Slide 1: Investor Conference Call to Discuss INTERCEPT-AD Results
Investor Conference Call to Discuss INTERCEPT-AD Results July 17, 2023 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: 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
Slide 4: ACU193: Novel mAb Targeting Amyloid Beta Oligomers, the Most Toxic Form of Aβ
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
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 • Pote
Slide 6: INTERCEPT-AD Results Confirm Proof of Mechanism for ACU193
INTERCEPT-AD Results Confirm Proof of Mechanism for ACU193 and Demonstrate Reduction in Amyloid Plaques at Higher Doses Studied 1 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 • Comparab
Slide 7: Highest Doses of ACU193 Demonstrate Rapid Reduction in Amyloid Plaque 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) Indexed Values Absolute Values (p=0.01 for change in amyloid plaque from baseline to endpoint within ACU193 cohort)
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 Donanemab2 Lecanemab3 ACU1934,5 (30 mg/kg) (20 mg/kg) (15 mg/kg) (25 mg/kg) ARIA-E rate 0% (0/6) 28.6% (2/7) 0% (0/6) 0% (0/6) Higher Doses Aducanumab1 Donanemab2 Lecanemab3 ACU1934 (60 mg/kg) (40 mg/kg) (60
Slide 9: 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 Potentially Therapeutic Doses Endpoint Critical Success Factors 10mg/kg 25mg/kg 60mg/kg • Deaths, SAEs Related to Study Drug None None None Safety & Tol
Slide 10: INTERCEPT-AD Summary
INTERCEPT-AD Summary Robust and well-designed study with well established (PK, ARIA) and novel endpoints Design (AβO target engagement, COGState/ASL) Execution 60 patients completed the study Proof-of-Mechanism achieved and new learnings demonstrated through statistically Data significant plaque red
Slide 11: INTERCEPT-AD Topline Results
INTERCEPT-AD Topline Results
Slide 12: 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: PART A: ≥ 1wk 60 mg/kg ACU193 SINGLE- or Placebo ASCENDING DOSE COHORT 3: n = 8 per cohort (32 total) ≥ 1wk 25 mg/kg ACU193 25mg or Placebo COHORT 2: ≥ 1wk 10 mg/kg ACU193 ≥ 1wk 10mg or Placebo ≥ 1wk COHORT 1:
Slide 13: INTERCEPT-AD Baseline Characteristics
INTERCEPT-AD Baseline Characteristics Modified intent to treat Characteristic ACU193 Placebo N=48 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
Slide 14: Treatment Emergent SAEs
SAFETY Treatment Emergent SAEs Treatment Action SAE Verbatim Severity Relationship Outcome Assignment Taken 10mg/kg Dose Not Ovarian Fibroma 3 Not Related Resolved (Cohort 5, MAD) Changed 10mg/kg Dose Not Pneumonia 3 Unlikely Related Resolved (Cohort 5, MAD) Changed 10mg/kg Dose Not Altered Mental S
Slide 15: TEAEs >3% and ACU193>Placebo
SAFETY TEAEs >3% and ACU193>Placebo TEAE ACU193 (N=48) Placebo (N=14) n (%) n (%) ≥ 1 TEAE 27 (56.3) 6 (42.9) COVID-19 3 (6.3) 0 Bronchitis 2 (4.2) 0 Headache 2 (4.2) 0 ARIA-H 4 (8.3) 1 (7.1) ARIA-E 5 (10.4) 0 Hypersensitivity 3 (6.3) 0 Fall 2 (4.2) 0 Post LP syndrome 2 (4.2) 0 15
Slide 16: ARIA-E Summary for INTERCEPT-AD
SAFETY ARIA-E Summary for INTERCEPT-AD 2 mg/kg 10 mg/kg 25 mg/kg 60 mg/kg Cohort 1 Cohorts 2, 5 Cohorts 3, 7 Cohorts 4, 6 ApoE D21 D140 ApoE D21 D140 ApoE D21 D140 ApoE D21 D140 3,4 3,4 PBO PBO 3,3 4,4 PBO PBO 3,3 PBO PBO 3,3 3,3 PBO PBO 3,4 SAD 3,4 3,3 4,4 3,4 PBO PBO 2,3 3,4 3,3 3,3 3,4 PBO PBO 3,
Slide 17: Safety Update: ARIA-E, Total 5 Cases
SAFETY Safety Update: ARIA-E, Total 5 Cases Baseline/Endpoint Plaque Cohort ApoE4 Gender Age Severity by FDA Criteria Load (Centiloids) C4 Heterozygote F 58 93.1/83.8 Moderate - Asymptomatic SAD 60 mg/kg C5 Mild - Asymptomatic Heterozygote F 72 78.2/62.2 10 mg/kg Q4W 3rd/final dose on D56 Moderate -
Slide 18: Aβ PET: Mean Changes in Amyloid Plaque in SAD and MAD Cohorts
EXPLORATORY MEASURES Aβ PET: Mean Changes in Amyloid Plaque in SAD and MAD Cohorts Single Dose Cohorts Multiple Dose Cohorts*+ Means + SD. Error bars shown only for pooled placebo group. Means + SD. Rapid, dose-related, statistically significant reduction of plaque load based on florbetapir PET pres
Slide 19: Aβ PET: Individual Patient Changes in Amyloid Plaque
EXPLORATORY MEASURES 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 19
Slide 20: ACU193 Serum PK
PHARMACOKINETICS ACU193 Serum PK Single Dose Cohorts Multiple Dose Cohorts Serum exposure is dose proportional without accumulation Estimated serum terminal T1/2 of 5-7 days 20
Slide 21: Immunogenicity (preliminary assessment)
PHARMACOKINETICS Immunogenicity (preliminary assessment) • 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 reveals no apparent effect on serum P
Slide 22: Dose-Related CSF ACU193 Exposure: Above Endogenous CSF AβO Levels
PHARMACOKINETICS 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
Slide 23: Target Engagement Assessed by Measuring ACU193-AbO Complex in CSF
TARGET ENGAGEMENT Target Engagement Assessed by Measuring ACU193-AbO Complex in CSF MSD S-Plex (Turbo) Immunoassay ACU193-AbO Complex AbO selective detection (anti-AbO mAb) Only drug/oligomer complex is measurable ACU193 drug specific capture (anti-ACU193 idiotype mAb) Novel assay configuration tail
Slide 24: Target Engagement of ACU193 with AβOs is Dose Proportional
TARGET ENGAGEMENT Target Engagement of ACU193 with AβOs is Dose Proportional Single Dose Cohorts Multiple Dose Cohorts* No Significant p = 0.0007 30 Differences p = 0.03 CSF ACU193-Aβ Oligomer Complex (AU/mL) p = 0.001 20 at Visit 8 (Day 21) 10 0 2 mg/kg 10 mg/kg 25 mg/kg 60 mg/kg ACU193 IV Infusion
Slide 25: Maximal TE Response Observed at Doses of 25 mg/kg Q2W and 60 mg/kg Q4W
TARGET ENGAGEMENT 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 Taken together with compelling safety profile and rapid plaque reduc
Slide 26: 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 trial demonstrated proof-of-mechanism for ACU193, the first clinical stage AβO- targeting antibody ACU193 was wel
Slide 27: 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 th
Slide 28: Q&A
Q&A