestorsRoivant Investor Relationsir@roivant.com MediaStephanie LeeRoivant Sciencesstephanie.lee@roivant.com

Roivant Sciences is expanding its scope to the lungs, unveiling a new subsidiary whose main asset, licensed from Bayer, offers the potential to bring patients a novel treatment for a rare type of pulmonary hypertension currently served by only one FDA-approved therapy. The new Roivant company revealed Tuesday is named Pulmovant. Roivant, whose business model involves in-licensing drugs shelved by big pharmaceutical companies and then forming subsidiaries it calls “Vants” to advance their development, disclosed the new Vant and asset last year. But Roivant did not identify the drug or its indication until Tuesday, when it presented proof-of-concept clinical data during the European Respiratory Society Congress in Vienna, Austria. The Pulmovant drug, mosliciguat, is being developed as a treatment for pulmonary hypertension associated with interstitial lung disease (PH-ILD) — high blood pressure in the lungs due to interstitial lung disease, a group of chronic lung disorders that lead to inflammation and scarring. The results presented are from a Phase 1b study that enrolled 38 adults with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Waltham, Massachusetts-based Pulmovant said the 1 mg, 2 mg, and 4 mg doses led to average peak percentage reductions in pulmonary vascular resistance (a measure of resistance against blood flow from the pulmonary veins) of -25.9%, -38.1%, and -36.3% respectively. These results were sustained and clinically meaningful. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum Pulmovant said a similar effect on pulmonary vascular resistance was observed in a pharmacodynamic analysis of 37 patients, including those responsive and non-responsive to inhaled nitric oxide. These results suggest mosliciguat may work across the spectrum of pulmonary hypertension, the company said. The drug is administered as a single dose taken daily via a dry powder inhaler. In the broader Phase 1 population spanning 170 healthy volunteers and pulmonary hypertension patients, Roivant said mosliciguat was safe and well tolerated with low rates of adverse effects observed. The World Health Organization categorizes pulmonary hypertension in five groups according to disease cause and comorbidities. PH-ILD falls under Group 3 pulmonary hypertension. This disease is rare, affecting an estimated 200,000 patients in the U.S. and Europe. Standard treatment is United Therapeutics’ Tyvaso, a drug that was initially approved to treat pulmonary arterial hypertension. Tyvaso expanded its approved uses to include PH-ILD in 2021. The inhaled therapy, administered via dry powder inhalation or a nebulizer in nine to 12 puffs taken four times daily, lowers blood pressure by widening blood vessels. United Therapeutics reported more than $1.2 billion in global Tyvaso sales in 2023, a more than 41% increase over the product’s 2022 sales. The U.S. is the only market where this drug is commercialized. Pulmovant’s mosliciguat takes a different approach to PH-ILD by activating sGC, an enzyme in a signaling pathway that’s key to maintaining homeostasis of blood vessels. While sGC stimulators can be used to treat pulmonary hypertension, these drugs require heme (an iron-containing component of hemoglobin) and nitric oxide. In pulmonary hypertension, heme is oxidized and nitric oxide levels are depleted. Pulmovant says mosliciguat works without heme and nitric oxide, allowing it to potentially retain its efficacy in a highly oxidative environment where stimulators are expected to lose efficacy. Also, unlike the multiple puffs of Tyvaso taken throughout the day, mosliciguat, administered by dry powder inhalation, requires just one puff daily. Based on Tyvaso’s $300,000 a year price, PH-ILD represents a more than $6 billion market opportunity in the U.S. and Europe, Roivant said in an investor presentation. Without naming mosliciguat, Roivant disclosed the licensing of the drug last year in a regulatory filing that was scant on details. The company said its then unnamed new subsidiary had paid $14 million up front and agreed to pay up to $280 million more if the asset achieved milestones. It will also pay royalties on sales of a commercialized product. presented by Health Tech The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani The unveiling of Pulmovant and the mosliciguat comes one day after another Vant, Immunovant, announced progress in Graves’ disease, an autoimmune condition characterized by excess thyroid hormone production. Phase 2 data for batoclimab showed strong response rates and lowering of levels of an antibody associated with the disease. In addition, Immunovant said it has FDA permission to begin a Phase 3 test of another potential Graves’ disease drug, IMVT-1402. Speaking during a Tuesday conference call, Roivant CEO Matt Gline described mosliciguat as “a compelling addition to our pipeline.” This immunology and inflammation pipeline represents more than $10 billion in potential revenue, he said. “We think this program has certainly got multi-blockbuster potential in an indication with very high unmet patient need and not a lot of other (treatment) options,” Gline said. “It’s exactly the kind of partnership we like working on for exactly the kind of program and patient population we are excited about.” Pulmovant plans to advance mosliciguat to a global, placebo-controlled Phase 2 study in PH-ILD. The company said the study, expected to enroll about 120 patients, will start imminently. The main goal is to measure, from baseline, the change in pulmonary vascular resistance. Image: Magicmine, Getty Images