Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Investor Presentation (May 2024)
41 slides from Acumen Pharmaceuticals's investor presentation, May 14, 2024
Slide 1: Corporate Presentation May 2024
Corporate Presentation May 2024 1 Exhibit 99.2
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
Slide 3: Advancing a Potential Best-In-Class Antibody Targeting Toxic Amyloid Beta Oligomers
Positive Phase 1 clinical trial results presented in 2H 2023 3 Advancing a Potential Best-In-Class 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 sele
Slide 4: Early AD Patient Population Represents Significant Market Opportunity
Early AD Patient Population Represents Significant Market Opportunity 4 STAGES AND CHARACTERISTICS OF AD PROGRESSION Severe DementiaModerate DementiaMild Dementia Mild Cognitive Impairment (MCI) Preclinical AD ~5 Million1 ~2 Million1 Early Alzheimer’s Disease in the U.S. Acumen’s commercial priority
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: AβOs are Widely Recognized as Highly Toxic Agents in AD Pathophysiology
Amyloid Beta Oligomers (AβOs) are Widely Recognized as Highly Toxic Agents in AD Pathophysiology 7 1. Lacor et al., 2004 & 2007; Townsend et al., 2006; Batista et al., 2018 2. Cleary et al., 2005; Poling et al., 2008; Cline et al., 2019 3. De Felice et al., 2008; Zempel et al., 2010 Monomers Oligome
Slide 8: What is an Aβ Oligomer?
8 AOs May Consist of 2 to >200 A PeptidesWhat is an Aβ Oligomer? ____________________ Source: Kelley et al. J Chem Physics 2008. Figure 1. AOs composed of 3 (a) and 18 (b) A peptides are depicted below. ____________________ Source: Relini et al. Biomolecules 2014. Figure 2. Atomic force microsco
Slide 9: Sabirnetug: Potential Best-in-Class Immunotherapy for Early AD
Sabirnetug: Potential Best-in-Class Immunotherapy for Early AD Sabirnetug's High Selectivity for Toxic AβOs May Provide Meaningful Cognitive Efficacy and Improved Safety 9 Monomers Oligomers Protofibrils Fibrils Plaques Soluble Amyloid Insoluble Amyloid Humanized, affinity matured mAb developed to t
Slide 10: Sabirnetug: Value Proposition
Sabirnetug: Value Proposition 10 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 treatment of choice. Market will likely remain consolidated with A
Slide 11: Positive INTERCEPT-AD Phase 1 Results for Sabirnetug
Positive INTERCEPT-AD Phase 1 Results for Sabirnetug
Slide 12: 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 13: Target Engagement Assessed by Measuring Sabirnetug-AβO Complex in CSF
Sabirnetug drug specific capture (anti-sabirnetug idiotype mAb) 13 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 14: Target Engagement of Sabirnetug with AβOs is Dose Proportional
Target Engagement of Sabirnetug with AβOs is Dose Proportional 14 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 15: Doses Approaching Maximal Target Engagement Support Sabirnetug Mechanism
Doses Approaching Maximal Target Engagement Support Sabirnetug AO Mechanism and Helped Guide Dose Selection for Next Study Phase 15 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 16: Nearly All High Dose MAD Patients 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 16 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 17: Highest Doses Reduced Amyloid Plaque at Similar Rate and Magnitude 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 18: Sabirnetug Serum Exposure is Dose Proportional Without Accumulation
Sabirnetug Serum Exposure is Dose Proportional Without Accumulation 18 Single Dose Cohorts Multiple Dose Cohorts PHARMACOKINETICS Estimated serum terminal T1/2 of 5-7 days
Slide 19: Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional
Sabirnetug CSF Exposure is Dose and Dose-Regimen Proportional 19 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 20: Importance of Key Fluid Biomarkers Associated with AD Pathology
Importance of Key Fluid Biomarkers Associated with AD Pathology 20 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 21: 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 21 CSF BIOMARKERS pTau181 NeurograninA 42/40 Ratio VAMP2 Tau pathologyAmyloid pathology Synaptic injury n = 8 subjects/treated group; 6 subjects in pooled placebo
Slide 22: Trend Toward Normalizing Plasma Biomarkers
Trend Toward Normalizing Plasma Biomarkers with 10 mg/kg and 60 mg/kg Q4W 22 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 23: 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 23 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 24: Key Takeaways from INTERCEPT-AD
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 24 Compelling safety profile with low incidence of ARIA-E Absence of ARIA-E observed in ApoE4 homozygotes Broad therap
Slide 25: Clinical Development Plans & Strategic Considerations
Clinical Development Plans & Strategic Considerations
Slide 26: ALTITUDE-AD Study Design
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 27: Simulated CSF Target Engagement at Steady-State for ALTITUDE-AD Doses
27© 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 28: Sabirnetug Subcutaneous Formulation Under Development 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 29: 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 ROBERT DEAN, MD, PHD Sr. Development Advisor, Biomarkers and Analytical Methods JASNA JERECIC, PHD Analytic
Slide 30: 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 31: Significant Milestones Achieved in 2023 and 2024
Significant Milestones Achieved in 2023 and 2024 ~$297M Cash, cash equivalents and marketable securities as of Mar. 31, 2024 31 STATUS/ EXPECTED TIMING MILESTONES Proof-of-mechanism topline results Biomarker results from Phase 1 study End of Phase 2 meeting with FDA Initiation of ALTITUDE-AD tri
Slide 32: Summary
Summary 32 Significant and growing Alzheimer's population in need of additional treatment options Sabirnetug demonstrates high selectivity for toxic AβOs in AD patients Highly experienced clinical, regulatory and development leaders driving sabirnetug 's development Positive Phase 1 data str
Slide 33: Appendix
Appendix www.acumenpharm.com 33
Slide 34: Preclinical Data
Preclinical Data
Slide 35: 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 36: 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 37: Sabirnetug Binds to a Wide Range of Oligomeric Species of Aβ
Comparison of Aβ species-mAb complex signals across SEC fractions SELECTIVITY Sabirnetug binds to oligomeric species of A that are differentiated from those bound by hu266 (solanezumab) or hu3D6 (bapineuzumab) Sabirnetug Binds to a Wide Range of Oligomeric Species of A 37
Slide 38: Sabirnetug is Highly Selective for AβOs Versus Aβ Plaques
AD Hippocampus ThioS/amyloid plaque AD Hippocampus ACU193/AOs species ____________________ Sources: E. Cline et al. CTAD 2019. Sabirnetug is Highly Selective for AβOs Versus Aβ Plaques 38 Sabirnetug staining in human AD brain slices sabirnetug (red) binds non-Thioflavin S positive A (green) SELECT
Slide 39: AβOs Bind to Neurons and are Toxic; Mouse Analogue Prevents Toxicity
PHARMACOLOGYSELECTIVITY After binding to neurons, AOs disrupt Long Term Potentiation (LTP) and cause pathologic increases in intracellular calcium that is destructive to cells. AβOs Bind to Neurons and are Toxic; Mouse Analogue of Sabirnetug Prevents Toxicity 39 ACU3B3 prevents AβO inhibition of hi
Slide 40: Treatment of a Transgenic Mouse Model of AD Results in Behavioral Improvements
Murine parent version of sabirnetug (ACU3B3) was used to treat younger mice with depositing plaque or older mice with abundant plaque Treatment of a Transgenic Mouse Model of AD Results in Behavioral Improvements 40 Deficits in younger (5-7 months) transgenic mice are markedly reduced with treatment
Slide 41: Sabirnetug engages target AβOs in transgenic mouse brain and is found in CSF
Sabirnetug engages target AβOs in transgenic mouse brain (tg2576) and is found in CSF of patients with early AD PK/PD Sabirnetug Enters the CNS and Binds to AOs in Transgenic Mice and Patients with Early AD in a Dose Dependent Manner 41 PHARMACOLOGYSELECTIVITY Target Engagement Data* from INTERCEPT
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