Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS

Acumen Pharmaceuticals — Investor Presentation (January 2026)

57 slides from Acumen Pharmaceuticals's investor presentation, Jan 12, 2026

1. Slide 1: Corporate Presentation January 2026

   Corporate Presentation January 2026 1

2. 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

3. Slide 3: Advancing Next Generation Treatments Targeting Toxic Amyloid Beta Oligomers

   3 Advancing Next Generation Treatments Targeting Toxic Amyloid Beta Oligomers (AβOs) for Early Alzheimer’s Disease (AD) With passion, expertise, and perseverance, we are forging a path toward innovative treatments that preserve quality time for all people impacted by Alzheimer’s and other neurodegen

4. Slide 4: Early AD Patient Population Represents Significant and Growing Market

   Early AD Patient Population Represents Significant and Growing Market 4 STAGES AND CHARACTERISTICS OF AD PROGRESSION Severe DementiaModerate DementiaMild Dementia Mild Cognitive Impairment (MCI) Preclinical AD ~5 Million* ~2 Million* Early Alzheimer’s Disease in the U.S. Cognitive Decline Behavioral

5. Slide 5: AD Treatment Landscape Continues to Evolve

   AD Treatment Landscape Continues to Evolve 5 Future of AD Landscape Broadens Growth Prospects • New blood-based biomarkers and imaging tools will improve diagnostic and monitoring capabilities • Expansion into preclinical AD will significantly increase the addressable population • Combinations with

6. 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 EBD-ACU193 Pre-clinical candidate (PCC) data expected early 2026, option to develop up to two EB

7. 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 Analytical Methods Leader, R

8. Slide 8: Milestones Achieved and Upcoming

   Milestones Achieved and Upcoming ~$136M Cash, cash equivalents and marketable securities as of Sept. 30, 2025 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 ✓ EBDTM non-clinical

9. Slide 9: Amyloid Beta Oligomers in AD

   Amyloid Beta Oligomers in AD Sabirnetug (ACU193): monoclonal antibody (mAb) highly selective for toxic AβOs

10. 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

11. 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

12. Slide 12: Sabirnetug

    Sabirnetug

13. 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

14. Slide 14: Doses Approaching Maximal Target Engagement Support Sabirnetug AβO Mechanism

    Doses Approaching Maximal Target Engagement Support Sabirnetug AO 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

15. 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: A 42/40 Astrocytic Activation: GFAP • Biomarkers from cerebrospinal fluid and plasma capture neuronal, synaptic, and axo

16. 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 NeurograninA 42/40 Ratio VAMP2 Tau pathologyAmyloid pathology Synaptic injury n = 8 subjects/treated group; 6 subjects in pooled placebo

17. Slide 17: Sabirnetug Shows Greater or Similar Improvement in Multiple CSF Biomarkers

    Sabirnetug Shows Greater or Similar Improvement in Multiple CSF Biomarkers as Compared to Other A Agents 17 CSF BIOMARKERS CSF NeurograninCSF pTau181 50 100 -35 -25 -15 -5 5 15 Weeks C S F p T a u 1 8 1 (M e a n % c h a n g e f ro m b a s e li n e ) Gantenerumab (510 mg Q2W) Gantenerumab Placebo AC

18. Slide 18: Sabirnetug Shows Greater or Similar Improvement in Plasma pTau217 Biomarker

    Sabirnetug Shows Greater or Similar Improvement in Plasma pTau217 Biomarker as Compared to Other A 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

19. Slide 19: Highest Doses of INTERCEPT-AD Reduced Amyloid Plaque Similar 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

20. 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

21. 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

22. Slide 22: ALTITUDE-AD Phase 2 Study Results Expected in Late 2026

    R a n d o m iz a ti o 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 eff

23. 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

24. 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

25. Slide 25: Enhanced Brain Delivery (EBD)

    Enhanced Brain Delivery (EBDTM)

26. Slide 26: Delivering Antibodies to the Brain via the Transferrin Receptor

    Image courtesy of JCR Pharmaceuticals 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 • Low

27. Slide 27: Acumen EBD: Differentiated Cargo + Validated Carrier Technology

    Acumen EBDTM: Differentiated Cargo + Validated Carrier Technology 27 ✓ JCR brings validated blood-brain barrier (BBB) delivery, with an approved therapy in Japan • Established leader in BBB technology • Established safety profile • Transferrin-receptor-targeting platform includes both scFv and VHHs,

28. 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

29. 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 EBD Program 29 Single & Multiple Dose Cohorts - Exposure Response Relationship (Emax Model) Em

30. 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 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 AOs Cline et al., CT

31. Slide 31: 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.

32. 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 • The brain exposure of the three fusion proteins was 63- to 68-fold higher compared to ACU193 and ACU234 • Higher concen

33. Slide 33: Robust Data Package Supporting Selection of EBD Constructs Expected in Early 2026

    Anemia Risk Robust Data Package, Inclusive of Nonhuman (NHP) Primate Data, Supporting Selection of EBD Constructs Expected in Early 2026 Brain Distribution Stability / Manufacturability Aβ Oligomer Binding Pharmacokinetics TfR Affinity

34. Slide 34: Acumen Positioned to Deliver Potential Next Generation 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

35. Slide 35: Appendix

    Appendix www.acumenpharm.com 35

36. Slide 36: Current Anti-Abeta Antibodies in Preclinical & Clinical Development

    36 Current Anti-Abeta Antibodies in Preclinical & Clinical Development O li g o m e rs T a rg e t Preclinical Phase 1 Phase 2 Phase 3 Launched Sabirnetug Acumen PMN310 ProMIS CM383 KeyMed Trontinemab Roche ~2028 Leqembi Eisai/Biogen Kisunla Lilly Remternetug Lilly 2026 ALIA-1758 AbbVie TAPAS LifeArc

37. Slide 37: Non-clinical Sabirnetug Data

    Non-clinical Sabirnetug Data

38. Slide 38: Amyloid Beta Oligomers in Alzheimer's Disease Pathology

    38 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. Neurot

39. Slide 39: 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

40. Slide 40: 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 40 M urin e D

41. Slide 41: 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 41 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 L

42. Slide 42: Sabirnetug is Selective for AβOs Versus Aβ Plaques

    42 AD Hippocampus ThioS/amyloid plaque AD Hippocampus ACU193/AOs 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

43. Slide 43: Amyloid Plaques are Surrounded by a Halo of AβOs

    43 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 AOs (AW7) Plaque (Thi

44. Slide 44: 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 selectiv

45. Slide 45: 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

46. Slide 46: Sabirnetug Recognizes a Wide Range of Oligomeric Species of Aβ

    46 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

47. Slide 47: Functional Consequences of AβO Clearance: Restoring Plasticity

    1. Prevention of hippocampal LTP impairment Functional Consequences of AβO Clearance: Restoring Plasticity 47 • 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

48. Slide 48: Functional Consequences Following ACU3B3 Treatment

    Functional Consequences Following ACU3B3 Treatment 48 • 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

49. Slide 49: Phase 1 INTERCEPT-AD

    Phase 1 INTERCEPT-AD

50. Slide 50: Target Engagement Assessed by Measuring Sabirnetug-AβO Complex in CSF

    Sabirnetug drug specific capture (anti-sabirnetug idiotype mAb) 50 Target Engagement Assessed by Measuring Sabirnetug-AO Complex in CSF AO selective detection (anti-A mAb) Only Sabirnetug-AO complex is measurable • Novel assay configuration tailored to selectively detect sabirnetug-AβO complex

51. Slide 51: Target Engagement of Sabirnetug with AβOs is Dose Proportional

    Target Engagement of Sabirnetug with AβOs is Dose Proportional 51 Single Dose Cohorts Multiple Dose Cohorts* 2 mg/kg 10 mg/kg 25 mg/kg 60 mg/kg 0 10 20 30 ACU193 IV Infusion Dose C S F A C U 1 9 3 -A β O li g o m e r C o m p le x ( A U /m L ) a t V is it 8 ( D a y 2 1 ) *One patient from Cohort 5 (1

52. Slide 52: 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 52 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 e n ti lo id s 20 21 22 23 24 25 26 27 0 15 30 45 60 75 0 25 50 75 1

53. Slide 53: Sabirnetug Serum Exposure is Dose Proportional Without Accumulation

    Sabirnetug Serum Exposure is Dose Proportional Without Accumulation 53 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

54. Slide 54: Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional

    Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional 54 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

55. Slide 55: Trend Toward Normalizing Plasma Biomarkers

    Trend Toward Normalizing Plasma Biomarkers with 10 mg/kg and 60 mg/kg Q4W 55 M A D P B O 10 m g/k g Q 4W 25 m g/k g Q 2W 60 m g/k g Q 4W -100 -50 0 50 100 150 P la s m a G F A P (% c h a n g e f ro m b a s e li n e ) M A D P B O 10 m g/k g Q 4W 25 m g/k g Q 2W 60 m g/k g Q 4W -50 0 50 100 P la s m a

56. Slide 56: Phase 2 ALTITUDE-AD

    Phase 2 ALTITUDE-AD

57. Slide 57: 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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