A Phase 3, Multi-center, Randomized Withdrawal and Long Term Extension Study of Ampreloxetine for the Treatment of Symptomatic Neurogenic Orthostatic Hypotension in Participants With Multiple System Atrophy

This is a Phase 3, multi-center, randomized withdrawal study to evaluate the efficacy and durability of ampreloxetine in participants with MSA and symptomatic nOH after 20 weeks of treatment. This study includes 4 periods: Screening, open label, randomized withdrawal, and long-term treatment extension (LTE).

Start Date27 Jun 2023

Sponsor / Collaborator

Theravance Biopharma, Inc.

NCT04688632

/ CompletedPhase 1

A Phase 1, Randomized, Double-Blind, Placebo- and Positive-Controlled, Thorough QT Study to Evaluate the Effect of Ampreloxetine on Cardiac Repolarization in Healthy Subjects

A double-blind study to characterize the effect of ampreloxetine on cardiac repolarization in healthy subjects.

Start Date18 Jan 2021

Sponsor / Collaborator

Theravance Biopharma, Inc.

NCT04200573

/ CompletedPhase 1

A Phase 1, Open-Label, Single Dose Study to Evaluate the Pharmacokinetics of Ampreloxetine Following a Single-dose in Subjects With Mild, Moderate, and Severe Hepatic Impairment and in Matching Healthy Subjects

An open-label study to characterize the effects of mild, moderate, and severe Hepatic Impairment (HI) on the pharmacokinetics (PK) of ampreloxetine following a single oral dose in comparison with healthy volunteers with normal hepatic function.

Start Date13 Jan 2020

Sponsor / Collaborator

Theravance Biopharma, Inc.

100 Clinical Results associated with Ampreloxetine hydrochloride

100 Translational Medicine associated with Ampreloxetine hydrochloride

100 Patents (Medical) associated with Ampreloxetine hydrochloride

Literatures (Medical) associated with Ampreloxetine hydrochloride

01 Jul 2024·Clinical pharmacology and therapeutics

Hepatic Dysfunction Quantified by HepQuant DuO Outperforms Child‐Pugh Classification in Predicting the Pharmacokinetics of Ampreloxetine

Article

Author: McRae, Michael P. ; Everson, Gregory T. ; Giovinazzo, Hugh ; Bourdet, David L. ; Kanodia, Jitendra ; Helmke, Steve M. ; Yates, Wayne

HepQuant tests quantify liver function from clearance of deuterium‐ and 13C‐labeled cholates administered either intravenously and orally (SHUNT) or orally (DuO). Hepatic impairment studies have relied on clinical or laboratory criteria like Child‐Pugh classification to categorize the degree of hepatic dysfunction. We compared HepQuant tests with Child‐Pugh classification in predicting the pharmacokinetics of ampreloxetine. Twenty‐one subjects with hepatic impairment (8 Child‐Pugh A, 7 Child‐Pugh B, and 6 Child‐Pugh C), and 10 age‐ and sex‐matched controls were studied. The pharmacokinetics of ampreloxetine were measured after oral administration of a single dose of 10 mg. Disease severity index (DSI), portal‐systemic shunting (SHUNT%), hepatic reserve, and hepatic filtration rates (HFRs) were measured from serum samples obtained after intravenous administration of [24‐13C]‐cholate and oral administration of [2,2,4,4‐2H]cholate. Ampreloxetine plasma exposure (AUC0‐inf) was similar to controls in Child‐Pugh A, increased 1.7‐fold in subjects with Child‐Pugh B, and 2.5‐fold in subjects with Child‐Pugh C and correlated with both Child‐Pugh score and HepQuant parameters. The variability observed in ampreloxetine exposure (AUC0‐inf) in subjects with moderate (Child‐Pugh B) and severe hepatic impairment (Child‐Pugh C) was explained by HepQuant parameters. Multivariable regression models demonstrated that DSI, SHUNT%, and Hepatic Reserve from SHUNT and DuO were superior predictors of ampreloxetine exposure (AUC0‐inf) compared to Child‐Pugh score. HepQuant DSI, SHUNT%, and hepatic reserve were more useful predictors of drug exposure than Child‐Pugh class for ampreloxetine and thus may better optimize dose recommendations in patients with liver disease. The simple‐to‐administer, oral‐only DuO version of the HepQuant test could enhance clinical utility.

11 May 2023·Cureus

Ampreloxetine Versus Droxidopa in Neurogenic Orthostatic Hypotension: A Comparative Review

Review

Author: Hoxhaj, Pranvera ; Goyal, Abhishek ; Razzaq, Waleed ; Khawaja, Imran ; Gupta, Ishita ; Khan, Wajiha ; Botlaguduru, Deepti ; Shah, Shruti ; Collado, Gaudy F ; Sadeghzadegan, Amirali ; Abdin, Zain U ; Singh, Saumya ; Muyolema Arce, Veronica E

Neurogenic orthostatic hypotension (nOH) is a disabling problem of autonomic dysfunction in patients with Parkinson's disease, which is associated with poor quality of life and higher mortality rates. The purpose of this literature review was to explore and compare the efficacy and safety of droxidopa (an existing treatment) and ampreloxetine (a newer medication) in the treatment of nOH. We used a mixed-method literature review that addresses the epidemiology, pathophysiology, and pharmacological and non-pharmacological management of nOH in Parkinson's disease in a general way, with a more exploratory approach to droxidopa- and ampreloxetine-controlled trial studies. We included a total of 10 studies of randomized controlled trials with eight studies focused on droxidopaand two studies focused on ampreloxetine. These two drugs were analyzed and compared based on the collected individual study results. Treatment of nOH in Parkinson's disease patients with droxidopa or ampreloxetine showed clinically meaningful and statistically significant improvements relative to placebo on the components of the OHSA (Orthostatic Hypotension Symptom Assessment) composite score and OHDAS (Orthostatic Hypotension Daily Activity Scale composite scores) composite score. Droxidopa had an improved effect on daily activities, with an associated increase in standing systolic blood pressure (BP), but the long-term efficacy of droxidopa has not been documented. Standing systolic BP was maintained by ampreloxetine and worsened after the withdrawal phase. This highlights the importance of conducting further research which will help us to improve the therapeutic approach for patients with nOH and Parkinson's disease.

01 Dec 2021·Clinical autonomic research : official journal of the Clinical Autonomic Research SocietyQ3 · MEDICINE

Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial

Q3 · MEDICINE

Article

Author: Norcliffe-Kaufmann, Lucy ; Shibao, Cyndya A ; Kanodia, Jitendra ; Haumann, Brett ; Wang, Whedy ; Biaggioni, Italo ; Vickery, Ross ; Kaufmann, Horacio

Abstract:

Purpose:

In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective norepinephrine reuptake inhibitor, increases circulating norepinephrine levels. This study explored the safety of ampreloxetine and its effect on blood pressure and symptoms in patients with neurogenic orthostatic hypotension.

Methods:

A multicenter ascending-dose trial (range 1–20 mg, Part A) was followed by a 1 day, double-blind, randomized, placebo-controlled study (median dose 15 mg, Part B). Eligible patients then enrolled in a 20-week, open-label, steady-state extension phase (median dose 10 mg, Part C) followed by a 4-week withdrawal. Assessments included the Orthostatic Hypotension Symptom Assessment Scale (item 1), supine/seated/standing blood pressure, and safety.

Results:

Thirty-four patients (age 66 ± 8 years, 22 men) were enrolled. Part A: The proportion of participants with a positive response (i.e., increase from baseline in seated systolic blood pressure of ≥ 10 mmHg) was greater with the 5 and 10 mg ampreloxetine doses than with placebo or other active ampreloxetine doses. Part B: Seated blood pressure increased 15.7 mmHg 4 h after ampreloxetine and decreased 14.2 mmHg after placebo [least squares mean difference (95% CI) 29.9 mmHg (7.6–52.3); P = 0.0112]. Part C: Symptoms of dizziness/lightheadedness improved 3.1 ± 3.0 points from baseline and standing systolic blood pressure increased 11 ± 12 mmHg. After 4 weeks of withdrawal, symptoms returned to pretreatment levels. The effect of ampreloxetine on supine blood pressure was minimal throughout treatment duration.

Conclusion:

Ampreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure.

Trial registration:

NCT02705755 (first posted March 10, 2016).

News (Medical) associated with Ampreloxetine hydrochloride

25 Aug 2025

·investor.theravance.com

Theravance Biopharma Completes Enrollment in Pivotal Phase 3 CYPRESS Study of Ampreloxetine in Patients with Symptomatic Neurogenic Orthostatic Hypotension due to Multiple System Atrophy

Topline results anticipated in Q1 2026 and, if successful, planning for expedited NDA submission If approved, ampreloxetine could address a critical unmet need as the first therapy with the potential to provide durable benefit for the 40,000 patients in the U.S. with symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA) Ampreloxetine has Orphan Drug Designation in the U.S. , underscoring the unmet need in symptomatic nOH due to MSA DUBLIN , Aug. 25, 2025 /PRNewswire/ -- Theravance Biopharma , Inc. (" Theravance Biopharma " or the "Company") (NASDAQ: TBPH), today announced completion of enrollment in the open-label portion of its pivotal Phase 3 CYPRESS study in patients with symptomatic neurogenic orthostatic hypotension (nOH) due to multiple system atrophy (MSA), a rare and progressive neurodegenerative disorder. nOH is a devastating condition affecting approximately 80% of MSA patients and is characterized by sudden drops in blood pressure upon standing, leading to symptoms such as dizziness, fainting, and blurry vision. These symptoms can lead to serious consequences, including falls, disability, and loss of independence. Despite its severity and impact, there is a lack of effective and durable treatment options that are specifically designed to treat nOH in patients with MSA. "nOH is one of the most debilitating manifestations of MSA, which affects about 40,000 patients in the U.S. alone. Yet current therapies often fail to provide lasting symptoms relief, require frequent dosing and carry a boxed warning for supine hypertension," said Dr. Horacio Kaufmann , F. B. Axelrod Professor of Neurology and Professor of Medicine at NYU Grossman School of Medicine . "Ampreloxetine is designed to address the underlying cause of nOH. In Study 0170, it showed compelling improvement in OHSA composite score without worsening supine hypertension.1 If these benefits are confirmed, I would expect to use ampreloxetine in the majority of my patients living with nOH due to MSA. I am encouraged that enrollment in CYPRESS, the first randomized-withdrawal trial designed specifically for the MSA population, has been completed, and I look forward to seeing the data early next year." The registration-enabling Phase 3 CYPRESS (NCT05696717) study is a global, randomized-withdrawal study evaluating ampreloxetine in patients with symptomatic nOH due to clinically diagnosed MSA. Patients were enrolled in the 12-week open-label portion of the study at sites across four continents. At the end of the open-label portion, responders are randomized 1:1 to continue ampreloxetine or switch to placebo for eight weeks in the randomized-withdrawal portion of the study. The primary endpoint is change in orthostatic hypotension symptom assessment (OHSA) composite score from randomized-withdrawal baseline to Week 8. "Completing enrollment in CYPRESS marks a major step toward bringing this potentially transformative therapy to patients with symptomatic nOH due to MSA – an underserved patient population in dire need for a new, effective and durable treatment with a favorable safety profile," said Áine Miller, Ph.D., Head of Development at Theravance Biopharma . "Ampreloxetine is intended to target the root cause driving MSA-associated nOH by selectively inhibiting norepinephrine reuptake, and demonstrated benefit in this patient population in Study 0170. The CYPRESS randomized withdrawal trial was designed with insights from Study 0170, and we are confident that, along with our careful study execution, this derisked program strongly positions us to evaluate ampreloxetine's full potential in this patient population." The Company expects to report topline data from the Phase 3 CYPRESS trial in Q1 2026. In parallel, Theravance is preparing for an expedited NDA submission following the results and is planning to request priority FDA review, if data are supportive. This milestone reinforces our strategic focus and delivers on Theravance's commitment to advancing high-impact catalysts, as previously highlighted in our recent Q2 earnings call. About Ampreloxetine Ampreloxetine, an investigational, once-daily, selective norepinephrine reuptake inhibitor in development for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA). The unique benefits of ampreloxetine treatment reported in MSA patients from Study 0170 included an increase in norepinephrine levels, a favorable impact on blood pressure, clinically meaningful and durable symptom improvement, and no signal for worsening of supine hypertension. In the US, the Company has been granted an Orphan Drug Designation for ampreloxetine for the treatment of symptomatic nOH in patients with MSA and, if results from the ongoing Phase 3 CYPRESS study are supportive, plans to file an NDA for full approval in this indication. About the Phase 3 CYPRESS (Study 0197) Study The CYPRESS Study (NCT05696717) is a registrational Phase 3, multi-center, randomized withdrawal study to evaluate the efficacy and durability of ampreloxetine in participants with MSA and symptomatic nOH after 20 weeks of treatment; the primary endpoint of the study is change in the Orthostatic Hypotension Symptom Assessment (OHSA) composite score. The Study includes four periods: screening, open label (12-week period, participants will receive a single daily 10 mg dose of ampreloxetine), randomized withdrawal (eight-week period, double-blind, placebo-controlled, participants will receive a single daily 10 mg dose of placebo or ampreloxetine), and a long-term treatment extension. Secondary outcome measures include change from baseline in Orthostatic Hypotension Daily Activity Scale (OHDAS) item 1 (activities that require standing for a short time) and item 3 (activities that require walking for a short time). About the Phase 3 SEQUOIA (Study 0169) and REDWOOD (Study 0170) Studies Study 0169 (NCT03750552) was a Phase 3, 4-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of ampreloxetine compared to placebo in patients with symptomatic nOH (n=195). Patients from Study 0169 were eligible to enter into Study 0170 (NCT03829657), a Phase 3, multi-center, 22-week study comprising a 16-week open-label period and a 6-week double-blind, placebo-controlled, randomized withdrawal period to evaluate the sustained benefit in efficacy and safety of ampreloxetine in patients with symptomatic nOH. The primary endpoint for Study 0170 of treatment failure at week 6 was defined as a worsening of both Orthostatic Hypotension Symptom Assessment Scale (OHSA) question #1 and Patient Global Impression of Severity (PGI-S) scores by 1.0 point. After Study 0169 did not meet its primary endpoint, the Company took actions to close out the ongoing clinical program including Study 0170. The study was more than 80% enrolled (n=128/154 planned) despite stopping early. The primary endpoint was not statistically significant for the overall population of patients which included patients with Parkinson's disease, pure autonomic failure and MSA (odds ratio=0.6; p-value=0.196). The pre-specified subgroup analysis by disease type suggests the benefit seen in patients receiving ampreloxetine was largely driven by MSA patients (n=40). An odds ratio of 0.28 (95% CI: 0.05, 1.22) was observed in MSA patients indicating a 72% reduction in the odds of treatment failure with ampreloxetine compared to placebo. The benefit to MSA patients was observed in multiple endpoints including OHSA composite, Orthostatic Hypotension Daily Activities Scale (OHDAS) composite, Orthostatic Hypotension Questionnaire (OHQ) composite and OHSA #1.1 About Multiple System Atrophy (MSA) and Symptomatic Neurogenic Orthostatic Hypotension (nOH) MSA is a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls body functions that are mostly involuntary. One of the most frequent autonomic symptoms associated with MSA is a sudden drop in blood pressure upon standing (nOH).2 There are approximately 50,000 MSA patients in the US3 and 70-90% of MSA patients experience nOH symptoms.4 Despite available therapies, many MSA patients remain symptomatic with nOH. Neurogenic orthostatic hypotension (nOH) is a rare disorder defined as a fall in systolic blood pressure of ⩾20 mm Hg or diastolic blood pressure of ⩾10 mm Hg, within 3 minutes of standing. Severely affected patients are unable to stand for more than a few seconds because of their decrease in blood pressure, leading to cerebral hypoperfusion and syncope. A debilitating disorder, nOH results in a range of symptoms including dizziness, lightheadedness, fainting, fatigue, blurry vision, weakness, trouble concentrating, and head and neck pain. About Theravance Biopharma Theravance Biopharma, Inc.'s focus is to deliver Medicines that Make a Difference® in people's lives. In pursuit of its purpose, Theravance Biopharma leverages decades of expertise, which has led to the development of FDA-approved YUPELRI® (revefenacin) inhalation solution indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Ampreloxetine, its late-stage investigational once-daily norepinephrine reuptake inhibitor in development for symptomatic neurogenic orthostatic hypotension (nOH) in patients with Multiple System Atrophy (MSA), has the potential to be a first in class therapy effective in treating a constellation of cardinal symptoms in MSA patients. The Company is committed to creating/driving shareholder value. For more information, please visit www.theravance.com. THERAVANCE BIOPHARMA ®, THERAVANCE®, and the Cross/Star logo are registered trademarks of the Theravance Biopharma group of companies (in the U.S. and certain other countries). YUPELRI® is a registered trademark of Mylan Specialty L.P., a Viatris company. Trademarks, trade names or service marks of other companies appearing on this press release are the property of their respective owners. Dr. Kaufmann is a member of an advisory committee supporting the CYPRESS clinical trial and a paid consultant to Theravance Biopharma . Forward-Looking Statements This press release will contain certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, expectations and future events. Theravance Biopharma, Inc. (the "Company") intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements relating to: the Company's expectations regarding its future profitability, expenses and uses of cash, the Company's goals, designs, strategies, plans and objectives, future growth of YUPELRI sales, future royalty payments, the ability to provide value to shareholders, the Company's regulatory strategies and timing of clinical studies, possible safety, efficacy or differentiation of our investigational therapy, the status of patent infringement litigation initiated by the Company and its partner against certain generic companies in federal district courts; contingent payments due to the Company from the sale of the Company's TRELEGY ELLIPTA royalty interests to Royalty Pharma, and expectations around the use of OHSA scores as endpoints for clinical trials. These statements are based on the current estimates and assumptions of the management of Theravance Biopharma as of the date of this press release and the conference call and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance Biopharma to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: factors that could increase the Company's cash requirements or expenses beyond its expectations and any factors that could adversely affect its profitability, whether the milestone thresholds can be achieved, delays or difficulties in commencing, enrolling or completing clinical studies, the potential that results from clinical or non-clinical studies indicate the Company's product candidates or product are unsafe, ineffective or not differentiated, risks of decisions from regulatory authorities that are unfavorable to the Company, dependence on third parties to conduct clinical studies, delays or failure to achieve and maintain regulatory approvals for product candidates, risks of collaborating with or relying on third parties to discover, develop, manufacture and commercialize products, and risks associated with establishing and maintaining sales, marketing and distribution capabilities with appropriate technical expertise and supporting infrastructure, the ability of the Company to protect and to enforce its intellectual property rights, volatility and fluctuations in the trading price and volume of the Company's shares, and general economic and market conditions. Other risks affecting the Company are in the Company's Form 10-Q filed with the SEC on August 13, 2025 , and other periodic reports filed with the SEC . In addition to the risks described above and in Theravance Biopharma's filings with the SEC , other unknown or unpredictable factors also could affect Theravance Biopharma's results. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance Biopharma assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law. Contact: investor.relations@theravance.com650-808-4045 1 https://www.medrxiv.org/content/10.1101/2025.08.12.25332833v1 Precision therapy with ampreloxetine for neurogenic orthostatic hypotension in multiple system atrophy Roy Freeman , Horacio Kaufmann , Italo Biaggioni, Valeria Iodice , Jens Jordan , Ross Vickery , Tadhg Geurin , Matthew J. Kmiecik , Lucy Norcliffe-Kaufmann 2https://medlineplus.gov/genetics/condition/multiple-system-atrophy/ 3 UCSD Neurological Institute (25K-75K, with ~10K new cases per year); NIH National Institute of Neurological Disorders and Stroke (15K-50K).4 Delveinsight MSA Market Forecast (2023); Symptoms associated with orthostatic hypotension in pure autonomic failure and multiple systems atrophy, CJ Mathias (1999). View original content to download multimedia:https://www.prnewswire.com/news-releases/theravance-biopharma-completes-enrollment-in-pivotal-phase-3-cypress-study-of-ampreloxetine-in-patients-with-symptomatic-neurogenic-orthostatic-hypotension-due-to-multiple-system-atrophy-302537380.html SOURCE Theravance Biopharma, Inc.

Clinical ResultPhase 3NDAOrphan Drug

12 Aug 2025

·www.prnewswire.com

Theravance Biopharma, Inc. Reports Second Quarter 2025 Financial Results and Provides Corporate Update

YUPELRI® (revefenacin) net sales of $66.3 million, recognized by Viatris, increased 22% year-over-year1 Pivotal Phase 3 CYPRESS study enrollment on track to complete by late summer Completed sale of TRELEGY ELLIPTA royalty interest to GSK for $225 million TRELEGY year-to-date sales on track to trigger $50 million milestone in 2025 Strong balance sheet with $339 million in cash and no debt DUBLIN, Aug. 12, 2025 /PRNewswire/ -- Theravance Biopharma, Inc. ("Theravance Biopharma" or the "Company") (NASDAQ: TBPH) today reported financial and operational results for the second quarter of 2025. "Strong execution across our business defined the second quarter, driven by commercial growth, disciplined operations, and continued progress on ampreloxetine. YUPELRI posted another strong quarter in the U.S., and its recent approval in China triggered a $7.5 million milestone payment. With the completion of the strategic monetization of our TRELEGY royalty interest, which brought in $225 million, these accomplishments have meaningfully strengthened our business," said Rick E Winningham, Chief Executive Officer of Theravance Biopharma. "We enter the second half of 2025 with momentum and a clear focus on ampreloxetine. We remain on track for completing the enrollment in our pivotal Phase 3 CYPRESS study in late summer, and continue to prepare for reporting top-line data approximately six months later." Second Quarter Operational Highlights: YUPELRI® (revefenacin) inhalation solution, the first and only once-daily, nebulized LAMA (long-acting muscarinic antagonist) bronchodilator approved in the US for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD): Achieved total U.S. net sales of $66.3 million in Q2 2025, increasing 22% year-over-year (Q2 2025 vs Q2 2024).1 Grew customer demand 4% for the quarter (Q2 2025 vs Q2 2024).2 Net sales benefited from continued improvement to net pricing and a one-time favorable adjustment to net price. Excluding the one-time adjustment, year-over-year net sales growth would have been in the mid-teens. Increased doses pulled through the hospital channel by 31% year-over-year (Q2 2025 vs Q2 2024), reflecting another quarter of strong momentum.3 Earned $7.5 million milestone payment from Viatris in Q2 2025 for YUPELRI approval in China. Ampreloxetine, an investigational, once-daily, selective norepinephrine reuptake inhibitor in development for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA): Pivotal Phase 3 CYPRESS study enrollment nearing completion with final patient expected to be enrolled by late summer; top-line data anticipated approximately six months later. Advancing pre-launch activities across medical affairs and commercial functions in preparation for the potential approval of ampreloxetine, a once-daily therapy aiming to transform treatment for symptomatic nOH in patients with MSA. TRELEGY GSK posted second quarter 2025 global net sales of approximately $1.1 billion (up 4% vs. the second quarter of 2024) and year-to-date net sales of approximately $2.0 billion (up 8% vs. 2024 year-to-date): Currently on track to exceed full year (FY) 2025 global net sales of ~$3.4 billion (representing minus 1% growth vs. 2024) required to trigger $50M milestone from Royalty Pharma. FY 2026 global net sales of ~$3.5 billion (representing 2% growth vs. 2024) required to trigger $100M milestone from Royalty Pharma. Sale of Remaining Royalty Interest in Trelegy Ellipta to GSK: One-time cash payment of $225 million received in late Q2 2025. This transaction represents the first outcome of the ongoing efforts of the Strategic Review Committee of the Board of Directors. Theravance Biopharma announced on November 12, 2024, that the Board of Directors had formed the Committee, composed entirely of independent directors, to assess all strategic alternatives available to the Company. The Company remains focused on disciplined capital allocation and returning excess cash to shareholders. The Committee will continue to evaluate a range of alternatives to further enhance shareholder value, though there can be no assurance that additional transactions will occur. Second quarter Financial Results: Revenue: Total revenue for the second quarter of 2025 was $26.2 million, consisting of $18.7 million of Viatris collaboration revenue and $7.5 million of licensing revenue from YUPELRI's regulatory approval in China. Viatris collaboration revenue increased by $4.4 million, or 31%, in the second quarter compared to the same period in 2024. The Viatris collaboration revenue represents amounts receivable from Viatris and comprises the Company's 35% share of net sales of YUPELRI, as well as its proportionate amount of the total shared commercial costs incurred by the two companies. The non-shared YUPELRI costs incurred by Theravance Biopharma are recorded within operating expenses. While Viatris records the total net sales of YUPELRI within its financial statements, Theravance Biopharma's implied 35% share of net sales of YUPELRI for the second quarter of 2025 was $23.2 million which represented a 22% increase compared to the same period in 2024. Research and Development (R&D) Expenses: R&D expenses for the second quarter of 2025 were $10.5 million, compared to $10.0 million in the same period in 2024. Second quarter R&D expenses included total non-cash share-based compensation of $1.0 million. Selling, General and Administrative (SG&A) Expenses: SG&A expenses for the second quarter of 2025 were $18.4 million, compared to $17.1 million in the same period in 2024. Second quarter SG&A expenses included total non-cash share-based compensation of $3.5 million. Share-Based Compensation: Share-based compensation expenses for the second quarter of 2025 were $4.5 million, compared to $5.4 million in the same period in 2024. Share-based compensation expenses consisted of $1.0 million for R&D and $3.5 million for SG&A in the second quarter of 2025, compared to $1.2 million and $4.2 million, respectively, in the same period in 2024. Net Gain on Realized Contingent Milestone and Royalty Assets: Net gain on contingent milestone and royalty assets (representing the sale of our remaining interest in TRELEGY royalties) was $75.1 million. The net gain was based on sales proceeds of $225.0 million less our carrying value of TRELEGY's contingent milestone and royalty assets of $144.2 million and less transaction costs of $5.7 million. Income Taxes: Income tax expense for the second quarter of 2025 was $18.4 million, compared to $1.3 million in the same period in 2024. The increase was driven by the net gain on contingent milestone and royalty assets arising from the sale of our remaining interest in TRELEGY royalties. Net Income (Loss) and Non-GAAP Net Loss from Operations4: Net income was $54.8 million in the second quarter of 2025 compared to a net loss of $16.5 million in the same period in 2024. Non-GAAP net loss from operations was $4.2 million in the second quarter 2025 compared to a non-GAAP net loss from operations of $6.3 million in the same period in 2024. See the section titled "Non-GAAP Financial Measures" for more information. Cash Position: Cash, cash equivalents and marketable securities totaled $338.8 million as of June 30, 2025. 2025 Financial Guidance: Operating Expenses ( excluding share-based compensation) : The Company continues to expect full year 2025 R&D expenses of $32 million to $38 million and SG&A expenses of $50 million to $60 million, in each case excluding share-based compensation. Share-Based Compensation: The Company continues to expect full year share-based compensation expenses of $18 million to $20 million. Non-GAAP Net Income (Loss) from Operations and Cash Burn4: The Company continues to expect 2025 levels of Non-GAAP Net Income (Loss) from Operations and Cash Burn in 2025 to be similar to levels incurred in 2024. Both Non-GAAP Net Income (Loss) from Operations and Cash Burn guidance metrics exclude one-time, non-recurring Revenue and Income items incurred throughout 2025. Conference Call and Live Webcast Today at 5:00 pm ET Theravance Biopharma will hold a conference call and live webcast accompanied by slides today at 5:00 pm ET / 2:00 pm PT / 9:00 pm GMT. To participate in the live call by telephone, please pre-register here. Those interested in listening to the conference call live via the internet may do so by clicking here or visiting the Events and Presentation page under the Investors Section on Theravance Biopharma's website. A replay of the webcast will be available on Theravance Biopharma's website for 30 days through September 11, 2025. About Ampreloxetine Ampreloxetine, an investigational, once-daily, selective norepinephrine reuptake inhibitor in development for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA). The unique benefits of ampreloxetine treatment reported in MSA patients from Study 0170 included an increase in norepinephrine levels, a favorable impact on blood pressure, clinically meaningful and durable symptom improvement, and no signal for worsening of supine hypertension. In the US, the Company has been granted an Orphan Drug Designation for ampreloxetine for the treatment of symptomatic nOH in patients with MSA and, if results from the ongoing Phase 3 CYPRESS study are supportive, plans to file an NDA for full approval in this indication. About CYPRESS (Study 0197), a Phase 3 Study Study 0197 (NCT05696717) is currently enrolling. This is a registrational Phase 3, multi-center, randomized withdrawal study to evaluate the efficacy and durability of ampreloxetine in participants with MSA and symptomatic nOH after 20 weeks of treatment; the primary endpoint of the study is change in the Orthostatic Hypotension Symptom Assessment (OHSA) composite score. The Study includes four periods: screening, open label (12-week period, participants will receive a single daily 10 mg dose of ampreloxetine), randomized withdrawal (eight-week period, double-blind, placebo-controlled, participants will receive a single daily 10 mg dose of placebo or ampreloxetine), and a long-term treatment extension. Secondary outcome measures include change from baseline in Orthostatic Hypotension Daily Activity Scale (OHDAS) item 1 (activities that require standing for a short time) and item 3 (activities that require walking for a short time). About Multiple System Atrophy (MSA) and Symptomatic Neurogenic Orthostatic Hypotension (nOH) MSA is a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls body functions that are mostly involuntary. One of the most frequent autonomic symptoms associated with MSA is a sudden drop in blood pressure upon standing (nOH).5 There are approximately 50,000 MSA patients in the US6 and 70-90% of MSA patients experience nOH symptoms.7 Despite available therapies, many MSA patients remain symptomatic with nOH. Neurogenic orthostatic hypotension (nOH) is a rare disorder defined as a fall in systolic blood pressure of ⩾20 mm Hg or diastolic blood pressure of ⩾10 mm Hg, within 3 minutes of standing. Severely affected patients are unable to stand for more than a few seconds because of their decrease in blood pressure, leading to cerebral hypoperfusion and syncope. A debilitating condition, nOH results in a range of symptoms including dizziness, lightheadedness, fainting, fatigue, blurry vision, weakness, trouble concentrating, and head and neck pain. About Theravance Biopharma Theravance Biopharma, Inc.'s focus is to deliver Medicines that Make a Difference® in people's lives. In pursuit of its purpose, Theravance Biopharma leverages decades of expertise, which has led to the development of FDA-approved YUPELRI® (revefenacin) inhalation solution indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Ampreloxetine, its late-stage investigational once-daily norepinephrine reuptake inhibitor in development for symptomatic neurogenic orthostatic hypotension (nOH) in patients with Multiple System Atrophy (MSA), has the potential to be a first in class therapy effective in treating a constellation of cardinal symptoms in MSA patients. The Company is committed to creating/driving shareholder value. For more information, please visit . THERAVANCE BIOPHARMA®, THERAVANCE® and the Cross/Star logo are registered trademarks of the Theravance Biopharma group of companies (in the U.S. and certain other countries). YUPELRI® is a registered trademark of Viatris Specialty LLC. Trademarks, trade names or service marks of other companies appearing on this press release are the property of their respective owners. Forward-Looking Statements This press release will contain certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, expectations and future events. Theravance Biopharma, Inc. (the "Company") intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements relating to: the Company's expectations regarding its future profitability, expenses and uses of cash, the Company's goals, designs, strategies, plans and objectives, future growth of YUPELRI sales, future milestone or royalty payments, the ability to provide value to shareholders, the Company's regulatory strategies and timing of clinical studies, the safety, efficacy or differentiation of our investigational therapy, the status of patent infringement litigation initiated by the Company and its partner against certain generic companies in federal district courts; , and expectations around the use of OHSA scores as endpoints for clinical trials. These statements are based on the current estimates and assumptions of the management of Theravance Biopharma as of the date of this press release and the conference call and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance Biopharma to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: factors that could increase the Company's cash requirements or expenses beyond its expectations and any factors that could adversely affect its profitability, whether the milestone thresholds can be achieved, delays or difficulties in commencing, enrolling or completing clinical studies, the potential that results from clinical or non-clinical studies indicate the Company's product candidates or product are unsafe, ineffective or not differentiated, risks of decisions from regulatory authorities that are unfavorable to the Company, dependence on third parties to conduct clinical studies, delays or failure to achieve and maintain regulatory approvals for product candidates, risks of collaborating with or relying on third parties to discover, develop, manufacture and commercialize products, and risks associated with establishing and maintaining sales, marketing and distribution capabilities with appropriate technical expertise and supporting infrastructure, the ability of the Company to protect and to enforce its intellectual property rights, volatility and fluctuations in the trading price and volume of the Company's shares, and general economic and market conditions. Other risks affecting the Company are in the Company's Form 10-Q filed with the SEC on May 12, 2025, and other periodic reports filed with the SEC. In addition to the risks described above and in Theravance Biopharma's filings with the SEC, other unknown or unpredictable factors also could affect Theravance Biopharma's results. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance Biopharma assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law. Non-GAAP Financial Measures Theravance Biopharma provides a non-GAAP profitability target and a non-GAAP metric in this press release. Theravance Biopharma believes that the non-GAAP profitability target and non-GAAP net income (loss) provide meaningful information to assist investors in assessing prospects for future performance and actual performance as they provide better metrics for analyzing the performance of its business by excluding items that may not be indicative of core operating results and the Company's cash position. Because non-GAAP financial targets and metrics, such as non-GAAP profitability and non-GAAP net loss, are not standardized, it may not be possible to compare these measures with other companies' non-GAAP targets or measures having the same or a similar name. Thus, Theravance Biopharma's non-GAAP measures should be considered in addition to, not as a substitute for, or in isolation from, the Company's actual GAAP results and other targets. Please see the appendix attached to this press release for a reconciliation of non-GAAP net loss to its corresponding measure, net income (loss). A reconciliation of non-GAAP net loss to its corresponding GAAP measure is not available on a forward-looking basis without unreasonable effort due to the uncertainty regarding, and the potential variability of, expenses and other factors in the future. Contact: [email protected] 650-808-4045 SOURCE Theravance Biopharma, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 3Financial StatementDrug ApprovalOrphan DrugLicense out/in

12 Aug 2025

·investor.theravance.com

Theravance Biopharma, Inc. Reports Second Quarter 2025 Financial Results and Provides Corporate Update

YUPELRI® (revefenacin) net sales of $66.3 million , recognized by Viatris, increased 22% year-over-year1 Pivotal Phase 3 CYPRESS study enrollment on track to complete by late summer Completed sale of TRELEGY ELLIPTA royalty interest to GSK for $225 million TRELEGY year-to-date sales on track to trigger $50 million milestone in 2025 Strong balance sheet with $339 million in cash and no debt DUBLIN , Aug. 12, 2025 /PRNewswire/ -- Theravance Biopharma, Inc. (" Theravance Biopharma " or the "Company") (NASDAQ: TBPH) today reported financial and operational results for the second quarter of 2025. "Strong execution across our business defined the second quarter, driven by commercial growth, disciplined operations, and continued progress on ampreloxetine. YUPELRI posted another strong quarter in the U.S. , and its recent approval in China triggered a $7.5 million milestone payment. With the completion of the strategic monetization of our TRELEGY royalty interest, which brought in $225 million , these accomplishments have meaningfully strengthened our business," said Rick E Winningham, Chief Executive Officer of Theravance Biopharma . "We enter the second half of 2025 with momentum and a clear focus on ampreloxetine. We remain on track for completing the enrollment in our pivotal Phase 3 CYPRESS study in late summer, and continue to prepare for reporting top-line data approximately six months later." Second Quarter Operational Highlights: YUPELRI® (revefenacin) inhalation solution, the first and only once-daily, nebulized LAMA (long-acting muscarinic antagonist) bronchodilator approved in the US for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD): Achieved total U.S. net sales of $66.3 million in Q2 2025, increasing 22% year-over-year (Q2 2025 vs Q2 2024).1 Grew customer demand 4% for the quarter (Q2 2025 vs Q2 2024).2 Net sales benefited from continued improvement to net pricing and a one-time favorable adjustment to net price. Excluding the one-time adjustment, year-over-year net sales growth would have been in the mid-teens. Increased doses pulled through the hospital channel by 31% year-over-year (Q2 2025 vs Q2 2024), reflecting another quarter of strong momentum.3 Earned $7.5 million milestone payment from Viatris in Q2 2025 for YUPELRI approval in China . Ampreloxetine, an investigational, once-daily, selective norepinephrine reuptake inhibitor in development for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA): Pivotal Phase 3 CYPRESS study enrollment nearing completion with final patient expected to be enrolled by late summer; top-line data anticipated approximately six months later. Advancing pre-launch activities across medical affairs and commercial functions in preparation for the potential approval of ampreloxetine, a once-daily therapy aiming to transform treatment for symptomatic nOH in patients with MSA. TRELEGY GSK posted second quarter 2025 global net sales of approximately $1.1 billion (up 4% vs. the second quarter of 2024) and year-to-date net sales of approximately $2.0 billion (up 8% vs. 2024 year-to-date): Currently on track to exceed full year (FY) 2025 global net sales of ~$3.4 billion (representing minus 1% growth vs. 2024) required to trigger $50M milestone from Royalty Pharma. FY 2026 global net sales of ~$3.5 billion (representing 2% growth vs. 2024) required to trigger $100M milestone from Royalty Pharma. Sale of Remaining Royalty Interest in Trelegy Ellipta to GSK: One-time cash payment of $225 million received in late Q2 2025. This transaction represents the first outcome of the ongoing efforts of the Strategic Review Committee of the Board of Directors. Theravance Biopharma announced on November 12, 2024 , that the Board of Directors had formed the Committee, composed entirely of independent directors, to assess all strategic alternatives available to the Company. The Company remains focused on disciplined capital allocation and returning excess cash to shareholders. The Committee will continue to evaluate a range of alternatives to further enhance shareholder value, though there can be no assurance that additional transactions will occur. Second quarter Financial Results: Revenue: Total revenue for the second quarter of 2025 was $26.2 million , consisting of $18.7 million of Viatris collaboration revenue and $7.5 million of licensing revenue from YUPELRI's regulatory approval in China . Viatris collaboration revenue increased by $4.4 million , or 31%, in the second quarter compared to the same period in 2024. The Viatris collaboration revenue represents amounts receivable from Viatris and comprises the Company's 35% share of net sales of YUPELRI, as well as its proportionate amount of the total shared commercial costs incurred by the two companies. The non-shared YUPELRI costs incurred by Theravance Biopharma are recorded within operating expenses. While Viatris records the total net sales of YUPELRI within its financial statements, Theravance Biopharma's implied 35% share of net sales of YUPELRI for the second quarter of 2025 was $23.2 million which represented a 22% increase compared to the same period in 2024. Research and Development (R&D) Expenses: R&D expenses for the second quarter of 2025 were $10.5 million , compared to $10.0 million in the same period in 2024. Second quarter R&D expenses included total non-cash share-based compensation of $1.0 million . Selling, General and Administrative (SG&A) Expenses: SG&A expenses for the second quarter of 2025 were $18.4 million , compared to $17.1 million in the same period in 2024. Second quarter SG&A expenses included total non-cash share-based compensation of $3.5 million . Share-Based Compensation: Share-based compensation expenses for the second quarter of 2025 were $4.5 million , compared to $5.4 million in the same period in 2024. Share-based compensation expenses consisted of $1.0 million for R&D and $3.5 million for SG&A in the second quarter of 2025, compared to $1.2 million and $4.2 million , respectively, in the same period in 2024. Net Gain on Realized Contingent Milestone and Royalty Assets: Net gain on contingent milestone and royalty assets (representing the sale of our remaining interest in TRELEGY royalties) was $75.1 million . The net gain was based on sales proceeds of $225.0 million less our carrying value of TRELEGY's contingent milestone and royalty assets of $144.2 million and less transaction costs of $5.7 million . Income Taxes: Income tax expense for the second quarter of 2025 was $18.4 million , compared to $1.3 million in the same period in 2024. The increase was driven by the net gain on contingent milestone and royalty assets arising from the sale of our remaining interest in TRELEGY royalties. Net Income (Loss) and Non-GAAP Net Loss from Operations4: Net income was $54.8 million in the second quarter of 2025 compared to a net loss of $16.5 million in the same period in 2024. Non-GAAP net loss from operations was $4.2 million in the second quarter 2025 compared to a non-GAAP net loss from operations of $6.3 million in the same period in 2024. See the section titled "Non-GAAP Financial Measures" for more information. Cash Position: Cash, cash equivalents and marketable securities totaled $338.8 million as of June 30, 2025 . 2025 Financial Guidance: Operating Expenses (excluding share-based compensation): The Company continues to expect full year 2025 R&D expenses of $32 million to $38 million and SG&A expenses of $50 million to $60 million , in each case excluding share-based compensation. Share-Based Compensation: The Company continues to expect full year share-based compensation expenses of $18 million to $20 million . Non-GAAP Net Income (Loss) from Operations and Cash Burn4: The Company continues to expect 2025 levels of Non-GAAP Net Income (Loss) from Operations and Cash Burn in 2025 to be similar to levels incurred in 2024. Both Non-GAAP Net Income (Loss) from Operations and Cash Burn guidance metrics exclude one-time, non-recurring Revenue and Income items incurred throughout 2025. Conference Call and Live Webcast Today at 5:00 pm ET Theravance Biopharma will hold a conference call and live webcast accompanied by slides today at 5:00 pm ET / 2:00 pm PT / 9:00 pm GMT . To participate in the live call by telephone, please pre-register here. Those interested in listening to the conference call live via the internet may do so by clicking here or visiting the Events and Presentation page under the Investors Section on Theravance Biopharma's website. A replay of the webcast will be available on Theravance Biopharma's website for 30 days through September 11, 2025 . About Ampreloxetine Ampreloxetine, an investigational, once-daily, selective norepinephrine reuptake inhibitor in development for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA). The unique benefits of ampreloxetine treatment reported in MSA patients from Study 0170 included an increase in norepinephrine levels, a favorable impact on blood pressure, clinically meaningful and durable symptom improvement, and no signal for worsening of supine hypertension. In the US, the Company has been granted an Orphan Drug Designation for ampreloxetine for the treatment of symptomatic nOH in patients with MSA and, if results from the ongoing Phase 3 CYPRESS study are supportive, plans to file an NDA for full approval in this indication. About CYPRESS (Study 0197), a Phase 3 Study Study 0197 (NCT05696717) is currently enrolling. This is a registrational Phase 3, multi-center, randomized withdrawal study to evaluate the efficacy and durability of ampreloxetine in participants with MSA and symptomatic nOH after 20 weeks of treatment; the primary endpoint of the study is change in the Orthostatic Hypotension Symptom Assessment (OHSA) composite score. The Study includes four periods: screening, open label (12-week period, participants will receive a single daily 10 mg dose of ampreloxetine), randomized withdrawal (eight-week period, double-blind, placebo-controlled, participants will receive a single daily 10 mg dose of placebo or ampreloxetine), and a long-term treatment extension. Secondary outcome measures include change from baseline in Orthostatic Hypotension Daily Activity Scale (OHDAS) item 1 (activities that require standing for a short time) and item 3 (activities that require walking for a short time). About Multiple System Atrophy (MSA) and Symptomatic Neurogenic Orthostatic Hypotension (nOH) MSA is a progressive brain disorder that affects movement and balance and disrupts the function of the autonomic nervous system. The autonomic nervous system controls body functions that are mostly involuntary. One of the most frequent autonomic symptoms associated with MSA is a sudden drop in blood pressure upon standing (nOH).5 There are approximately 50,000 MSA patients in the US6 and 70-90% of MSA patients experience nOH symptoms.7 Despite available therapies, many MSA patients remain symptomatic with nOH. Neurogenic orthostatic hypotension (nOH) is a rare disorder defined as a fall in systolic blood pressure of ⩾20 mm Hg or diastolic blood pressure of ⩾10 mm Hg, within 3 minutes of standing. Severely affected patients are unable to stand for more than a few seconds because of their decrease in blood pressure, leading to cerebral hypoperfusion and syncope. A debilitating condition, nOH results in a range of symptoms including dizziness, lightheadedness, fainting, fatigue, blurry vision, weakness, trouble concentrating, and head and neck pain. About Theravance Biopharma Theravance Biopharma, Inc.'s focus is to deliver Medicines that Make a Difference® in people's lives. In pursuit of its purpose, Theravance Biopharma leverages decades of expertise, which has led to the development of FDA-approved YUPELRI® (revefenacin) inhalation solution indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Ampreloxetine, its late-stage investigational once-daily norepinephrine reuptake inhibitor in development for symptomatic neurogenic orthostatic hypotension (nOH) in patients with Multiple System Atrophy (MSA), has the potential to be a first in class therapy effective in treating a constellation of cardinal symptoms in MSA patients. The Company is committed to creating/driving shareholder value. For more information, please visit www.theravance.com. THERAVANCE BIOPHARMA ®, THERAVANCE® and the Cross/Star logo are registered trademarks of the Theravance Biopharma group of companies (in the U.S. and certain other countries). YUPELRI® is a registered trademark of Viatris Specialty LLC. Trademarks, trade names or service marks of other companies appearing on this press release are the property of their respective owners. Forward-Looking Statements This press release will contain certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, expectations and future events. Theravance Biopharma, Inc. (the "Company") intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements relating to: the Company's expectations regarding its future profitability, expenses and uses of cash, the Company's goals, designs, strategies, plans and objectives, future growth of YUPELRI sales, future milestone or royalty payments, the ability to provide value to shareholders, the Company's regulatory strategies and timing of clinical studies, the safety, efficacy or differentiation of our investigational therapy, the status of patent infringement litigation initiated by the Company and its partner against certain generic companies in federal district courts; , and expectations around the use of OHSA scores as endpoints for clinical trials. These statements are based on the current estimates and assumptions of the management of Theravance Biopharma as of the date of this press release and the conference call and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance Biopharma to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: factors that could increase the Company's cash requirements or expenses beyond its expectations and any factors that could adversely affect its profitability, whether the milestone thresholds can be achieved, delays or difficulties in commencing, enrolling or completing clinical studies, the potential that results from clinical or non-clinical studies indicate the Company's product candidates or product are unsafe, ineffective or not differentiated, risks of decisions from regulatory authorities that are unfavorable to the Company, dependence on third parties to conduct clinical studies, delays or failure to achieve and maintain regulatory approvals for product candidates, risks of collaborating with or relying on third parties to discover, develop, manufacture and commercialize products, and risks associated with establishing and maintaining sales, marketing and distribution capabilities with appropriate technical expertise and supporting infrastructure, the ability of the Company to protect and to enforce its intellectual property rights, volatility and fluctuations in the trading price and volume of the Company's shares, and general economic and market conditions. Other risks affecting the Company are in the Company's Form 10-Q filed with the SEC on May 12, 2025 , and other periodic reports filed with the SEC . In addition to the risks described above and in Theravance Biopharma's filings with the SEC , other unknown or unpredictable factors also could affect Theravance Biopharma's results. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance Biopharma assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law. Non-GAAP Financial Measures Theravance Biopharma provides a non-GAAP profitability target and a non-GAAP metric in this press release. Theravance Biopharma believes that the non-GAAP profitability target and non-GAAP net income (loss) provide meaningful information to assist investors in assessing prospects for future performance and actual performance as they provide better metrics for analyzing the performance of its business by excluding items that may not be indicative of core operating results and the Company's cash position. Because non-GAAP financial targets and metrics, such as non-GAAP profitability and non-GAAP net loss, are not standardized, it may not be possible to compare these measures with other companies' non-GAAP targets or measures having the same or a similar name. Thus, Theravance Biopharma's non-GAAP measures should be considered in addition to, not as a substitute for, or in isolation from, the Company's actual GAAP results and other targets. Please see the appendix attached to this press release for a reconciliation of non-GAAP net loss to its corresponding measure, net income (loss). A reconciliation of non-GAAP net loss to its corresponding GAAP measure is not available on a forward-looking basis without unreasonable effort due to the uncertainty regarding, and the potential variability of, expenses and other factors in the future. Contact: investor.relations@theravance.com 650-808-4045 _____________________________________ 1 In the US, Viatris is leading the commercialization of YUPELRI, and the Company co-promotes the product under a profit and loss sharing arrangement (65% to Viatris; 35% to the Company).2 Source: Viatris Customer Demand (Q2'25).3 Source: IQVIA DDD, HDS, VA and Non-Reporting Hospital through Jun '25.4 Non-GAAP profit (loss) consists of GAAP net income (loss) before taxes less (i) share-based compensation expense, (ii) non-cash interest expense, (iii) non-cash impairment expense; and (iv) non-recurring revenue and income items. See the section titled "Non-GAAP Financial Measures" for more information.5 https://medlineplus.gov/genetics/condition/multiple-system-atrophy/ 6 UCSD Neurological Institute (25K-75K, with ~10K new cases per year); NIH National Institute of Neurological Disorders and Stroke (15K-50K).7 Delveinsight MSA Market Forecast (2023); Symptoms associated with orthostatic hypotension in pure autonomic failure and multiple systems atrophy, CJ Mathias (1999). THERAVANCE BIOPHARMA, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (In thousands) June 30 , December 31 , 2025 2024 Assets (Unaudited) (1) Current assets: Cash and cash equivalents and short-term marketable securities $ 338,804 $ 88,350 Receivables from collaborative arrangements 21,919 18,440 Receivables from milestone and royalty assets - 50,000 Other prepaid and current assets 5,571 4,277 Total current assets 366,294 161,067 Property and equipment, net 6,641 7,418 Operating lease assets 26,493 28,354 Future contingent milestone and royalty assets - 144,200 Restricted cash 836 836 Other assets 25,771 12,286 Total assets $ 426,035 $ 354,161 Liabilities and Shareholders' Equity Income tax payable $ 26,696 $ 5,853 Other current liabilities 27,937 26,232 Total current liabilities 54,633 32,085 Long-term operating lease liabilities 35,561 39,108 Future royalty payment contingency 31,640 30,334 Unrecognized tax benefits 77,805 75,199 Other long-term liabilities 1,548 1,890 Shareholders' equity 224,848 175,545 Total liabilities and shareholders' equity $ 426,035 $ 354,161 ________________________________ (1) The condensed consolidated balance sheet as of December 31, 2024 has been derived from the audited consolidated financial statements included in the Company's Annual Report on Form 10-K for the year ended December 31, 2024 . THERAVANCE BIOPHARMA, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (In thousands, except per share data) Three Months Ended June 30 , Six Months Ended June 30 , 2025 2024 2025 2024 (Unaudited) (Unaudited) Revenue: Viatris collaboration agreement (1) $ 18,695 $ 14,256 $ 34,083 $ 28,759 Licensing revenue 7,500 - 7,500 - Total revenue 26,195 14,256 41,583 28,759 Costs and expenses: Research and development (2) 10,490 9,954 21,942 18,922 Selling, general and administrative (2) 18,430 17,056 36,800 33,798 Impairment of long-lived assets (non-cash) - 2,951 - 2,951 Total costs and expenses 28,920 29,961 58,742 55,671 Loss from operations (2,725) (15,705) (17,159) (26,912) Net gain on realized contingent milestone and royalty assets 75,137 - 75,137 - Interest expense (non-cash) (663) (644) (1,306) (1,273) Interest income and other income, net 1,457 1,128 2,396 2,562 Loss before income taxes 73,206 (15,221) 59,068 (25,623) Provision for income tax expense (18,371) (1,308) (17,812) (2,570) Net income (loss) $ 54,835 $ (16,529) $ 41,256 $ (28,193) Net income (loss) per share: Net income (loss) per share - basic $ 1.09 $ (0.34) $ 0.83 $ (0.58) Net income (loss) per share - diluted $ 1.08 $ (0.34) $ 0.81 $ (0.58) Shares used to compute net income (loss) per share - basis 50,177 48,747 49,943 48,515 Shares used to compute net income (loss) per share - diluted 50,726 48,747 50,685 48,515 Non-GAAP net loss $ (4,225) $ (6,250) $ (12,843) $ (10,795) ________________________________ (1) While Viatris, Inc. records the total YUPELRI net sales, the Company is entitled to a 35% share of the net profit (loss) pursuant to a co-promotion agreement with Viatris as presented below: Three Months Ended June 30 , Six Months Ended June 30 , (In thousands) 2025 2024 2025 2024 YUPELRI net sales (100% recorded by Viatris) $ 66,330 $ 54,530 $ 124,674 $ 109,756 YUPELRI net sales ( Theravance Biopharma implied 35%) 23,216 19,085 43,636 38,415 (2) Amounts include share-based compensation expense as follows: Three Months Ended June 30 , Six Months Ended June 30 , (In thousands) 2025 2024 2025 2024 Research and development $ 987 $ 1,151 $ 2,057 $ 2,616 Selling, general and administrative 3,556 4,225 7,363 7,988 Total share-based compensation expense $ 4,543 $ 5,376 $ 9,420 $ 10,604 THERAVANCE BIOPHARMA, INC. Reconciliation of GAAP Net Income (Loss) to Non-GAAP Net Loss (In thousands) Three Months Ended June 30 , Six Months Ended June 30 , 2025 2024 2025 2024 (Unaudited) (Unaudited) GAAP net income (loss) $ 54,835 $ (16,529) $ 41,256 $ (28,193) Adjustments: Licensing revenue (1) (7,500) - (7,500) - Net gain on realized contingent milestone and royalty assets (1) (75,137) - (75,137) - Non-cash impairment expense of long-lived assets (1) - 2,951 - 2,951 Share-based compensation expense 4,543 5,376 9,420 10,604 Non-cash interest expense 663 644 1,306 1,273 Income tax expense 18,371 1,308 17,812 2,570 Non-GAAP net loss $ (4,225) $ (6,250) $ (12,843) $ (10,795) (1) Non-recurring item View original content to download multimedia:https://www.prnewswire.com/news-releases/theravance-biopharma-inc-reports-second-quarter-2025-financial-results-and-provides-corporate-update-302528141.html SOURCE Theravance Biopharma, Inc.

Phase 3Financial StatementDrug ApprovalOrphan DrugLicense out/in

100 Deals associated with Ampreloxetine hydrochloride

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KEGG	Wiki	ATC	Drug Bank
D11688	-	-	DB15348

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Multiple system atrophy, Parkinson's variant	Phase 3	United States	Theravance Biopharma, Inc.	27 Jun 2023
Multiple system atrophy, Parkinson's variant	Phase 3	Argentina	Theravance Biopharma, Inc.	27 Jun 2023
Multiple system atrophy, Parkinson's variant	Phase 3	Australia	Theravance Biopharma, Inc.	27 Jun 2023
Multiple system atrophy, Parkinson's variant	Phase 3	Austria	Theravance Biopharma, Inc.	27 Jun 2023
Multiple system atrophy, Parkinson's variant	Phase 3	Brazil	Theravance Biopharma, Inc.	27 Jun 2023
Multiple system atrophy, Parkinson's variant	Phase 3	Canada	Theravance Biopharma, Inc.	27 Jun 2023
Multiple system atrophy, Parkinson's variant	Phase 3	Denmark	Theravance Biopharma, Inc.	27 Jun 2023
Multiple system atrophy, Parkinson's variant	Phase 3	Estonia	Theravance Biopharma, Inc.	27 Jun 2023
Multiple system atrophy, Parkinson's variant	Phase 3	France	Theravance Biopharma, Inc.	27 Jun 2023
Multiple system atrophy, Parkinson's variant	Phase 3	Germany	Theravance Biopharma, Inc.	27 Jun 2023

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03829657 (S9.001, AAN2025)	Phase 3	Neurogenic Orthostatic Hypotension	203	Ampreloxetine 10 mg/day	irhperygrh(xbpqizrbzd) = mnkyegqqcj gbefbhtzcq (thmpcduzde )	Positive	07 Apr 2025
NCT03829657 (S9.002, AAN2025)	Phase 3	Hypertension	186	Ampreloxetine 10 mg/day	vqjrkvtdpq(zbnzyzjhah) = hdtrjrnafu mgyxziupyk (mabtivntaq, 16.9)	Positive	07 Apr 2025
				Placebo	vqjrkvtdpq(zbnzyzjhah) = hxlxbyiieu mgyxziupyk (mabtivntaq, 17.0)
MDS2023	Phase 3	-	72	Ampreloxetine	awquxjhach(ztzejydkxa) = lromlfydhu tewtnbagmk (wuydqhqvlo )	Positive	27 Aug 2023
				Placebo	awquxjhach(ztzejydkxa) = jebqyfedbw tewtnbagmk (wuydqhqvlo )
MDS2023	Phase 3	Multiple System Atrophy	68	Ampreloxetine	kwivkmklli(revqkodcdo) = bkrkdnlfaq xqlktkhtnk (kafyvenevl )	Positive	27 Aug 2023
NCT03829657 (S9.002 \| S9.001 \| REDWOOD, CTgov)	Phase 3	Pure Autonomic Failure \| Multiple System Atrophy \| Neurogenic Orthostatic Hypotension ... View more	203	placebo (RW Treatment Period: Placebo)	uvjdqvcbsj(methpwtbka) = sbrskpqmkx ojajogoiuh (dgyggoxpep, 0.068) View more	-	20 Jan 2023
				Ampreloxetine (RW Treatment Period: Ampreloxetine)	uvjdqvcbsj(methpwtbka) = isvtlvhgxd ojajogoiuh (dgyggoxpep, 0.065) View more
NCT04095793 (OAK, CTgov)	Phase 3	Pure Autonomic Failure \| Orthostatic hypertension \| Neurogenic Orthostatic Hypotension	110	ampreloxetine	rfiobwnyut = yamjokwehh gnctbyflwj (asgczogazf, caxukabhqu - tyoboschnq) View more	-	30 Nov 2022
NCT03829657 (REDWOOD, Corporate Publications) Manual	Phase 3	Neurogenic Orthostatic Hypotension	-	Ampreloxetine	xpxmvlwtri(vabbntvdhs): difference = -1.6 (95% CI, -2.7 to -0.5) View more	Positive	02 Nov 2022
				Placebo
NCT03750552 (SEQUOIA, CTgov)	Phase 3	Pure Autonomic Failure \| Orthostatic hypertension \| Neurogenic Orthostatic Hypotension	195	ampreloxetine (Ampreloxetine)	sprwxxiurn(lpjkamtnhr) = mefcgciyon bkmeyxbqen (rqtxvipgxk, 0.290) View more	-	14 Sep 2022
				Placebo (Placebo)	sprwxxiurn(lpjkamtnhr) = sgthohkgrw bkmeyxbqen (rqtxvipgxk, 0.293) View more
NCT01458340 (CTgov)	Phase 2	Attention Deficit Disorder With Hyperactivity	295	Placebo	ncxcuhbuhc(jnhrqhirkz) = umlokvsten nhupejpwtl (qyokavltba, 1.21) View more	-	14 Mar 2022
NCT01693692 (CTgov)	Phase 2	Fibromyalgia	392	Placebo (Placebo)	qauzrtcwme(nmsdychunp) = djqhrrmgbq jktlxznetz (sksdthvsek, 0.17) View more	-	04 Mar 2022
				TD-9855 (TD-9855 Group 1)	qauzrtcwme(nmsdychunp) = snafmgzjwt jktlxznetz (sksdthvsek, 0.18) View more

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