Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Investor Presentation (November 2024)
41 slides from Acumen Pharmaceuticals's investor presentation, Nov 12, 2024
Slide 1: Corporate Presentation November 2024
Corporate Presentation November 2024 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 a Next Generation Antibody Targeting Toxic Amyloid Beta Oligomers
Positive Phase 1 clinical trial results presented in 2H 2023 3 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 fo
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: AD, Amyloid & Abeta Oligomers
AD, Amyloid & Abeta Oligomers
Slide 6: Amyloid Beta Oligomers (AβOs) in Alzheimer's Disease Pathology
6 Amyloid Beta Oligomers (AβOs) in Alzheimer’s Disease Pathology
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 is Highly Selective for AβOs Versus Aβ Plaques
8 AD Hippocampus ThioS/amyloid plaque AD Hippocampus ACU193/AOs species Sabirnetug is Highly Selective for AβOs Versus Aβ Plaques Sabirnetug Thioflavin S Sabirnetug staining in human AD brain slices Adapted from Krafft et al. 2022
Slide 9: Amyloid Plaques are Surrounded by a Halo of AβOs
9 Amyloid Plaques are Surrounded by a Halo of AβOs Transgenic mouse model of AD Sabirnetug targets AβOs that form halos of soluble aggregates around dense core of plaques Sabirnetug binding to soluble AβOs Sabirnetug Plaque (ThioS) Spires-Jones et al. 2016 AOs (AW7) Plaque (ThioS) AD brain tissue L
Slide 10: Sabirnetug: Potential Next Generation Immunotherapy for Early AD
Sabirnetug: Potential Next Generation Immunotherapy for Early AD 10 • 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 FDA Interactions • FDA Fast T
Slide 11: Sabirnetug was Developed to Selectively Target AβOs
11 • Aβ monomers are ~7000x fold 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 was Developed to Selectively Target AβOs High sel
Slide 12: Sabirnetug is Highly Selective for Aβ Oligomers
12 Aducanumab Sabirnetug 1×10 -10 1×10 -9 1×10 -8 1×10 -7 1×10 -6 1×10 -5 Sabirnetug vs Aducanumab A ff in it y - K D ( M ) Aβ1-40 monomer Aβ oligomers 8750x 79.6x Sabirnetug is more selective for AβOs than aducanumab Sabirnetug is Highly Selective for Aβ Oligomers H ig h e r b in d in g a ff in it
Slide 13: Sabirnetug: Value Proposition
Sabirnetug: Value Proposition 13 The Alzheimer’s disease market is at a key inflection point with recent and expected 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 cons
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 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
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 *One patient from Cohort 5 (10 mg/kg
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 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
Slide 20: 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
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
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
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 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
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 Best-in-Class Efficacy and Safety
Potential for Differentiated Efficacy Potential for Differentiated Safety INTERCEPT-AD Phase 1 Data Support Potential for Sabirnetug to Offer Best-in-Class Efficacy and Safety 27 ✓ Compelling safety profile with low incidence of ARIA-E ✓ Absence of ARIA-E observed in ApoE4 homozygotes ✓ Broad therap
Slide 28: Clinical Development Plans & Strategic Considerations
Clinical Development Plans & Strategic Considerations
Slide 29: ALTITUDE-AD Study Currently Enrolling
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 Open label extension Objective: To evaluate the clinical efficacy, safe
Slide 30: Simulated CSF Target Engagement at Steady-State for ALTITUDE-AD Doses
30© Copyright 2020 Certara, L.P. All rights reserved. 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 pe
Slide 31: Sabirnetug Subcutaneous Formulation Under Development in Collaboration with Halozyme
Sabirnetug 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 sabirnetug • Halozyme’s drug delivery technolog
Slide 32: Ongoing Phase 1 Subcutaneous Healthy Volunteer Study
Population: Ongoing Phase 1 Subcutaneous Healthy Volunteer Study Topline Results Expected in Q1 2025 Output: IV dose (1/month) (n = 12) • Safety • Subcutaneous bioavailability • Information on flat dosing Subcutaneous dose (1/week) (n = 16) • Healthy volunteers • Age matched to AD population in sabi
Slide 33: 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 JANICE HITCHCOCK, PHD VP, Regulatory Affairs PAUL SHUGHRUE, PHD VP, Research & Strategy JASNA JERECIC, PHD Analytical Methods Leader, Research Scientist
Slide 34: 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 35: Milestones Achieved in 2024 and Anticipated in 2025
Milestones Achieved in 2024 and Anticipated in 2025 ~$259M Cash, cash equivalents and marketable securities as of Sept. 30, 2024 35 MILESTONES STATUS/ EXPECTED TIMING Initiation of ALTITUDE-AD Phase 2 trial ✓ Initiation of Phase 1 subcutaneous trial ✓ Expected Phase 1 subcutaneous topline results 1Q
Slide 36: Summary
Summary 36 ✓ Significant and growing Alzheimer's population in need of additional treatment options ✓ Sabirnetug demonstrates high selectivity for toxic AβOs in AD patients ✓ Positive Phase 1 data strengthen potential for sabirnetug to offer best-in-class efficacy and safety ✓ Phase 2 IV study and P
Slide 37: Appendix
Appendix www.acumenpharm.com 37
Slide 38: Sabirnetug is the First mAb Developed to Selectively Target AβOs
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 39: Sabirnetug Recognizes a Wide Range of Oligomeric Species of Aβ
39 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 40: Functional Consequences of AβO Clearance: Restoring Plasticity
1. Prevention of hippocampal LTP impairment Functional Consequences of AβO Clearance: Restoring Plasticity 40 • 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 41: Functional Consequences Following ACU3B3 Treatment
Functional Consequences Following ACU3B3 Treatment 41 • 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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