Theravance Biopharma, Inc. · NASDAQ:TBPH
Theravance Biopharma — Investor Day (December 2025)
44 slides from Theravance Biopharma's investor day presentation, Dec 8, 2025
Slide 1: Theravance Biopharma Ampreloxetine KOL Event
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.
Slide 2: Welcome and Opening Remarks
Welcome and Opening Remarks Rick Winningham Chief Executive Officer
Slide 3: Forward Looking Statements
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 B
Slide 4: Agenda
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 Researc
Slide 5: Commercial-Stage Biotech Focused on Respiratory and Neurological Diseases
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 orthostati
Slide 6: Neurogenic Orthostatic Hypotension in Multiple System Atrophy
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
Slide 7: Neurogenic Orthostatic Hypotension (nOH)
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
Slide 8: Blood pressure regulation by the autonomic nervous system
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
Slide 9: nOH: Failure to release norepinephrine and insufficient vasoconstriction
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/lightheadednes
Slide 10: Rapidly progressive features of MSA are distinct from Parkinson
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 To
Slide 11: Central vs. peripheral patterns of autonomic failure
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 compensati
Slide 12: Central vs. peripheral patterns of autonomic failure (MSA)
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 o
Slide 13: nOH in MSA: A pressing need for effective pharmacotherapy options
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 M
Slide 14: Current landscape management of nOH in MSA
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 de
Slide 15: nOH in MSA: A pressing need for effective pharmacotherapy options
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 pe
Slide 16: Ampreloxetine: A precision medicine approach to nOH
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
Slide 17: Initial Phase 3 program evaluating ampreloxetine
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 w
Slide 18: Orthostatic Hypotension Symptom Assessment (OHSA)
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
Slide 19: Results: Symptom burden and function
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.
Slide 20: Results: Symptom burden and function
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
Slide 21: Results: Blood pressure over time
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 analy
Slide 22: Results: NE, blood pressure and symptoms
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
Slide 23: Conclusions
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 co
Slide 24: Ampreloxetine: Discovery Through CYPRESS Design and Execution
Ampreloxetine : Discovery Through CYPRESS Design and Execution Dr. Áine Miller Theravance Biopharma SVP, Head of Development
Slide 25: Ampreloxetine: Intended to Address nOH in MSA
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,
Slide 26: Pivotal Phase 3 CYPRESS Trial Informed by REDWOOD Study Results
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 hypotens
Slide 27: CYPRESS Design and Execution Optimizes Probability of Success
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 l
Slide 28: Alignment with FDA on CYPRESS Design Derisks Regulatory Path
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 clin
Slide 29: Comprehensive Safety Database Supporting Ampreloxetine Development
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 P
Slide 30: CYPRESS Topline Readout will Provide an Extensive Data Set
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 a
Slide 31: Positioned to Capitalize Rapidly Upon Potential Positive CYPRESS Readout
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 com
Slide 32: Commercial Opportunity
Commercial Opportunity Rhonda Farnum Senior Vice President, Chief Business Officer
Slide 33: Concentrated, Rare Neurology Market with Potential Therapeutic Breakthrough
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 comma
Slide 34: Significant Commercial Opportunity for Ampreloxetine Given Available Treatments
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
Slide 35: Ampreloxetine has an Opportunity to Address Significant Unmet Need in nOH
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 (
Slide 36: Payers Acknowledge High Burden and Large Unmet Need
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 Pe
Slide 37: ~40,000 Patients with MSA Suffer from Symptomatic nOH in the U.S.
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
Slide 38: Launch Strategy to Establish Ampreloxetine as Standard of Care
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 St
Slide 39: Targeted Launch Plan Leverages Concentrated MSA Treatment Landscape
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://ww
Slide 40: Premium Value Opportunity Driven by Unmet Need and Clinical Impact
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) Dermato
Slide 41: Meaningful Market Opportunity for Ampreloxetine Exists in Europe and Asia
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/
Slide 42: Concentrated, Rare Neurology Market with Potential Therapeutic Breakthrough
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 comma
Slide 43: Ampreloxetine: Potential to Transform Care in a Rare and Debilitating Disease
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 ali
Slide 44: Questions? Answers.
44 Questions? Answers.