Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Investor Presentation (January 2024)
50 slides from Acumen Pharmaceuticals's investor presentation, Jan 12, 2024
Slide 1: Corporate Presentation January 2024
Corporate Presentation January 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 Potential Best-In-Class Antibody Targeting Toxic AβOs
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 ACU193: monoclonal antibody (mAb) highly selective for tox
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. Cleary et al., 2005; Townsend et al., 2006; Poling et al., 2008; Reed et al., 2011; Batista et al., 2018. 2. Ferreira, S. T., and Klein, W. L., 2011. 3. De Felice et al., 2008; Zempel et al., 2010;
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: 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 9 Monomers Oligomers Protofibrils Fibrils Plaques Soluble Amyloid Insoluble Amyloid Humanized, affinity matured mAb developed to target to
Slide 10: ACU193: Value Proposition
ACU193: 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 ACU193 is well-positioned to emerge as a potential treatment of choice. Market will likely remain consolidated with A therapi
Slide 11: Positive INTERCEPT-AD Phase 1 Results for ACU193
Positive INTERCEPT-AD Phase 1 Results for ACU193
Slide 12: INTERCEPT-AD: A Randomized Placebo Controlled Phase 1 in Early AD Patients
12 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 ACU193 or Placebo 2mg COHORT 2: 10 mg/
Slide 13: Target Engagement Assessed by Measuring ACU193-AβO Complex in CSF
ACU193 drug specific capture (anti-ACU193 idiotype mAb) 13 Target Engagement Assessed by Measuring ACU193-AO Complex in CSF AO selective detection (anti-A mAb) Only drug/AO complex is measurable Novel assay configuration tailored to selectively detect ACU193-AβO complex in CSF as direct measure
Slide 14: Target Engagement of ACU193 with AβOs is Dose Proportional
Target Engagement of ACU193 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 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 (10 mg
Slide 15: Doses Approaching Maximal Target Engagement Support ACU193 Mechanism
Doses Approaching Maximal Target Engagement Support ACU193 AO Mechanism and Helped Guide Dose Selection for Next Study Phase 15 Single & Multiple Dose Cohorts - Exposure Response Relationship (Emax Model) Emax: 22.7 AU/mL Complex EC50: 136 ng/mL ACU193 *One patient from Cohort 5 (10 mg/kg Q4W) excl
Slide 16: Reductions in Plaque Load in High Dose MAD Cohorts
Nearly All ACU193-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 C e n ti lo id s 20 21 22 23 24 25 26 27 0 15 30 45 60 75 0 25 50 75 100 1
Slide 17: ACU193 Highest Doses Reduced Amyloid Plaque Similar to Lecanemab
ACU193 Highest Doses 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 cognitive
Slide 18: ACU193 Serum Exposure is Dose Proportional Without Accumulation
ACU193 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: ACU193 CSF Exposure is Dose and Dose-Regimen Proportional
ACU193 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 Changes in CSF Amyloid, Tau and Synaptic Biomarkers
Consistent Changes in CSF Amyloid, Tau and Synaptic Biomarkers Indicate Downstream Pharmacology of ACU193 After Only Three Doses 21 CSF BIOMARKERS pTau181 NeurograninA 42/40 Ratio VAMP2 Tau pathologyAmyloid pathology Synaptic injury
Slide 22: Consistent Drug Effects Observed in 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 No trends observed for plasma Aβ 42/40 (drug interference testing pending); no consistent trends observed in 10 mg/kg Q4W or 25 mg/kg Q2W pTau18
Slide 23: ACU193 Demonstrates Potential for Best-in-Class Safety
ACU193 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 ARIA-E
Slide 24: Key Takeaways from INTERCEPT-AD
Potential for Differentiated Efficacy Potential for Differentiated Safety INTERCEPT-AD Phase 1 Data Support Potential for ACU193 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 therapeuti
Slide 25: ACU193: Preclinical Data
ACU193: Preclinical Data
Slide 26: ACU193: Extensive Data Package Supporting Development
ACU193: Extensive Data Package Supporting Development ACU193 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 selectivity for
Slide 27: 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 ACU193 to AβOs is unchanged Binding of ACU193 to AβOs >500x binding to Aβ monomer Log [Competing Antigen] μM ACU193 Selectivity ACU193 Selectivity in presence of 5μM monomeric Aβ ACU
Slide 28: ACU193 Binds to a Wide Range of Oligomeric Species of Aβ
Comparison of Aβ species-mAb complex signals across SEC fractions SELECTIVITY ACU193 binds to oligomeric species of A that are differentiated from those bound by hu266 (solanezumab) or hu3D6 (bapineuzumab) ACU193 Binds to a Wide Range of Oligomeric Species of A 28
Slide 29: ACU193 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. ACU193 is Highly Selective for AβOs Versus Aβ Plaques 29 ACU193 staining in human AD brain slices ACU193 (red) binds non-Thioflavin S positive A (green) SELECTIVITY ACU193
Slide 30: 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 ACU193 Prevents Toxicity 30 ACU3B3 prevents AβO inhibition of hippoc
Slide 31: Treatment of a Transgenic Mouse Model of AD Results in Behavioral Improvements
Murine parent version of ACU193 (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 31 Deficits in younger (5-7 months) transgenic mice are markedly reduced with treatment PHA
Slide 32: ACU193 Enters the CNS and Binds to AβOs in Transgenic Mice
ACU193 engages target AβOs in transgenic mouse brain (tg2576) in dose dependent manner; Ability to administer higher doses in patient clinical trials may provide increased target coverage PK/PD ACU193 Enters the CNS and Binds to AOs in Transgenic Mice in Dose Dependent Manner 32 PHARMACOLOGYSELECTI
Slide 33: Clinical Development Plans & Strategic Considerations
Clinical Development Plans & Strategic Considerations
Slide 34: Significant Milestones Achieved in 2023
Significant Milestones Achieved in 2023 ~$283M Cash, cash equivalents and marketable securities as of Sept 30, 2023 Up to $50M Debt financing secured from K2 HealthVentures in November 2023 34 MILESTONES STATUS/ EXPECTED TIMING Proof-of-mechanism topline results ✓ Biomarker results from Phase 1 stud
Slide 35: ALTITUDE-AD Study Design
R a n d o m iz a ti o n 1 :1 :1 ACU193 35mg/kg Q4W (n ~180) ACU193 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 and t
Slide 36: ACU193 Subcutaneous Formulation Under Development 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 • Halozyme’s drug delivery technology, ENHAN
Slide 37: 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 38: ACU193 IP & Market Exclusivity
ACU193 IP & Market Exclusivity • Exclusive, perpetual, irrevocable, worldwide, royalty-free license from Merck to its Amyloid Derived Diffusible Ligand (ADDL) IP including issued ACU193 patents • ACU193 Global IP estate: ✓ Issued patents in 19 countries ✓ Composition of matter patents and methods of
Slide 39: Summary
Summary 39 ✓ Significant and growing Alzheimer's population in need of additional treatment options ✓ ACU193 demonstrates high selectivity for toxic AβOs in AD patients ✓ Highly experienced clinical, regulatory and development leaders driving ACU193's development ✓ Positive Phase 1 data strengthen p
Slide 40: Appendix
Appendix www.acumenpharm.com 40
Slide 41: Aβ PET: Mean Changes in Amyloid Plaque in SAD and MAD Cohorts
Rapid, dose-related, statistically significant reduction of plaque load based on florbetapir PET present in 60 mg/kg Q4W and 25 mg/kg Q2W cohorts Means + SD. Means + SD. +p=0.01 from baseline to endpoint within cohorts 6 (60mg/kg Q4W) and 7 (25mg/kg Q2W); n=6 on placebo, and change observed in place
Slide 42: Significant Correlation Between Change in CSF Neurogranin and pTau181
Significant Correlation Between Change in CSF Neurogranin and pTau181 42 p < 0.0001 • Neurogranin is a synaptic protein that has been shown to modulate glutamatergic neuronal activity and may be linked to enhancement in synaptic plasticity and cognitive function.1,2 • Researchers in the field, such
Slide 43: CSF Biomarker Changes More Closely Related to Target Engagement Than Plaque Reduction
43 r = -0.433 p = 0.011 r = 0.152 p = 0.357 r = 0.219 p = 0.181 Changes in CSF Neurogranin and pTau181 are More Closely Related to Target Engagement (Binding to A Oligomers) Than Plaque Reduction T a rg e t E n g a g e m e n t P la q u e R e d u ct io n r = -0.276 p = 0.115 • These data are consist
Slide 44: Drug Effect on CSF Biomarkers in ApoE4 Homozygotes
Observed Apparent Drug Effect on CSF Biomarkers in the ApoE4 Homozygotes in Line With the Total Participant Population 44 All Participants Individual ApoE4 homozygotes (all patients for PBO) *A larger sample size is needed to know if ApoE4 carrier status has a quantitative effect on response. CSF BI
Slide 45: No Significant Drug Effect on CSF Neuropentraxin 2
No Significant Drug Effect Observed on CSF Levels of Neuropentraxin 2 45 Additional study will be required to understand more about this relatively new biomarker CSF BIOMARKERS
Slide 46: Lecanemab Suggests Plaque Reduction Alone is Insufficient
Lecanemab Phase 2 Suggests Amyloid Plaque Reduction Alone is Insufficient to Optimize Alzheimer's Disease Slowing* 46 *Persistence Of BAN2401-Mediated Amyloid Reductions Post-treatment: A Preliminary Comparison of Amyloid Status Between the Core Phase of BAN2401-G000-201 and Baseline of the Open-Lab
Slide 47: ACU193 Targeting Relative to Late-Stage and Approved Anti-Aβ/Plaque mAbs
47 * IgG1 monoclonal antibodies that bind amyloid plaque are associated with high rates of ARIA-E. See e.g., Plotkin, Neurobiology of Disease, 2020. • There have been no head-to-head clinical trials between any of the product candidates listed above. Study designs and protocols for each product cand
Slide 48: mAb Target Selectivity, Safety and Efficacy Profile Comparison
(1) There have been no head-to-head trials between any of the product candidates listed above. Study designs and protocols for each product candidate were different, and results may not be comparable between product candidates. (2) Goure et al. (2014). Targeting the proper amyloid-beta neuronal toxi
Slide 49: Efficacy Results From Recent Phase 3 Anti-Amyloid mAb AD Studies
Measured Outcome** solanezumab EXPEDITION 3 (Phase 3) aducanumab EMERGE (Phase 3) aducanumab ENGAGE (Phase 3) lecanemab Clarity-AD (Phase 3)+ donanemab TRAILBLAZER-2 (Phase 3)++ (Intermediate & High Tau) donanemab TRAILBLAZER-2 (Phase 3)++ (Intermediate Tau) ADAS-cog -11% -27% -12% -26% -20% -32% AD
Slide 50: Safety Results From Recent Anti-Amyloid mAb AD Studies
TARGETING AB MONOMERS solanezumab EXPEDITION 3 (Phase 3) aducanumab EMERGE (Phase 3) aducanumab ENGAGE (Phase 3) donanemab (Phase 2) donanemab (Phase 3)++ (Intermediate & High Tau) lecanemab (Phase 2) lecanemab (Phase 3)+ PC Treated PC Low High PC Low High PC Treated PC Treated PC High PC Treated AR
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