Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Investor Day (September 2026)
59 slides from Acumen Pharmaceuticals's investor day presentation, September 2026
Slide 1: Investor Day
ad NCUME Investor Day September 2026
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: Speakers & Agenda
Speakers & Agenda The Potential of ALTITUDE-AD: A Well-Powered AβO-Directed Phase 2 Study Designed to Test Therapies the AβO Hypothesis DANIEL O'CONNELL ERIC SIEMERS, MD Chief Executive Chief Medical Officer Officer Q&A 6 min 22 min 20 min 18 min Sabirnetug’s MOA and Enhanced Brain Delivery: A Poten
Slide 4: The Potential of AβO-Directed Therapies
The Potential of AβO-Directed Therapies Daniel O'Connell Chief Executive Officer
Slide 5: Early Alzheimer's Disease 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 6: Global Sales of Approved anti-Aβ mAbs Growing and Poised to Accelerate
Global Sales of Approved anti-A mAbs Growing and Poised to Accelerate Amyloid beta market surpassing $1B run rate in spite of infrastructure challenges, efficacy & ARIA concerns Quarterly Global Sales of Approved anti-A mAbs Annual Consensus Estimates of Approved anti-A mAbs $400 Leqembi ($M) Kis
Slide 7: Adoption of BBBs Expected to Accelerate Growth & Potentially Improve Care
Adoption of BBBs Expected to Accelerate Growth & Potentially Improve Care Evolution of Alzheimer’s diagnosis from tissue to blood Pre-2005 ~2005 – 2025+ 2025 → Autopsy Amyloid PET CSF Assays Blood-Based Biomarkers Post-mortem neuropathology, In vivo imaging · PiB 2004; Lumbar puncture · Aβ42/40 Plas
Slide 8: Growth Drivers in AD Market Expected to Support Increased Adoption of anti-Aβ Treatments
Growth Drivers in AD Market Expected to Support Increased Adoption of anti-A Treatments Current Market Growth Drivers Alzheimer’s Disease Continued buildout of infrastructure supporting AD Anti-amyloid antibodies treatment deployment Continued adoption of Alzheimer’s fluid biomarkers for SALES
Slide 9: 2026 a Pivotal Year for Acumen's Innovative anti-AβO Pipeline
2026 a Pivotal Year for Acumen’s Innovative anti-AβO Pipeline Sabirnetug global Phase 2 study results & next generation EBD® candidate selection Preclinical Phase 1 Phase 2 Phase 3 Sabirnetug (ACU193) Phase 2 topline results Intravenous (IV) expected late 2026 Phase 1 topline results announced March
Slide 10: Acumen's Compelling Value Proposition & Strategy
Acumen’s Compelling Value Proposition & Strategy Growing and Novel AO- Phase 2 study Compelling Phase 1 diverse AD selective ongoing and next- results in AD patients population in need MOA in generation EBD increases POS for of improved validated program expands AβO-selective treatment options amyl
Slide 11: Sabirnetug's Mechanism of Action and Potential Differentiation from Other DMTs
Sabirnetug’s Mechanism of Action and Potential Differentiation from Other Disease Modifying Therapies (DMTs) James Doherty, PhD President and Chief Development Officer
Slide 12: How Does Sabirnetug Differentiate From Approved Anti-Aβ DMTs?
How Does Sabirnetug Differentiate From Approved Anti-A DMTs*? • Like approved Anti-A DMTs, sabirnetug is an amyloid protein-targeting monoclonal antibody • Unlike approved Anti-A DMTs, sabirnetug targets soluble A oligomers • Potential effects on efficacy: Direct removal of toxic agents that dis
Slide 13: Amyloid Species and Disease Relevance
Amyloid Species and Disease Relevance The role of A oligomers Amyloid-β Species Continuum Amyloid-β exists in forms from monomers to insoluble plaques along a dynamic continuum. • The classical idea was that a linear amyloid cascade moved from smaller aggregates to larger aggregates • This has evol
Slide 14: Aβ Aggregates and Species Have Different Effects on Brain Function
A Aggregates and Species Have Different Effects on Brain Function Monomers Protofibrils Oligomers Fibrils Toruński et al., 2026. • Oligomeric Aβ (AβOs) exert extensive effects on neuronal and glial • Aβ protofibrils (PFs) can insert into membranes, cause lipid physiology, including: bilayer thinnin
Slide 15: Amyloid Beta Oligomer Levels: Clinical Implications in MCI/Mild AD
Amyloid Beta Oligomer (AO) Levels: Clinical Implications in MCI/Mild AD Soluble oligomers are an early and persistent feature of AD AO elevation in early AD and APOE 4 carriers • Soluble Aβ oligomers appear very early, likely years before plaques are detectable o Amyloid PET positivity then devel
Slide 16: AβO Hypothesis
AO Hypothesis Plaques are the visible pathology, but hard-to-detect oligomers are the most synaptotoxic species • It has been long-appreciated that amyloid plaque load does not correlate well with Toxicity of Soluble Oligomers progression of cognitive decline in AD, and Soluble oligomers are the mo
Slide 17: Osaka Mutation: AβOs Are Associated with Cognitive Impairment in AD
Osaka Mutation: AOs Are Associated with Cognitive Impairment in AD A rare human mutation that supports the oligomer hypothesis • Extremely rare inherited mutation of APP AD protein first identified in several Japanese families that is linked to early-onset familial Alzheimer's disease Osaka 1 • APP
Slide 18: Sabirnetug: First Oligomer-Selective Immunotherapy to Reach POC
Sabirnetug: First Oligomer-Selective Immunotherapy to Reach POC Sabirnetug: First Oligomer-Selective Immunotherapy to Reach POC Specifically developed against globular AOs – amyloid-derived diffusible ligands (ADDLs) Soluble Amyloid Insoluble Amyloid Monomers Oligomers Protofibrils Fibrils Plaques
Slide 19: 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 20: 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 21: 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 22: Infusion-Related Reactions in Lecanemab and Donanemab Phase 3 Studies
Infusion-Related Reactions in Lecanemab and Donanemab Phase 3 Studies % of Infusion-Related Reactions 30 1 Infusion-related reaction 20 8 26 Hypersensitivity including 10 3 anaphylaxis 16 9 0 Clarity AD Core (N=898) Trailblazer-ALZ & ALZ 2 (N=984) Trailblazer-ALZ 6 (N=212) Lecanemab Donanemab There
Slide 23: Incidence and Severity of ARIA with Approved anti-Aβ DMTs
Incidence and Severity of ARIA with Approved anti-A DMTs % of Symptomatic and Serious ARIA-E 8 6 Symptomatic 4 ARIA-E 2 0 Clarity AD Core Clarity AD Core + Trailblazer-ALZ & Open-Label Trailblazer-ALZ 6 Extension (N=1047) ALZ 2 (N=984) OLE (N=1612) (N=898) (N=212) Lecanemab Donanemab Lecanemab Dona
Slide 24: Adoption of BBBs Expected to Accelerate Growth & Potentially Improve Care
Adoption of BBBs Expected to Accelerate Growth & Potentially Improve Care Evolution of Alzheimer’s diagnosis from tissue to blood Pre-2005 ~2005 – 2025+ 2025 → Autopsy Amyloid PET CSF Assays Blood-Based Biomarkers Post-mortem neuropathology, In vivo imaging · PiB 2004; Lumbar puncture · Aβ42/40 Plas
Slide 25: Four FDA Clearances in 15 Months Are Unlocking a Fast-Growing Blood-Based Diagnostics Market
Four FDA Clearances in 15 Months Are Unlocking a Fast-Growing Blood- Based Diagnostics Market S E Q U E N T I A L R E G U L AT O RY A P P RO VA L S U.S. clearances and EU CE marks, May 2025 to date MAY 2025 AUG 2025 MA Y 2 0 2 6 JUL 2026 AUG 20, 2026 AUG 24, 2026 Fujirebio Lumipulse Labcorp national
Slide 26: Measuring Key AD-associated Fluid Biomarkers in INTERCEPT and ALTITUDE
Measuring Key AD-associated Fluid Biomarkers in INTERCEPT and ALTITUDE CSF and plasma markers of amyloid pathology, tau pathology, and synaptic injury Astrocytic Amyloid Pathology: Activation: • Biomarkers from cerebrospinal fluid and Aβ 42/40 plasma capture neuronal, synaptic, and GFAP axonal injur
Slide 27: Improvement in Amyloid, Tau and Synaptic Biomarkers in INTERCEPT-AD
INTERCEPT-AD Study: CSF BIOMARKERS Improvement in Amyloid, Tau and Synaptic Biomarkers in INTERCEPT-AD Improvement in Amyloid, Tau and Synaptic Biomarkers in INTERCEPT-AD Consistent reduction of elevated CSF biomarkers after only three administrations of sabirnetug Amyloid pathology Tau pathology Sy
Slide 28: Sabirnetug Rapidly Reduced CSF Biomarkers in INTERCEPT-AD
Sabirnetug Rapidly Reduced CSF Biomarkers in INTERCEPT-AD CSF pTau181 CSF Neurogranin ACU193 (60 mg/kg Q4W) ACU193 (25 mg/kg Q2W) Gantenerumab (510 mg Q2W) Lecanemab (10 mg/kg Q2W) ACU193 (10 mg/kg Q4W) Gantenerumab Placebo Lecanemab Placebo Pooled Placebo ACU193 *There have been no head-to-head cli
Slide 29: Summary and Conclusions
Summary and Conclusions • Sabirnetug preferentially binds to soluble oligomers, a low abundance, highly toxic form of A that appears during the early phases of disease; this profile offers the opportunity to differentiate from currently approved anti-A DMTs that target other forms of Aβ • Sabirnet
Slide 30: ALTITUDE-AD: A Well-Powered Phase 2 Study Designed to Test the Oligomer Hypothesis
ALTITUDE-AD: A Well-Powered Phase 2 Study Designed to Test the Oligomer Hypothesis Eric Siemers, MD Chief Medical Officer
Slide 31: ALTITUDE-AD Late 2026 Readout: Efficacy, Safety, and Biomarker Profile
ALTITUDE-AD Late 2026 Readout: Efficacy, Safety, and Biomarker Profile (2) safety endpoints (ARIA rate, (3) biomarkers Symptomatic ARIA rate) across ApoE4 homozygotes, ApoE4 heterozygotes, non-carriers Clinical Endpoints Safety Biomarkers Primary: iADRS ARIA: (total and by APOE4 genotype) CSF Biomar
Slide 32: ALTITUDE-AD: Phase 2 Study Design of Sabirnetug for Early AD
ALTITUDE-AD: Phase 2 Study Design of Sabirnetug for Early AD 542 participants randomized 1:1:1 OLE* Follow-up (up to 52 Weeks) (70 Days after Screening Double Blind Treatment Period Last dose) (120 days) (80 weeks) Follow-up (70 Days after Last dose) Sabirnetug 35 mg/kg Q4W Primary Endpoint Change i
Slide 33: Phase 1 Data Demonstrate Sabirnetug's Potential to Achieve More Optimal Benefit-to-Risk Profile
Phase 1 Data Demonstrate Sabirnetug's Potential to Achieve More Optimal Benefit-to- Risk Profile than Existing Options 3 Potential Potential for 1 2 Potential for for improved improved Maximal target AD fluid biomarker Wider therapeutic improved benefit-to-risk engagement of toxic trend to benefit-t
Slide 34: Phase 1 Data Demonstrate Sabirnetug's Potential to Achieve More Optimal Benefit-to-Risk Profile
Phase 1 Data Demonstrate Sabirnetug's Potential to Achieve More Optimal Benefit-to- Risk Profile than Existing Options 1 2 3 Potential for Potential for Maximal target improved improved AD fluid biomarker Wider therapeutic engagement of toxic trend to benefit-to-risk benefit-to-risk index AβOs norma
Slide 35: Phase 1 Data Demonstrate Sabirnetug's Potential to Achieve More Optimal Benefit-to-Risk Profile
Phase 1 Data Demonstrate Sabirnetug's Potential to Achieve More Optimal Benefit-to- Risk Profile than Existing Options 1 2 3 Potential for Maximal target AD fluid biomarker Wider therapeutic improved engagement of toxic trend to index benefit-to-risk AβOs normalization profile INTERCEPT-AD Phase 1 S
Slide 36: iADRS as Primary Endpoint
iADRS as Primary Endpoint • The iADRS was developed to improve sensitivity to treatment effects and disease progression in earlier AD populations • Measures the two domains most relevant to disease progression — cognitive decline and loss of everyday functioning • Aligns well with the view that a cl
Slide 37: ALTITUDE-AD Readout Includes the iADRS as the Primary Outcome and the CDR-SB as an Important Secondary Outcome
ALTITUDE-AD Readout Includes the iADRS as the Primary Outcome and the CDR-SB as an Important Secondary Outcome The iADRS and CDR-SB are both composites of cognitive and functional measures iADRS CDR-SB Number of cognitive measures 13 items (from ADAS-cog13) 3 items Number of functional measures 18 i
Slide 38: Screening with Plasma pTau217 Greatly Reduced Screen Failure due to Amyloid PET
Screening with Plasma pTau217 Greatly Reduced Screen Failure due to Amyloid PET Final US data Preliminary global data 38
Slide 39: ALTITUDE-AD Participant Enrollment Completed in 10 Months
ALTITUDE-AD Participant Enrollment Completed in 10 Months ALTITUDE-AD Enrollment Trajectory • PTau217 screener contributed to the rapid enrollment rate o Expect an increase in the use of such blood-based biomarker screeners by clinical practices in the future • Positive feedback received from site i
Slide 40: Baseline ALTITUDE-AD Characteristics Similar to CLARITY-AD
Baseline ALTITUDE-AD Characteristics Similar to CLARITY-AD ALTITUDE-AD CLARITY (randomized patients) (active treatment only)* N 542 859 Age (years) [mean (range) or SD] 73.6 (50-89) 71.4 (+/- 7.9) Sex (% female) 53.0 51.6 ApoE genotype ApoE e4 homozygotes 10.3% 15.8% ApoE e4 heterozygotes 46.3% 53.1
Slide 41: ALTITUDE-AD Late 2026 Readout: Efficacy, Safety, and Biomarker Profile
ALTITUDE-AD Late 2026 Readout: Efficacy, Safety, and Biomarker Profile (2) safety endpoints (ARIA rate, (3) biomarkers Symptomatic ARIA rate) across ApoE4 homozygotes, ApoE4 heterozygotes, non-carriers Clinical Endpoints Safety Biomarkers Primary: iADRS ARIA: (total and by APOE4 genotype) CSF Biomar
Slide 42: ALTITUDE-AD Takeaways
ALTITUDE-AD Takeaways • Large, well-powered, registration-quality ALTITUDE-AD Phase 2 study currently ongoing o Baseline demographics as expected and similar to CLARITY-AD baseline population o Two doses studied that have potential to both prove efficacious • Phase 1 study results demonstrating targ
Slide 43: Enhanced Brain Delivery (EBD) a Promising Next-Generation Pipeline Addition
Enhanced Brain Delivery (EBD®) a Promising Next-Generation Pipeline Addition Paul Shughrue, PhD VP, Program Lead and Head of Research
Slide 44: Inherent Challenges with Therapeutic Monoclonal Antibodies and Neurodegenerative Diseases
Inherent Challenges with Therapeutic Monoclonal Antibodies and Neurodegenerative Diseases Monoclonal antibodies show poor penetration of Blood-Brain Barrier the blood-brain barrier (BBB), limiting drug delivery Challenge to the intended target High systemic doses are required to get drug into High S
Slide 45: The Use of TfR-Mediated Transcytosis to Shuttle Large Molecules May Help Overcome the BBB Challenge
The Use of TfR-Mediated Transcytosis to Shuttle Large Molecules, such as Monoclonal Antibodies, May Help Overcome the BBB Challenge The transferrin receptor (TfR) is expressed in the Active Transport fine capillary beds on the BBB and is used to Mechanism transport transferrin/iron into the brain An
Slide 46: Program Concept: Building a Bispecific Antibody
Program Concept: Building a Bispecific Antibody • The Cargo determines the Aβ species (oligomer, monomer, plaque, pyroglutamate) targeted by the bispecific antibody • Efficacy is dependent on the Cargo The Cargo • The Transporter determines the mechanism used to Linker cross the BBB as well as brain
Slide 47: Use of anti-Aβ Oligomer Antibodies as the Cargo Differentiates Acumen from Competitors
Use of anti-A Oligomer Antibodies as the Cargo Differentiates Acumen from Competitors • Clinical candidate ACU193 and a newly developed anti-AβO antibody ACU234 were both used as “Cargo” in the program • The use of anti-AβO antibodies as Cargo sets us apart from our competitors The Cargo • ACU193 a
Slide 48: Use of a Proven TfR Transporter Increases the Chance of Success and Reduces the Risk of Anemia
Use of a Proven TfR Transporter Increases the Chance of Success and Reduces the Risk of Anemia • The Anti-TfR scFv and VHH “Transporter” used is a fragment of JCR’s approved drug IZCARGO • IZCARGO binds TfR efficiently, low nM range, and The Transporter is readily transported into brain • The little
Slide 49: Identification of Program Leads from a Diverse anti-TfR Fragment Library
Identification of Program Leads from a Diverse anti-TfR Fragment Library TfR Affinity Architecture Valency AβO Selectivity Heavy Affinity Range scFv or Chain vs Selectivity Range VHH Light Chain 20,000x Monovalent 5,000x Bivalent TfR: transferrin receptor; scFv: single chain variable fragment antibo
Slide 50: Program Leads: ACU301 and ACU401
Program Leads: ACU301 and ACU401 • ACU301 and ACU401 have high affinity for hTfR, 2.81 nM and 2.35 nM, and release into the parenchyma after dosing ACU301 ACU401 o The high affinity binding to TfR enables the use of small doses of antibody to deliver meaningful drug levels into the brain ACU193 ACU2
Slide 51: Program Leads Had Excellent Plasma PK and High Brain Exposure After SC Dosing
Program Leads Had Excellent Plasma PK and High Brain Exposure After SC Dosing of hTfR Transgenic mice Plasma PK Brain PK 100 0.45 scFv ACU401 SC 0.40 Drug Concentration in Plasma ACU401 Drug Concentration in Brain 10 0.35 ACU234 IV ACU401 SC (μg/g of wet tissue) ACU401 IV 0.30 1 (μg/mL) 0.25 ACU401
Slide 52: Cross-Over Study to Investigate the Plasma and Brain PK Profile after SC vs. IV Dosing
Cross-Over Study to Investigate the Plasma and Brain PK Profile after SC vs. IV Dosing in Cynomolgus Monkeys SC Dosing Arm IV Dosing Arm SC Dose (5 mpk) IV Dose (2 mpk) All NHPs 0 .083 1 3 6 12 1 2 3 7 14 21 28 35 0 .083 1 3 6 12 24 Crossed Over to IV Hours after Dosing Hours after Dosing Days after
Slide 53: Robust and Rapid Uptake of ACU401 in Plasma after SC Dosing
Robust and Rapid Uptake of ACU401 in Plasma after SC Dosing 1000000 1000000 ACU234 SC Concentration (pM) Concentration (pM) 100000 ACU401 SC 100000 ACU234 SC ACU401 SC 10000 10000 1000 1000 100 100 0 8 16 24 0 48 96 144 192 240 288 336 Time (Hours) Time (Hours) A B Shughrue et al., AAIC 2026 • After
Slide 54: Analysis of Three Brain Regions Showed Enhancement of ACU401 Delivery Compared to ACU234
Analysis of Three Brain Regions Showed a 35 – 40x Enhancement of ACU401 Delivery Compared to Monoclonal Antibody ACU234 Prefrontal Cortex Putamen Hippocampus* 60 60 60 Drug Concentration (pM) Drug Concentration (pM) Drug Concentration (pM) 40x 35x 40 40 40 22x 20 20 15x 20 0 0 0 ACU234 ACU401 ACU234
Slide 55: Analysis of Hematology Endpoints after SC Dosing Suggest a Low Risk for Anemia
Analysis of a Panel of Hematology Endpoints after SC Dosing of Monkeys Suggest a Low Risk for Anemia Red Blood Cells Hemoglobin Hematocrit Reticulocyte Count 1.5 1.5 1.5 1.5 Reticulocyte Count Ratio (post/pre) Ratio (post/pre) Ratio (post/pre) Ratio (post/pre) Hemoglobin Hematocrit 1.0 1.0 1.0 1.0 R
Slide 56: Key Takeaways from the NHP Study
Key Takeaways from the NHP Study ✓ Robust Brain Delivery of ACU401 The EBD candidate achieved up to 40x higher brain exposure and extensive brain distribution compared to the monoclonal antibody ACU234 ✓ Low Anemia Risk A hematology panel showed no meaningful changes after SC dosing with ACU401 and
Slide 57: Lead Candidates Achieved Requirements to Move Forward with Development
Lead Candidates Achieved Requirements to Move Forward with Development EBD Program: Lead Candidate Profile BBB Penetration Up to 40x monoclonal antibody levels Oligomer Binding High selectivity versus monomer TfR Binding High affinity binding to TfR & release into parenchyma Anemia None observed; di
Slide 58: Next Steps
Next Steps • Complete a follow-on PK study in cynomolgus monkeys with ACU301 and ACU401 to assess the uptake of bispecific antibody after SC dosing o The results will be used to select doses for the planned Phase 1 EBD clinical study for the lead candidate • Additional IND enabling studies, includin
Slide 59: Q&A
Q&A
Acumen Pharmaceuticals — Investor Day (September 2026) on 6ix