Slide 1: Latest interim results from the Brainshuttle AD study of trontinemab
LATEST INTERIM RESULTS FROM THE BRAINSHUTTLETM AD STUDY, A PHASE IB/IIA STUDY OF TRONTINEMAB IN PEOPLE WITH ALZHEIMER’S DISEASE Luka Kulic1, Fabien Alcaraz1, Gregory Klein1, Carsten Hofmann2, Stella Yilmaz2, João A. Abrantes2, Denise Sickert2, Maddalena Marchesi3, Jakub Wojtowicz3, Ruth Croney4, Dav
Slide 2: Affiliations
Affiliations 1. Neuroscience and Rare Diseases, Roche Pharma Early Research and Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland 2. Pharmaceutical Sciences, Roche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland 3. Product Development, Safety Risk Manageme
Slide 3: Disclosures
Disclosures ▪ Luka Kulic, Fabien Alcaraz, Gregory Klein, Carsten Hofmann, João A. Abrantes, Denise Sickert, Maddalena Marchesi, Jakub Wojtowicz, Ruth Croney, David Agnew, Paul Delmar, Hanno Svoboda, and Iris Wiesel are full-time employees and own stock in F. Hoffmann-La Roche Ltd. ▪ Stella Yilmaz is
Slide 4: Trontinemab - a novel Brainshuttle antibody targeting Aβ
Trontinemab - a novel BrainshuttleTM antibody targeting Aβ Active transport across the BBB significantly increases brain penetration and target engagement Trontinemab Endothelial cell Microglia (brain capillary) Anti-Aβ binder IgG1 Fc domain Transferrin Receptor 1 (TfR1) BrainshuttleTM Aggregated Aβ
Slide 5: Brainshuttle AD study design
BrainshuttleTM AD study design Phase Ib/IIa study assessing the safety, tolerability, PK and PD of trontinemab in participants with AD ▪ Study Population: MCI due to AD or mild-to-moderate AD1 (amyloid PET +; MMSE: 18–28; CDR-GS: 0.5-2) Study Population: MCI due to AD or mild-to-moderate AD1; amyloi
Slide 6: Brainshuttle AD study design
BrainshuttleTM AD study design Phase Ib/IIa study assessing the safety, tolerability, PK and PD of trontinemab in participants with AD ▪ Study Population: MCI due to AD or mild-to-moderate AD1 (amyloid PET +; MMSE: 18–28; CDR-GS: 0.5-2) Study Population: MCI due to AD or mild-to-moderate AD1; amyloi
Slide 7: Baseline characteristics at interim analysis
Baseline characteristics at interim analysis1 Analysis included 160 participants enrolled in Part 1 and Part 2 of the BrainshuttleTM AD study Completed1 Not yet completed (interim data) 1 PART 1 PART 2 (n=60) (n=100) Baseline demographic and Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 3 Cohort 4 0.2
Slide 8: Blinded safety profile
Blinded safety profile1 Number of participants with safety events or study discontinuations due to AE Completed1 Not yet completed (interim data) 1 PART 1 (n=60) PART 2 (n=100) Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 3 Cohort 4 Total number of participants 0.2 mg/kg or Pbo 0.6 mg/kg or Pbo 1.8 mg
Slide 9: Case of intracerebral macrohemorrhage in Part 2 of the study
Case of intracerebral macrohemorrhage in Part 2 of the study Key risk factor: probable cerebral amyloid angiopathy (CAA) with superficial siderosis at screening ▪ On study day 44, a 78-year-old woman in cohort 3 Part 2 experienced a right A MRI (T2*) B MRI (FLAIR) frontal lobar macrohemorrhage and p
Slide 10: Reduced incidence of IRR and limited, mostly mild anemia in Part 2
Reduced incidence of IRR and limited, mostly mild anemia in Part 2 so far Successful mitigation of IRR by implementation of premedication in cohort 4 (Part 1) and in Part 2. Lower incidence of anemia in Part 2 may be explained by lower blood volume drawn in Part 2 vs. Part 1. Completed1 Not yet comp
Slide 11: Latest interim results support low ARIA incidence with trontinemab
Latest interim results support low ARIA incidence with trontinemab 3 ARIA-E cases occurred in Part 1 and Part 2 as of snapshot date on September 2nd, 2024 Completed1 Not yet completed (interim data) 1 PART 1 PART 2 (n=60) (n=95) Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 3 Cohort 4 Total number of p
Slide 12: Amyloid PET in Part 1 (Snapshot date: 23 October 2023)
Amyloid PET in Part 1 (Snapshot date: 23 October 2023) Rapid and robust amyloid plaque depletion: -91 CL at 3.6 mg/kg after 12 weeks of treatment1 Snapshot date: 2 September 2024. 1 Mean values ±SE (standard errors) of available PET results at the different visit time points are plotted. CL, Centilo
Slide 13: Amyloid PET in Part 1 (Snapshot date: 2 September 2024)
Amyloid PET in Part 1 (Snapshot date: 2 September 2024) Rapid and robust amyloid plaque depletion: -107 CL at 3.6 mg/kg after 28 weeks of treatment1 Snapshot date: 2 September 2024. 1 Mean values ±SE (standard errors) of available PET results at the different visit time points are plotted. CL, Centi
Slide 14: Most participants on 3.6 mg/kg are amyloid negative at 28 weeks
Amyloid PET in Part 1 (Snapshot date: 2 September 2024) Most participants on 3.6 mg/kg are amyloid negative at 28 weeks1 Mean amyloid value in CL at visit (% amyloid negative (<24.1 CL)) Visit 0.2 0.6 1.8 3.6 Pbo mg/kg mg/kg mg/kg mg/kg 98 CL 91 CL 88 CL 100 CL 119 CL BL (0%) (0%) (0%) (0%) (0%) 114
Slide 15: Preliminary fluid biomarker results (Part 1)
Preliminary fluid biomarker results (Part 1) Dose-dependent, large magnitude effects of trontinemab on key downstream biomarkers in CSF CSF total tau (week 25) CSF ptau181 (week 25) CSF Neurogranin (week 25) ↓-30% ↓-34% ↓-29% Snapshot date: 2 September, 2024. CSF, cerebrospinal fluid. CSF samples we
Slide 16: Summary
Summary Trontinemab has an overall favourable safety profile with very limited ARIA-E observed. ○ Lobar macrohemorrhage in a participant with significant risk factors and probable CAA led to a protocol amendment and exclusion of participants with superficial siderosis from the study. Results from th
Slide 17: Acknowledgements
Acknowledgements We thank all the study participants and their families, the investigators, and site staff for their time and commitment to the BrainshuttleTM AD study 17