Slide 1: Corporate Presentation
Corporate Presentation August 2025 1
Slide 2: Forward-Looking Statements
Forward-Looking Statements 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 3: Advancing Next Generation Treatments Targeting Toxic Amyloid Beta Oligomers
Advancing Next Generation Treatments Targeting Toxic Amyloid Beta Oligomers (AβOs) for Early Alzheimer’s Disease (AD) Large market in need of additional treatment options Sabirnetug (ACU193): monoclonal antibody (mAb) highly selective for toxic AβOs with positive Phase 1 clinical trial results in AD
Slide 4: Early AD Patient Population Represents Significant and Growing Market
Early AD Patient Population Represents Significant and Growing Market STAGES AND CHARACTERISTICS OF AD PROGRESSION ~5 Million* ~2 Million* Mild Cognitive Impairment Preclinical AD Mild Dementia Moderate Dementia Severe Dementia (MCI) Cognitive Decline Functional Decline Behavioral and Psychological
Slide 5: Amyloid & Abeta Oligomers in AD
Amyloid & Abeta Oligomers in AD Sabirnetug (ACU193): monoclonal antibody (mAb) highly selective for toxic AβOs
Slide 6: Amyloid Beta Oligomers (AβOs) in Alzheimer's Disease Pathology
Amyloid Beta Oligomers (AβOs) in Alzheimer’s Disease Pathology Aβ plaques are relatively inert but serve as reservoirs for toxic species of amyloid: oligomers and protofibrils. Aβ monomers are normally produced, non- toxic and orders of magnitude more prevalent than other forms of amyloid. Neurotoxi
Slide 7: Soluble AβOs Contribute to Pathophysiological Processes Associated with Alzheimer's Disease
Soluble AβOs Contribute to Pathophysiological Processes Associated with Alzheimer’s Disease Impact on • Soluble Aβ forms appear early in the course Synaptic Deterioration Astrocytes/Microglia of disease pathophysiology Plasticity Dysfunction Disrupted Ca2+ Receptor Redistribution homeostasis • Toxic
Slide 8: Sabirnetug: Potential Next Generation Immunotherapy for Early AD
Sabirnetug: Potential Next Generation Immunotherapy for Early AD • Discovered in collaboration with Merck & Co. Large Pharma ✓ Acumen holds exclusive program rights with no Collaboration future financial or other obligations due to Merck Designed for • Humanized, affinity matured mAb developed to ta
Slide 9: Sabirnetug Demonstrates Low Affinity for Monomeric Aβ
Sabirnetug Demonstrates Low Affinity for Monomeric Aβ Aβ1-40 monomer binding • Aβ monomers are ~7000x higher 6×10 -6 concentration than AβOs in AD CSF 5215.5 nM Higher binding affinity Affinity - KD (M) 4×10 -6 • Higher affinity for monomeric Aβ will reduce functional selectivity due to high monomer
Slide 10: Sabirnetug is Highly Selective for AβOs Versus Aβ Monomers
Sabirnetug is Highly Selective for Aβ Oligomers Versus Aβ Monomers Relative Selectivity for AβO versus Monomeric Aβ Measured with SPR Sabirnetug is more selective for AβOs than aducanumab or lecanemab Sabirnetug vs Lecanemab and Aducanumab 1×10 -5 Aβ1-40 monomer Higher binding affinity 1×10 -6 Affin
Slide 11: Sabirnetug is Selective for AβOs Versus Aβ Plaques
Sabirnetug is Selective for AβOs Versus Aβ Plaques Sabirnetug Binds AβOs Not Associated with Plaques in Human AD Brain Slices AD Hippocampus AD Hippocampus ACU193/AOs species ThioS/amyloid plaque Sabirnetug Thioflavin S Adapted from Krafft et al. 2022 11
Slide 12: Amyloid Plaques are Surrounded by a Halo of AβOs
Amyloid Plaques are Surrounded by a Halo of AβOs AβOs can form halos of soluble aggregates Transgenic around dense core of amyloid plaques, to which mouse model sabirnetug also binds of AD Sabirnetug Plaque (ThioS) Lab of William Klein, NU, 2017 AD human brain tissue Sabirnetug binding to soluble Aβ
Slide 13: Sabirnetug: Value Proposition
Sabirnetug: Value Proposition The Alzheimer’s disease market is at a Stakeholders are encouraged about the advancements in the key inflection point with AD treatment landscape and Market will likely remain are working together to enable broader patient access consolidated with A recent approvals pa
Slide 14: Positive INTERCEPT-AD Phase 1 Results for Sabirnetug
Positive INTERCEPT-AD Phase 1 Results for Sabirnetug
Slide 15: INTERCEPT-AD: A Randomized Placebo Controlled Phase 1 in Early AD Patients
INTERCEPT-AD: A Randomized Placebo Controlled Phase 1 in Early AD Patients COHORT 4: 60mg PART A: ≥ 1wk 60 mg/kg Sabirnetug SINGLE-ASCENDING DOSE or Placebo n = 8 per cohort (32 total) COHORT 3: 6:2 per cohort ≥ 1wk 25 mg/kg Sabirnetug 25mg or Placebo COHORT 2: ≥ 1wk 10 mg/kg Sabirnetug 10mg ≥ 1wk o
Slide 16: Target Engagement Assessed by Measuring Sabirnetug-AβO Complex in CSF
TARGET ENGAGEMENT Target Engagement Assessed by Measuring Sabirnetug-AO Complex in CSF MSD S-Plex (Turbo) Immunoassay • Novel assay configuration tailored to selectively detect sabirnetug-AβO complex in CSF as direct measure of AO selective detection target engagement (anti-A mAb) Only Sabirnetu
Slide 17: Target Engagement of Sabirnetug with AβOs is Dose Proportional
TARGET ENGAGEMENT Target Engagement of Sabirnetug with AβOs is Dose Proportional Single Dose Cohorts Multiple Dose Cohorts* No Significant p = 0.0007 30 Differences p = 0.03 CSF ACU193-Aβ Oligomer Complex (AU/mL) p = 0.001 20 at Visit 8 (Day 21) 10 0 2 mg/kg 10 mg/kg 25 mg/kg 60 mg/kg ACU193 IV Infu
Slide 18: Doses Approaching Maximal Target Engagement Support Sabirnetug AβO Mechanism
TARGET ENGAGEMENT Doses Approaching Maximal Target Engagement Support Sabirnetug AO Mechanism and Helped Guide Dose Selection for Next Study Phase Single & Multiple Dose Cohorts - Exposure Response Relationship (Emax Model) 30 ACU193-AβO Complex (AU/mL) Target SAD 2 mg/kg Engagement SAD 10 mg/kg 20
Slide 19: Nearly All Sabirnetug-Treated Patients in High Dose MAD Cohorts Showed Reductions in Plaque Load
PLAQUE REDUCTION Nearly All Sabirnetug-Treated Patients in High Dose MAD Cohorts Showed Reductions in Plaque Load After Three Doses at 63 or 70 days 25 25 mg/kg mg/kg Q2WQ2W MAD MAD 60mg/kg 60 mg/kgQ4W Q4WMAD MAD 125 20 125 28 21 100 100 29 22 30 Centiloids Centiloids 75 23 75 31 24 50 50 32 25 33 2
Slide 20: Highest Doses of INTERCEPT-AD Reduced Amyloid Plaque at Similar Rate and Magnitude to Lecanemab
PLAQUE REDUCTION Highest Doses of INTERCEPT-AD Reduced Amyloid Plaque at Similar Rate and Magnitude to Lecanemab at Comparable Timepoints Mean reduction in amyloid plaque (centiloids)* 6% slowing of cognitive decline 8% slowing of cognitive decline -2% slowing of cognitive decline 22% slowing of cog
Slide 21: Sabirnetug Serum Exposure is Dose Proportional Without Accumulation
PHARMACOKINETICS Sabirnetug Serum Exposure is Dose Proportional Without Accumulation Single Dose Cohorts Multiple Dose Cohorts Estimated serum terminal T1/2 of 5-7 days E. Siemers, et al. INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild d
Slide 22: Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional
PHARMACOKINETICS Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional Single Dose Cohorts Multiple Dose Cohorts* *One patient from Cohort 5 (10 mg/kg Q4W) excluded because only received one administration of drug (study drug discontinued after lacunar infarct). E. Siemers, et al. INTERCEPT-
Slide 23: Importance of Key Fluid Biomarkers Associated with AD Pathology
Importance of Key Fluid Biomarkers Associated with AD Pathology Astrocytic Amyloid Pathology: Activation: • Biomarkers from cerebrospinal fluid and A 42/40 GFAP plasma capture neuronal, synaptic, and axonal injury and reflect the cumulative outcome of different pathological Synaptic Injury: Amyloid
Slide 24: Consistent Improvement in CSF Amyloid, Tau and Synaptic Biomarkers
CSF BIOMARKERS Consistent Improvement in CSF Amyloid, Tau and Synaptic Biomarkers Indicate Downstream Pharmacology of Sabirnetug After Only Three Doses A 42/40 Ratio pTau181 Neurogranin VAMP2 Amyloid pathology Tau pathology Synaptic injury n = 8 subjects/treated group; 6 subjects in pooled placebo
Slide 25: Trend Toward Normalizing Plasma Biomarkers with 10 mg/kg and 60 mg/kg Q4W
PLASMA BIOMARKERS Trend Toward Normalizing Plasma Biomarkers with 10 mg/kg and 60 mg/kg Q4W GFAP pTau181 pTau217 AD Progression Normalization 150 100 150 (% change from baseline) (% change from baseline) (% change from baseline) 1-6 wk post-dosing 100 100 Plasma pTau217 Plasma pTau181 Plasma GFAP 50
Slide 26: Sabirnetug Demonstrates Potential for Best-in-Class Safety
SAFETY Sabirnetug Demonstrates Potential for Best-in-Class Safety Compelling Overall Safety Profile, with Low Incidence of ARIA-E INTERCEPT-AD Phase 1 Safety Data ✓ Limited incidence of ARIA-E 5 Total ARIA-E cases, or ~10% • 10 mg/kg Q4W: 1 asymptomatic case • 25 mg/kg Q2W: 1 asymptomatic case • 60
Slide 27: INTERCEPT-AD Phase 1 Data Support Potential for Next Generation Efficacy and Safety
INTERCEPT-AD Phase 1 Data Support Potential for Sabirnetug to Offer Next Generation Efficacy and Safety Key Takeaways from INTERCEPT-AD ✓ First mAb to demonstrate selective target engagement of AβOs (most toxic form of Aβ) Potential for ✓ Rapid, significant plaque reduction comparable to the current
Slide 28: Clinical Development Plans & Strategic Considerations
Clinical Development Plans & Strategic Considerations
Slide 29: Current Phase 2 ALTITUDE-AD Study
Current Phase 2 ALTITUDE-AD Study Objective: To evaluate the clinical efficacy, safety and tolerability of sabirnetug Patient population: Patients with early AD (MCI or mild dementia due to early AD) Sabirnetug 35mg/kg Q4W (n ~180) Primary Endpoint Randomization 1:1:1 Change in iADRS1 at 18 months O
Slide 30: Simulated CSF Target Engagement at Steady-State for ALTITUDE-AD Doses
Simulated CSF Target Engagement at Steady-State for ALTITUDE-AD Doses • CSF target engagement was simulated at a candidate list of doses given Q4W at steady-state Ph2 Dosing Strategy (ALTITUDE-AD) upper dose: 50 mg/kg Q4W lower dose: 35 mg/kg Q4W • Notable diminishing differentiation as dose increas
Slide 31: Subcutaneous Formulation Well-Tolerated in Phase 1 Healthy Volunteer Study
Subcutaneous Formulation Well-Tolerated in Phase 1 Healthy Volunteer Study Potential to Dose Once-Weekly with Single Injection to Broaden Patient Access and Increase Treatment Convenience Phase 1 Subcutaneous Healthy Volunteer Study Phase 1 study to compare the pharmacokinetics of subcutaneous form
Slide 32: Enhanced Brain Delivery (EBD) Collaboration with JCR Pharmaceuticals
Enhanced Brain Delivery (EBDTM) Collaboration with JCR Pharmaceuticals Collaboration, Option and License Agreement Announced in July 2025 Objective Next Steps • To develop an oligomer-targeted EBD • A non-clinical candidate data package therapy, initially for early Alzheimer’s including non-human pr
Slide 33: Delivering Antibodies to the Brain via the Transferrin Receptor (TfR)
Delivering Antibodies to the Brain via the Transferrin Receptor (TfR) Aim to Widen the Therapeutic Window to Increase Efficacy, Safety, and Convenience Enhanced Brain Delivery (EBDTM) Opportunities: • Increased brain exposure may enhance efficacy • Wider capillary distribution may reduce ARIA-E risk
Slide 34: Acumen EBD: Differentiated Cargo + Validated Carrier Technology
Acumen EBDTM: Differentiated Cargo + Validated Carrier Technology ✓ Sabirnetug demonstrates a differentiated profile vs. plaque-targeted therapies (Phase 1) • Confirmed target engagement of synaptotoxic AOs • Strong plaque reduction Oligomer-selective • Low ARIA-E overall; no ARIA-E observed in APO
Slide 35: 2025 Focus on Execution and Portfolio Expansion
2025 Focus on Execution and Portfolio Expansion Advancing Sabirnetug in Global Phase 2 Study with Next Generation EBDTM Preclinical Phase 1 Phase 2 Phase 3 Fully enrolled, Phase 2 topline sabirnetug (IV) results expected late 2026 • Phase 1 topline results announced March sabirnetug (subcutaneous) 2
Slide 36: Acumen Leadership Team
Acumen Leadership Team Experienced in AD/Neuro Drug Development MATT ZUGA Chief Financial Officer & Chief Business Officer DANIEL O'CONNELL JAMES DOHERTY, PHD ERIC SIEMERS, MD Chief Executive Officer President & Chief Medical Officer Chief Development Officer AMY SCHACTERLE, PHD Chief Regulatory Off
Slide 37: Sabirnetug IP & Market Exclusivity
Sabirnetug IP & Market Exclusivity • Exclusive, perpetual, irrevocable, worldwide, royalty-free license from Merck to its Amyloid Derived Diffusible Ligand (ADDL) IP including issued sabirnetug patents • Sabirnetug Global IP estate: ✓ Issued patents in 19 countries ✓ Composition of matter patents an
Slide 38: Milestones Achieved and Upcoming
Milestones Achieved and Upcoming MILESTONES TIMING STATUS Initiation of ALTITUDE-AD Phase 2 trial 2Q2024 ✓ Initiation of Phase 1 subcutaneous trial 3Q2024 ✓ ~$166M Cash, cash equivalents and Phase 1 subcutaneous topline results 1Q2025 ✓ marketable securities as of June 30, 2025 Completion of enrollm
Slide 39: Summary
Summary Key Takeaways Next Steps ✓ Significant and growing Alzheimer’s population in need of additional treatment options ❑ EBDTM program non-clinical data package ✓ Sabirnetug demonstrates high selectivity for expected in early 2026 synaptotoxic AβOs in AD patients ❑ Topline results from ALTITUDE-A
Slide 40: Appendix
Appendix www.acumenpharm.com 40
Slide 41: Non-clinical Data
Non-clinical Data on
Slide 42: Sabirnetug: Extensive Data Package Supporting Development
Sabirnetug: Extensive Data Package Supporting Development Nanomolar affinity for AβOs, >500-fold greater selectivity for AβOs over Aβ monomer, SELECTIVITY with limited or no discernable binding to vascular amyloid or dense core amyloid plaques Binds broad range of endogenous Aβ, from dimers to h
Slide 43: Sabirnetug is the First mAb Developed to Selectively Target AβOs
Sabirnetug is the First mAb Developed to Selectively Target AβOs Highly selective for Aβ oligomers versus Aβ monomers Sabirnetug Selectivity Sabirnetug Selectivity in presence of 5μM monomeric Aβ Log [Competing Antigen] μM ACU193 Log μM Binding of sabirnetug to AβOs >500x Even in the presence of a l
Slide 44: Sabirnetug Recognizes a Wide Range of Oligomeric Species of Aβ
Sabirnetug Recognizes a Wide Range of Oligomeric Species of Aβ Broad AβO size distribution recognized by Sabirnetug dose dependently binds to AβOs in sabirnetug in human AD brain brain tissue from Tg2576 mice ~18-100 mers ~3-8 mers 1.2 1 Immunoreactivity with Sabirnetug Relative AβO 0.8 0.6 0.4 0.2
Slide 45: Functional Consequences of AβO Clearance: Restoring Plasticity
Functional Consequences of AβO Clearance: Restoring Plasticity 1. Prevention of hippocampal LTP impairment Time course of LTP induction • Aβ at 50 nM markedly reduced HFS-induced LTP in wildtype slices • Pre-treatment with ACU3B3 oligomer-selective antibody prevented Aβ1-42-induced LTP deficits From
Slide 46: Functional Consequences Following ACU3B3 Treatment
Functional Consequences Following ACU3B3 Treatment 2. Reduced amyloid deposition and increased spine density • ACU3B3 (murine oligomer selective antibody) treatment prior to plaque pathology leads to reduced amyloid deposition in J20 Tg model (5-7 months) • Treatment effects are less prominent in ag