Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Investor Presentation (December 2023)
51 slides from Acumen Pharmaceuticals's investor presentation, Dec 4, 2023
Slide 1: Corporate Presentation December 2023
Corporate Presentation December 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-In-Class Antibody Product for Early Alzheimer's disease
3 Advancing a Potential Best-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 • ACU193: First, clinical-stage monoclonal antibody (mAb) to selectiv
Slide 4: Acumen Business Strategy: 2023 - 2026
Acumen Business Strategy: 2023 - 2026 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: Amyloid Beta Oligomers (AβOs) in Alzheimer's Disease Pathology
6 Amyloid Beta Oligomers (AβOs) in Alzheimer’s Disease Pathology
Slide 7: Toxic AβOs Represent an Ideal Alzheimer's Disease Drug Target
Toxic AβOs Represent an Ideal Alzheimer’s Disease Drug Target 7 AβOs are widely recognized as key pathogenic structures in 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. T., and Klein, W. L., 2011. 4L
Slide 8: ACU193: A Monoclonal Antibody that Selectively Binds Toxic AβOs
• Humanized, affinity matured mAb developed to target toxic Aβ oligomers • >500-fold greater selectivity for AβOs over Aβ monomers • >85-fold selectivity for AbOs over Ab fibrils • IgG2 subclass mAb with reduced effector function • Potential for more selective targeting of AβOs and lower ARIA-E rela
Slide 9: What is an Aβ Oligomer?
9 AbOs May Consist of 2 to >200 Ab PeptidesWhat is an Aβ Oligomer? ____________________ Source: Kelley et al. J Chem Physics 2008. Figure 1. AbOs composed of 3 (a) and 18 (b) Ab peptides are depicted below. ____________________ Source: Relini et al. Biomolecules 2014. Figure 2. Atomic force microsco
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 drug, population, dosing and value proposition
DRUG: ACU193 is a humanized, affinity-matured, mAb with high selectivity for toxic AβOs vs. Aβ monomers (>500x), >85-fold selectivity for AbOs over Ab fibrils ACU193 is an IgG2 subclass mAb which has a reduced effector function. POPULATION: Early AD - Mild Cognitive Impairment and Mild Dementia due
Slide 12: ACU193 selectivity and profile versus other antibodies
(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 13: ACU193: Value Proposition
ACU193: Value Proposition 13 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 Ab therapi
Slide 14: Positive INTERCEPT-AD Phase 1 Results for ACU193
Positive INTERCEPT-AD Phase 1 Results for ACU193
Slide 15: INTERCEPT-AD: A Randomized Placebo Controlled Phase 1 in Early AD patients
INTERCEPT-AD: A Randomized Placebo Controlled Phase 1 in Early AD patients 15 Q2W: Dosing every two weeks; Q4W: Dosing every four weeks. PART A: SINGLE- ASCENDING DOSE n = 8 per cohort (32 total) PART B: MULTIPLE- ASCENDING DOSE n = 10 per cohort (30 total) 3 administrations of drug or placebo; 8:2
Slide 16: Topline results summary: plaque reduction, target engagement, safety
16 Rapid, dose-related, statistically significant amyloid plaque reduction observed at higher doses studied (60 mg/kg Q4W and 25 mg/kg Q2W cohorts)* • Comparable to currently approved Aβ monoclonal antibodies at similar time points in their clinical development First antibody to demonstrate target e
Slide 17: Proof of Mechanism Demonstrated
Proof of Mechanism Demonstrated Low Levels of ARIA-E, Dose-Related Target Engagement, CSF ACU193 Levels Exceeding AbO Levels, Supporting Q4W Dosing 17 Potentially Therapeutic Doses Endpoint Critical Success Factors 10mg/kg 25mg/kg 60mg/kg Safety & Tolerability • Deaths, SAEs Related to Study Drug No
Slide 18: Dose-related reduction of plaque load based on florbetapir PET
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 19: Aβ PET: Individual Patient Changes in Amyloid Plaque
Aβ PET: Individual Patient Changes in Amyloid Plaque in Cohort 6 at 60 mg/kg Q4W and Cohort 7 at 25 mg/kg Q2W 19 Majority of patients in 60 mg/kg Q4W and 25 mg/kg Q2W cohorts showed reductions in plaque load after 63 or 70 days EXPLORATORY MEASURES
Slide 20: Highest Doses of ACU193 Demonstrate Rapid Reduction in Amyloid Plaque
30 40 50 60 70 80 90 Day 0 Day 63 Day 70 Day 90 Highest Doses of ACU193 Demonstrate Rapid Reduction in Amyloid Plaque Reduction Comparable to Lecanemab (in Phase 3) at Similar Timeframe 20 Mean Reduction in Amyloid Plaque (Centiloids) ACU193 60 mg/kg Q4W (n=8)* ACU193 25 mg/kg Q2W (n=8)* Lecanemab 1
Slide 21: ARIA-E Summary for INTERCEPT-AD
SAD MAD 10 mg/kg Cohorts 2, 5 25 mg/kg Cohorts 3, 7 60 mg/kg Cohorts 4, 6 NO ARIA-E Asymptomatic ARIA-E Symptomatic ARIA-E Discontinued ApoE D21 D140 3,4 PBO PBO 3,3 3,3 3,4 3,4 PBO PBO 3,4 3,4 3,4 ApoE D28 D63 D126 3,4 3,3 3,3 4,4 4,4 PBO PBO PBO 3,3 3,4 3,4 3,4 PBO PBO PBO 3,3 ApoE D28 D70 D196 2,
Slide 22: ACU193 Serum PK
ACU193 Serum PK 22 Single Dose Cohorts Multiple Dose Cohorts Serum exposure is dose proportional without accumulation PHARMACOKINETICS Estimated serum terminal T1/2 of 5-7 days
Slide 23: Dose-Related CSF ACU193 Exposure
Dose-Related CSF ACU193 Exposure: Above Endogenous CSF AβO Levels 23 Single Dose Cohorts Multiple Dose Cohorts* CSF exposure is dose & dose-regimen proportional *One patient from Cohort 5 (10 mg/kg Q4W) excluded because only received one administration of drug (study drug discontinued after lacunar
Slide 24: Target Engagement Assessed by Measuring ACU193-AβO Complex in CSF
ACU193 drug specific capture (anti-ACU193 idiotype mAb) 24 Target Engagement Assessed by Measuring ACU193-AbO Complex in CSF AbO selective detection (anti-AbO mAb) Only drug/AbO complex is measurable Novel assay configuration tailored to selectively detect ACU193-AβO complex in CSF as direct measure
Slide 25: Target Engagement of ACU193 with AβOs is Dose Proportional
Target Engagement of ACU193 with AβOs is Dose Proportional 25 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 ) Dose-related target engagement *O
Slide 26: Maximal Target Engagement Response Observed at Higher Doses
Maximal TE Response Observed at Doses of 25 mg/kg Q2W and 60 mg/kg Q4W 26 Single & Multiple Dose Cohorts - Exposure Response Relationship (Emax Model) Emax: 23.2 AU/mL ACU193-AβO complex EC50: 1.43 x 105 pg/mL ACU193 TARGET ENGAGEMENT *One patient from Cohort 5 (10 mg/kg Q4W) excluded because only r
Slide 27: Consistent Drug Effects in CSF Biomarkers in MAD Cohorts
Consistent Drug Effects Observed in the Multiple Ascending Dose Cohorts in the INTERCEPT-AD Trial for CSF Phospho-tau181, Total Tau, Neurogranin and the Ab 42/40 Ratio 27 CSF biomarker changes reinforce downstream pharmacology of ACU193 in addition to the previously presented target engagement and a
Slide 28: Significant Correlation Between Change in CSF Neurogranin and pTau181
Significant Correlation Between Change in CSF Neurogranin and pTau181 28 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 29: Changes in Neurogranin and pTau181 Related to Target Engagement
29 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 Ab 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 30: No Significant Drug Effect Observed on CSF Neuropentraxin 2
No Significant Drug Effect Observed on CSF Levels of Neuropentraxin 2 30 Additional study will be required to understand more about this relatively new biomarker CSF BIOMARKERS
Slide 31: Consistent Drug Effects Observed in Plasma Biomarkers
Consistent Drug Effects Observed in Plasma Biomarkers in the 60 mg/kg Multiple Ascending Dose Cohort 31 50 100 150 -80 -60 -40 -20 0 20 40 60 80 Days after first dose P la s m a G F A P (% c h a n g e f ro m b a s e li n e ) 60 mg/kg Q4W (n = 8) Pooled Q4W Placebo (n = 4) Dose Dose Dose 50 100 150 -
Slide 32: Phase 1 Data Supports Advancing to Phase 2
Phase 1 Data Supports Advancing to Phase 2 Rapid, dose-related, statistically significant amyloid plaque reduction observed within higher dose cohorts Topline results from INTERCEPT-AD trial demonstrated proof-of-mechanism for ACU193, the first clinical stage AβO- targeting antibody ACU193 was well-
Slide 33: ACU193: Preclinical Data
ACU193: Preclinical Data
Slide 34: 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 35: 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 36: 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 Ab that are differentiated from those bound by hu266 (solanezumab) or hu3D6 (bapineuzumab) ACU193 Binds to a Wide Range of Oligomeric Species of Ab 36
Slide 37: 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 37 ACU193 staining in human AD brain slices ACU193 (red) binds non-Thioflavin S positive Ab (green) SELECTIVITY ACU193
Slide 38: AβOs Bind to Neurons and are Toxic; Mouse Analogue Prevents Toxicity
PHARMACOLOGYSELECTIVITY 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 38 ACU3B3 prevents AβO inhibition of hippoc
Slide 39: 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 39 Deficits in younger (5-7 months) transgenic mice are markedly reduced with treatment PHA
Slide 40: 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 AbOs in Transgenic Mice in Dose Dependent Manner 40 PHARMACOLOGYSELECTI
Slide 41: Clinical Development Plans & Strategic Considerations
Clinical Development Plans & Strategic Considerations
Slide 42: 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 43: ACU193 Development Summary
ACU193 Development Summary 43 Differentiated profile: Nonclinical and Phase 1 data consistent with toxicity of Ab oligomers and selective binding of ACU193 to Ab oligomers Positive topline results from Phase1 study assessing safety, PK, and target engagement Anticipate Phase 2 clinical study,
Slide 44: 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 45: 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 45 MILESTONES STATUS/ EXPECTED TIMING Proof-of-mechanism topline results ✓ Biomarker results from Phase 1 stud
Slide 46: 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 Positive Phase 1 clinical data presented in July 2023 Differentiated product candidate targeting toxic AbOs Blue chip investors and
Slide 47: Appendix
Appendix www.acumenpharm.com 47
Slide 48: Apparent 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 48 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.
Slide 49: Lecanemab Phase 2 Suggests Amyloid Plaque Reduction Alone is Insufficient
Lecanemab Phase 2 Suggests Amyloid Plaque Reduction Alone is Insufficient to Optimize Alzheimer's Disease Slowing* 49 *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 50: 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 51: 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
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