Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Q3 2026 Earnings Presentation
49 slides from Acumen Pharmaceuticals's earnings presentation, Oct 26, 2026
Slide 1: Corporate Presentation
Corporate Presentation October 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
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 Alzheimer’s Disease (AD) Patient Population Represents Significant and Growing Market; Preclinical AD a Potential Future Addressable Population STAGES AND CHARACTERISTICS OF AD PROGRESSION ~5 Million* ~2 Million* Preclinical AD Mild Cognitive Impairment Mild Dementia Moderate Dementia Severe D
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) Expect to report Phase 2 Intravenous (IV) topline results in Nov. 2026 Phase 1 topline results announced Mar. 2025 Subcu
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 ✓ ~$79M Cash, cash equivalents and Phase 1 subcutaneous topline results 1Q2025 ✓ marketable securities as of Sept. 30, 2026 EBD® non-clinical data
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 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 18: 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 19: 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 20: 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 21: 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 22: Enhanced Brain Delivery (EBD)
Enhanced Brain Delivery (EBD®)
Slide 23: 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 24: 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 25: 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 26: 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 27: 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 28: 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 29: 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 30: 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 30
Slide 31: 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 32: 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 33: Appendix
Appendix 33
Slide 34: Selection of Non-clinical Sabirnetug Data
Selection of Non-clinical Sabirnetug Data
Slide 35: 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 36: 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 37: Differences in the Profile of Sabirnetug Relative to Approved anti-Aβ DMTs
Differences in the Profile of Sabirnetug Relative to Approved anti-A DMTs: Greater AO selectivity against A monomers and linear fibrillar species Greater selectivity against monomeric A Greater selectivity for soluble A species isolated from human AD brain Sabirnetug vs Lecanemab and Aducanumab
Slide 38: Vascular Aβ Binding Profile in a Murine Model of Vascular CAA
Vascular A Binding Profile in a Murine Model of Vascular CAA Immunohistochemical comparison of vascular A binding in the APP:hE4 mouse brain Cortex Cerebellum • Sabirnetug (ACU193) and lecanemab showed qualitatively similar overall staining in both cortex and cerebellum • But sabirnetug had signif
Slide 39: Sabirnetug is an IgG2 Antibody, Which May Lower Risk of ARIA and IRR
Sabirnetug is an IgG2 Antibody, Which May Lower Risk of ARIA and IRR Differences in effector coupling may influence inflammatory risk profile IgG1 antibodies (lecanemab, donanemab) Potential Impact on Safety: strongly bind Fcγ1 receptors and C1q, triggering complement • IgG1-based anti-A DMTs (leca
Slide 40: Phase 1 INTERCEPT-AD
Phase 1 INTERCEPT-AD on
Slide 41: 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 42: 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 43: Reductions in Plaque Load in High Dose MAD Cohorts
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 44: 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 45: 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 46: 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 47: ARIA-E Summary for INTERCEPT-AD
SAFETY ARIA-E Summary for INTERCEPT-AD 2 mg/kg 10 mg/kg 25 mg/kg 60 mg/kg Cohort 1 Cohorts 2, 5 Cohorts 3, 7 Cohorts 4, 6 ApoE D21 D140 ApoE D21 D140 ApoE D21 D140 ApoE D21 D140 3,4 3,4 PBO PBO 3,3 4,4 PBO PBO 3,3 PBO PBO 3,3 3,3 PBO PBO 3,4 SAD 3,4 3,3 4,4 3,4 PBO PBO 2,3 3,4 3,3 3,3 3,4 PBO PBO 3,
Slide 48: Phase 2 ALTITUDE-AD
Phase 2 ALTITUDE-AD on
Slide 49: 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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