Slide 1: Investor Conference Call to Discuss INTERCEPT-AD Results
Investor Conference Call to Discuss INTERCEPT-AD Results July 17, 2023 Exhibit 99.2
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: Agenda
Agenda Introduction Alex Braun, Head of Investor Relations ACU193 & INTERCEPT-AD Topline Results Dan O’Connell, Chief Executive Officer Dr. Eric Siemers, Chief Medical Officer Topline Results Q&A Dr. Eric Siemers, Chief Medical Officer Dr. Steven DeKosky, Deputy Director of the McKnight Brain Instit
Slide 4: ACU193: Novel mAb Targeting Amyloid Beta Oligomers
ACU193: Novel mAb Targeting Amyloid Beta Oligomers (AβOs), the Most Toxic Form of Aβ
Slide 5: 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 relative to Aβ
Slide 6: Key topline findings: plaque reduction, target engagement, safety
Rapid, dose-related, statistically significant amyloid plaque reduction observed at higher doses studied (60 mg/kg Q4W and 25 mg/kg Q2W cohorts)* at 6-12 weeks Comparable to currently approved Aβ monoclonal antibodies at similar time points in their clinical development First antibody to demonstrate
Slide 7: Highest Doses of ACU193 Demonstrate Rapid Amyloid Plaque Reduction Comparable to Lecanemab
Highest Doses of ACU193 Demonstrate Rapid Reduction in Amyloid Plaque Reduction Comparable to Lecanemab (in Phase 3) at Similar Timeframe Mean Reduction in Amyloid Plaque (Centiloids) ACU193 60 mg/kg Q4W (n=8)* ACU193 25 mg/kg Q2W (n=8)* Lecanemab 10 mg/kg Q2W (n=344) Indexed Values Absolute Values
Slide 8: Low ARIA-E at Elevated Single Doses Enables Broad Therapeutic Index
Low ARIA-E at Elevated Single Doses Enables Broad Therapeutic Index Lower Doses Aducanumab1 (30 mg/kg) Donanemab2 (20 mg/kg) Lecanemab3 (15 mg/kg) ACU1934,5 (25 mg/kg) ARIA-E rate 0% (0/6) 28.6% (2/7) 0% (0/6) 0% (0/6) Higher doses Ferrero et al. Alzheimer’s & Dementia: Translational Research & Clin
Slide 9: Proof of Mechanism Achieved
Proof of Mechanism Achieved Low Levels of ARIA-E, Dose-Related Target Engagement, CSF ACU193 Levels Exceeding AbO Levels, Supporting Q4W Dosing Potentially Therapeutic Doses Endpoint Critical Success Factors 10mg/kg 25mg/kg 60mg/kg Safety & Tolerability Deaths, SAEs Related to Study Drug None None N
Slide 10: INTERCEPT-AD Summary
INTERCEPT-AD Summary Robust and well-designed study with well established (PK, ARIA) and novel endpoints (AβO target engagement, COGState/ASL) Execution 60 patients enrolled, no training difficulties observed Proof-of-Mechanism achieved and new learnings demonstrated through statistically signific
Slide 11: INTERCEPT-AD Topline Results
INTERCEPT-AD Topline Results
Slide 12: INTERCEPT-AD: A Randomized Placebo Controlled Phase in Early AD Patients
INTERCEPT-AD: A Randomized Placebo Controlled Phase 1 in Early AD patients 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 per
Slide 13: INTERCEPT-AD Baseline Characteristics
INTERCEPT-AD Baseline Characteristics Characteristic ACU193 N=48 Placebo N=14 Age, mean (SD) 72.3 (7.9) 71.5 (7.5) Gender Female, n (%) 27 (56.3) 7 (50) Race Caucasian, n (%) 46 (95.8) 14 (100) Ethnicity non-Latino, n (%) 41 (85.4) 13 (92.9) BMI, mean (SD) 28.0 (5.4) 28.9 (5.7) MMSE, mean (SD) 24.1
Slide 14: Treatment Emergent SAEs
Treatment Emergent SAEs All SAEs for patients taking ACU193 were deemed unrelated or unlikely related by the site Principal Investigator Treatment Assignment SAE Verbatim Severity Relationship Action Taken Outcome 10mg/kg (Cohort 5, MAD) Ovarian Fibroma 3 Not Related Dose Not Changed Resolved 10mg/k
Slide 15: 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 16: Safety Update: ARIA-E, Total Cases
Safety Update: ARIA-E, Total 5 Cases Of 5 total ARIA-E cases, 1 was symptomatic (2.1% overall) and symptoms resolved with resolution of radiographic ARIA-E; All cases showed radiographic resolution or improvement SAFETY Cohort ApoE4 Gender Age Baseline/Endpoint Plaque Load (Centiloids) Severity by F
Slide 17: Aβ PET: Mean Changes in Amyloid Plaque in SAD and MAD Cohorts
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. Error bars shown only for pooled placebo group. Means + SD. *Placebo patients not included in MAD due to limited patient numbers and varying d
Slide 18: 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 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 19: ACU193 Serum PK
ACU193 Serum PK Single Dose Cohorts Multiple Dose Cohorts Serum exposure is dose proportional without accumulation PHARMACOKINETICS Estimated serum terminal T1/2 of 5-7 days
Slide 20: Immunogenicity (preliminary assessment)
Immunogenicity (preliminary assessment) Evidence of low titer treatment emergent immunogenicity Some evidence of treatment emergent immunogenicity was observed Observations more common in the MAD cohorts vs. SAD cohorts Treatment emergent ADAs are consistently low titer Preliminary assessment reveal
Slide 21: Dose-Related CSF ACU193 Exposure: Above Endogenous CSF AβO Levels
Dose-Related CSF ACU193 Exposure: Above Endogenous CSF AβO Levels 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 inf
Slide 22: Target Engagement Assessed by Measuring ACU193-AβO Complex in CSF
Target Engagement Assessed by Measuring ACU193-AbO Complex in CSF AbO selective detection (anti-AbO mAb) Only drug/oligomer complex is measurable ACU193 drug specific capture (anti-ACU193 idiotype mAb) Novel assay configuration tailored to selectively detect ACU193-AβO complex in CSF as direct measu
Slide 23: Target Engagement of ACU193 with AβOs is Dose Proportional
Target Engagement of ACU193 with AβOs is Dose Proportional Single Dose Cohorts Multiple Dose Cohorts* Dose-related target engagement *One patient from Cohort 5 (10 mg/kg Q4W) excluded because only received one administration of drug (study drug discontinued after lacunar infarct). TARGET ENGAGEMENT
Slide 24: Maximal TE Response Observed at Higher Doses
Maximal TE Response Observed at Doses of 25 mg/kg Q2W and 60 mg/kg Q4W 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 rece
Slide 25: Phase 1 Data Supports Advancing to Phase 2/3
Phase 1 Data Supports Advancing to Phase 2/3 Rapid, dose-related, statistically significant amyloid plaque reduction observed within higher dose cohorts Topline results from INTERCEPT-AD demonstrated proof-of-mechanism for ACU193, the first clinical stage AβO-targeting antibody ACU193 well-tolerated
Slide 26: Future Strategic Plans
Future Strategic Plans Anticipated interaction with the FDA in Q4 2023 to inform our proposed Phase 2/3 study Further investigate the development of a subcutaneous administration of ACU193 Evaluate potential next generation product opportunities Explore partnership opportunities that have the potent
Slide 27: Q&A
Q&A