Slide 1: Corporate Presentation March 2026
Corporate Presentation March 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 late 2026 Enhanced Brain Delivery (EBDTM) program to de
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 Severe DementiaModerate DementiaMild DementiaMild Cognitive ImpairmentPreclinical AD ~5 Million* ~2 Million* Early Alzheimer’s Disease in the U.S. Cognitive Decline Behavioral and Psych
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) Fully enrolled, Phase 2 topline results expected late 2026 Phase 1 topline results announced March 2025 support further development TfR-Brain transporter + anti-AβO mAb (SC) Option to develop up to two EBD development candidates
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 ~$117M Cash, cash equivalents and marketable securities as of Dec. 31, 2025 On March 16, 2026, the Company completed a private placement, with gross proceeds totaling $35.75M 8 MILESTONES TIMING STATUS Initiation of ALTITUDE-AD Phase 2 trial 2Q2024 Completion of en
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 • 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 Encouraging Regulatory Interactions • FDA Fast Track designation for
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: Greater or Similar Improvement in Multiple CSF Biomarkers vs Other Aβ Agents
Sabirnetug Shows Greater or Similar Improvement in Multiple CSF Biomarkers as Compared to Other Aβ Agents 17 CSF BIOMARKERS CSF NeurograninCSF pTau181 ACU193 (60 mg/kg Q4W) ACU193 (25 mg/kg Q2W) ACU193 (10 mg/kg Q4W) Pooled Placebo ACU193 Gantenerumab (510 mg Q2W) Gantenerumab Placebo Lecanemab (10
Slide 18: Greater or Similar Improvement in Plasma pTau217 vs Other Aβ Agents
Sabirnetug Shows Greater or Similar Improvement in Plasma pTau217 Biomarker as Compared to Other Aβ Agents 18 PLASMA BIOMARKERS Plasma pTau217 *There have been no head-to-head clinical trials between the product candidates listed above. Study designs and protocols for each product candidate were dif
Slide 19: Highest Doses Reduced Amyloid Plaque at Similar Rate to Lecanemab
Highest Doses of INTERCEPT-AD Reduced Amyloid Plaque at Similar Rate and Magnitude to Lecanemab at Comparable Timepoints 6% slowing of cognitive decline 8% slowing of cognitive decline -2% slowing of cognitive decline 22% slowing of cognitive decline 27% slowing of cognitive decline 23% slowing of c
Slide 20: 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 20 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 21: 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 21 Compelling safety profile with low incidence of ARIA-E Absence of ARIA-E observed in ApoE4 homozygotes Broad pote
Slide 22: 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 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 Topline results announced in March 2025 show systemic exposure supports further clinical development of the subc
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
26 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 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 (AβO-selective mAb) 27 Differentiated Aβ targeting Validated TfR-binding Validated BBB Carrier Technology (TfR-targeting) Acumen EBD Candidates • Targets synaptotoxic AβΟ species • Ro
Slide 28: Acumen Explored Broad Parameters to Develop a TfR-Mediated AβO Product
Acumen Explored Broad Parameters to Develop a TfR-Mediated AβO Product 28 TfR Affinity Architecture Valency AβO Selectivity scFv or VHH Heavy Chain vs Light Chain Monovalent Bivalent Affinity Range Selectivity Range SQ Properties 14,000x 5,000x Dosing, Formulation, Stability TfR: transferrin recepto
Slide 29: 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 EBDTM Program 29 Single & Multiple Dose Cohorts - Exposure Response Relationship (Emax Model)
Slide 30: Mouse Surrogate Antibodies Developed to Explore EBD and Target Engagement
Mouse Surrogate Antibodies Developed to Explore EBDTM and Target Engagement in a Mouse Model of Alzheimer’s Disease 30 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.,
Slide 31: EBD Fusion Proteins Showed Increased Brain Exposure in Wild-Type Mice
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 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) Animals dosed at IV 2 mpk Cline et al., CTAD, 2025 ~ 63X ~ 68X ~ 65X 32 • The brain exposure of the three fusion proteins was 63- to 68-fold higher compared to ACU193 and A
Slide 33: Robust Data Package Supporting EBD Construct Selection
Robust Data Package Supporting EBDTM Construct Selection Inclusive of NHP Primate Data Anemia Risk Brain Distribution Stability & Manufacturability Pharmacokinetics TfR Affinity 33 Aβ Oligomer Binding
Slide 34: Key Takeaways from NHP Study Results
Key Takeaways from NHP Study Results 34 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 targeted for 2027 Subcutaneous Dosing Capability Favorable stability profile
Slide 35: 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 36: Appendix
Appendix www.acumenpharm.com 36
Slide 37: Current Anti-Aβ Antibodies in Preclinical/Clinical Development or Launched
Current Anti-Aβ Antibodies in Preclinical/Clinical Development or Launched O lig om er s Target Preclinical Phase 1 Phase 2 Phase 3 Launched Sabirnetug Acumen PMN310 ProMIS CM383 KeyMed Trontinemab Roche Leqembi Eisai/Biogen Kisunla Lilly Remternetug Lilly ALIA-1758 AbbVie TAPAS LifeArc ILM-01 Illim
Slide 38: Non-clinical Sabirnetug Data
Non-clinical Sabirnetug Data
Slide 39: 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 40: Soluble AβOs Contribute to Pathophysiological Processes: Literature Selection
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 41: Sabirnetug Demonstrates Low Affinity for Monomeric Aβ
• Aβ monomers are ~7000x higher concentration than AβOs in AD CSF • Higher affinity for monomeric Aβ will reduce functional selectivity due to high monomer levels • Sabirnetug has much lower affinity than other mAbs for Aβ monomers Sabirnetug Demonstrates Low Affinity for Monomeric Aβ 41 Murin e D o
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 42 Sabirnetug is more selective for AβOs than aducanumab or lecanemab Aducanumab Lecanemab Sabirnetug 1×10-10 1×10-9 1×10-8 1×10-7 1×10-6 1×10-5 Sabirnetug vs Lecanem
Slide 43: Sabirnetug is Selective for AβOs Versus Aβ Plaques
43 AD Hippocampus ThioS/amyloid plaque AD Hippocampus ACU193/AβOs species Sabirnetug is Selective for AβOs Versus Aβ Plaques Sabirnetug Thioflavin S Sabirnetug Binds AβOs Not Associated with Plaques in Human AD Brain Slices Adapted from Krafft et al. 2022
Slide 44: Amyloid Plaques are Surrounded by a Halo of AβOs
44 Amyloid Plaques are Surrounded by a Halo of AβOs Transgenic mouse model of AD AβOs can form halos of soluble aggregates around dense core of amyloid plaques, to which sabirnetug also binds Sabirnetug binding to soluble AβOs Sabirnetug Plaque (ThioS) Spires-Jones et al. 2014 AβOs (AW7) Plaque (Thi
Slide 45: Sabirnetug: Extensive Data Package Supporting Development
Sabirnetug: Extensive Data Package Supporting Development Sabirnetug is a promising immunotherapy for early AD expected to provide meaningful cognitive and functional benefits, slow disease progression, and offer an attractive safety profile Nanomolar affinity for AβOs, >500-fold greater selectivi
Slide 46: Highly Selective for Aβ Oligomers Versus Aβ Monomers
Highly selective for Aβ oligomers versus Aβ monomers Even in the presence of a large excess of Aβ monomer, binding of sabirnetug to AβOs is unchanged Binding of sabirnetug to AβOs >500x binding to Aβ monomer Log [Competing Antigen] μM Sabirnetug Selectivity Sabirnetug Selectivity in presence of 5μM
Slide 47: Sabirnetug Recognizes a Wide Range of Oligomeric Species of Aβ
47 Sabirnetug Recognizes a Wide Range of Oligomeric Species of Aβ Broad AβO size distribution recognized by sabirnetug in human AD brain Sabirnetug dose dependently binds to AβOs in brain tissue from Tg2576 mice Data from lab of William Klein, NU, 2018 Merck internal data, 2011 0 0.2 0.4 0.6 0.8 1 1
Slide 48: Functional Consequences of AβO Clearance: Restoring Plasticity
1. Prevention of hippocampal LTP impairment Functional Consequences of AβO Clearance: Restoring Plasticity 48 • 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 Time course of LTP induction F
Slide 49: Functional Consequences Following ACU3B3 Treatment
Functional Consequences Following ACU3B3 Treatment 49 • 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 aged animals (16-23 months) • Evidence of synaptic recove
Slide 50: Phase 1 INTERCEPT-AD
Phase 1 INTERCEPT-AD
Slide 51: Target Engagement Assessed by Measuring Sabirnetug-AβO Complex in CSF
Sabirnetug drug specific capture (anti-sabirnetug idiotype mAb) 51 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 52: Target Engagement of Sabirnetug with AβOs is Dose Proportional
Target Engagement of Sabirnetug with AβOs is Dose Proportional 52 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 53: Nearly All 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 53 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 54: Sabirnetug Serum Exposure is Dose Proportional Without Accumulation
Sabirnetug Serum Exposure is Dose Proportional Without Accumulation 54 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 55: Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional
Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional 55 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 56: Trend Toward Normalizing Plasma Biomarkers
Trend Toward Normalizing Plasma Biomarkers with 10 mg/kg and 60 mg/kg Q4W 56 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 57: Phase 2 ALTITUDE-AD
Phase 2 ALTITUDE-AD
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 • Notable diminishing differentiation as dose increases • Doses were selected with peak-trough variation in mind: select doses based on t