Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Investor Presentation (February 2023)
35 slides from Acumen Pharmaceuticals's investor presentation, Feb 1, 2023
Slide 1: Corporate Presentation February 2023
Exhibit 99.1 Corporate Presentation February 2023 1
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
Slide 3: Advancing a Potential Best-/First-In-Class Antibody for Early Alzheimer's Disease
Advancing a Potential Best-/First-In-Class Antibody Product for Early Alzheimer’s disease (AD) $ Alzheimer’s Scientific Experienced Strong Phase 1 Clinical ACU193: First, Represents an Consensus Clinical-Stage Leadership Team Balance Sheet: Trial in Early AD Enormous Market Supports Amyloid- Monoclo
Slide 4: Acumen Business Strategy: 2023 - 2025
Acumen Business Strategy: 2023 - 2025 → Rapidly advance ACU193 through clinical development in patients with early AD; → Evaluate combination approaches to complement our core ACU193 monotherapy strategy; → Selectively explore potential of ACU193 for other diseases; → Expand our product portfolio by
Slide 5: INTERCEPT-AD Trial Update – February 2023
INTERCEPT-AD Trial Update – February 2023 • INTERCEPT-AD: Phase 1 clinical trial of ACU193 in patients with early Alzheimer’s disease (AD) (RCT) → Topline results, safety and clinical proof-of-mechanism following full database lock expected in Q3 2023 → Enrollment expected to be complete in Q1 2023
Slide 6: INTERCEPT-AD Randomized Placebo Controlled Phase 1 in Early AD Patients
INTERCEPT-AD a Randomized Placebo Controlled Phase 1 in Early AD patients 60mg COHORT 4: ≥ 1wk 60 mg/kg ACU193 PART A: or Placebo SINGLE- COHORT 3: ASCENDING DOSE 25mg ≥ 1wk 25 mg/kg ACU193 n = 8 per cohort (32 total) or Placebo COHORT 2: ≥ 1wk 10 mg/kg ACU193 ≥ 1wk 10mg or Placebo ≥ 1wk COHORT 1: 2
Slide 7: AD, Amyloid & Abeta Oligomers
AD, Amyloid & Abeta Oligomers
Slide 8: Alzheimer's Pathophysiology
Alzheimer’s Pathophysiology Build-up of amyloid-beta (Ab) is believed to lead to neurodegeneration and dementia Previous and current anti-amyloid and related drug targets have attempted to intervene g secretase Amyloid β (Aβ) Inhibitors Anti- Ab monomer mAb Amyloid plaque Aβ monomers Anti-amyloid pl
Slide 9: Scientific Evidence Supports AβO Hypothesis
Scientific Evidence Supports AβO Hypothesis Predominant forms of Ab in AD: Ab monomers (non-toxic), AbOs, Ab fibrils, and amyloid plaques Aβ monomers Aβ oligomers AβOs bind to neurons, impair synaptic function, contribute to Amyloid plaque impairment of memory and cognition, and plaques serve induce
Slide 10: What is an Aβ Oligomer?
What is an Aβ Oligomer? AbOs May Consist of 2 to >200 Ab Peptides Figure 1. AbOs composed of 3 (a) and 18 (b) Ab peptides are depicted below. (a) (b) ____________________ Source: Kelley et al. J Chem Physics 2008. Quaternary structures of Aβ oligomers, protofibrils, and fibrils Figure 2. Atomic forc
Slide 11: Positive Signals and Proof of Concept From Recent Phase 2-3 Anti-Amyloid mAb AD Studies
Positive Signals and Proof of Concept From Recent Phase 2-3 Anti-Amyloid mAb AD Studies Percent Slowing of Cognitive/Functional Decline* solanezumab aducanumab aducanumab lecanemab lecanemab EXPEDITION 3 EMERGE ENGAGE donanemab BAN2401 Clarity-AD + Measured Outcome** (Phase 3) (Phase 3) (Phase 3) (P
Slide 12: Anti-Plaque mAbs Demonstrate Dose-Related ARIAs That Will Likely Limit Their Use
Anti-Plaque mAbs Demonstrate Dose-Related ARIAs That Will Likely Limit Their Use Percent of ARIA Events for Anti-Aβ/plaque mAbs* TARGETING TARGETING TARGETING AB MONOMERS AMYLOID PLAQUES PROTOFIBRILS solanezumab aducanumab aducanumab lecanemab lecanemab donanemab EXPEDITION 3 EMERGE ENGAGE BAN2401 B
Slide 13: ACU193 Positioning Relative to Late-Stage and Approved Anti-Ab/Plaque mAbs
ACU193 Positioning Relative to Late-Stage and Approved Anti-Ab/Plaque mAbs bapineuzumab* solanezumab crenezumab IgG1, Ph3 stop, A4, DIAN negative IgG1, Ph3 stop IgG4, Ph3 stop, API negative Aβ oligomers Aβ protofibrils ACU193 aducanumab* lecanemab donanemab* gantenerumab* IgG2, Ph1 IgG1 IgG1 IgG1 Ig
Slide 14: ACU193's High Selectivity for Toxic AβOs and Expected Low Rate of ARIA
ACU193’s High Selectivity for Toxic AβOs, Combined With its Expected Low Rate of ARIA, is Anticipated to Provide Superior Efficacy Compared to Peers + TARGET SELECTIVITY SAFETY PROFILE Company Asset Amyloid plaque Aβ fibrils Aβ monomers Aβ oligomers Low rate of ARIA ACU193 û untested Expected û ✓ TM
Slide 15: ACU193: Our Differentiated Approach
ACU193: Our Differentiated Approach
Slide 16: ACU193 Target Product Profile: Best-in-Class, 1st Line, Anti-AβO Immunotherapy for Early AD
ACU193 Target Product Profile: Best-in-Class, 1st Line, Anti-AβO, Disease- Modifying Immunotherapy for Early AD DRUG: ACU193 is a humanized, affinity-matured, mAb with high selectivity for toxic AβOs vs. Aβ monomers (>500x) and limited to no binding to amyloid plaques. ACU193 is an IgG2 subclass mAb
Slide 17: ACU193: Extensive Pre-Clinical Data Package Supporting Development
ACU193: Extensive Pre-Clinical Data Package Supporting Development — Nanomolar affinity for AβOs, >500-fold greater selectivity for AβOs over Aβ monomer, with limited or no discernable binding to vascular amyloid or dense core amyloid plaques SELECTIVITY — Binds broad range of endogenous AβOs presen
Slide 18: ACU193 is the First mAb Developed to Selectively Target AβOs
SELECTIVITY ACU193 is the First mAb Developed to Selectively Target AβOs Highly selective for Aβ oligomers versus Aβ monomers ACU193 Selectivity in presence of ACU193 Selectivity 5μM monomeric Aβ Log [Competing Antigen] μM ACU193 Log μM Even in the presence of a large excess of Aβ monomer, Binding o
Slide 19: ACU193 Has a Greater Preference for AβOs Than Other mAbs
SELECTIVITY ACU193 Has a Greater Preference for AbOs Than Other mAbs Comparison of Aβ species-mAb complex signals across SEC fractions ACU193 binds to a wide range of oligomeric species of Ab that are differentiated from those bound by hu266 (solanezumab) or hu3D6 (bapineuzumab). 19
Slide 20: ACU193 is Highly Selective for AβOs Versus Aβ Plaques
SELECTIVITY ACU193 is Highly Selective for AβOs Versus Aβ Plaques ACU193 staining in human AD brain slices ACU193 (red) binds non-Thioflavin S positive Ab (green) AD Hippocampus AD Hippocampus ThioS/amyloid plaque ACU193/AbOs species ACU193 has little or no binding to thioflavin S positive fibrillar
Slide 21: AβOs Bind to Neurons and are Toxic; Mouse Analogue of ACU193 Prevents Toxicity
SELECTIVITY PHARMACOLOGY AβOs Bind to Neurons and are Toxic; Mouse Analogue of ACU193 Prevents Toxicity After binding to neurons, AbOs disrupt Long Term Potentiation (LTP) and cause pathologic increases in intracellular calcium that is destructive to cells. ACU3B3 prevents AβO inhibition of ACU3B3 p
Slide 22: Treatment of a Transgenic Mouse Model of AD Results in Behavioral Improvements
SELECTIVITY PHARMACOLOGY 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 MWM swim speed Open field total abnormality distance measurement,
Slide 23: ACU193 Enters the CNS and Binds to AβOs in Transgenic Mice
SELECTIVITY PHARMACOLOGY PK/PD ACU193 Enters the CNS and Binds to AbOs in Transgenic Mice in Dose Dependent Manner 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 covera
Slide 24: Clinical Development Plans
Clinical Development Plans io
Slide 25: INTERCEPT-AD Trial: Phase Overview
(ACU-001) INTERCEPT-AD Trial: Phase 1 Overview TRIAL Randomized Placebo Controlled Phase 1 DESIGN: • Part A : Single-Ascending Doses • Part B : Multiple-Ascending Doses ENROLLMENT Early AD CRITERIA: • Mild Cognitive Impairment and Mild Dementia due to AD (amyloid positive by PET) TRIAL Proof of Mech
Slide 26: Phase Objectives: Proof of Mechanism – Ability to Move to Phase 2/3
Phase 1 Objectives: Proof of Mechanism – Ability to Move to Phase 2/3 1. SAFETY AND TOLERABILITY • Assessment of ARIA-E • Absence of problematic immunogenicity PROOF OF MECHANISM 2. PHARMACOKINETICS Requirements for Phase 2/3 • Peripheral and Central ✓ Acceptable safety and 3. EVIDENCE OF TARGET ENG
Slide 27: Cogstate computerized test battery (exploratory)
Cogstate computerized test battery (exploratory) Test Domains tested Time (minutes) International shopping list test Immediate recall 5 (immediate) Cogstate brief battery Attention, working memory, 15 learning International shopping list test (delayed) Delayed recall 1 Groton maze learning test Exec
Slide 28: Arterial Spin Labelling (ASL) as an MRI Measure of Cerebral Blood Flow
Arterial Spin Labelling (ASL) as an MRI Measure of Cerebral Blood Flow • Mild cognitive impairment patients show hypoperfusion in parietal cortex, precuneus, posterior cingulate cortex and medial temporal lobe • AD patients show global hypoperfusion, but especially cingulate, precuneus, parietal lob
Slide 29: ACU193 Development Summary
ACU193 Development Summary Þ Differentiated profile: Nonclinical data consistent with toxicity of Ab oligomers and selective binding of ACU193 to Ab oligomers Þ Enrollment in an ongoing Phase 1 study assessing safety, PK, and target engagement is expected to be complete in Q1 2023 Þ Although unlikel
Slide 30: Business Considerations
Business Considerations io
Slide 31: Acumen Leadership Team Experienced in AD/Neuro Drug Development
Acumen Leadership Team Experienced in AD/Neuro Drug Development ERIC SIEMERS, MD JANICE HITCHCOCK, PHD MATT ZUGA DANIEL O'CONNELL Chief Medical Officer VP, Regulatory Affairs Chief Financial Officer & President & CEO Chief Business Officer RUSSELL BARTON ROBERT DEAN, MD, PHD LIEAN SCHENK SIEW TIN GA
Slide 32: 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 o
Slide 33: Acumen is Well Capitalized, With Expected Cash Runway Through 2025
Acumen is Well Capitalized, With Expected Cash Runway Through 2025 STATUS/ MILESTONES EXPECTED TIMING ~$200M Initiated Ph1 clinical trial INTERCEPT-AD ✓ Cash, cash equivalents and marketable securities as of September 30, 2022 INTERCEPT-AD enrollment complete Q1 2023 Proof-of-mechanism topline resul
Slide 34: ABOS: Key Takeaways
ABOS: Key Takeaways Massive unmet need in AD, recent favorable trends and cumulative learnings position field for future successes Upcoming sector catalysts 2H22 - 1H23 Differentiated product candidate targeting toxic AbOs Experienced AD drug development team Blue chip investors, very strong balance
Slide 35: Thank You
Thank You
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