# EDGAR Filing Document

**Accession Number:** 0001583107
**File Stem:** 0001104659-25-119032
**Filing Date:** 2025-12
**Character Count:** 45141
**Document Hash:** 70583fc40f45d81858f4ad9f8629e7ee
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001104659-25-119032.hdr.sgml**: 20251208

**ACCESSION NUMBER**: 0001104659-25-119032

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 57

**CONFORMED PERIOD OF REPORT**: 20251208

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20251208

**DATE AS OF CHANGE**: 20251208

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** Theravance Biopharma, Inc.
- **CENTRAL INDEX KEY:** 0001583107
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 000000000
- **STATE OF INCORPORATION:** CA
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-36033
- **FILM NUMBER:** 251554564

**BUSINESS ADDRESS:**
- **STREET 1:** UGLAND HOUSE, SOUTH CHURCH STREET
- **CITY:** GEORGE TOWN, GRAND CAYMAN
- **STATE:** CA
- **ZIP:** KY1-1104
- **BUSINESS PHONE:** 650-808-6000

**MAIL ADDRESS:**
- **STREET 1:** UGLAND HOUSE, SOUTH CHURCH STREET
- **CITY:** GEORGE TOWN, GRAND CAYMAN
- **STATE:** CA
- **ZIP:** KY1-1104

?xml version='1.0' encoding='ASCII'?

**UNITED STATES**

**SECURITIES AND EXCHANGE COMMISSION**

**Washington, DC 20549**

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**FORM 8-K**

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**Current Report Pursuant**

**to Section 13 or 15(d) of the**

**Securities Exchange Act of 1934**

Date of Report (Date of earliest event Reported): **December 8, 2025**

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**THERAVANCE BIOPHARMA, INC.**

(Exact Name of Registrant as Specified in its Charter)

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| | | |
|:---|:---|:---|
| **Cayman Islands** | **001-36033** | **98-1226628** |
| (State or Other Jurisdiction of | (Commission File Number) | (I.R.S. Employer Identification |
| Incorporation) |  | Number) |

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**C/O Theravance Biopharma US, LLC**

**901 Gateway Boulevard**

**South San Francisco** **, CA 94080**

**(650) 808-6000**

(Addresses, including zip code, and telephone numbers, including area code, of principal executive offices)

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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

◻Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

◻Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

◻Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

◻Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

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| | | |
|:---|:---|:---|
| Title of each class | Trading<br> Symbol(s) | Name of each exchange<br> on which registered |
| Ordinary Share $0.00001 Par Value | TBPH | NASDAQ Global Market |

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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ◻

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ◻

**Item 8.01 Other Events.**

 ****

***Ampreloxetine KOL Event for Investors***

On December 8, 2025, Theravance Biopharma, Inc. (the "Company") is holding a virtual key opinion leader (KOL) investor event. A copy of materials that will be presented during the event is furnished as Exhibit 99.1 to this Current Report.

***2026 Annual General Meeting of Shareholders***

The Company will hold its 2026 Annual General Meeting of Shareholders on June 12, 2026, in Dublin, Ireland. Further information regarding the Annual General Meeting will be provided in the Company's proxy materials, which will be filed with the SEC and made available to shareholders prior to the Annual General Meeting.

*The information in this Current Report (including Exhibit 99.1) is being furnished and shall not be deemed "filed" for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section. The information in this Current Report (including Exhibit 99.1) shall not be incorporated by reference into any registration statement or other document pursuant to the Securities Act of 1933, as amended, except as shall be expressly set forth by specific reference in such filing.*

**Item 9.01. Financial Statements and Exhibits.**

(d) Exhibits.

[99.1](tm2532919d1_ex99-1.htm) [Slide deck entitled Ampreloxetine KOL Event](tm2532919d1_ex99-1.htm) <br> 104 Cover Page Interactive Data File (cover page XBRL tags embedded within the Inline XBRL document)

**SIGNATURE** 

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

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| | | |
|:---|:---|:---|
|  | **THERAVANCE BIOPHARMA, INC.** | **THERAVANCE BIOPHARMA, INC.** |
| Date: December 8, 2025 | By: | /s/ Aziz Sawaf |
|  |  | Aziz Sawaf |
|  |  | Senior Vice President and Chief Financial Officer |

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## Exhibit 99.1

**Exhibit 99.1**

![](tm2532919d1_ex99-1img001.jpg)

THERAVANCE BIOPHARMA® , THERAVANCE® , the Cross/Star logo and MEDICINES THAT MAKE A DIFFERENCE® are registered trademarks of the Theravance Biopharma group of companies (in the U.S. and certain other countries). All third - party trademarks used herein are the property of their respective owners.© 2025 Theravance Biopharma. All rights reserved. Theravance Biopharma Ampreloxetine KOL Event December 8, 2025

![](tm2532919d1_ex99-1img002.jpg)

Welcome and Opening Remarks Rick Winningham Chief Executive Officer

![](tm2532919d1_ex99-1img003.jpg)

3 Forward Looking Statements This presentation contains 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" or "Theravance Biopharma") intends such forward - looking statements to be covered by the safe harbor provisions for forward - looking statements contained in Section 21 E 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 or milestone payments, the ability to provide value to shareholders, the Company's regulatory strategies and timing of clinical studies, possible ultimate safety, efficacy or differentiation of our investigational therapy, commercial opportunities, 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 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, the results of the patent infringement litigation initiated by the Company and its partner against certain generic companies in federal district courts, 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 November 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 . Important Note Ampreloxetine is an investigational product being studied for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) in patients with multiple system atrophy (MSA) . It has not been approved by the FDA or any other regulatory agency in the world and the safety and efficacy of ampreloxetine has not been established . This document is developed to share background information including current landscape of the disease state and stakeholders for purposes of investor communication only . The information are not intended to be promotional or commercial in nature . Per Theravance Biopharma policy, any implementation of commercial strategy or tactic are subject to internal review and approval . Presenting KOL Disclosure Dr . Kaufmann is a member of advisory committees supporting the CYPRESS clinical trial and paid consultant to Theravance Biopharma . The views and opinions expressed by Dr . Kaufmann are his own and do not necessarily reflect the views and opinions of Theravance Biopharma .

![](tm2532919d1_ex99-1img004.jpg)

4 Agenda 10:30 10:35 11:05 11:20 Welcoming and Opening Remarks Rick Winningham: Chief Executive Officer Neurogenic Orthostatic Hypotension in Multiple System Atrophy and Ampreloxetine as a Potential Precision Medicine Therapy Dr. Horacio Kaufmann: Felicia B. Axelrod Professor of Dysautonomia Research, Department of Neurology at NYU Grossman School of Medicine Phase 3 CYPRESS Trial Commercial Opportunity Closing Remarks & Q&A Dr. Á ine Miller: Senior Vice President, Head of Development Rhonda Farnum: Senior Vice President, Chief Business Officer Rick Winningham / All Presenters 10:55

![](tm2532919d1_ex99-1img005.jpg)

5 Commercial - Stage Biotech Focused on Respiratory and Neurological Diseases Strong Financial Position and Cash - Generating YUPELRI® Set the Foundation for Near - Term Ampreloxetine Phase 3 Catalyst FDA, U.S. Food and Drug Administration; MSA, multiple system atrophy ; nOH , neurogenic orthostatic hypotension. 1. Cash balance of $332.7M as of 9/30/25; cash flow guidance excludes potential one - time milestones (and associated taxes). 2. P ayments from Royalty Pharma (RP) will be triggered if RP receives certain minimum royalty payments from GSK based on TRELEGY global net sales. 3. In the U.S., Viatris is leading the commercialization of YUPELRI, and Theravance Biopharma co - promotes the product under a profit and loss sharing a rrangement (65% to Viatris ; 35% to Theravance Biopharma). Refer to our SEC filings for further information. 4. Addressable patient population quantifies the number of patients within the intended target profile. 5. Palma, Kaufmann. Epid emi ology, Diagnosis, and Management of Neurogenic Orthostatic Hypotension; Kalra DK, et al. Clin Med Insights: Cardiol . 2020 14:1179546820953415 . 6. Kaplan et al., Parkinsonism Relat Disord . 2023 Dec:117:105920; UCSD Dept. of Neurosciences : https://neurosciences.ucsd.edu/centers - programs/movement - disorders/communit y/disease - overview/msa.html; Internal claims analyses (IQVIA, Veeva, Real Chemistry), CD - 10 Codes: G90.3, G23.2. Completed Phase 3 CYPRESS enrollment in Q3 2025; topline data in Q1 2026 FDA Orphan Drug Designation Targets ~40,000 underserved patients in the U.S. with symptomatic nOH due to MSA 5,6 Ampreloxetine Upcoming Phase 3 Data Launched in the U.S. in 2019; 35% U.S. profit share with Viatris 3 Strong cash flow from U.S. profit share with IP protection in the U.S. into 2039 Sizable addressable patient population remains 4 YUPELRI Strong Cash Flow Generation ~$333M in cash and no debt; breakeven in Q3 2025 1 , expected to remain at similar levels in Q4 2025 $175M in near - term, high probability TRELEGY 2 and YUPELRI sales - based milestones Commitment to return excess capital to shareholders Strong Financial Position Demonstrated Success in Advancing In - House Developed Assets through Approval and Successful Commercialization

![](tm2532919d1_ex99-1img006.jpg)

Neurogenic Orthostatic Hypotension in Multiple System Atrophy Horacio Kaufmann, MD FAAN The F. B. Axelrod Professor of Neurology and Professor of Medicine at NYU Grossman School of Medicine

![](tm2532919d1_ex99-1img007.jpg)

7 Neurogenic Orthostatic Hypotension (nOH) Kaplan et al., Parkinsonism Relat Disord . 2023 Dec:117:105920 . Kaufmann et al., N Engl J Med 2020;382:163 - 178 • A sustained fall in blood pressure upon standing • Chronic and disabling condition • Present in diseases that damage or impair central and/or peripheral nerves that regulate blood pressure when standing • Highly prevalent in the synucleinopathies U.S. PREVALENCE OF nOH IN SYNUCLEINOPATHIES DEMENTIA WITH LEWY BODIES ~600,000 PURE AUTONOMIC FAILURE ~10,000 PARKINSON DISEASE ~800,000 MULTIPLE SYSTEM ATROPHY ~40,000 ~ 1.4M

![](tm2532919d1_ex99-1img008.jpg)

8 Blood pressure regulation by the autonomic nervous system Triggers a reflex response NE released vasoconstriction Compensation normal BP standing No symptoms Central Peripheral AUTONOMIC NERVOUS SYSTEM nOH occurs when this reflex response fails Gravity pools blood Orthostatic stress

![](tm2532919d1_ex99-1img009.jpg)

9 nOH : Failure to release norepinephrine and insufficient vasoconstriction Impaired physiologic response to changes in posture • Inability to adjust blood pressure to changes in posture • Hypoperfusion of the vital organs and incapacitating symptoms of ischemia • Persistent dizziness/lightheadedness on sitting and standing • Inability to stand, walk, perform activities of daily living • Can result in faints or falls • Major reason for not being mobile • Major impact on quality of life • Important to recognize and treat early Disabling symptoms of postural hypotension

![](tm2532919d1_ex99-1img010.jpg)

10 Rapidly progressive features of MSA are distinct from Parkinson (PD) Similarities with PD Adult - onset neurodegenerative disease More rapidly progressive Survival 8Y Rare disease mid 60's Earlier age at onset More severe motor deficits (Parkinsonism/ataxia) Frequently presents with severe nOH Toxic alpha - synuclein deposits Distinct differences 3 - Y spared NE neurons Well - defined central autonomic pathology 40K

![](tm2532919d1_ex99-1img011.jpg)

11 Crucial difference: Central vs. peripheral patterns of autonomic failure Therapy could be tailored to the pathophysiological lesion NE Low Central Peripheral NERVOUS SYSTEM (PERIPHERAL) PARKINSON DISEASE DEMENTIA WITH LEWY BODIES PURE AUTONOMIC FAILURE Inadequate release on standing No compensation Fall in BP Symptoms = alpha - synuclein deposits

![](tm2532919d1_ex99-1img012.jpg)

12 Crucial difference: Central vs. peripheral patterns of autonomic failure Therapy could be tailored to the pathophysiological lesion Spared neurons NE Normal Central Peripheral NERVOUS SYSTEM Failure to activate additional NE release on standing No compensation Fall in BP Symptoms • Degeneration of the central autonomic network is a pathology unique to MSA • These patients have intact peripheral autonomic neurons, with stores of NE, and are still capable of releasing some NE (CENTRAL) MULTIPLE SYSTEM ATROPHY = alpha - synuclein deposits

![](tm2532919d1_ex99-1img013.jpg)

13 70 - 80% of patients with MSA will develop nOH in their lifetime 1 - 3. This adds significant disability, functional decline, and risk of early death from all - cause mortality Despite adherence to treatment with available pressor agents, 68% of MSA patients with nOH remain symptomatic 4 nOH in MSA: A pressing need for effective pharmacotherapy options 1 Low PA, Lancet Neurol. 2015 May 27;14(7):710 – 719, 2 Vichayanrat Neurology. 2022 Sep 13;99(11):e1168 – e1177; 3 Palma and Kaufmann. 2017. Mov Disord Clin Pract ; 4 (3):298 - 308. 4 NYU MSA Database Statistics.

![](tm2532919d1_ex99-1img014.jpg)

14 Current landscape management of nOH in MSA HTN=hypertension. Fludrocortisone Expand volume Midodrine (direct agonist) Droxidopa (NE precursor) • Can require complex titration and 3X daily dosing • Increase blood pressure in all positions • Carry Box Warning for supine hypertension • Effect may decrease over time • Efficacy beyond 2 weeks has not been proven Off - Label Approved Rarely effective alone in MSA direct agonist MIDODRINE Pressor agents Clear opportunity to develop a targeted, effective, durable, safe treatment that targets blood pressure in the upright positi on, without worsening supine HTN, with a single daily dosing regimen NON - PHARMACOLOGICAL PHARMACOLOGICAL Approaches target improving venous return, increasing blood volume, and avoiding triggers

![](tm2532919d1_ex99-1img015.jpg)

15 nOH in MSA: A pressing need for effective pharmacotherapy options It has been over a decade since the FDA last approved a drug for nOH 1 Low PA. 2008. Clin Auton Res. 2008. Suppl 1:8 - 13. 2 NYU MSA Database Statistics. • No drug has been developed for nOH specifically for patients with intact peripheral autonomic neurons still capable of releasing NE • Ampreloxetine is a novel, long - acting, once - daily, norepinephrine reuptake inhibitor being tested as a treatment for nOH in patients with MSA in a phase III program

![](tm2532919d1_ex99-1img016.jpg)

16 Ampreloxetine : A precision medicine approach to nOH Peripheral sympathetic nerve Blood vessel NE release ⍺ 1 - receptor VASOCONSTRICTION NET reuptake reused degraded enhances NE AMPRELOXETINE • Uniquely suited to MSA patients with relative sparing of peripheral sympathetic neurons NE re - uptake inhibition ACTIVATION Reflects expectations for ampreloxetine. Ampreloxetine is in development and not approved for any indication. No conclusion can be drawn regarding its safety or efficacy.

![](tm2532919d1_ex99-1img017.jpg)

17 Initial Phase 3 program evaluating ampreloxetine SAP included a hypothesis - driven, pre - specified subgroup analysis of MSA in the REDWOOD randomized withdrawal design study to determine the effect of ampreloxetine on symptoms, activity and blood pressure 1 Freeman R, et al. Precision therapy with ampreloxetine for neurogenic orthostatic hypotension in multiple system atrophy. MedRxiv . https://doi.org/10.1101/2025.08.12.25332833. 1. REDWOOD primary endpoint was not met. Full analysis set included 40 patients with MSA, 20 ampreloxetine , 20 placebo

![](tm2532919d1_ex99-1img018.jpg)

18 Worst Possible Orthostatic Hypotension Symptom Assessment (OHSA) 1 0 item - symptom, validated scale, accepted by the FDA for drug approvals nOH Symptoms Assessment (OHQ) MEASURABLE OUTCOME Orthostatic Hypotension Questionnaire (OHQ) No Symptoms Complete interference Orthostatic Hypotension Daily Activity Scale (OHDAS) No interference &UUJFWTS XYFSINSL

![](tm2532919d1_ex99-1img019.jpg)

19 Results: Symptom burden and function REDWOOD pre - specified MSA subgroup analysis, Full analysis set n=40 OHSA -1.6 [-2.7, -0.5] Dizziness -1.5 [-3.2, 0.2] Vision -1.7 [-3.2, -0.3] Weakness -0.7 [-2.3, 0.9] Fatigue -1.5 [-3.1, 0.1] Trouble Concentrating -1.8 [-3.3, -0.4] Head/Neck Discomfort -2.2 [-3.7, -0.7] OHDAS -0.8 [-2.1, 0.4] Standing Short Time -2.0 [-3.6, -0.4] Standing Long Time -0.3 [-1.8, 1.2] Walking Short Time -0.7 [-2.4, 1.0] Walking Long Time 0.4 [-1.2, 2.1] OHQ -1.2 [-2.3, -0.2] -4 -3 -2 -1 0 1 LS Mean Difference [95% CI] OHQ Composite Scores OHSA Items OHDAS Items FINDINGS • The greatest difference was observed in the 6 - item OHSA composite score • Most Individual items on the OHQ favor ampreloxetine over placebo Favors ampreloxetine Favors placebo

![](tm2532919d1_ex99-1img020.jpg)

20 FINDINGS • Self - reported scores showed symptomatic benefit with improvement in standing that was lost after ampreloxetine was withdrawn COMPOSITE SCORE Open Label Placebo Ampreloxetine STANDING SHORT TIME Item 1 Standing for a short time morning hygiene, brushing your teeth, brushing your hair Item 2 Standing for a long time waiting in a line at the post office, standing on public transport, cooking a meal Item 3 Waking for a short time walking around the house from one room to another. Walking across the parking lot Item 3 Waking for a long time going for a leisure walk/hike, grocery shopping, walking the dog Examples Results: Symptom burden and function FAS=full analysis set. REDWOOD pre - specified MSA subgroup analysis, Full analysis set n=40

![](tm2532919d1_ex99-1img021.jpg)

21 FINDINGS • A sustained improvement in orthostatic BP was observed over 16 - weeks of open - label treatment, that was lost after 6 - weeks of placebo withdrawal Results: Blood pressure over time OPEN-LABEL 16 weeks RWD 6 week 3 min FAS=full analysis set. REDWOOD pre - specified MSA subgroup analysis, Full analysis set n=40

![](tm2532919d1_ex99-1img022.jpg)

22 FINDINGS • Ampreloxetine increased NE and standing blood pressure, and reduced orthostatic symptoms NE\* Norepinephrine (pg /ml " SE) Results: NE, blood pressure and symptoms Favors ampreloxetine Favors placebo †P - values vs placebo are based on LS mean difference in change between the start and end of RW, \*Norepinephrine data from baseli ne and at the end of the 4 - week from SEQUOIA Study REDWOOD pre - specified MSA subgroup analysis, Full analysis set n=40

![](tm2532919d1_ex99-1img023.jpg)

23 The pre - specified subgroup analysis suggest that ampreloxetine could improve the ability to maintain an upright posture, lessen the functional burden of the disease, and could improve quality of life in MSA patients The ampreloxetine CYPRESS study in patients with MSA (NCT05696717) nearing completion If CYPRESS is positive, and the drug is approved, ampreloxetine would be the first example of a tailored treatment for nOH in this rare and fatal disease Conclusions

![](tm2532919d1_ex99-1img024.jpg)

Ampreloxetine : Discovery Through CYPRESS Design and Execution Dr. Áine Miller Theravance Biopharma SVP, Head of Development

![](tm2532919d1_ex99-1img025.jpg)

25 Ampreloxetine : Intended to Address nOH in MSA A potent high affinity NET inhibitor with a durable mechanism of action FDA, U.S. Food and Drug Administration; MSA, multiple system atrophy; NDA, new drug application; NET, norepinephrine transporter; nOH , neurogenic orthostatic hypotension; PK/PD, pharmacokinetics/pharmacodynamics; QD, once daily. Discovery/Early Development Discovered and developed in house with a desirable PK/PD profile that supports QD dosing ; demonstrated sustained, clinically meaningful symptom improvement in Phase 2 CYPRESS Design and Execution Pivotal CYPRESS study designed to confirm the clinically meaningful results seen in REDWOOD (Study 0170) in patients with MSA Regulatory Preparation Clear FDA regulatory path forward; p reparing for expedited NDA submission to capitalize rapidly and efficiently upon CYPRESS's potential success

![](tm2532919d1_ex99-1img026.jpg)

26 Pivotal Phase 3 CYPRESS Trial was Informed by REDWOOD Study Results in Patients with nOH due to MSA MSA, multiple system atrophy; nOH , neurogenic orthostatic hypotension; OHDAS, orthostatic hypotension daily activity scale; OHQ, orthostatic hypotension quest ion naire; OHSA, orthostatic hypotension symptom assessment; PGI - C, patient global impression of change; PGI - S, patient global impression of severity; PK/PD, pharmacokin etics/pharmacodynamics; QD, once daily; RW, randomized withdrawal. Completers to enter 2 - year long - term extension. 8 - week double blind RW 12 - week open - label Entry Results Ampreloxetine 10 mg QD Week 8 Enrichment: Reduction of ≥ 2 Points in OHSA #1 N>100 to be enrolled N>60 Completers Ampreloxetine 10 mg QD Placebo QD Week 12 OHSA #1 ≤ 7 Completers Enter 2 Year Long Term Extension Randomization Baseline Primary endpoint: OHSA composite score Secondary endpoints: • OHDAS Standing: Change from baseline in ability to stand for a short time (item 1) • OHDAS Walking: Change from baseline in ability to walk for a short time (item 3) Exploratory Endpoints: • Standing blood pressure • OHQ items score • Composite OHDAS Score • Hospital Anxiety and Depression Scale (HADS) score • PGI - S and PGI - C • PK/PD CYPRESS Study Design

![](tm2532919d1_ex99-1img027.jpg)

27 CYPRESS Design and Execution Optimizes Probability of Success Replicating the elements that led to the observed benefits in patients with MSA in the REDWOOD study KOL, key opinion leader; MSA, multiple system atrophy; OHSA, orthostatic hypotension symptom assessment . CYPRESS protocol leverages learnings from REDWOOD (Study 0170) to enhance the likelihood of reproducing benefits observed in MSA patients through using the composite OHSA primary endpoint, the randomized withdrawal design, and the same enrichment criteria. Protocol Design Engagement with leading KOLs, MSA centers of excellence, and top academic sites from REDWOOD. Investigators and Site Selection Using the same external enrollment committee as REDWOOD ensures study integrity and patient quality through consistent enrollment criteria and independent review of MSA diagnosis. Patient Selection & Management Direct study management enables real - time oversight and agile execution, supported by training focused on study conduct, retention and minimizing variability . Study Conduct

![](tm2532919d1_ex99-1img028.jpg)

28 Alignment with FDA on CYPRESS Design Derisks Regulatory Path CMC, chemistry, manufacturing and conrols; FDA, U.S. Food and Drug Administration; NDA, new drug application; OHSA, orthostatic hypotension symptom assessment; RW, randomized withdrawal. 1. Kaufmann H, et al. Establishing minimally clinically important differences for the orthostatic hypotension questionnaire (OHQ). Clin Auton Res . 2025 Oct 24. doi : 10.1007/s10286 - 025 - 01168 - y. Aligned with FDA on CYPRESS design: • RW design including the use of the OHSA composite as primary endpoint • Successful outcome, with Study 170 results as supportive, would fulfill requirement for a full approval Ongoing collaborative interactions to ensure alignment on regulatory expectations Use of FDA - supported, Anchor - Based Analysis • Established clinically meaningful thresholds for patient - reported outcomes measures • ~1 point change in OHSA Composite identified as clinically meaningful 1 Aligned with FDA on key components to support full NDA: • Addressed majority of pre - NDA topics and aligned on content of NDA • Built on previous successful interactions where we aligned on other critical components of the NDA eg nonclinical, CMC and clinical pharmacology Successful Type C Meeting June 2022 CYPRESS Initiation March 2023 Successful Type C Meeting Dec 2024

![](tm2532919d1_ex99-1img029.jpg)

29 Comprehensive Safety Database Supporting Ampreloxetine Development Safety profile established in >800 subjects ADHD, attention - deficit/hyperactivity disorder; MSA, multiple system atrophy; nOH , neurogenic orthostatic hypotension; PAF, pure autonomic failure; PD, Parkinson disease. 29 Phase 2 Phase 3 Phase 1 registration package • Healthy volunteer studies • Clinical pharmacology studies • Ampreloxetine was generally safe and well - tolerated • No unexpected safety concerns occurred throughout the duration of the studies • Safety profile for the MSA subgroup was also consistent with that of the overall nOH population • No signal for worsening of supine hypertension Phase 1 Safety Profile To Date Fibromyalgia Adult ADHD Symptomatic nOH Symptomatic nOH • 208 patients with MSA, PD & PAF exposed to ampreloxetine in initial P3 program • 110 patients exposed to ampreloxetine for >6 months and 67 patients >12 months • CYPRESS exposure will add to safety database

![](tm2532919d1_ex99-1img030.jpg)

30 CYPRESS Topline Readout will Provide an Extensive Data Set CYPRESS study replicated the elements that led to the observed benefits in patients with MSA in the REDWOOD study Population • Patient disposition: status during OL and RW • Baseline characteristics: demography, clinical characteristics and OHQ scores Efficacy • Primary endpoint: OHSA composite score • Secondary endpoints: OHDAS1 and OHDAS3 • Exploratory endpoint: blood pressure (seated, supine and standing) • Forest plot of OHQ compositions score and individual items (e.g., dizziness, etc.), longitudinal analysis Safety Adverse events and serious adverse events Clinical meaningfulness Meaningful change thresholds for OHSA composite score OHDAS, orthostatic hypotension daily activity scale; OHQ, orthostatic hypotension questionnaire; OHSA, orthostatic hypotension symptom assessment; OL, open - label; RW, randomized withdraw al.

![](tm2532919d1_ex99-1img031.jpg)

31 Positioned to Capitalize Rapidly Upon Potential Positive Readout from Pivotal Phase 3 CYPRESS Trial FDA, U.S. Food and Drug Administration; NDA, new drug application. Alignment with FDA achieved; NDA preparations underway NDA Readiness Completed enrollment in Q3 2025; open - label portion now complete Completed Enrollment Topline readout anticipated in Q1 2026 Topline Data Readout If positive, incorporate CYPRESS data into NDA and request priority review Expedited NDA Filing

![](tm2532919d1_ex99-1img032.jpg)

Commercial Opportunity Rhonda Farnum Senior Vice President, Chief Business Officer

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33 Concentrated, Rare Neurology Market with Potential Therapeutic Breakthrough High Potential Adoption Value of Innovation Addressable Patients • Potential to be first therapy to deliver durable, clinically meaningful improvement in nOH in patients with MSA • Chronic neurology orphan therapies command rare - disease pricing • 40,000 MSA patients 1,2 / nOH in the U.S. • High disease burden; many underdiagnosed • Concentrated care among small number of specialists • Limited alternatives and high unmet need • Supported by market research and consistent KOL feedback Concentrated rare neuro market + high unmet need globally + rare disease economics = Blockbuster Potential KOL, key opinion leader, MSA, multiple system atrophy; nOH , neurogenic orthostatic hypotension. 1. Palma, Kaufmann. Epidemiology, Diagnosis, and Management of Neurogenic Orthostatic Hypotension; Kalra DK, et al. Clin Med Insights: Cardiol . 2020 14:1179546820953415 . 2. Kaplan et al., Parkinsonism Relat Disord . 2023 Dec:117:105920; UCSD Dept. of Neurosciences : https://neurosciences.ucsd.edu/centers - programs/movement - disorders/communit y/disease - overview/msa.html; Internal claims analyses (IQVIA, Veeva, Real Chemistry), CD - 10 Codes: G90.3, G23.2.

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34 Significant Commercial Opportunity for Ampreloxetine Given Available Treatments MSA, multiple system atrophy; nOH , neurogenic orthostatic hypotension; OHSA, orthostatic hypotension symptom assessment. 1. Veeva Compass patient - level claims data, MSA patients (G90.3) with at least 1 Rx from 2020 - 2023. Product share defined as to tal "days supplied" in this patient population. MSA, multiple system atrophy; nOH neurogenic orthostatic hypotension. . 2. Reflects Theravance Biopharma's expectations for ampreloxetine . Ampreloxetine is in development and not approved for any indication. No conclusion can be drawn regarding its safety or efficacy. Data on file. 3. The information in the table presen ts factual information gathered from approved product prescribing information and are not intended to make comparisons of available therapies and investigational drug as there are no head - to - head comparativ e studies or data supporting any such comparisons. Only ~34% of patients are treated, current therapies limited in this patient population 1 Droxidopa Midodrine Ampreloxetine (investigational) 2 Symptomatic nOH Symptomatic OH Symptomatic nOH in patients with MSA Indication OHSA Item #1 Increase in systolic blood pressure OHSA Composite Score Efficacy - Primary Endpoint Effectiveness beyond 2 weeks has not been established Effectiveness not studied beyond 3 - 4 weeks 20 weeks (CYPRESS Study Design) Durability of Response 3x/day Requires titration 3x/day 1x/day No titration or dose adjustment Dosing Boxed warning for increased risk of supine hypertension No worsening of supine hypertension observed in clinical studies to date Supine Hypertension Current Treatment Landscape 3 Fludocortisone is used off - label as volume expander, despite limited evidence, with 1x/day dosing (requires titration). Adverse events include hypertension, edema and congestive heart failure; requires strict monitoring of blood pressure and potassium

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35 Ampreloxetine has an Opportunity to Address the Significant Unmet Need In nOH Treatment with its Unique Target Product Attributes HCP, healthcare professional; MSA, multiple system atrophy; nOH , neurogenic orthostatic hypotension. 1. N=200 board certified neurologists (n=150) and cardiologists (n=50) treating MSA patients and familiar with nOH diagnosis and treatment. Survey Questions: Based on your experience in managing MSA patients with symptomatic nOH , please indicate your level of agreement with the following statements. Please use a 7 - point scale where 1=Do not agree at all and 7=Strongly agree. Assuming coverage and cost to the patient is on par with existing treatments, and assuming full FDA approval, how like ly would you be to prescribe Product X [ ampreloxetine ] in the future? Majority of HCPs acknowledge significant unmet need for better nOH treatments in MSA Majority of HCPs have favorable reactions to ampreloxetine's target product profile 0% 100% 0% 100% of Cardiologists… of Neurologists… of Cardiologists… of Neurologists… 80% 62% 90% strongly agree there is significant unmet need for better therapies for patients with symptomatic nOH & MSA 1 are likely or very likely to prescribe ampreloxetine based on the target product profile 71% Options are generally limited to begin with. But given the efficacy, lack of supine hypertension and convenience of dosing, it would be a no - brainer . Neurologist Easier to use with less side effects. Once daily is very attractive. Also, no dosage adjustments needed for multiple medical conditions is attractive. Cardiologist

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36 Payers Acknowledge its High Burden and Large Unmet Need for Novel Treatments CVL, covered lives; MSA, multiple system atrophy; nOH , neurogenic orthostatic hypotension. Source: Trinity Pre - Topline Ampreloxetine Pricing and Demand Opportunity Assessment June 2025 (N=10 Payers). Disease Burden Perceptions of Unmet Need Economic Burden Payers recognize high disease burden of MSA, driven by mortality, disability, and nOH's impact on daily living Payers acknowledge the economic burden of MSA - related nOH is driven mainly by indirect / medical costs , such as hospitalizations from falls Payers are aware of unmet need for novel nOH treatments Enhanced symptomatic agents that improve quality of life and avoid costly complications would be valued (CVL - Weighted Average) LOW (1) HIGH (7) (CVL - Weighted Average) LOW (1) HIGH (7) LOW (1) HIGH (7) (CVL - Weighted Average) 6.0 5.2 5.4 I think [ nOH ] is a major consideration because that immediately impacts activities of daily living, functionality , etc. You're completely debilitated to a certain extent. Payer …the syncope related to nOH is a problem because this is an older population and falls put patients at this age in the hospital . Payer

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37 ~40,000 Patients with MSA Suffer from Symptomatic nOH in the U.S. MSA is underdiagnosed and often misdiagnosed 1 - 3 ~80% have symptomatic nOH 4,5 ~40K with symptomatic nOH ~50K Patients w/ MSA 6,8,9 Estimated patient population for symptomatic nOH due to MSA in the U.S. Epidemiology supported by detailed claims analysis, substantiated by several leading institutions Claims level analysis supports epidemiology assumptions: • U.S. patient - level claims data using ICD - 10 codes most commonly associated with MSA 6 • Coding practices validated through external experts 7 • S imilar claims - based analysis published in 2023 8 • Leading institutions support estimated epidemiology (e.g., UCSD 9 , NIH) Linking patients to treating specialists: • Initial targeting efforts suggest treating physicians are highly concentrated within autonomic and movement disorder centers, large neurology groups, and select academic institutions • Approach enables efficient deployment of commercial and medical resources across a small, specialized physician universe MSA, multiple system atrophy; nOH, neurogenic orthostatic hypotension. 1. Krismer F, et al. Lancet Neurol. nOH 2024;23(12):1252-1266. 2. DeRight J. Multiple System Atrophy. In: Essential Neuropsychology: A Concise Handbook for Adult Practitioners. Springer; 2021. 3. Goolla M, et al. Frontiers in Neurology. 2023;14:1210220. 4. Palma, Kaufmann. Epidemiology, Diagnosis, and Management of Neurogenic Orthostatic Hypotension. 5. Kalra DK, et al. Clin Med Insights: Cardiol . 2020 14:1179546820953415. 6. Internal claims analyses (IQVIA, Veeva, Real Chemistry); ICD - 10 Codes: G90.3, ~90% of patients, and G23.2, ~10%. 7. Medical coding consultant, as well as primary market res earch with EHR specialists, billing & coding specialists, neurologists, and movement disorder specialists. 8. Estimating the prevalence and incidence of multiple system atrophy in the USA: Insights from a national claims database, Park ins onism and Related Disorders 11/4/2023. 9. UCSD Dept. of Neurosciences (25K - 75K): https://neurosciences.ucsd.edu/centers - programs/movement - disorders/community/disease - overview/msa.html.

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38 Drive urgency to improve outcomes in patients with nOH due to MSA Establish ampreloxetine as the only treatment studied and approved for patients with nOH due to MSA Create a seamless, positive customer experience with ampreloxetine Launch Strategy to Focus on Establishing Ampreloxetine as the Standard of Care for Patients with nOH Due to MSA MSA, multiple system atrophy; nOH , neurogenic orthostatic hypotension. Insights from Rare Disease Launches • Centers of excellence are critical • Peer - to - peer influence • Early engagement with payers builds understanding • Patient advocacy groups serve as "disease authority" • Patients and caregivers are highly connected knowledge seekers Strategic Priorities for Ampreloxetine Successful Launch 3 1 2

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39 Targeted Launch Plan Leverages Concentrated MSA Treatment Landscape MSA, multiple system atrophy. 1. Veeva Compass patient - level claims data, MSA patients (G90.3), 2022 - 2024. 2. Centers of Excellence: https://missionmsa.org/re source - library/centers - of - excellence - overview/, https://www.psp.org/centers - of - care, accessed Nov 5, 2024. 40 MSA Centers of Excellence 26 CYPRESS Trial Sites (U.S.) ~550 High Volume MSA Accounts 1 ~90 MSA Specialists with 10+ Patients 1 Lean commercial infrastructure required for focused execution Investment plans aligned with lean, rare - disease industry benchmarked spend High Volume MSA Accounts 1 and Centers of Excellence 2 High Volume MSA Accounts MSA Centers of Excellence

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40 Premium Value Opportunity Driven by Unmet Need and Clinical Impact Rare Disease Launches ('21 - '24) Average launch price ($K) for chronic therapies by therapeutic area (n=52) $579 $399 $396 $355 $337 $333 $310 $255 Metabolism (n=9) Immunology (n=10) Hepatology (n=1) Musculoskeletal (n=6) Dermatology (n=2) Hematology (n=8) Neurology (n=7) Cancer (n=9) MSA, multiple system atrophy; nOH , neurogenic orthostatic hypotension. Source: Cantor Fitzgerald, Biotechnology Equity Research, April 11, 2024. Includes 63 drugs approved in the US between 1/22/ 202 1 - 3/21/2024; average launch price based on WAC (wholesale acquisition cost). 1. Palma, Kaufmann. Epidemiology, Diagnosis, and Management of Neurogenic Orthostatic Hypotension; Kalra DK, et al. Clin Med Insights: Cardiol . 2020 14:1179546820953415 . 2. Kaplan et al., Parkinsonism Relat Disord . 2023 Dec:117:105920; UCSD Dept. of Neurosciences : https://neurosciences.ucsd.edu/centers - programs/movement - disorders/communit y/disease - overview/msa.html; Internal claims analyses (IQVIA, Veeva, Real Chemistry), CD - 10 Codes: G90.3, G23.2. Ampreloxetine is well positioned to redefine expectations for patients with nOH due to MSA Serious disorder with negative consequences For ~80% of patients with MSA, nOH is a driver of morbidity, mortality, and healthcare burden Value for patients and caregivers Treating nOH equates to functional benefit — reducing dependency and the burden of the constellation of symptoms patients experience Targeted, Orphan Drug Opportunity Overall low total budget impact; potential ~40K patients in the U.S. 1,2 Pricing Expectations Consistent with Recent Rare Disease Approvals

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41 Meaningful Market Opportunity for Ampreloxetine Exists in Europe and Asia Patients with MSA Patients with nOH due to MSA Patients with MSA Patients with nOH due to MSA • 28 CYPRESS study sites in EU • Existing relationships with KOLs and patient advocacy groups • Will seek EMA scientific advice/ marketing authorization following CYPRESS readout • nOH included in medical treatment guidelines for patients with MSA • Specialist networks in place • Droxidopa is the only approved medication in Japan EMA, European Medicines Agency; EU, European Union; KOL, key opinion leader; MSA, multiple system atrophy; nOH , neurogenic orthostatic hypotension.

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42 Concentrated, Rare Neurology Market with Potential Therapeutic Breakthrough High Potential Adoption Value of Innovation Addressable Patients • Potential to be first therapy to deliver durable, clinically meaningful improvement in nOH in patients with MSA • Chronic neurology orphan therapies command rare - disease pricing • 40,000 MSA patients 1,2 / nOH in the U.S. • High disease burden; many underdiagnosed • Concentrated care among small number of specialists • Limited alternatives and high unmet need • Supported by market research and consistent KOL feedback Concentrated rare neuro market + high unmet need globally + rare disease economics = Blockbuster Potential KOL, key opinion leader, MSA, multiple system atrophy; nOH , neurogenic orthostatic hypotension. 1. Palma, Kaufmann. Epidemiology, Diagnosis, and Management of Neurogenic Orthostatic Hypotension; Kalra DK, et al. Clin Med Insights: Cardiol . 2020 14:1179546820953415 . 2. Kaplan et al., Parkinsonism Relat Disord . 2023 Dec:117:105920; UCSD Dept. of Neurosciences : https://neurosciences.ucsd.edu/centers - programs/movement - disorders/communit y/disease - overview/msa.html; Internal claims analyses (IQVIA, Veeva, Real Chemistry), CD - 10 Codes: G90.3, G23.2.

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43 Ampreloxetine : Potential to Transform Care in a Rare and Debilitating Disease FDA, U.S. Food and Drug Administration; MSA, multiple system atrophy; nOH , neurogenic orthostatic hypotension. Rare disease neurology market with blockbuster potential De - risked Phase 3 program designed FDA with alignment Potential to become standard of care for symptomatic nOH in MSA Lean commercial model enabled by concentrated treatment landscape Meaningful ex - U.S. opportunity Near - term catalyst: Phase 3 data expected Q1 2026

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44 Questions? Answers.