Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Investor Presentation (August 2021)
33 slides from Acumen Pharmaceuticals's investor presentation, Aug 31, 2021
Slide 1: Corporate Overview 3Q 2021
Corporate Overview 3Q 2021 Exhibit 99.1
Slide 2: Acumen Safe Harbor Statement
Acumen Safe Harbor Statement NOTES REGARDING THIS PRESENTATION This presentation may contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, operations, and financial conditions, including but not limited to current be
Slide 3: Advancing a Potential Best-In-Class Antibody for Early Alzheimer's Disease
Acumen: Advancing a Potential Best-In-Class Antibody for Early Alzheimer’s disease (Early AD) AD Represents an Enormous Market Driven by High Unmet Need and Recent Scientific and Regulatory Momentum Growing Scientific Consensus Supports Amyloid-Beta Oligomers (AβOs) as the Most Neurotoxic Form of Aβ
Slide 4: Acumen Leadership Team
Experienced in AD drug development ACUMEN LEADERSHIP TEAM DANIEL O'CONNELL President & CEO JANICE HITCHCOCK, PHD VP Regulatory Affairs RUSSELL BARTON Chief Operating Officer JASNA JERECIC, PHD Analytical Methods Leader, Research Scientist ERIC SIEMERS, MD Chief Medical Officer ROBERT DEAN, MD, PHD S
Slide 5: Aduhelm Approved under Accelerated Approval Pathway
Aduhelm Approved under Accelerated Approval Pathway First disease-modifying drug approved for Alzheimer’s Approved under accelerated approval based on reduction in amyloid beta plaques1 ____________________ 1https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761178s000lbl.pdf Aduhelm approval
Slide 6: Growing Interest in the Anti-AβO Hypothesis
The only approved antibody for AD preferentially targets amyloid plaques with only limited effects on oligomeric forms of Aβ. Acumen’s drug candidate ACU193 targets AbOs. Growing Interest in the Anti-AβO Hypothesis Growing understanding of disease mechanisms indicate that AβOs are the most toxic Aβ
Slide 7: ACU193 Positioning Relative to Late-stage and Approved Anti-Aβ/plaque mAbs
ACU193 Positioning Relative to Late-stage and Approved Anti-Ab/plaque mAbs * IgG1 monoclonal antibodies that bind amyloid plaque are associated with high rates of ARIA-E solanezumab IgG1, Ph3 stop, A4, DIAN lecanemab/BAN2401 IgG1, Ph3 Aduhelm/aducanumab* IgG1, Approved 7-Jun-21 ACU193 IgG2m4, Ph1a/b
Slide 8: Upcoming Milestones: ACU193 Development Plan
Upcoming Milestones: ACU193 Development Plan Expected to Demonstrate Proof of Mechanism by YE 2022 ACU193 Phase 1 Proof of Mechanism results are expected to inform dose selection and regulatory strategy for the Phase 2/3 trial 2023 2022 2021 Open IND Initiate Ph1a/b trial YE 2022: Report Ph1a/b Proo
Slide 9: AD Drug Development: Amyloid Hypothesis
AD Drug Development: Amyloid Hypothesis CONFIDENTIAL & PROPRIETARY
Slide 10: AD is One of the World's Largest Unmet Medical Needs
AD is One of the World’s Largest Unmet Medical Needs AD is a progressive, uniformly fatal neurodegenerative disorder and is the most common form of dementia Memory loss is the key symptom of AD In advanced stages of the disease, complications from severe loss of brain function — such as dehydration,
Slide 11: Amyloid β oligomers are the most toxic species
Emerging data indicate that amyloid β oligomers are the most toxic species and should be preferentially targeted for removal Aβ fibrils Alzheimer’s Pathophysiology Previous and current anti-amyloid and related drug targets have attempted to intervene BACE inhibitors Build-up of amyloid-beta (Ab) is
Slide 12: Recent anti-amyloid mAb results establish biological foothold
Recent anti-amyloid mAb results (anti-Ab/plaque) establish biological foothold for treating disease EFFICACY: Reduced cognitive decline ~11% - 47% at ~18 months TARGET ENGAGEMENT: Positive effects on imaging and fluid biomarkers Potential for current generation anti-Ab/plaque mAbs to serve as ‘first
Slide 13: Percent Slowing of Cognitive/Functional Decline in Phase 2-3 Studies
Measured Outcome** solanezumab EXPEDITION 3 (Phase 3) aducanumab EMERGE (Phase 3) aducanumab ENGAGE (Phase 3) lecanemab BAN2401 (Phase 2) donanemab (Phase 2) ADAS-cog -11% -27% -12% -47% -39% ADCS-ADL -15% -40% -18% N.A. -23% CDR-SB -15% -23% 2% -26% -23% MMSE -13% -15% 3% N.A. -21% iADRS -11% N.A.
Slide 14: ARIA-E Rates in Anti-Amyloid mAb Studies
TARGETING AB MONOMERS TARGETING AMYLOID PLAQUES solanezumab EXPEDITION 3 (Phase 3) aducanumab EMERGE (Phase 3) aducanumab ENGAGE (Phase 3) lecanemab BAN2401 (Phase 2) donanemab (Phase 2) PC Treated PC Low High PC Low High PC High PC Treated ARIA-E 0.2% 0.1% 2.2% 26.1% 34.4% 3.0% 25.6% 35.7% 0.8% 9.9
Slide 15: ACU193's High Selectivity for AβOs and Expected Lack of ARIA
ACU193’s High Selectivity for AβOs, Combined with its Expected Lack of ARIA-related Safety Concerns, Is Anticipated to Provide Superior Efficacy Compared to Peers TARGET SELECTIVITY+ SAFETY PROFILE Company Asset Amyloid plaque Aβ fibrils Aβ monomers Aβ oligomers Lack of ARIA ACU193 û untested û ü ü
Slide 16: ACU193: Our differentiated approach
ACU193: Our differentiated approach CONFIDENTIAL & PROPRIETARY
Slide 17: ACU193 is a humanized, affinity-matured mAb selective for toxic AβOs
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 inflammatory effector functions of other IgG subclasses. POPULATION: Early AD - Mild Cognitive Impairment and Mild Dementi
Slide 18: 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 Binds broad range of endogenous AβOs present in transgenic mice and huma
Slide 19: What is an Aβ Oligomer?
AbOs may consist of 2 to >200 Ab peptides. AbOs composed of 3 (a) and 18 (b) Ab peptides are depicted below. ____________________ Sources: Kelley et al. J Chem Physics 2008. What is an Aβ Oligomer? AbOs are present in brain in a wide range of sizes (a) (b)
Slide 20: ACU193 is the First mAb Developed to Selectively Target AβOs
Even in the presence of a large excess of Aβ monomer, binding of ACU193 to AβOs is unchanged Highly selective for Aβ oligomers versus Aβ monomers ACU193 is the First mAb Developed to Selectively Target AβOs Binding of ACU193 to AβOs >500x binding to Aβ monomer SELECTIVITY ACU193 selective binding to
Slide 21: ACU193 has a greater preference for AβOs than other mAbs
ACU193 has a greater preference for AbOs than other mAbs Comparison of Aβ species-mAb complex signals across SEC fractions SELECTIVITY ACU193 binds to a wide range of oligomeric species of Ab that are differentiated from those bound by hu266 (solanezumab) or hu3D6 (bapineuzumab) Synthetic AbOs SEC
Slide 22: ACU193 is highly selective for AβOs versus Aβ plaques
AD Hippocampus ThioS/amyloid plaque AD Hippocampus ACU193/AbOs species ____________________ Sources: E. Cline et al. CTAD 2019. 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) SELECTIVITY ACU193 ha
Slide 23: AβOs Bind to Neurons and are Toxic; mouse analogue prevents toxicity
PHARMACOLOGY SELECTIVITY After binding to neurons, AbOs 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 ACU3B3 prevents AβO inhibition of hippocam
Slide 24: Treatment of a Transgenic Mouse Model of AD Results in Behavioral Improvements
Murine version of ACU193 (3B3) 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 Deficits in younger (5-7 months) transgenic mice are markedly reduced with treatment PHARMACOLOGY SEL
Slide 25: 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 push doses higher in patient clinical trials may provide increased target coverage. PK/PD ACU193 Enters the CNS and Binds to AbOs in Transgenic Mice in Dose Dependent Manner PHARMACOLOGY SELECTIVITY
Slide 26: Clinical Development Plans
Clinical Development Plans CONFIDENTIAL & PROPRIETARY
Slide 27: Phase Overview
Phase 1 Overview TRIAL DESIGN: Randomized Placebo Controlled Phase 1a/b Part A : Single-Ascending Doses Part B : Multiple-Ascending Doses ENROLLMENT CRITERIA: Early AD Mild Cognitive Impairment and Mild Dementia due to AD (amyloid positive by PET) TRIAL OBJECTIVES: Proof of Mechanism (PoM) Safety an
Slide 28: Randomized Placebo Controlled Phase 1a/b in Early AD Patients
Randomized Placebo Controlled Phase 1a/b in Early AD patients - Started 2Q 2021 PART A: SINGLE- ASCENDING DOSE n = 8 per cohort (32 total) PART B: MULTIPLE- ASCENDING DOSE n = 10 per cohort (30 total) COHORT 1: 2 mg/kg ACU193 or Placebo 2mg COHORT 2: 10 mg/kg ACU193 or Placebo 10mg COHORT 3: 25 mg/k
Slide 29: Phase Objectives: Proof of Mechanism
Phase 1 Objectives: Proof of Mechanism PROOF OF MECHANISM Requirements for Phase 2/3 Acceptable safety and tolerability Show ACU193 gets into central compartment Target engagement Other indicators of target mechanism of action 1. SAFETY AND TOLERABILITY Assessment of ARIA-E Absence of problematic im
Slide 30: ACU193 IP & Market Exclusivity; Commercial Considerations
ACU193 IP & Market Exclusivity; Commercial Considerations 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: Issued patents in 17 countries, pending in 2 countries Composi
Slide 31: Well Capitalized to Achieve Important Clinical Development Milestones
Acumen is Well Capitalized to Achieve Important Clinical Development Milestones MILESTONES STATUS/EXPECTED TIMING IND submission ü Initiated Ph1a/b clinical trial ü Ph1a/b trial updates Periodic 2021-2022 Ph1a/b Proof of Mechanism Top-Line results YE 2022 Initiate Ph2/3 Clinical trial 2023 $235m Pro
Slide 32: Board of Directors and Advisory Board
Experienced in AD drug development BOARD OF DIRECTORS JEFF IVES, PHD Director, Strategic Advisor SEAN STALFORT Chairman President, PBM Capital NATHAN FOUNTAIN, MD Professor, Department of Neurology, University of Virginia JEFFREY SEVIGNY, MD Chief Medical Officer, Prevail Therapeutics DANIEL O'CONNE
Slide 33: Advancing a Potential Best-In-Class Antibody for Early Alzheimer's Disease
Acumen: Advancing a Potential Best-In-Class Antibody for Early Alzheimer’s disease (Early AD) AD Represents an Enormous Market Driven by High Unmet Need and Recent Scientific and Regulatory Momentum Growing Scientific Consensus Supports Amyloid-Beta Oligomers (AβOs) as the Most Neurotoxic Form of Aβ
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