Slide 1: CYPRESS Study 0197 Update
CYPRESS Study 0197 Update 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 o
Slide 2: Executive Summary for CYPRESS (Study 0197)
Executive Summary for CYPRESS (Study 0197 ) ‣ The primary endpoint, the change in OHSA composite score at week 8 during the double - blind randomized withdrawal period, was not statistically significant ‣ Similar trends were observed in the secondary endpoints at week 8 ‣ Changes in blood pressure,
Slide 3: CYPRESS Study 0197 Protocol Design
CYPRESS Study 0197 Protocol Design OL: Open label; OHSA: Orthostatic hypotension symptom assessment; QD: Once daily 3 Ampreloxetine (10 mg QD) Placebo Eligibility Screening 0 8 OL 12 OL 0 RW 2 RW 6 RW Year 1 - 2 4 RW 8 RW Visit 1 6 4 10 2 5 7 8 9 3 4 OL Week Ampreloxetine (10 mg QD) Ampreloxetine (1
Slide 4: Primary Endpoint at Week 8 - OHSA Composite Score
Primary Endpoint at Week 8 - OHSA Composite Score Similar worsening observed in both arms during the RW period. OHSA: Orthostatic hypotension symptom assessment; OL: Open label; RW: Randomized withdrawal; TD - 9855: Ampreloxetine Statistical analysis plan primary efficacy analysis population (n=50)
Slide 5: Key Secondary Endpoint at Week 8 - OHDAS Composite Score
Key Secondary Endpoint at Week 8 - OHDAS Composite Score Ampreloxetine stable until RW Week 6 but worsening observed between Week 6 and 8. OHDAS: Orthostatic hypotension daily activity scale; OL: Open label; RW: Randomized withdrawal; TD - 9855: Ampreloxetine Statistical analysis plan primary effica
Slide 6: Plasma Norepinephrine Levels from Baseline to Week 8 of RW
Plasma Norepinephrine Levels from Baseline to Week 8 of RW Changes in norepinephrine levels consistent with expectations. RW: Randomized withdrawal; NE: Norepinephrine Plot displaying geometric mean ± geometric standard error Full RW analysis Set (n=78) 6
Slide 7: Blood Pressure and Heart Rate Responses at Week 8 of RW
Blood Pressure and Heart Rate Responses at Week 8 of RW Changes in blood pressure and heart rate confirmed a consistent pressor effect. RW: Randomized withdrawal; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; SEM: Standard error of the mean Full RW analysis set (n=78) 7
Slide 8: Treatment-Emergent Adverse Events: Overall Summary, Open-Label Period
8 Total TD - 9855 (N=129) Subjects With Any Treatment - Emergent 83 (64.3%) Adverse Event (AE) 15 (11.6%) AE Related to Study Drug 10 ( 7.8%) Serious Adverse Event (SAE) 2 ( 1.6%) SAE Related to Study Drug 11 ( 8.5%) AE Leading to Permanent Study Drug Discontinuation 5 ( 3.9%) AE Leading to Temporar
Slide 9: Treatment-Emergent Adverse Events: Overall Summary, Randomized-Withdrawal Period
TD - 9855: Ampreloxetine 9 Total (N=78) TD - 9855 10mg (N=40) Placebo (N=38) Subjects With Any Treatment - Emergent: 46 (59.0%) 22 (55.0%) 24 (63.2%) Adverse Event (AE) 3 (3.8%) 1 (2.5%) 2 (5.3%) AE Related to Study Drug 5 (6.4%) 1 (2.5%) 4 (10.5%) Serious Adverse Event (SAE) 0 0 0 SAE Related to St
Slide 10: CYPRESS Post Hoc Data Analyses
CYPRESS Post Hoc Data Analyses
Slide 11: Overview: Post Hoc Analyses
Overview: Post Hoc Analyses Although CYPRESS missed the primary endpoint, a more in - depth analysis addressed the signal to noise ratio observed PRO: Patient reported outcome, OHQ: Orthostatic hypotension questionnaire; nOH: Neurogenic orthostatic hypotension; RW: Rando miz ed withdrawal 11 Conclus
Slide 12: Average Treatment Effects for OHSA, OHDAS, and OHQ - Confirmed Symptomatic nOH Population
OHSA: Orthostatic hypotension symptom assessment; OHDAS: Orthostatic hypotension daily activity scale, OHQ: Orthostatic hypotens ion questionnaire; LS: Least squares 12 Average Treatment Effects for OHSA, OHDAS, and OHQ - Confirmed Symptomatic nOH Population (n=47) Confirmed Symptomatic nOH Populati
Slide 13: Overview of FDA Interactions
Overview of FDA Interactions
Slide 14: FDA Interactions
FDA Interactions ‣ In May 2026 we held a Type B meeting with the FDA regarding the interpretation of the complete Phase 3 CYPRESS Study dataset, at which the agency indicated that, while the existing clinical data package would not support approval on the current data, an additional pivotal trial le