Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Q2 2026 Earnings Presentation
58 slides from Acumen Pharmaceuticals's earnings presentation, Aug 12, 2026
Slide 1: Corporate Presentation
Corporate Presentation August 2026 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 for Early Alzheimer's Disease (AD)
Advancing Next Generation Treatments for Early Alzheimer’s Disease (AD) Targeting Toxic Amyloid Beta Oligomers (AβOs) Large and growing market in need of additional treatment options Sabirnetug (ACU193): monoclonal antibody (mAb) highly selective for toxic AβOs with positive Phase 1 clinical trial r
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* Preclinical AD Mild Cognitive Impairment Mild Dementia Moderate Dementia Severe Dementia Cognitive Decline Functional Decline Behavioral and Psychological Compli
Slide 5: AD Treatment Landscape Continues to Evolve
AD Treatment Landscape Continues to Evolve Approved Therapies Establish Momentum and Next-generation Approaches Expand Impact Current AD Treatments Opportunities for New Future of AD Landscape Offer Hope for People Living with Anti-amyloid Therapies Broadens Growth Prospects AD to Strengthen Risk-Be
Slide 6: 2026 a Pivotal Year for Acumen's Pipeline
2026 a Pivotal Year for Acumen’s Pipeline Sabirnetug Global Phase 2 Study Results & Next Generation EBD Candidate Selection Preclinical Phase 1 Phase 2 Phase 3 Sabirnetug (ACU193) Fully enrolled, Phase 2 topline Intravenous (IV) results expected late 2026 Phase 1 topline results announced March 2025
Slide 7: 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 8: Milestones Achieved and Upcoming
Milestones Achieved and Upcoming MILESTONES TIMING STATUS Initiation of ALTITUDE-AD Phase 2 trial 2Q2024 ✓ Completion of enrollment of ALTITUDE-AD 1Q2025 ✓ ~$110M Cash, cash equivalents and Phase 1 subcutaneous topline results 1Q2025 ✓ marketable securities as of June 30, 2026 EBDTM non-clinical dat
Slide 9: Amyloid Beta Oligomers in AD
Amyloid Beta Oligomers in AD Sabirnetug (ACU193): monoclonal antibody (mAb) highly selective for toxic AβOs
Slide 10: Soluble AβOs Contribute to Pathophysiological Processes Associated with Alzheimer's Disease
Soluble AβOs Contribute to Pathophysiological Processes Associated with Alzheimer’s Disease Model of Aβ oligomer levels • Toxic consequences of soluble Aβ oligomer production include synapse dysfunction and loss, tau hyperphosphorylation, immune cell activation and functional impairment • Reduced ne
Slide 11: Sabirnetug: Potential Next Generation Immunotherapy for Early AD
Sabirnetug: Potential Next Generation Immunotherapy for Early AD Soluble Amyloid Insoluble Amyloid Monomers Oligomers Protofibrils Fibrils Plaques Designed for • Humanized, affinity matured mAb developed Improved to target toxic Aβ oligomers Efficacy & • IgG2 subclass mAb with reduced Safety effecto
Slide 12: Sabirnetug
Sabirnetug on
Slide 13: 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 ≥ 1wk 60 mg/kg PART A: sabirnetug or Placebo SINGLE-ASCENDING DOSE COHORT 3: n = 8 per cohort (32 total) ≥ 1wk 25 mg/kg 25mg 6:2 per cohort sabirnetug or Placebo COHORT 2: ≥ 1wk 10 mg/kg ≥ 1wk 10mg sabirnetug o
Slide 14: Doses Approaching Maximal Target Engagement Support Sabirnetug AβO Mechanism
TARGET ENGAGEMENT Doses Approaching Maximal Target Engagement Support Sabirnetug AβO Mechanism and Helped Guide Dose Selection for Next Study Phase Single & Multiple Dose Cohorts - Exposure Response Relationship Sabirnetug-AO Complex (Emax Model) 30 ACU193-AβO Complex (AU/mL) • Acumen developed a n
Slide 15: 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 Aβ 42/40 plasma capture neuronal, synaptic, and GFAP axonal injury and reflect the cumulative outcome of different pathological Synaptic Injury: Amyloid
Slide 16: 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 Normalization AD Progression AD Progression AD Progression AD Progression Normalization Normalization Norma
Slide 17: Sabirnetug Shows Greater or Similar Improvement in Multiple CSF Biomarkers
CSF BIOMARKERS Sabirnetug Shows Greater or Similar Improvement in Multiple CSF Biomarkers as Compared to Other Aβ Agents CSF pTau181 CSF Neurogranin (Mean % change from baseline) 15 Gantenerumab (510 mg Q2W) 5 Gantenerumab Placebo CSF pTau181 -5 50 100 ACU193 (60 mg/kg Q4W) Gantenerumab (510 mg Q2W)
Slide 18: Sabirnetug Shows Greater or Similar Improvement in Plasma pTau217 Biomarker
PLASMA BIOMARKERS Sabirnetug Shows Greater or Similar Improvement in Plasma pTau217 Biomarker as Compared to Other Aβ Agents Plasma pTau217 Acumen Pharmaceuticals, data on file; AAIC 2023; Sims et al 2023 JAMA; ADPD 2025. *There have been no head-to-head clinical trials between the product candidate
Slide 19: Highest Doses of INTERCEPT-AD Reduced Amyloid Plaque at Similar Rate 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 20: Sabirnetug Demonstrates Potential for Best-in-Class Safety Profile
SAFETY Sabirnetug Demonstrates Potential for Best-in-Class Safety Profile Compelling Overall Safety Profile, with Low Incidence of ARIA-E in the INTERCEPT-AD study 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
Slide 21: 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, meaningful plaque reduction comparable to the current
Slide 22: ALTITUDE-AD Phase 2 Study Results Expected in Late 2026
ALTITUDE-AD Phase 2 Study Results Expected in Late 2026 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 Key Highlights (n ~180) Primary Endpoint • 542-particip
Slide 23: 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 24: 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 25: Enhanced Brain Delivery (EBD)
Enhanced Brain Delivery (EBDTM)
Slide 26: 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 (EBD) Opportunities: • Increased brain exposure may enhance efficacy • Wider capillary distribution may reduce ARIA-E risk •
Slide 27: Acumen's EBD May Improve Efficacy, Safety and Delivery
Acumen's EBD May Improve Efficacy, Safety and Delivery Compared to Non-AβO Selective Antibodies Differentiated Cargo Validated BBB Carrier Acumen EBD Candidates (AβO-selective mAb) Technology (TfR-targeting) Differentiated Aβ targeting = Validated TfR-binding • Targets synaptotoxic A species • Enh
Slide 28: Acumen Explored Broad Parameters to Develop a TfR-Mediated AβO Product
Acumen Explored Broad Parameters to Develop a TfR-Mediated AβO Product TfR Affinity Architecture Valency AβO Selectivity SC Properties Heavy Affinity Range scFv or Chain vs Selectivity Range VHH Light Chain 14,000x Monovalent Dosing, 5,000x Formulation, Bivalent Stability TfR: transferrin receptor;
Slide 29: Phase 1 Results Provide Foundation for EBD Program
Phase 1 Results Provide Foundation for EBD Program Multiple Dose Cohorts* Half-life/Dosing Interval Once monthly dosing Dosing Exposure 35 mg/kg and 50 mg/kg in Phase 2 IV Single & Multiple Dose Cohorts - Exposure Response Relationship (Emax Model) 30 ACU193-AβO Complex (AU/mL) SAD 2 mg/kg SAD 10 mg
Slide 30: Mouse Surrogate Antibodies Developed to Explore EBD and Target Engagement
Mouse Surrogate Antibodies Developed to Explore EBD and Target Engagement in a Mouse Model of Alzheimer’s Disease ACU193 234 0.33 nM 5.34 nM 3.52 nM 0 nM Oligomer 0.319 * Binding 0.595 nM 0.448 nM 2.475 nM 2.182 nM Monomer Binding 6.914 M 5.871 M 8.6 M 3.761 M Cline et al., CTAD, 2025 *Cline et
Slide 31: In Wild-Type Mice, All EBD Fusion Proteins Showed Increased Brain Exposure
In Wild-Type Mice, All EBD Fusion Proteins Showed Increased Brain Exposure Compared to Sabirnetug (ACU193) • Higher brain exposure was observed for all fusion proteins compared to ACU193: o mBBB.193-1 exhibited ~35-fold higher brain exposure at 3 hours ~ 35x @ 3 hrs o mBBB.193-2 and mBBB.234-2 ~ 17x
Slide 32: Surrogate Antibodies Show Enhanced Delivery to the AD Mouse Brain
Surrogate Antibodies Show Enhanced Delivery to the AD Mouse Brain, when Compared with ACU193 and ACU234 AD Mouse Model (ATRE10) • The brain exposure of the three fusion proteins was 63- to 68-fold ~ 63X ~ 65X higher compared to ACU193 and ~ 68X ACU234 • Higher concentrations of all three fusion prot
Slide 33: Robust Data Package Supporting EBD Construct Selection
Robust Data Package Supporting EBD Construct Selection Inclusive of NHP Primate Data Stability & TfR Affinity Manufacturability Pharmacokinetics Brain Distribution Aβ Oligomer Binding Anemia Risk 33
Slide 34: Key Takeaways from NHP Study Results
Key Takeaways from NHP Study Results ✓ Enhanced Brain Penetration EBD candidates achieved 14-40x higher brain levels in non-human primates compared to native antibodies 24 hours after dosing ✓ Low Anemia Risk • Hematology data in non-human primates indicate low potential for anemia: At 24 hours afte
Slide 35: Acumen Positioned to Deliver Potential Next-Gen Treatment for Early AD
Acumen Positioned to Deliver Potential Next-Gen Treatment for Early AD Key Takeaways ✓ Significant and growing Alzheimer’s population in need of additional treatment options ✓ Synaptotoxic AβOs appear early in Alzheimer’s Disease and contribute to its pathophysiological processes; sabirnetug demonst
Slide 36: Appendix
Appendix www.acumenpharm.com 36
Slide 37: Current Anti-Aβ Antibodies in Preclinical/Clinical Development or Launched
Current Anti-A Antibodies in Preclinical/Clinical Development or Launched Target Preclinical Phase 1 Phase 2 Phase 3 Launched DNL921 morADC AβO TfR EBD PMN310 Sabirnetug Denali AC Immune Acumen/JCR Oligomers ProMIS Acumen ATV:Abeta ILM-01 ALZ-201 Denali Illimis Alzinova ABY1125 TAPAS Abyssinia Life
Slide 38: Non-clinical Sabirnetug Data
Non-clinical Sabirnetug Data
Slide 39: 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 40: Literature Selection: Soluble AβOs Contribute to Pathophysiological Processes
Literature Selection: Soluble AβOs Contribute to Pathophysiological Processes Associated with Alzheimer’s Disease Synapse deterioration Receptor Impact on Selective Oxidative stress Zhao et al, 2006 Redistribution astrocytes/microglia neuron death Longo et al, 2000 Lacor et al, 2007 Snyder et al, 20
Slide 41: 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 42: Sabirnetug is Highly Selective for Aβ Oligomers 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 43: 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 43
Slide 44: 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 45: 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 46: 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 47: 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 48: 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 49: 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
Slide 50: Phase 1 INTERCEPT-AD
Phase 1 INTERCEPT-AD on
Slide 51: 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 52: 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 53: Nearly All Sabirnetug-Treated Patients in High Dose MAD Cohorts Showed Plaque Reductions
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 54: 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 55: 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 56: 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 57: Phase 2 ALTITUDE-AD
Phase 2 ALTITUDE-AD on
Slide 58: 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
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