Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Investor Presentation (August 2025)
46 slides from Acumen Pharmaceuticals's investor presentation, Aug 12, 2025
Slide 1: Corporate Presentation August 2025
Corporate Presentation August 2025 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 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
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
Slide 5: Amyloid & Abeta Oligomers in AD
Amyloid & Abeta Oligomers in AD Sabirnetug (ACU193): monoclonal antibody (mAb) highly selective for toxic AβOs
Slide 6: Amyloid Beta Oligomers (AβOs) in Alzheimer's Disease Pathology
6 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. Neuroto
Slide 7: Soluble AβOs Contribute to Pathophysiological Processes Associated with Alzheimer's Disease
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 transport Pigino et al, 20
Slide 8: Sabirnetug: Potential Next Generation Immunotherapy for Early AD
Sabirnetug: Potential Next Generation Immunotherapy for Early AD 8 • Humanized, affinity matured mAb developed to target toxic Aβ oligomers • IgG2 subclass mAb with reduced effector function Designed for Improved Efficacy & Safety Large Pharma Collaboration Encouraging Regulatory Interactions • FDA
Slide 9: 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 9 M urin e Don
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 10 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 11: Sabirnetug is Selective for AβOs Versus Aβ Plaques
11 AD Hippocampus ThioS/amyloid plaque AD Hippocampus ACU193/AOs 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 12: Amyloid Plaques are Surrounded by a Halo of AβOs
12 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 AOs (AW7) Plaque (Thi
Slide 13: Sabirnetug: Value Proposition
Sabirnetug: Value Proposition 13 The Alzheimer’s disease market is at a key inflection point with recent approvals paving a new path for the treatment of AD … … and sabirnetug is well-positioned to emerge as a potential next generation treatment of choice. Market will likely remain consolidated with
Slide 14: Positive INTERCEPT-AD Phase 1 Results for Sabirnetug
Positive INTERCEPT-AD Phase 1 Results for Sabirnetug
Slide 15: 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 16: Target Engagement Assessed by Measuring Sabirnetug-AO Complex in CSF
Sabirnetug drug specific capture (anti-sabirnetug idiotype mAb) 16 Target Engagement Assessed by Measuring Sabirnetug-AO Complex in CSF AO selective detection (anti-A mAb) Only Sabirnetug-AO complex is measurable • Novel assay configuration tailored to selectively detect sabirnetug-AβO complex
Slide 17: Target Engagement of Sabirnetug with AβOs is Dose Proportional
Target Engagement of Sabirnetug with AβOs is Dose Proportional 17 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 19 3- A β O lig o m er C o m p le x (A U /m L ) a t V is it 8 ( D ay 2 1 ) *One patient from Cohort 5 (10 mg/
Slide 18: Doses Approaching Maximal Target Engagement Support Sabirnetug AO Mechanism
Doses Approaching Maximal Target Engagement Support Sabirnetug AO Mechanism and Helped Guide Dose Selection for Next Study Phase 18 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 19: Nearly All Sabirnetug-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 19 Plaque load based on florbetapir PET 0 15 30 45 60 75 0 25 50 75 100 125 25 mg/kg Q2W MAD Days 20 21 22 23 24 25 26 27 0 15 30 45 60 75 0 25 50 75 100 125 60 mg/kg Q
Slide 20: Highest Doses of INTERCEPT-AD 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 21: Sabirnetug Serum Exposure is Dose Proportional Without Accumulation
Sabirnetug Serum Exposure is Dose Proportional Without Accumulation 21 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 22: Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional
Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional 22 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 23: Importance of Key Fluid Biomarkers Associated with AD Pathology
Importance of Key Fluid Biomarkers Associated with AD Pathology 23 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
Slide 24: 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 24 CSF BIOMARKERS pTau181 NeurograninA 42/40 Ratio VAMP2 Tau pathologyAmyloid pathology Synaptic injury n = 8 subjects/treated group; 6 subjects in pooled placebo
Slide 25: Trend Toward Normalizing Plasma Biomarkers
Trend Toward Normalizing Plasma Biomarkers with 10 mg/kg and 60 mg/kg Q4W 25 M AD P BO 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 p T au 1 81 (% c h a n g e f ro m b a s e li n e) M AD P BO 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
Slide 26: Sabirnetug Demonstrates Potential for Best-in-Class Safety
Sabirnetug Demonstrates Potential for Best-in-Class Safety Compelling Overall Safety Profile, with Low Incidence of ARIA-E 26 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 cases; 1 symptomatic case No ARI
Slide 27: 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 27 Compelling safety profile with low incidence of ARIA-E Absence of ARIA-E observed in ApoE4 homozygotes Broad ther
Slide 28: Clinical Development Plans & Strategic Considerations
Clinical Development Plans & Strategic Considerations
Slide 29: Current Phase 2 ALTITUDE-AD Study
Ra nd om iz a tio 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 Open label extension Objective: To evaluate the clinical efficacy, safety a
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 • Notable diminishing differentiation as dose increases • Doses were selected with peak-trough variation in mind: select doses based on t
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 Topline results announced in March 2025 show systemic exposure supports further clinical development of the subc
Slide 32: Enhanced Brain Delivery (EBD) Collaboration with JCR Pharmaceuticals
• A preclinical candidate data package including non-human primate data expected in early 2026 • Acumen holds exclusive option to license and develop up to two candidates under terms of agreement • To develop an oligomer-targeted EBD therapy, initially for early Alzheimer’s disease, combining Acumen
Slide 33: Delivering Antibodies to the Brain via the Transferrin Receptor
Image courtesy of JCR Pharmaceuticals 33 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
Slide 34: Acumen EBD: Differentiated Cargo + Validated Carrier Technology
Acumen EBDTM: Differentiated Cargo + Validated Carrier Technology 34 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,
Slide 35: Focus on Execution and Portfolio Expansion
35 Phase 1 Phase 2 Phase 3Preclinical sabirnetug (IV) sabirnetug (subcutaneous) Fully enrolled, Phase 2 topline results expected late 2026 • Phase 1 topline results announced March 2025 support further development • Further data analyses ongoing Enhanced brain delivery (EBD) Preclinical candidate da
Slide 36: 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
Slide 37: 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 38: Milestones Achieved and Upcoming
Milestones Achieved and Upcoming ~$166M Cash, cash equivalents and marketable securities as of June 30, 2025 38 STATUSTIMINGMILESTONES 2Q2024Initiation of ALTITUDE-AD Phase 2 trial 3Q2024Initiation of Phase 1 subcutaneous trial 1Q2025Phase 1 subcutaneous topline results 1Q2025Completion of enrol
Slide 39: Summary
EBDTM program preclinical data package expected in early 2026 Topline results from ALTITUDE-AD Phase 2 IV study evaluating the clinical efficacy and safety of sabirnetug in patients with MCI or mild dementia due to Alzheimer’s expected in late 2026 Significant and growing Alzheimer’s populatio
Slide 40: Appendix
Appendix www.acumenpharm.com 40
Slide 41: Nonclinical Data
Nonclinical Data
Slide 42: 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
Slide 43: 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 44: Sabirnetug Recognizes a Wide Range of Oligomeric Species of Aβ
44 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 45: Functional Consequences of AβO Clearance: Restoring Plasticity
1. Prevention of hippocampal LTP impairment Functional Consequences of AβO Clearance: Restoring Plasticity 45 • 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 46: Functional Consequences Following ACU3B3 Treatment
Functional Consequences Following ACU3B3 Treatment 46 • 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
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