Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — AD/PD 2024
14 slides from Acumen Pharmaceuticals's conference presentation, Mar 8, 2024
Slide 1: Sabirnetug (ACU193) Lowers CSF Neurogranin & pTau181 Levels in INTERCEPT-AD Study in Early AD
Sabirnetug (ACU193) Lowers CSF Neurogranin & pTau181 Levels in INTERCEPT-AD Study in Early AD Erika N Cline, PhD Acumen Pharmaceuticals AD/PD Lisbon, Portugal March 8, 2024
Slide 2: Disclosures
Disclosures Dr. Cline is an employee and shareholder at Acumen Pharmaceuticals. 2
Slide 3: Forward Looking Statement
Forward Looking Statement This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Any statement describing Acumen’s goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and
Slide 4: Acknowledgements
Acknowledgements Participants and their Study Partners • We acknowledge with gratitude the individuals who enrolled in the INTERCEPT-AD trial as well as their family, study partners, and friends who supported them. Site Staff and Study Team Members • We would also like to acknowledge the site staff,
Slide 5: Sabirnetug (ACU193) is a Monoclonal Antibody that is Highly Selective for Soluble Amyloid β Oligomers
Sabirnetug (ACU193) is a Monoclonal Antibody that is Highly Selective for Soluble Amyloid β Oligomers, a Synaptotoxic Form of Amyloid β Amyloid β oligomers (AβOs): • Impair synaptic function1 • Induce tau hyperphosphorylation2 • Contribute to impairment of memory & cognition3 1. Lacor et al., 2004 &
Slide 6: INTERCEPT-AD: A Randomized Placebo Controlled Phase 1 Study in Early AD Patients
INTERCEPT-AD: A Randomized Placebo Controlled Phase 1 Study in Early AD Patients COHORT 4: PART A: ≥ 1wk 60 mg/kg Sabirnetug SINGLE-ASCENDING DOSE (SAD) or Placebo COHORT 3: n = 8 per cohort (32 total) 6:2 per cohort ≥ 1wk 25 mg/kg Sabirnetug or Placebo COHORT 2: ≥ 1wk 10 mg/kg Sabirnetug ≥ 1wk or P
Slide 7: Key CSF Biomarkers Associated with AD Pathology were Assessed
Key CSF Biomarkers Associated with AD Pathology were Assessed Amyloid Pathology: Ab 40 Ab 42 Amyloid plaque Ab oligomer Tau Pathology: pTau181 pTau217 Synaptic Injury: Neuronal Injury: Neurogranin Total tau 1. Tarawneh, R. Biomarkers: Our Path Towards a Cure for Alzheimer Disease. Biomarker Insights
Slide 8: Sabirnetug-Associated Changes in CSF Aβ and Synaptic Biomarkers Indicate Downstream Pharmacology After 3 Doses
Sabirnetug-Associated Changes in CSF Aβ and Synaptic Biomarkers Indicate Downstream Pharmacology After 3 Doses Ab 42/40 Ratio Neurogranin Normalization AD progression AD progression Normalization Amyloid pathology Synaptic injury • Aβ assays: Lumipulse • n = 8 subjects/treated group; 6 subjects in p
Slide 9: Sabirnetug-Associated Changes in CSF Tau Proteoforms are Consistent with Downstream Pharmacology After 3 Doses
Sabirnetug-Associated Changes in CSF Tau Proteoforms are Consistent with Downstream Pharmacology After 3 Doses pTau181 pTau217 tTau AD progression AD progression AD progression Normalization Normalization Normalization Tau pathology Neuronal injury • All assays: Lumipulse • n = 8 subjects/treated gr
Slide 10: CSF Biomarker Responses to Sabirnetug Are Dose & Duration Dependent
CSF Biomarker Responses to Sabirnetug Are Dose & Duration Dependent Neurogranin tTau pTau181 AD progression p-value = 0.007 p-value = 0.005 p-value = 0.001 Pearson r = -0.423 Pearson r = -0.439 Pearson r = -0.504 Normalization • LP = lumbar puncture • Neurogranin: ELISA • n = 40 subjects • Tau assay
Slide 11: Changes in CSF Neurogranin & Aβ42/40 Correlate with Target Engagement
Changes in CSF Neurogranin & Aβ42/40 Correlate with Target Engagement (Defined as Sabirnetug Binding to CSF Aβ Oligomers ) Aβ 42/40 Neurogranin AD progression p-value = 0.0005 p-value = 0.0105 Pearson r = -0.433 Normalization Pearson r = 0.566 Normalization AD progression • Aβ assays: Lumipulse • n
Slide 12: Changes in CSF Total & Hyperphosphorylated Tau Do Not Significantly Correlate with Target Engagement
Changes in CSF Total & Hyperphosphorylated Tau Do Not Significantly Correlate with Target Engagement (Defined as Sabirnetug Binding to Aβ Oligomers in CSF ) tTau pTau181 pTau217 p-value = 0.094 p-value = 0.065 p-value= 0.058 Pearson r = -0.296 Pearson r = -0.325 Pearson r = -0.345 • All assays: Lumi
Slide 13: Conclusions
Conclusions • Sabirnetug (ACU193) significantly lowers CSF neurogranin (-13.9 %) and pTau181 (-13.0 %) after only three administrations of 60 mg/kg Q4W • Reduction of the synaptic marker neurogranin correlated significantly with sabirnetug engagement with AβO target • Long term changes in biomarkers
Slide 14: Thank you!
Thank you! CSF Biomarker Measurements And to colleagues at Acumen Pharmaceuticals Department of Laboratory Medicine, Neurochemistry Lab, Data Analysis & QC Amsterdam UMC Karen Sundell Daniel Antwi-Berko Elizabeth Johnson Marleen JA Koel-Simmelink Gopalan Sethuraman Charlotte Teunissen Biomarker Stud