Ampreloxetine Data in Neurogenic Orthostatic Hypotension to be Presented at the 33rd International Symposium on the Autonomic Nervous System

• Totality of Evidence from the Phase 3 Clinical Program Demonstrates Ampreloxetine was Effective in Treating Symptoms and Improving Activities of Daily Living in MSA Patients with Neurogenic Orthostatic Hypotension
• Safety Profile of Ampreloxetine was Similar to that of Placebo

DUBLIN, Nov. 2, 2022 /PRNewswire/ -- Theravance Biopharma, Inc. ("Theravance Biopharma" or the "Company") (NASDAQ: TBPH) today will present new ampreloxetine data in neurogenic orthostatic hypotension (nOH) from the Company's Phase 3 program at the 33rd International Symposium on the Autonomic Nervous System, a meeting of the American Autonomic Society (AAS). Ampreloxetine is an investigational, once-daily norepinephrine reuptake inhibitor in development for the treatment of symptomatic nOH in patients with multiple system atrophy (MSA).

"These ampreloxetine data are encouraging for patients with MSA suffering with neurogenic orthostatic hypotension. There is an urgency to treat MSA patients with nOH due to the impact on quality of life and the extreme caregiver burden. Ampreloxetine appears to broadly impact a critical group of symptoms related to blood pressure control and may represent a potential therapy for MSA patients," said Roy Freeman, MBChB, Professor of Neurology, Director, Center for Autonomic and Peripheral Nerve Disorders, Beth Israel Deaconess Medical Center, who assisted in the design and interpretation of the ampreloxetine Phase 3 program and is an author on all three abstracts presented at the AAS meeting.

Disclosure: Dr. Freeman is a consultant serving as an advisor for drug development and clinical trial design for Theravance Biopharma.

Study results presented at the 2022 AAS meeting, session 1 include:

Clinical Effectiveness of Ampreloxetine

• Clinically meaningful and nominal statistically significant (p < 0.05) differences relative to placebo in MSA patients on the following endpoints in Study 0170:
• Orthostatic Hypotension Symptom Assessment Scale (OHSA) composite score (LS mean difference: -1.6 [95% CI: -2.7, -0.5])
• Orthostatic Hypotension Questionnaire (OHQ) composite score (LS mean difference: -1.2 [95% CI: -2.3, -0.2])
• Orthostatic Daily Activities Scale (OHDAS) Item 1 – Standing a short time (LS mean difference: -2.0 [95% CI: -3.6, -0.4])

• Symptomatic improvement in patients with MSA was broadly demonstrated on the individual components of the OHSA composite in Study 0170 including:
• dizziness (LS mean difference: -1.5 [95% CI: -3.2, 0.2])
• vision (LS mean difference: -1.7 [95% CI: -3.2, -0.3])
• weakness (LS mean difference: -0.7 [95% CI: -2,3, 0.9])
• fatigue (LS mean difference: -1.5 [95% CI: -3.1, 0.1])
• trouble concentrating (LS mean difference -1.8 [95% CI: -3.3, -0.4])
• head/neck discomfort (LS mean difference: -2.2 [95% CI: -3.7, -0.7])

• Durability of clinical effect was demonstrated by ampreloxetine in MSA patients as reflected in the reduction of the OHSA composite score and OHDAS item 1 over the course of 20 weeks (5 months) across the Phase 3 program (studies 0169 and 0170 open-label period).

Blood Pressure and Pharmacodynamics

• Standing systolic blood pressure across all studied patients (including MSA, Parkinson's disease and Pure Autonomic Failure) with nOH was maintained by ampreloxetine and worsened after withdrawal to placebo [treatment difference: 8.6 mm Hg; p