Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Investor Presentation (September 2022)
35 slides from Acumen Pharmaceuticals's investor presentation, Sep 12, 2022
Slide 1: Corporate Overview September 2022
Exhibit 99.1 Corporate Overview September 2022 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 (Early AD) $ ACU193: First, Alzheimer’s Experienced Phase 1 Clinical Scientific Strong Clinical-Stage Represents an Consensus Leadership Trial in Early AD Balance Sheet: Monoclonal Enormous Market Supports Comp
Slide 4: Acumen Business Strategy – 2022-2025
Acumen Business Strategy – 2022-2025 → 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 – 3Q 2022
INTERCEPT-AD Trial Update – 3Q 2022 • INTERCEPT-AD: Phase 1 clinical trial of ACU193 in patients with early AD (RCT) → Topline results (Proof of Mechanism) following full database lock expected in 1H 2023 § Safety / ARIA-E § PK § Target engagement → Trial enrollment on-going at 15 active sites, 2 ad
Slide 6: AD, Amyloid & Abeta Oligomers
AD, Amyloid & Abeta Oligomers
Slide 7: Alzheimer's Pathophysiology
Alzheimer’s Pathophysiology Build-up of amyloid-beta (Aβ) is believed to lead to neurodegeneration and dementia Previous and current anti-amyloid and related drug targets have attempted to intervene γ secretase Amyloid β (Aβ) Inhibitors Anti-monomer Aβ mAb Amyloid plaque Aβ monomers Anti-amyloid pla
Slide 8: What is an Aβ Oligomer?
What is an Aβ Oligomer? AβOs may consist of 2 to >200 Aβ peptides. Figure 1. AβOs composed of 3 (a) and 18 (b) Aβ peptides are depicted below. (b) (a) ____________________ Sources: Kelley et al. J Chem Physics 2008. Quaternary structures of Aβ oligomers, protofibrils and fibrils Figure 2. Atomic for
Slide 9: Scientific Evidence Supports Anti-AβO Hypothesis
Scientific Evidence Supports Anti-AβO Hypothesis Predominant forms of Aβ in AD: Aβ monomers (non-toxic), AβOs, Aβ fibrils, and amyloid plaques Aβ Oligomers Aβ monomers AβOs bind to neurons, impair synaptic function, contribute to Amyloid plaque impairment of memory and cognition, and plaques serve i
Slide 10: ACU193 Positioning Relative to Late-stage and Approved Anti-Aβ/plaque mAbs
ACU193 Positioning Relative to Late-stage and Approved Anti-Aβ/plaque mAbs crenezumab bapineuzumab* solanezumab IgG4, Ph3 stop, API 1H22 IgG1, Ph3, stop IgG1, Ph3 stop, A4, DIAN Aβ oligomers Aβ protofibrils ACU193 lecanemab donanemab* gantenerumab* aducanumab* IgG2m4, Ph1 IgG1 IgG1 IgG1 IgG1 AAP fil
Slide 11: Positive Signals and Proof of Concept from Recent Phase 2-3 Anti-Amyloid mAb 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 EXPEDITION 3 EMERGE ENGAGE BAN2401 donanemab Measured Outcome** (Phase 3) (Phase 3) (Phase 3) (Phase 2) (Phase 2) ADAS-
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 AB MONOMERS AMYLOID PLAQUES solanezumab aducanumab aducanumab lecanemab donanemab EXPEDITION 3 EMERGE ENGAGE BAN2401 (Phase 2) (Phase 3) (Phase 3) (Pha
Slide 13: ACU193's High Selectivity for toxic AβOs Anticipated to Provide Superior Efficacy
ACU193’s High Selectivity for toxic AβOs, Combined with its Expected Lack of ARIA- related Safety Concerns, Is Anticipated to Provide Superior Efficacy Compared to Peers + TARGET SELECTIVITY SAFETY PROFILE Lack of ARIA-related Company Asset Amyloid plaque Aβ fibrils Aβ monomers Aβ oligomers safety c
Slide 14: ACU193: Our differentiated approach
ACU193: Our differentiated approach
Slide 15: Target Product Profile: ACU193
Target Product Profile: ACU193 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 amyloid plaques. ACU193 is an IgG2m4 subclass mAb which lacks inflammator
Slide 16: ACU193: Extensive Data Package Supporting Development
ACU193: Extensive 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 present in transgen
Slide 17: 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 18: ACU193 has a greater preference for AβOs than other mAbs
SELECTIVITY ACU193 has a greater preference for AβOs than other mAbs Comparison of Aβ species-mAb complex signals across SEC fractions Synthetic AβOs SEC ACU193 binds to a wide range of oligomeric species of Aβ that are differentiated from those bound by hu266 (solanezumab) or hu3D6 (bapineuzumab).
Slide 19: 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 Aβ (green) AD Hippocampus AD Hippocampus ACU193/AβOs species ThioS/amyloid plaque ACU193 has little or no binding to thioflavin S positive fibrillar
Slide 20: 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, AβOs 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 21: 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 Morris Water Maze Open Field MWM swim speed Open field total abnor
Slide 22: ACU193 Enters the CNS and Binds to AβOs in Transgenic Mice
SELECTIVITY PHARMACOLOGY PK/PD ACU193 Enters the CNS and Binds to AβOs in Transgenic Mice in Dose Dependent Manner ACU193 engages target AβOs in transgenic mouse brain (tg2576) in dose dependent manner. Ability to push doses higher in patient clinical trials may provide increased target coverage. 22
Slide 23: Clinical Development Plans
Clinical Development Plans dic
Slide 24: INTERCEPT-AD trial: Phase 1 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 25: INTERCEPT-AD a 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 10mg or Placebo ≥ 1wk COHORT 1: 2 mg/kg
Slide 26: Phase 1 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 ENGA
Slide 27: Cogstate computerized test battery
Cogstate computerized test battery 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 Executive function
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 Literature supports use of ASL to assess hypoperfusion in AD • Mild cognitive impairment patients show hypoperfusion in parietal cortex, precuneus, posterior cingulate cortex and medial temporal lobe • AD patients show global hyp
Slide 29: ACU193 Development Summary
ACU193 Development Summary ⇒ Non-clinical data consistent with toxicity of Aβ oligomers and selective binding of ACU193 to Aβ oligomers – differentiated profile ⇒ Enrollment in a Phase 1study assessing safety, PK and target engagement is ongoing ⇒ Although unlikely with this small sample size, the p
Slide 30: Business Considerations
Business Considerations dic
Slide 31: Acumen Leadership Team
Experienced in AD/neuro drug development ACUMEN LEADERSHIP TEAM ERIC SIEMERS, MD JANICE HITCHCOCK, PHD DANIEL O'CONNELL Chief Medical Officer VP Regulatory Affairs President & CEO ROBERT DEAN, MD, PHD RUSSELL BARTON MATT ZUGA Sr. Development Advisor Chief Operating Officer Chief Financial Officer &
Slide 32: ACU193 IP & Market Exclusivity
ACU193 IP & Market Exclusivity • Exclusive, perpetual, worldwide, royalty-free license from Merck to all Merck Amyloid Derived Diffusible Ligand (ADDL) IP including, issued ACU193 patents • ACU193 Global IP estate: ü Issued patents in 19 countries ü Composition of matter patents and methods of use r
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 ~$210M Initiated Ph1 clinical trial INTERCEPT-AD ü Cash, cash equivalents and marketable securities as of June 30, 2022 INTERCEPT-AD Trial updates 2022 Proof of Mechanism Topline Results 1H 2023 We
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 AβOs Experienced AD drug development team Blue chip investors, very strong balance
Slide 35: Thank you!
Thank you! 35
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