Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Investor Presentation (October 2026)
49 slides from Acumen Pharmaceuticals's investor presentation, Oct 26, 2026
Slide 1: Corporate Presentation October 2026
Corporate Presentation October 2026 1
Slide 2: Forward-Looking Statements
Forward-Looking Statements 2 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 a
Slide 3: Advancing Next Generation Treatments for Early Alzheimer's Disease
3 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 results in AD patients; Phase 2 (IV) topline results expected November 2026 Enhanced Brain Delivery (EBD®) program to
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 *Alzheimer's Association An estimated 7.2 million* Americans age 65 and older live with Alzheimer’s dementia today STAGES AND CHARACTERISTICS OF AD PR
Slide 5: AD Treatment Landscape Continues to Evolve
5 *ARIA-E: Amyloid-related imaging abnormalities - edema AD Treatment Landscape Continues to Evolve Approved Therapies Establish Momentum and Next-generation Approaches Expand Impact Future of AD Landscape Broadens Growth Prospects • New blood-based biomarkers and imaging tools will improve diagnost
Slide 6: 2026 a Pivotal Year for Acumen's Pipeline
6 Phase 1 Phase 2 Phase 3Preclinical Intravenous (IV) Subcutaneous (SC) Expect to report Phase 2 topline results in Nov. 2026 Phase 1 topline results announced Mar. 2025 support further development TfR-Brain transporter + anti-AβO mAb (SC) Option exercised to develop up to two EBD development candid
Slide 7: Acumen Leadership Team Experienced in AD/Neuro Drug Development
Acumen Leadership Team Experienced in AD/Neuro Drug Development Acumen team has decades of experience in Alzheimer’s drug discovery and development AMY SCHACTERLE, PHD Chief Regulatory Officer, Head of Quality PAUL SHUGHRUE, PHD VP, Research & Strategy JASNA JERECIC, PHD Disease Area Strategy Lead E
Slide 8: Milestones Achieved and Upcoming
Milestones Achieved and Upcoming ~$79M Cash, cash equivalents and marketable securities as of Sept. 30, 2026 8 MILESTONES TIMING STATUS Initiation of ALTITUDE-AD Phase 2 trial 2Q2024 Completion of enrollment of ALTITUDE-AD 1Q2025 Phase 1 subcutaneous topline results 1Q2025 EBD® non-clinical da
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 AD
Soluble AβOs Contribute to Pathophysiological Processes Associated with Alzheimer’s Disease • Toxic consequences of soluble Aβ oligomer production include synapse dysfunction and loss, tau hyperphosphorylation, immune cell activation and functional impairment • Reduced neuronal toxicity and interven
Slide 11: Sabirnetug: Potential Next Generation Immunotherapy for Early AD
Sabirnetug: Potential Next Generation Immunotherapy for Early AD 11 • Humanized, affinity matured mAb developed to target toxic Aβ oligomers • IgG2 subclass mAb with reduced effector function Designed for Improved Efficacy & Safety Regulatory Interactions • FDA Fast Track designation for the treatme
Slide 12: Sabirnetug
Sabirnetug
Slide 13: INTERCEPT-AD: A Randomized Placebo Controlled Phase 1 in Early AD Patients
Q2W: Dosing every two weeks; Q4W: Dosing every four weeks. PART A: SINGLE-ASCENDING DOSE n = 8 per cohort (32 total) 6:2 per cohort PART B: MULTIPLE-ASCENDING DOSE n = 10 per cohort (30 total) 3 administrations of drug or PBO 8:2 per cohort COHORT 1: 2 mg/kg sabirnetug or Placebo 2mg COHORT 2: 10 mg
Slide 14: Doses Approaching Maximal Target Engagement Support Sabirnetug AβO Mechanism
Doses Approaching Maximal Target Engagement Support Sabirnetug AβO Mechanism and Helped Guide Dose Selection for Next Study Phase 14 Single & Multiple Dose Cohorts - Exposure Response Relationship (Emax Model) Emax: 22.71 AU/mL Complex EC50: 136 ng/mL sabirnetug 0 600 1200 1800 0 10 20 30 CSF [ACU19
Slide 15: Importance of Key Fluid Biomarkers Associated with AD Pathology
Importance of Key Fluid Biomarkers Associated with AD Pathology 15 Tau Pathology: pTau181 pTau217 Neuronal Injury: Total tau Synaptic Injury: Neurogranin VAMP2 Amyloid Pathology: Aβ 42/40 Astrocytic Activation: GFAP • Biomarkers from cerebrospinal fluid and plasma capture neuronal, synaptic, and axo
Slide 16: Consistent Improvement in CSF Amyloid, Tau and Synaptic Biomarkers
Consistent Improvement in CSF Amyloid, Tau and Synaptic Biomarkers Indicate Downstream Pharmacology of Sabirnetug After Only Three Doses 16 CSF BIOMARKERS pTau181 NeurograninAβ 42/40 Ratio VAMP2 Tau pathologyAmyloid pathology Synaptic injury n = 8 subjects/treated group; 6 subjects in pooled placebo
Slide 17: Sabirnetug Demonstrates Potential for Best-in-Class Safety Profile
Sabirnetug Demonstrates Potential for Best-in-Class Safety Profile Compelling Overall Safety Profile, with Low Incidence of ARIA-E in the INTERCEPT-AD study 17 SAFETY Limited incidence of ARIA-E • 10 mg/kg Q4W: 1 asymptomatic case • 25 mg/kg Q2W: 1 asymptomatic case • 60 mg/kg Q4W: 2 asymptomatic
Slide 18: INTERCEPT-AD Phase 1 Data Support Potential for Next Generation Efficacy and Safety
Potential for Differentiated Efficacy Potential for Differentiated Safety INTERCEPT-AD Phase 1 Data Support Potential for Sabirnetug to Offer Next Generation Efficacy and Safety 18 Compelling safety profile with low incidence of ARIA-E Absence of ARIA-E observed in ApoE4 homozygotes Broad pote
Slide 19: ALTITUDE-AD Phase 2 Study Results Expected in Late 2026
Ra nd om iz at io n 1: 1: 1 Sabirnetug 35mg/kg Q4W (n ~180) Sabirnetug 50mg/kg Q4W* (n ~180) Placebo Q4W (n ~180) Primary Endpoint Change in iADRS1 at 18 months Secondary Endpoints1 CDR-SB, ADAS- Cog13, ADCS-ADL, AD biomarkers 12-month open label extension Objective: To evaluate the clinical efficac
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 Topline results announced in March 2025 show systemic exposure supports further clinical development of the subc
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
23 Delivering Antibodies to the Brain via the Transferrin Receptor (TfR) Aim to Widen the Therapeutic Window to Increase Efficacy, Safety, and Convenience • Increased brain exposure may enhance efficacy • Wider capillary distribution may reduce ARIA-E risk • Lower dose volumes enable convenient subc
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 (AβO-selective mAb) 24 Differentiated Aβ targeting Validated TfR-binding Validated BBB Carrier Technology (TfR-targeting) Acumen EBD Candidates • Targets synaptotoxic AβΟ species • Ro
Slide 25: Acumen Explored Broad Parameters to Develop a TfR-Mediated AβO Product
Acumen Explored Broad Parameters to Develop a TfR-Mediated AβO Product 25 TfR Affinity Architecture Valency AβO Selectivity scFv or VHH Heavy Chain vs Light Chain Monovalent Bivalent Affinity Range Selectivity Range SC Properties 14,000x 5,000x Dosing, Formulation, Stability TfR: transferrin recepto
Slide 26: 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 Target Engagement Maximal TE of AβOs observed Phase 1 Results Provide Foundation for EBD Program 26 Single & Multiple Dose Cohorts - Exposure Response Relationship (Emax Model) Em
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 27 The fusion of anti-oligomer antibodies and J-Brain Cargo (anti-TfR scFv) did not alter the ability of constructs to bind TfR or alter the preferential binding to AβOs Cline et al., CT
Slide 28: In Wild-Type Mice, All EBD Fusion Proteins Showed Increased Brain Exposure
Animals dosed IV at 2 mpk Cline et al., CTAD, 2025 • 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 o mBBB.193-2 and mBBB.234-2 exhibited ~17-fold higher brain exposure at 24 hours • mBBB.193-2 and mBBB.
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) Animals dosed at IV 2 mpk Cline et al., CTAD, 2025 ~ 63X ~ 68X ~ 65X 29 • The brain exposure of the three fusion proteins was 63- to 68-fold higher compared to ACU193 and A
Slide 30: Robust Data Package Supporting EBD Construct Selection
Robust Data Package Supporting EBD Construct Selection Inclusive of NHP Primate Data Anemia Risk Brain Distribution Stability & Manufacturability Pharmacokinetics TfR Affinity 30 Aβ Oligomer Binding
Slide 31: Key Takeaways from NHP Study Results
Key Takeaways from NHP Study Results 31 Enhanced Brain Penetration EBD candidates achieved 14-40x higher brain levels in non-human primates compared to native antibodies 24 hours after dosing Lead clinical candidate IND filing targeted for 2027 Subcutaneous Dosing Capability Favorable stability
Slide 32: Acumen Positioned to Deliver Potential Next-Gen Treatment for Early AD
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 demonstrates high selectivity for AβOs in AD patients Positive Phase 1 data strengthen pot
Slide 33: Appendix
Appendix 33
Slide 34: Selection of Non-clinical Sabirnetug Data
Selection of Non-clinical Sabirnetug Data
Slide 35: Amyloid Beta Oligomers in Alzheimer's Disease Pathology
Amyloid Beta Oligomers (AβOs) in Alzheimer’s Disease Pathology Aβ monomers are normally produced, non- toxic and orders of magnitude more prevalent than other forms of amyloid. Aβ plaques are relatively inert but serve as reservoirs for toxic species of amyloid: oligomers and protofibrils. Neurotoxi
Slide 36: Literature Selection: Soluble AβOs Contribute to Pathophysiological Processes
Literature Selection: Soluble AβOs Contribute to Pathophysiological Processes Associated with Alzheimer’s Disease Disrupted Ca2+ homeostasis Demuro et al, 2005 De Felice et al, 2007 Alberdi et al, 2010 Wang et al, 2018 ChAT loss Heinitz et al, 2006 Nunes-Tavares et al, 2012 Inhibition of axonal tran
Slide 37: Differences in the Profile of Sabirnetug Relative to Approved anti-Aβ DMTs
Differences in the Profile of Sabirnetug Relative to Approved anti-Aβ DMTs: Greater AβO selectivity against Aβ monomers and linear fibrillar species Aducanumab Lecanemab Sabirnetug 1×10-10 1×10-9 1×10-8 1×10-7 1×10-6 1×10-5 Sabirnetug vs Lecanemab and Aducanumab A ffi ni ty - K D (M ) Aβ1-40 monomer
Slide 38: Vascular Aβ Binding Profile in a Murine Model of Vascular CAA
Vascular Aβ Binding Profile in a Murine Model of Vascular CAA Immunohistochemical comparison of vascular Aβ binding in the APP:hE4 mouse brain • Sabirnetug (ACU193) and lecanemab showed qualitatively similar overall staining in both cortex and cerebellum • But sabirnetug had significantly less cereb
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 IgG1 antibodies (lecanemab, donanemab) strongly bind Fcγ1 receptors and C1q, triggering complement activation and antibody- dependent cellular phagocytosis (ADCP), causing inflammation and triggering strong cytokine release. IgG2 a
Slide 40: Phase 1 INTERCEPT-AD
Phase 1 INTERCEPT-AD
Slide 41: Target Engagement Assessed by Measuring Sabirnetug-AβO Complex in CSF
Sabirnetug drug specific capture (anti-sabirnetug idiotype mAb) 41 Target Engagement Assessed by Measuring Sabirnetug-AβO Complex in CSF AβO selective detection (anti-AβΟ mAb) Only Sabirnetug-AβO complex is measurable • Novel assay configuration tailored to selectively detect sabirnetug-AβO complex
Slide 42: Target Engagement of Sabirnetug with AβOs is Dose Proportional
Target Engagement of Sabirnetug with AβOs is Dose Proportional 42 Single Dose Cohorts Multiple Dose Cohorts* 2 mg/kg 10 mg/kg 25 mg/kg 60 mg/kg 0 10 20 30 *One patient from Cohort 5 (10 mg/kg Q4W) excluded because only received one administration of drug (study drug discontinued after lacunar infarc
Slide 43: Nearly All Sabirnetug-Treated Patients in High Dose MAD Cohorts Showed Reductions in Plaque Load
Nearly All Sabirnetug-Treated Patients in High Dose MAD Cohorts Showed Reductions in Plaque Load After Three Doses at 63 or 70 days 43 Plaque load based on florbetapir PET 0 15 30 45 60 75 0 25 50 75 100 125 25 mg/kg Q2W MAD Days C en til oi ds 20 21 22 23 24 25 26 27 0 15 30 45 60 75 0 25 50 75 100
Slide 44: Sabirnetug Serum Exposure is Dose Proportional Without Accumulation
Sabirnetug Serum Exposure is Dose Proportional Without Accumulation 44 Single Dose Cohorts Multiple Dose Cohorts PHARMACOKINETICS 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 mil
Slide 45: Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional
Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional 45 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). PHARMACOKINETICS E. Siemers, et al. INTERCE
Slide 46: Trend Toward Normalizing Plasma Biomarkers
Trend Toward Normalizing Plasma Biomarkers with 10 mg/kg and 60 mg/kg Q4W 46 MAD PBO 10 m g/kg Q 4W 25 m g/kg Q 2W 60 m g/kg Q 4W -100 -50 0 50 100 150 Pl as m a G FA P (% c ha ng e fr om b as el in e) MAD PBO 10 m g/kg Q 4W 25 m g/kg Q 2W 60 m g/kg Q 4W -50 0 50 100 Pl as m a pT au 18 1 (% c ha ng
Slide 47: ARIA-E Summary for INTERCEPT-AD
SAD MAD 10 mg/kg Cohorts 2, 5 25 mg/kg Cohorts 3, 7 60 mg/kg Cohorts 4, 6 NO ARIA-E Asymptomatic ARIA-E Symptomatic ARIA-E Discontinued ApoE D21 D140 3,4 PBO PBO 3,3 3,3 3,4 3,4 PBO PBO 3,4 3,4 3,4 ApoE D28 D63 D126 3,4 3,3 3,3 4,4 4,4 PBO PBO PBO 3,3 3,4 3,4 3,4 PBO PBO PBO 3,3 ApoE D28 D70 D196 2,
Slide 48: Phase 2 ALTITUDE-AD
Phase 2 ALTITUDE-AD
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 • Notable diminishing differentiation as dose increases • Doses were selected with peak-trough variation in mind: select doses based on t
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