Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS

Acumen Pharmaceuticals — J.P. Morgan Healthcare Conference 2024

23 slides from Acumen Pharmaceuticals's conference presentation, Jan 11, 2024

  1. Slide 1: J.P. Morgan Healthcare Conference

    Dan O’Connell, CEO J.P. Morgan Healthcare Conference January 11, 2024 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 Potential Best-In-Class Antibody Targeting Toxic Amyloid Beta Oligomers for Early AD

    Advancing a Potential Best-In-Class Antibody Targeting Toxic Amyloid Beta Oligomers (AβOs) for Early Alzheimer’s Disease (AD) $ Large ACU193: Positive Experienced Strong Expect to market in monoclonal Phase 1 leadership balance sheet initiate Phase need of antibody clinical trial team with supportin

  4. Slide 4: Early AD Patient Population Represents Significant Market Opportunity

    Early AD Patient Population Represents Significant Market Opportunity STAGES AND CHARACTERISTICS OF AD PROGRESSION ~5 Million1 ~2 Million1 Mild Cognitive Preclinical AD Mild Dementia Moderate Dementia Severe Dementia Impairment (MCI) Cognitive Decline Functional Decline Behavioral and Psychological

  5. Slide 5: Amyloid Beta Oligomers are Widely Recognized as Highly Toxic Agents in AD Pathophysiology

    Amyloid Beta Oligomers (AβOs) are Soluble Amyloid Insoluble Amyloid Widely Recognized as Highly Toxic Monomers Oligomers Protofibrils Fibrils Plaques Agents in AD Pathophysiology Neurotoxic Impair synaptic function1 Contribute to impairment of memory and cognition2 Induce tau hyperphosphorylation3 M

  6. Slide 6: ACU193: Potential Best-in-Class Immunotherapy for Early AD

    ACU193: Potential Best-in-Class Immunotherapy for Early AD ACU193's High Selectivity for Toxic AβOs May Provide Meaningful Cognitive Efficacy and Improved Safety Soluble Amyloid Insoluble Amyloid Rationally Humanized, affinity matured mAb developed to target Oligomers Fibrils Plaques Designed toxic

  7. Slide 7: INTERCEPT-AD Phase 1 Data Support Potential for Best-in-Class Efficacy and Safety

    INTERCEPT-AD Phase 1 Data Support Potential for ACU193 to Offer Best-in-Class 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 Diffe

  8. Slide 8: 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 ACU193 SINGLE-ASCENDING DOSE or Placebo COHORT 3: n = 8 per cohort (32 total) 6:2 per cohort ≥ 1wk 25 mg/kg ACU193 25mg or Placebo COHORT 2: ≥ 1wk 10 mg/kg ACU193 10mg ≥ 1wk or Placebo ≥

  9. Slide 9: Doses Approaching Maximal Target Engagement Support ACU193 Mechanism

    TARGET ENGAGEMENT Doses Approaching Maximal Target Engagement Support ACU193 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 SAD

  10. Slide 10: Nearly All ACU193-Treated Patients in High Dose MAD Cohorts Showed Plaque Reductions

    PLAQUE REDUCTION Nearly All ACU193-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 25 26

  11. Slide 11: ACU193 Highest Doses Reduced Amyloid Plaque at Similar Rate to Lecanemab

    PLAQUE REDUCTION ACU193 Highest Doses 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 achieved 22% slowing of cog

  12. Slide 12: 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

  13. Slide 13: Consistent Changes in CSF Amyloid, Tau and Synaptic Biomarkers

    CSF BIOMARKERS Consistent Changes in CSF Amyloid, Tau and Synaptic Biomarkers Indicate Downstream Pharmacology of ACU193 After Only Three Doses A 42/40 Ratio pTau181 Neurogranin VAMP2 Amyloid pathology Tau pathology Synaptic injury 13

  14. Slide 14: Consistent Drug Effects Observed in Plasma Biomarkers in 60 mg/kg MAD Cohort

    PLASMA BIOMARKERS Consistent Drug Effects Observed in Plasma Biomarkers in 60 mg/kg MAD Cohort After Dosing Completed, Biomarkers Rebounded, Supportive of ACU193 Drug Effect GFAP pTau181 pTau217 se se se Do Do Do se se se (% change from baseline) Do Do Do 40 (% change from baseline) Plasma pTau217 Q

  15. Slide 15: ACU193 Compares Favorably on CSF Biomarkers to Lecanemab

    CSF BIOMARKERS ACU193 Compares Favorably on CSF A 42/40 Ratio, pTau181 and Neurogranin at Early Timepoints to Lecanemab* A 42/40 Ratio pTau181 Neurogranin (Mean % Change from baseline) 80 Lecanemab 60 (10 mpk Q2W) CSF Aβ 42/40 40 60 mpk Q4W 20  = ACU193 Lecanemab 25 mpk Q2W Placebo 0 10 mpk Q4W 5

  16. Slide 16: Key Takeaway: ACU193 Demonstrates Potential for Best-in-Class Efficacy

    Key Takeaway: ACU193 Demonstrates Potential for Best-in-Class Efficacy Engaged Toxic AβOs, Reduced Plaque at Comparable Rates to Market Leader, and Demonstrated Strong Downstream Pharmacology Target Engagement in CSF Plaque Reduction Biomarker Effects 0 p = 0.03 Markers of amyloid plaque load -5 • A

  17. Slide 17: ACU193 Demonstrates Potential for Best-in-Class Safety

    SAFETY ACU193 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 mg/k

  18. Slide 18: Experienced Clinical, Regulatory and Development Leaders

    Experienced Clinical, Regulatory and Development Leaders with Substantial Experience Executing Early Through Late-Stage Alzheimer’s Disease Trials DANIEL O'CONNELL ERIC SIEMERS, MD RUSSELL BARTON JANICE HITCHCOCK, PHD President & CEO Chief Medical Officer Chief Operating Officer VP, Regulatory Affai

  19. Slide 19: Acumen has the Expertise and Resources to Advance ACU193 into Second Half of 2026

    $ Acumen has the Expertise and Resources to Advance ACU193 into the Second Half of 2026 Cash, cash equivalents and marketable securities as of Sept 30, 2023 ~$283M Debt financing secured from K2 HealthVentures up to $50M in November 2023 Debt financing Strong Balance Sheet and High-Quality Life Scie

  20. Slide 20: ALTITUDE-AD Phase 2/3 Study Design

    ALTITUDE-AD Phase 2/3 Study Design Objective: To evaluate the clinical efficacy, safety and tolerability of ACU193 Patient population: Patients with early AD (MCI or mild dementia due to early AD) ACU193 35mg/kg Q4W (n ~180) Primary Endpoint Randomization 1:1:1 Change in iADRS1 at 18 months Open lab

  21. Slide 21: ACU193 Subcutaneous Formulation Under Development in Collaboration with Halozyme

    ACU193 Subcutaneous Formulation Under Development in Collaboration with Halozyme Potential to Broaden Patient Access and Increase Treatment Convenience • Announced partnership with Halozyme in November 2023 to develop subcutaneous dosing option for ACU193 Plan to initiate Phase 1 bioavailability stu

  22. Slide 22: Summary

    Summary Key Takeaways Next Steps ✓ Significant and growing Alzheimer's population in need of additional Anticipate Phase 2/3 clinical study, treatment options ALTITUDE-AD, initiation in 1H 2024 ✓ ACU193 demonstrates high selectivity Two treatment arms versus placebo: 50 for toxic AβOs in AD patients

  23. Slide 23: Thank you

    Thank you www.acumenpharm.com 23

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