Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Investor Presentation (May 2023)
37 slides from Acumen Pharmaceuticals's investor presentation, May 9, 2023
Slide 1: Corporate Presentation May 2023
Corporate Presentation May 2023 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-/First-In-Class Antibody for Early Alzheimer's Disease
3 Advancing a Potential Best-/First-In-Class Antibody Product for Early Alzheimer’s disease (AD) • Large market • High unmet need • Recent scientific & regulatory momentum • Amyloid-beta oligomers (AβOs) accepted as most toxic form of Aβ • Novel target for effective AD treatment ACU193: First, clini
Slide 4: Acumen Business Strategy: 2023 - 2025
Acumen Business Strategy: 2023 - 2025 4 → Rapidly advance ACU193 through clinical development in patients with early AD; → Evaluate combination approaches to complement our core ACU193 monotherapy strategy; → Expand our product portfolio by in-licensing and/or developing additional candidates and/or
Slide 5: AD, Amyloid & Abeta Oligomers
AD, Amyloid & Abeta Oligomers
Slide 6: Alzheimer's Pathophysiology
Alzheimer’s Pathophysiology 6 Previous and current anti-amyloid and related drug targets have attempted to intervene Build-up of amyloid-beta (Aβ) is believed to lead to neurodegeneration and dementia Aβ fibrils BACE inhibitors Anti-amyloid plaque mAb Tau destabilization Symptomatic and neuroprotect
Slide 7: AβOs are the most toxic Aβ species
7 Growing understanding of disease mechanisms indicate that AβOs are the most toxic Aβ species and have the potential to be an ideal target for effective AD therapy AβOs bind to neurons, impair synaptic function, contribute to impairment of memory and cognition, and induce tau hyper phos- phorylatio
Slide 8: What is an Aβ Oligomer?
8 AβOs May Consist of 2 to >200 Aβ PeptidesWhat is an Aβ Oligomer? ____________________ Source: Kelley et al. J Chem Physics 2008. Figure 1. AβOs composed of 3 (a) and 18 (b) Aβ peptides are depicted below. ____________________ Source: Relini et al. Biomolecules 2014. Figure 2. Atomic force microsco
Slide 9: Toxic AβOs Represent an Ideal Alzheimer's Disease Drug Target
10 Toxic AβOs Represent an Ideal Alzheimer’s Disease Drug Target Targeting the right form of amyloid may be a key to slowing disease progression in early AD 1Cleary et al., 2005; Townsend et al., 2006; Poling et al., 2008; Reed et al., 2011; Batista et al., 2018. 2Shankar et al., 2007. 3Ferreira, S.
Slide 10: ACU193 Positioning Relative to Late-Stage and Approved Anti-Aβ/Plaque mAbs
10 * 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 11: ACU193 selectivity and expected lower ARIA versus peers
12 ACU193’s high selectivity for toxic AβOs, combined with its expected lower rate of ARIA, is anticipated to provide superior efficacy and safety compared to peers (1) There have been no head-to-head trials between any of the product candidates listed above. Study designs and protocols for each pro
Slide 12: ACU193: Our Differentiated Approach
ACU193: Our Differentiated Approach
Slide 13: ACU193 drug profile: selective mAb for toxic AβOs
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 which has a reduced effector function. POPULATION: Early AD - Mild Cognitive Impairment and Mild Dementia due t
Slide 14: 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 15: 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 16: 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 Aβ that are differentiated from those bound by hu266 (solanezumab) or hu3D6 (bapineuzumab) ACU193 Binds to a Wide Range of Oligomeric Species of Aβ 16
Slide 17: ACU193 is Highly Selective for AβOs Versus Aβ Plaques
AD Hippocampus ThioS/amyloid plaque AD Hippocampus ACU193/AβOs species ____________________ Sources: E. Cline et al. CTAD 2019. ACU193 is Highly Selective for AβOs Versus Aβ Plaques 17 ACU193 staining in human AD brain slices ACU193 (red) binds non-Thioflavin S positive Aβ (green) SELECTIVITY ACU193
Slide 18: AβOs Bind to Neurons and are Toxic; Mouse Analogue Prevents Toxicity
PHARMACOLOGYSELECTIVITY After binding to neurons, AβOs 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 18 ACU3B3 prevents AβO inhibition of hippoc
Slide 19: Treatment of a Transgenic Mouse Model 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 19 Deficits in younger (5-7 months) transgenic mice are markedly reduced with treatment PHA
Slide 20: 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 AβOs in Transgenic Mice in Dose Dependent Manner 20 PHARMACOLOGYSELECTI
Slide 21: Clinical Development Plans
Clinical Development Plans
Slide 22: INTERCEPT-AD Trial: Phase Overview
(ACU-001) INTERCEPT-AD Trial: Phase 1 Overview TRIAL DESIGN: Randomized Placebo Controlled Phase 1 • 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: P
Slide 23: INTERCEPT-AD Randomized Placebo Controlled Phase 1 in Early AD
INTERCEPT-AD a Randomized Placebo Controlled Phase 1 in Early AD patients 23 *On January 30, 2023, Acumen submitted a protocol amendment to FDA to reduce the dose in Cohort 7 to 25 mg/kg Q2W from 60 mg/kg Q2W. This was based on a blinded review of preliminary pharmacokinetic data, inclusive of plasm
Slide 24: INTERCEPT-AD Trial Update – February 2023
24 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 completed in February 2023 → Coh
Slide 25: Phase Objectives: Proof of Mechanism
Phase 1 Objectives: Proof of Mechanism – Ability to Move to Phase 2/3 PROOF OF MECHANISM Requirements for Phase 2/3 ✓ Acceptable safety and tolerability ✓ Show ACU193 gets across the blood brain barrier and into central compartment ✓ Target engagement 1. SAFETY AND TOLERABILITY • Assessment of ARIA-
Slide 26: CSF Target Engagement Assay
26 CSF Target Engagement Assay (CSF-TE) Expected to Show Presence of ACU193-AβO Complex Unique assay configuration tailored to detect ACU193-AβO complex in CSF MSD S-PLEX (Turbo) Immunoassay AβO selective detection (anti-AβΟ mAb) Only drug/oligomer complex is measurable ACU193 drug specific capture
Slide 27: Cogstate computerized test battery
Cogstate computerized test battery (exploratory) Test Domains tested Time (minutes) International shopping list test (immediate) Immediate recall 5 Cogstate brief battery Attention, working memory, learning 15 International shopping list test (delayed) Delayed recall 1 Groton maze learning test Exec
Slide 28: Arterial Spin Labelling 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 29 ⇒ Differentiated profile: Nonclinical data consistent with toxicity of Aβ oligomers and selective binding of ACU193 to Aβ oligomers ⇒ Topline results from Phase1 study assessing safety, PK, and target engagement expected in Q3 2023 ⇒ Although unlikely with this small sa
Slide 30: Business Considerations
Business Considerations
Slide 31: 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 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 of
Slide 33: Acumen is Well Capitalized, With Expected Cash Runway Through 2025
Acumen is Well Capitalized, With Expected Cash Runway Through 2025 We believe that Acumen has the organizational expertise and cash and marketable securities on hand to advance ACU193 through 2025 ~$184M Cash, cash equivalents and marketable securities as of March 31, 2023 33 MILESTONES STATUS/ EXPE
Slide 34: ABOS: Key Takeaways
ABOS: Key Takeaways Experienced AD drug development team Massive unmet need in AD, recent favorable trends and cumulative learnings position field for future successes Upcoming sector catalysts throughout 2023 Differentiated product candidate targeting toxic AβOs Blue chip investors, very strong bal
Slide 35: Appendix
Appendix www.acumenpharm.com
Slide 36: Positive Signals 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 37: Anti-Plaque mAbs Demonstrate Dose-Related ARIAs
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
Acumen Pharmaceuticals — Investor Presentation (May 2023) on 6ix