Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS

Acumen Pharmaceuticals — Q1 2025 Earnings Presentation

42 slides from Acumen Pharmaceuticals's earnings presentation, May 13, 2025

1. Slide 1: Corporate Presentation

   Corporate Presentation May 2025 1

2. 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

3. Slide 3: Advancing a Next Generation Antibody Targeting Toxic Amyloid Beta Oligomers for Early AD

   Advancing a Next Generation Antibody Targeting Toxic Amyloid Beta Oligomers (AβOs) for Early Alzheimer’s Disease (AD) Large market in need of additional treatment options Sabirnetug (ACU193): monoclonal antibody (mAb) highly selective for toxic AβOs Positive Phase 1 clinical trial results presented

4. 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 ~5 Million* ~2 Million* Mild Cognitive Impairment Preclinical AD Mild Dementia Moderate Dementia Severe Dementia (MCI) Cognitive Decline Functional Decline Behavioral and Psychological

5. Slide 5: Amyloid & Abeta Oligomers in AD

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

6. Slide 6: Amyloid Beta Species and Therapeutic Targets in AD

   Amyloid A Beta Species andOligomers (AβOs) Therapeutic in Alzheimer’s Targets in AD 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

7. Slide 7: Soluble AβOs Contribute to Pathophysiological Processes Associated with Alzheimer's Disease

   Soluble AβOs Contribute to Pathophysiological Processes Associated with Alzheimer’s Disease Impact on • Soluble Aβ forms appear early in the course Synaptic Deterioration Astrocytes/Microglia of disease pathophysiology Plasticity Dysfunction Disrupted Ca2+ Receptor Redistribution homeostasis • Toxic

8. Slide 8: Sabirnetug: Potential Next Generation Immunotherapy for Early AD

   Sabirnetug: Potential Next Generation Immunotherapy for Early AD • Discovered in collaboration with Merck & Co. Large Pharma ✓ Acumen holds exclusive program rights with no Collaboration future financial or other obligations due to Merck Designed for • Humanized, affinity matured mAb developed to ta

9. Slide 9: Sabirnetug was Developed to Target AβOs

   Sabirnetug was Developed to Target AβOs Sabirnetug demonstrates high selectivity for AβOs versus monomeric Aβ Aβ1-40 monomer binding 6×10 -6 5215.5 nM • Aβ monomers are ~7000x higher Higher binding affinity concentration than AβOs in AD CSF Affinity - KD (M) 4×10 -6 • Higher affinity for monomeric A

10. Slide 10: 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 Sabirnetug is more selective for AβOs than aducanumab or lecanemab Sabirnetug vs Lecanemab and Aducanumab 1×10 -5 Aβ1-40 monomer Higher binding affinity 1×10 -6 Affin

11. Slide 11: Sabirnetug is Highly Selective for AβOs Versus Aβ Plaques

    Sabirnetug is Highly Selective for AβOs Versus Aβ Plaques Sabirnetug staining in human AD brain slices AD Hippocampus AD Hippocampus ACU193/AOs species ThioS/amyloid plaque Sabirnetug Thioflavin S Adapted from Krafft et al. 2022 11

12. Slide 12: Amyloid Plaques are Surrounded by a Halo of AβOs

    Amyloid Plaques are Surrounded by a Halo of AβOs Sabirnetug targets AβOs that form halos of Transgenic soluble aggregates around dense core of mouse model plaques of AD Sabirnetug Plaque (ThioS) Lab of William Klein, NU, 2017 AD brain tissue Sabirnetug binding to soluble AβOs AOs (AW7) Plaque (Thio

13. Slide 13: Sabirnetug: Value Proposition

    Sabirnetug: Value Proposition The Alzheimer’s disease market is at a Stakeholders are encouraged about the advancements in the key inflection point with AD treatment landscape and Market will likely remain are working together to enable broader patient access consolidated with A recent approvals pa

14. Slide 14: Positive INTERCEPT-AD Phase 1 Results for Sabirnetug

    Positive INTERCEPT-AD Phase 1 Results for Sabirnetug

15. Slide 15: 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 PART A: ≥ 1wk 60 mg/kg Sabirnetug SINGLE-ASCENDING DOSE or Placebo n = 8 per cohort (32 total) COHORT 3: 6:2 per cohort ≥ 1wk 25 mg/kg Sabirnetug 25mg or Placebo COHORT 2: ≥ 1wk 10 mg/kg Sabirnetug 10mg ≥ 1wk o

16. Slide 16: Target Engagement Assessed by Measuring Sabirnetug-AβO Complex in CSF

    TARGET ENGAGEMENT Target Engagement Assessed by Measuring Sabirnetug-AO Complex in CSF MSD S-Plex (Turbo) Immunoassay • Novel assay configuration tailored to selectively detect sabirnetug-AβO complex in CSF as direct measure of AO selective detection target engagement (anti-A mAb) Only Sabirnetu

17. Slide 17: 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

18. Slide 18: Doses Approaching Maximal Target Engagement Support Sabirnetug AβO Mechanism

    TARGET ENGAGEMENT Doses Approaching Maximal Target Engagement Support Sabirnetug AO Mechanism and Helped Guide Dose Selection for Next Study Phase Single & Multiple Dose Cohorts - Exposure Response Relationship (Emax Model) 30 ACU193-AβO Complex (AU/mL) Target SAD 2 mg/kg Engagement SAD 10 mg/kg 20

19. Slide 19: Nearly All Sabirnetug-Treated Patients in High Dose MAD Cohorts Showed Plaque Reductions

    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

20. Slide 20: Highest Doses Reduced Amyloid Plaque at Similar Rate and Magnitude to Lecanemab

    PLAQUE REDUCTION Highest Doses of INTERCEPT-AD Reduced Amyloid Plaque at Similar Rate and Magnitude to Lecanemab at Comparable Timepoints Mean reduction in amyloid plaque (centiloids)* 6% slowing of cognitive decline 8% slowing of cognitive decline -2% slowing of cognitive decline 22% slowing of cog

21. Slide 21: 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

22. Slide 22: 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-

23. Slide 23: 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 A 42/40 GFAP plasma capture neuronal, synaptic, and axonal injury and reflect the cumulative outcome of different pathological Synaptic Injury: Amyloid

24. Slide 24: 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 Amyloid pathology Tau pathology Synaptic injury n = 8 subjects/treated group; 6 subjects in pooled placebo

25. Slide 25: 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

26. Slide 26: Sabirnetug Demonstrates Potential for Best-in-Class Safety

    SAFETY Sabirnetug Demonstrates Potential for Best-in-Class Safety Compelling Overall Safety Profile, with Low Incidence of ARIA-E 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/kg Q2W: 1 asymptomatic case • 60

27. Slide 27: 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, significant plaque reduction comparable to the current

28. Slide 28: Clinical Development Plans & Strategic Considerations

    Clinical Development Plans & Strategic Considerations

29. Slide 29: Current Phase 2 ALTITUDE-AD Study

    Current Phase 2 ALTITUDE-AD Study 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 (n ~180) Primary Endpoint Randomization 1:1:1 Change in iADRS1 at 18 months O

30. Slide 30: 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

31. Slide 31: 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

32. Slide 32: Acumen Leadership Team

    MATT ZUGA Chief Financial Officer & Acumen Leadership Team Chief Business Officer Experienced in AD/Neuro Drug Development DANIEL O'CONNELL JAMES DOHERTY, PHD ERIC SIEMERS, MD AMY SCHACTERLE, PHD Chief Executive Officer President & Chief Medical Officer Chief Regulatory Officer, Chief Development Of

33. Slide 33: 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

34. Slide 34: Milestones Achieved in 2024 and 2025

    Milestones Achieved in 2024 and 2025 STATUS/ MILESTONES EXPECTED TIMING Initiation of ALTITUDE-AD Phase 2 trial ✓ Initiation of Phase 1 subcutaneous trial ✓ ~$198M Cash, cash equivalents and marketable securities as of Phase 1 subcutaneous topline results ✓ Mar. 31, 2025 Completion of enrollment of

35. Slide 35: Summary

    Summary Key Takeaways Next Steps ✓ Significant and growing Alzheimer's population in need of additional treatment options Topline results from ALTITUDE- ✓ Sabirnetug demonstrates high selectivity for toxic AβOs in AD patients AD Phase 2 IV study ✓ Positive Phase 1 data strengthen evaluating the clin

36. Slide 36: Appendix

    Appendix www.acumenpharm.com 36

37. Slide 37: Nonclinical Data

    Nonclinical Data on

38. Slide 38: Sabirnetug: Extensive Data Package Supporting Development

    Sabirnetug: Extensive Data Package Supporting Development  Nanomolar affinity for AβOs, >500-fold greater selectivity for AβOs over Aβ monomer, SELECTIVITY with limited or no discernable binding to vascular amyloid or dense core amyloid plaques  Binds broad range of endogenous Aβ, from dimers to h

39. Slide 39: Sabirnetug is the First mAb Developed to Selectively Target AβOs

    Sabirnetug is the First mAb Developed to Selectively Target AβOs Highly selective for Aβ oligomers versus Aβ monomers Sabirnetug Selectivity Sabirnetug Selectivity in presence of 5μM monomeric Aβ Log [Competing Antigen] μM ACU193 Log μM Binding of sabirnetug to AβOs >500x Even in the presence of a l

40. Slide 40: Sabirnetug Recognizes a Wide Range of Oligomeric Species of Aβ

    Sabirnetug Recognizes a Wide Range of Oligomeric Species of Aβ Broad AβO size distribution recognized by Sabirnetug dose dependently binds to AβOs in sabirnetug in human AD brain brain tissue from Tg2576 mice ~18-100 mers ~3-8 mers 1.2 1 Immunoreactivity with Sabirnetug Relative AβO 0.8 0.6 0.4 0.2

41. Slide 41: Functional Consequences of AβO Clearance: Restoring Plasticity

    Functional Consequences of AβO Clearance: Restoring Plasticity 1. Prevention of hippocampal LTP impairment Time course of LTP induction • 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 From

42. Slide 42: Functional Consequences Following ACU3B3 Treatment

    Functional Consequences Following ACU3B3 Treatment 2. Reduced amyloid deposition and increased spine density • 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 ag

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