Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — CTAD 2021
15 slides from Acumen Pharmaceuticals's conference presentation, 2021
Slide 1: Phase 1 trial design for ACU193, a monoclonal antibody that selectively binds soluble Aβ oligomers
Phase 1 trial design for ACU193, a monoclonal antibody that selectively binds soluble Aβ oligomers Eric Siemers1, Janice Hitchcock1, Karen Sundell1, James Senetar1, Robert Dean1, Jasna Jerecic2, Erika Cline2, Kent Iverson2, Kathleen Powell2, Jerry Moore2, Deven Dandekar2, Chris Edgar3, Richard Manbe
Slide 2: Forward-Looking Statements and Notes Regarding This Presentation
FORWARD-LOOKING STATEMENTS AND NOTES REGARDING THIS PRESENTATION This presentation may contain 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 b
Slide 3: Disclosures for Eric Siemers
Disclosures for Eric Siemers Chief Medical Officer Not-for-profit activity (unpaid) Acumen Pharmaceuticals Inc. Alzheimer’s Association Bright Focus Foundation Huntington Study Group Consulting Agreements (2019 or later) Michael J. Fox Foundation Acelot Inc. Aquestive Therapeutics Inc. Athira Pharma
Slide 4: Quaternary structures of Aβ Oligomers, protofibrils and fibrils
Quaternary structures of Aβ Oligomers, protofibrils and fibrils AβOs may consist of 2 to >200 Aβ peptides. Kelley et al. Simulating oligomerization at experimental concentrations and long timescales: A Markov state model approach. J Chem Physics 2008. Relini et al. Misfolding of amyloidogenic protei
Slide 5: ACU193 is the first mAb developed to selectively target AβOs
SELECTIVITY ACU193 is the first mAb developed to selectively target AβOs Highly selective for Aβ oligomers versus Aβ monomers ACU193 Selectivity ACU193 Selectivity in presence of 5μM monomeric Aβ AβOs binding (RLUs) % Percent Control Log [Competing Antigen] μM ACU193 Log μM Binding of ACU193 to AβOs
Slide 6: ACU193 is highly selective for AβOs versus Aβ plaques
SELECTIVITY ACU193 is highly selective for AβOs versus Aβ plaques ACU193 staining in human AD brain slices from hippocampus: ACU193 (red) binds non-Thioflavin S positive Aβ (green) AD Hippocampus AD Hippocampus ACU193/AβOs ThioS/amyloid plaque ACU193 has limited to no binding to thioflavin S positiv
Slide 7: AβOs bind to neurons and are toxic; the murine parent of ACU193 prevents toxicity
SELECTIVITY PHARMACOLOGY AβOs bind to neurons and are toxic; the murine IgG1 parent of ACU193 (ACU3B3) prevents toxicity After binding to neurons, AβOs disrupt Long Term Potentiation (LTP) and cause pathologic increases in intracellular calcium that is destructive to cells. ACU3B3 prevents AβO inhib
Slide 8: Treatment of a transgenic mouse model of AD reduces behavioral deficits
SELECTIVITY PHARMACOLOGY Treatment of a transgenic mouse model of AD results in reduction of behavioral deficits Dodart JC et al. Passive immunization with the anti-Aβ oligomer antibody ACU-3B3 improves behavioral deficits in hAPPSL tg mice. SfN, Washington, DC 2014. Ma K. et al. Soluble Aβ-Oligomer
Slide 9: Phase 1 overview
Phase 1 overview TRIAL Randomized Placebo Controlled Phase 1 DESIGN: • Part A : Single-Ascending Dose • Part B : Multiple-Ascending Doses ENROLLMENT Early AD CRITERIA: • Mild Cognitive Impairment and Mild Dementia due to AD (amyloid positive by PET) TRIAL Proof of Mechanism (PoM) OBJECTIVES: Safet
Slide 10: Randomized Placebo Controlled Phase 1 in Early AD patients: INTERCEPT-AD
Randomized Placebo Controlled Phase 1 in Early AD patients: INTERCEPT-AD COHORT 4: 60mg PART A: ≥ 1wk 60 mg/kg ACU193 SINGLE- or Placebo ASCENDING DOSE COHORT 3: n = 8 per cohort (32 total) ≥ 1wk 25 mg/kg ACU193 25mg or Placebo COHORT 2: ≥ 1wk 10 mg/kg ACU193 10mg or Placebo ≥ 1wk COHORT 1: 2 mg/kg
Slide 11: Cogstate computerized test battery
Cogstate computerized test battery Test Domains tested Time (minutes) International shopping list test Immediate recall 5 (immediate) Cogstate brief battery Attention, working memory, 15 learning International shopping list test Delayed recall 1 (delayed) Groton maze learning test Executive function
Slide 12: Arterial Spin Labelling (ASL) as an MRI outcome
Arterial Spin Labelling (ASL) as an MRI outcome * Acumen believes additional literature supports use of ASL to assess hypoperfusion in AD • MCI patients show hypoperfusion in parietal cortex, precuneus, posterior cingulate cortex and medial temporal lobe • AD patients show global hypoperfusion, but
Slide 13: Lower cerebral perfusion is associated with tau-PET in the entorhinal cortex
Lower cerebral perfusion is associated with tau-PET in the entorhinal cortex across the Alzheimer’s continuum Anna Rubinski?, Duygu Tosun», Nicolai Franzmeier?, Julia Neitzel*, Lukas Frontzkowski®, Michael Weiner”, Michael Ewers*“* Neurobiology of Aging 102 (2021) 111-118 Braak stage | 104 e@cN ewcl
Slide 14: Summary
Summary • Non-clinical data consistent with toxicity of Aβ oligomers and selective binding of ACU193 to Aβ oligomers • Enrollment in a Phase 1study assessing safety and target engagement is ongoing • Although unlikely with this small sample size, the possibility of improvement in cognition and cereb
Slide 15: Thank you!
Thank you! • Study participants and study partners • ACU-001 sites • Acumen collaborators 15