Slide 1: Overview of product candidate ACU193 and the ongoing Phase 1 INTERCEPT-AD trial
Overview of product candidate ACU193 and the ongoing Phase 1 INTERCEPT-AD trial November 2021 Exhibit 99.1
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: AβOs may consist of 2 to >200 Aβ peptides
AbOs may consist of 2 to >200 Ab peptides. Kelley et al. Simulating oligomerization at experimental concentrations and long timescales: A Markov state model approach. J Chem Physics 2008. Quaternary structures of Aβ Oligomers, protofibrils and fibrils Relini et al. Misfolding of amyloidogenic protei
Slide 4: ACU193 is highly selective for Aβ oligomers versus Aβ monomers
Even in the presence of a large excess of Aβ monomer, binding of ACU193 to AβOs is unchanged Highly selective for Aβ oligomers versus Aβ monomers ACU193 is the first mAb developed to selectively target AβOs Binding of ACU193 to AβOs >500x binding to Aβ monomer SELECTIVITY ACU193 selective binding to
Slide 5: ACU193 is highly selective for AβOs versus Aβ plaques
AD Hippocampus ThioS/amyloid plaque AD Hippocampus ACU193/AbOs 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 Ab (green) SELECTIVITY ACU193 has limited to no binding to thioflavin S positiv
Slide 6: AβOs bind to neurons and are toxic; ACU3B3 prevents toxicity
PHARMACOLOGY SELECTIVITY After binding to neurons, AbOs disrupt Long Term Potentiation (LTP) and cause pathologic increases in intracellular calcium that is destructive to cells. AβOs bind to neurons and are toxic; the murine IgG1 parent of ACU193 (ACU3B3) prevents toxicity ACU3B3 prevents AβO inhib
Slide 7: Treatment of a transgenic mouse model of AD reduces behavioral deficits
Murine parent of ACU193 (3B3) was used to treat younger mice with depositing plaque or older mice with abundant plaque Treatment of a transgenic mouse model of AD results in reduction of behavioral deficits Deficits in younger (5-7 months) transgenic mice are markedly reduced with treatment PHARMACO
Slide 8: Phase 1 overview
Phase 1 overview TRIAL DESIGN: Randomized Placebo Controlled Phase 1 Part A : Single-Ascending Dose Part B : Multiple-Ascending Doses ENROLLMENT CRITERIA: Early AD Mild Cognitive Impairment and Mild Dementia due to AD (amyloid positive by PET) TRIAL OBJECTIVES: Proof of Mechanism (PoM) Safety and to
Slide 9: Randomized placebo controlled Phase 1 in early AD patients: INTERCEPT-AD
Randomized Placebo Controlled Phase 1 in Early AD patients: INTERCEPT-AD PART A: SINGLE- ASCENDING DOSE n = 8 per cohort (32 total) PART B: MULTIPLE- ASCENDING DOSE n = 10 per cohort (30 total) COHORT 1: 2 mg/kg ACU193 or Placebo 2mg COHORT 2: 10 mg/kg ACU193 or Placebo 10mg COHORT 3: 25 mg/kg ACU19
Slide 10: Cogstate computerized test battery
Cogstate computerized test battery Test Domains tested Time (minutes) International shopping list test (immediate) Immediate recall 5 Cogstate brief battery Attention, working memory, learning 15 International shopping list test (delayed) Delayed recall 1 Groton maze learning test Executive function
Slide 11: Arterial Spin Labelling (ASL) as an MRI outcome
Arterial Spin Labelling (ASL) as an MRI outcome MCI patients show hypoperfusion in parietal cortex, precuneus, posterior cingulate cortex and medial temporal lobe AD patients show global hypoperfusion, but especially cingulate, precuneus, parietal lobes and inferior frontal regions Perfusion correla
Slide 12: Lower cerebral perfusion is associated with tau-PET in the entorhinal cortex
Michael Weiner, Michael Ewers*“* Neurobiology of Aging 102 (2021) 111-118 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*, CBF 0 B=-0.971, p<0.001 Braak
Slide 13: Summary
Summary Non-clinical data consistent with toxicity of Ab oligomers and selective binding of ACU193 to Ab 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 cerebral bl
Slide 14: Thank you!
Thank you! Study participants and study partners ACU-001 sites Acumen collaborators