Slide 1: A Phase IIa Study Investigating a γ-Secretase Modulator in Individuals at Risk for or at the Prodromal Stage of Alzheimer's Disease
A PHASE IIA STUDY INVESTIGATING A γ- SECRETASE MODULATOR IN INDIVIDUALS AT RISK FOR OR AT THE PRODROMAL STAGE OF ALZHEIMER’S DISEASE Rosanna Tortelli1,Annamarie Vogt1, Enrique Gaspar1, Macarena Garcia Valdecasas Colell1, Fabien Alcaraz1, Tianxu Yang2, Debbie Panton3, Kalbinder Mahil3, Ruth Croney3,
Slide 2: Affiliations
Affiliations 1. Neuroscience and Rare Diseases, Roche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland 2. Product Development Safety Risk Management (PDS), Roche (China) Holding Ltd, Beijing, China 3. Roche Innovation Center Welwyn, Roche Pharma Research and Early
Slide 3: Disclosures
Disclosures § RT and TY are full-time employees of F. Hoffmann-La Roche, Ltd § AV, EG, MGVC, FA, TV, LS, SDB, TM, GK, LK, GAK and IG are full-time employees and stockholders of F. Hoffmann-La Roche, Ltd. § DP and RC are full-time employees and stockholders of Roche Products, Ltd § KM is a paid consu
Slide 4: Modulating γ-Secretase is a Compelling Therapeutic Approach
Modulating γ-Secretase is a Compelling Therapeutic Approach Targeting amyloid precursor protein processing and Aβ-aggregation upstream γ-secretase modulators alter APP processing without changing the total amount of Aβ Non-aggregating Toxic, aggregating Aβ37 and Aβ38 Aβ42 § The mechanism of action o
Slide 5: RG6289 Reduces Amylogenic Aβ Species
RG6289 Reduces Amylogenic Aβ Species Reduction of Aβ42 and proportional elevation of Aβ38 - Selective for APP with no Effect on Notch RG6289 In vitro effect on Aβ fragments1 § Highly potent GSM ❑ IC50 < 10 nM ❑ Reduces Aβ42 and Aβ40, proportionally increases Aβ38 and Aβ37 ❑ No change of enzyme activ
Slide 6: RG6289 Modulates γ-Secretase in Healthy Individuals
RG6289 Modulates γ-Secretase in Healthy Individuals Dose-dependent effect of RG6289 on Aβ monomers in CSF PD profile of RG6289 in the EiH Phase I study1 § Results from the EiH study in young Placebo (N=4) Low dose (N=3) Interim dose (N=6) and elderly healthy volunteers Mean change from High dose (N=
Slide 7: GABriella Tests RG6289 Safety and Effects on AD-Related Biomarkers
GABriella Tests RG6289 Safety and Effects on AD-Related Biomarkers In a population of individuals at risk for or at the prodromal stage of AD Study rationale Selected study population GABriella will investigate over 18 months: Baseline amyloid burden optimized for high amyloid accumulation rate1: §
Slide 8: GABriella is a Phase IIa study starting to recruit in H1 2024
GABriella is a Phase IIa study starting to recruit in H1 2024 Double blind, parallel-group, randomised, placebo controlled study design with 4 cohorts A total of 78 sites in Canada, Chile, Denmark, France, Germany, Italy, Poland, South Korea, Spain, UK and US Screening Baseline Treatment period EoT
Slide 9: GABriella study endpoints
GABriella study endpoints Safety and biomarkers Primary - Evaluate safety, tolerability and effect Secondary - Evaluate PK and PD of RG6289 on amyloid accumulation of RG6289 Safety: Nature, frequency, severity, and timing of AEs PK: Plasma and CSF concentration at different timepoints Brain amyloid
Slide 10: GABriella study: Key inclusion and exclusion criteria
GABriella study: Key inclusion and exclusion criteria Key Inclusion criteria Key exclusion criteria § 60-85 years of age § ANY condition other than AD that may affect cognition § Cognitively unimpaired or with diagnosis of MCI due to § Major psychiatric disorders AD per NIA-AA criteria1 § Active inf
Slide 11: Commitment to inclusive research and diversity
Commitment to inclusive research and diversity Patient representatives contributed to the design of the GABriella study § Addressing the scientific and medical questions § Measuring meaningful outcomes § Considering the impact of trial participation in people’s lives Proactive community engagements
Slide 12: Summary
Summary GABriella is the first Phase II study investigating a γ- secretase modulator in individuals at risk for or at the prodromal stage of Alzheimer’s disease ❑ Recruitment starting in H1 2024 GABriella will investigate safety, tolerability and the effects of RG6289 on AD-related biomarkers GABrie
Slide 13: Acknowledgements
Acknowledgements to everyone involved in the study We thank the investigators, and site staff for their time and commitment to prepare for GABriella 13