Slide 1: Prasinezumab in early-stage Parkinson's disease: Additional data from the PADOVA study
Prasinezumab in early-stage Parkinson’s disease: Additional data from the PADOVA study Tania Nikolcheva,1 Gennaro Pagano,2,3 Judith Anzures-Cabrera,4 Tanya Simuni,5 Kenneth Marek,6 Nicola Pavese,7 Klaus Seppi,8 Fabrizio Stocchi,9 Ronald B. Postuma,10 Nathalie Pross,1 Annabelle Monnet,11 Geoffrey A.
Slide 2: Affiliations
Affiliations 1. Product Development Neurology, F. Hoffmann-La Roche Ltd, Basel, Switzerland 2. Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center, F. Hoffmann-La Roche Ltd, Basel, Switzerland 3. University of E
Slide 3: Disclosures
Disclosures ▪ Tania Nikolcheva, Gennaro Pagano, Judith Anzures-Cabrera, Nathalie Pross, Annabelle Monnet, Geoffrey A. Kerchner, Patrik Brundin and Azad Bonni: Full-time employees and own shares of F. Hoffmann-La Roche Ltd ▪ Tanya Simuni: Consultant for AcureX, Adamas, AskBio, Amneal, Blue Rock Thera
Slide 4: Prasinezumab is a humanised IgG1 monoclonal antibody that selectively binds aggregated α-synuclein
Prasinezumab is a humanised IgG1 monoclonal antibody that selectively binds aggregated α-synuclein1,2 Prasinezumab’s proposed mode of action for the treatment of Parkinson’s disease1 Prasinezumab selectively binds aggregated α-synuclein Proposed effects: ▪ Reducing neuronal toxicity ▪ Preventing cel
Slide 5: PADOVA assessed prasinezumab effect on top of symptomatic therapy
PADOVA assessed prasinezumab effect on top of symptomatic therapy Global Phase IIb study in early-stage Parkinson’s disease with a novel time-to-event approach 110 sites in Austria, Canada, France, Italy, Luxembourg, Poland, Spain, Key inclusion UK and US criteria Screening Double-blind treatment OL
Slide 6: Baseline characteristics well balanced across arms
Baseline characteristics well balanced across arms Population consistent with early-stage PD; ~74% of participants on L-DOPA Placebo Prasinezumab All Key baseline demographic and disease characteristics n=293 n=293 N=586 Age (yr) mean (SD) 64.4 (7.5) 64.0 (7.2) 64.2 (7.3) Sex, male n (%) 189 (64.5)
Slide 7: Prasinezumab continues to show favourable safety & tolerability
Prasinezumab continues to show favourable safety & tolerability ▪ Strong safety profile and extensive patient exposure ❑ Prasinezumab has demonstrated a favourable safety and tolerability profile across over 900 Parkinson's disease study participants, with more than 500 treated for 2.5 to 5 years ▪
Slide 8: Prasinezumab showed a trend towards delaying motor progression
Primary endpoint Overall Prasinezumab showed a trend towards delaying motor progression Signal of efficacy on top of effective symptomatic therapy 100 Time to ≥5 points MDS-UPDRS Part III OFF Proportion of participants with progression 90 Cumulative incidence of confirmed 80 motor progression event
Slide 9: Prasinezumab showed a trend towards delaying motor progression (L-DOPA)
Primary endpoint L-DOPA Prasinezumab showed a trend towards delaying motor progression Signal of efficacy more pronounced in pre-specified L-DOPA subgroup (~74% of total study population) 100 Time to ≥5 points MDS-UPDRS Part III OFF Proportion of participants with progression 90 Cumulative incidence
Slide 10: Consistent trends in favour of prasinezumab in prespecified subgroups
Consistent trends in favour of prasinezumab in prespecified subgroups Signal of efficacy on top of effective symptomatics across majority of subgroups Prasinezumab Placebo Baseline risk factors Total n HR 95% CI better better PD medication at baseline* L-DOPA 435 0.79 (0.63, 0.99) MAO-Bi 151 0.96 (0
Slide 11: Consistent trends in favour of prasinezumab across TTE endpoints
Primary and secondary endpoints Overall Consistent trends in favour of prasinezumab across TTE endpoints Clinical signals extend beyond motor signs Time to ≥5 point in MDS UPDRS Part III OFF Primary endpoint (confirmed) Time to ≥3 points in MDS-UPDRS Part II in the presence of confirmed motor event
Slide 12: First biomarker evidence of prasinezumab impacting disease pathology
Exploratory endpoint Overall First biomarker evidence of prasinezumab impacting disease pathology Prasinezumab associated with stabilisation of neuromelanin and reduced iron accumulation in key brain regions Neuromelanin MRI at Week 76 Iron (R2*) MRI at Week 76 Substantia nigra pars compacta intensi
Slide 13: Biomarker evidence suggests impact on underlying disease pathology
Exploratory endpoint Overall Biomarker evidence suggests impact on underlying disease pathology Imaging biomarkers show biological convergence of common pathways and potential link to clinical changes Biological convergence of imaging biomarker Longitudinal NM MRI changes correlate results at baseli
Slide 14: Treatment effect more pronounced in the prespecified L-DOPA subgroup
Treatment effect more pronounced in the prespecified L-DOPA subgroup Time to confirmed motor event (MDS-UPDRS Part III OFF) Change from Baseline to Week 104 MDS-UPDRS Part III OFF 100 7 90 HR=0.79 6 40% confirmed motor progression (95% CI: 0.63, 0.99) Cumulative probability of Adjusted mean change 8
Slide 15: Subgroup outcomes impacted by sample size and baseline balance
Subgroup outcomes impacted by sample size and baseline balance L-DOPA cohort provides robust signal; MAO-Bi data limited by sample size Sample size constraints Baseline imbalances Population MAO-Bi active MAO-Bi Age L-DOPA versus placebo n=151 n=435 L-DOPA active Sex (female) ? versus placebo High D
Slide 16: Large increase in background therapy masked effect in MAO-Bi subgroup
Large increase in background therapy masked effect in MAO-Bi subgroup Symptomatic treatment adjustments likely confounded the efficacy signal in this subgroup MAO-Bi: high increase L-DOPA: stable dose (masking) 117% 16% increase Increase LEDD (mg) LEDD (mg) Baseline 76 weeks Baseline 76 weeks Potent
Slide 17: L-DOPA subgroup provides reliable signal of efficacy
L-DOPA subgroup provides reliable signal of efficacy Methodological reasons likely contributed to lower treatment effect in MAO-Bi subgroup Sample size constraints Baseline imbalances Symptomatic masking Population Age MAO-Bi: high increase L-DOPA: stable dose MAO-Bi L-DOPA Sex (female) (masking) Di
Slide 18: Persistent reduction of motor progression: 6-month OLE
Persistent reduction of motor progression: 6-month OLE Consistently stronger signal in L-DOPA subgroup over 2.5 years; mirrors PASADENA results 9 Exploratory endpoint Adjusted mean change from baseline Placebo (only double-blind period) Secondary endpoint 7 Prasinezumab 1500 mg (double-blind plus ad
Slide 19: PARAISO builds on learnings from the PADOVA trial
PARAISO builds on learnings from the PADOVA trial Global Phase III study will randomise ~900 participants across 18 locations Screening Double-blind treatment OLE or safety follow-up Prasinezumab IV Q4W Early-stage PD on Prasinezumab stable L-DOPA IV Q4W Placebo IV Q4W 104 weeks minimum treatment du
Slide 20: PARAISO: global study now recruiting
PARAISO: global study now recruiting Global . Phase III study will randomise ~900 participants across 18 locations Austria, Denmark, the Netherlands, Poland Canada France, Germany, USA Italy, Portugal, China South Korea Spain, UK Taiwan Brazil Australia ClinicalTrials.gov. NCT07174310. PARAISO Phase
Slide 21: Summary
Summary Prasinezumab demonstrates potential to delay Parkinson’s progression ❏ Delayed motor progression on top of effective symptomatic therapy ❏ First biomarker evidence of impact underlying disease pathology ❏ Clinical signal maintained through 6-month open-label extension ❏ Favourable safety and
Slide 22: Acknowledgements
Acknowledgements We thank all the study participants and their families, and investigators and site staff, for their time and commitment to the prasinezumab clinical development programme https://go.roche.link/bcjhx4