Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Technical Presentation (2023)
43 slides from Acumen Pharmaceuticals's technical presentation, 2023
Slide 1: Baseline characteristics of INTERCEPT-AD
Baseline characteristics of INTERCEPT-AD: A phase 1 trial with ACU193 targeting soluble amyloid beta oligomers for the treatment of early Alzheimer’s disease Todd Feaster, PsyD Acumen Pharmaceuticals, Inc
Slide 2: Disclosure
Disclosure • Dr. Feaster is an employee shareholder at Acumen Pharmaceuticals, Inc. 2
Slide 3: Forward Looking Statement
Forward Looking Statement 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 4: ACU193: A Monoclonal Antibody that Selectively Binds Soluble Aβ Oligomers
ACU193: A Monoclonal Antibody that Selectively Binds Soluble Aβ Oligomers • ACU193 is a humanized, affinity-matured, IgG2 subclass monoclonal antibody targeting soluble amyloid beta oligomers (sAβOs) • Considering the evidence, blocking the toxicity of sAβOs with ACU193 is a promising approach for t
Slide 5: Study Population
Study Population • Diagnosis of MCI or Mild AD dementia (NIA-AA criteria) • Key Inclusion criteria: • Age 55-90 years • MMSE total score 18-30 inclusive • CDR Global Score 0.5 or 1 • Confirmation of amyloid pathology via Amyloid PET • Apolipoprotein E (APOE) genotype is recorded • Measures of cognit
Slide 6: Study Objectives
Study Objectives Primary Objective: • Determine the safety and tolerability of a single and multiple IV doses of ACU193 Secondary Objective: • Estimate serum PK of ACU193 following single and multiple IV doses of ACU193 Exploratory Objectives (following single and multiple IV doses of ACU193): • Det
Slide 7: Study Design
Study Design COHORT 4: 60mg PART A: ≥ 1wk 60 mg/kg ACU193 SINGLE-ASCENDING or Placebo 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: 2 mg/kg ACU193 or Placebo 2mg COHORT 7: 25mg ≥ 1wk 25 mg/kg ACU
Slide 8: Participant Disposition
Participant Disposition Participants Screened N=260 Participants Enrolled N=65 Screen Failures (N=195) Sites in U.S. Did Not Meet Incl/Excl Criteria 187 (96%) N=17 Discontinued Before Dosing 3 (1.5%) Enrollment at Capacity 5 (2.5%) ACU193 Treatment (N=49) Placebo (N=16) Completed Study 46 (93.9%) Co
Slide 9: Primary Reasons for Screen Failures
Primary Reasons for Screen Failures CS Lab Abnormality (1%) History of Malignant Eligible-Study at Disease (1%) Capacity (3%) Neurological Illness (1%) No Study Partner (2%) MMSE (3%) CDR (4%) Withdrew Consent (10%) PET (60%) Unstable Clinical Illness (2%) Anticoagulants (1%) MRI Abnormality (4%) EC
Slide 10: Baseline Demographics
Baseline Demographics Characteristic ACU193 (N=49) Placebo (N=16) Age, median (range), years 72.3 (56,85) 71.3 (59,83) Female, n (%) 27 (55.1) 8 (50.0) Race, n (%) Asian 0 (0) 0 (0) Black/African American 2 (4.1) 1 (6.3) Caucasian 46 (93.9) 15 (93.7) American Indian/Alaskan 1(2.0) 0 (0) Ethnicity, n
Slide 11: Baseline Clinical Characteristics
Baseline Clinical Characteristics Characteristic ACU193 (N=49) Placebo (N=15) APOE4 Status, n (%) Noncarrier 21 (43.75) 4 (28.6) Heterozygous Carrier 21 (43.75) 8 (57.1) Homozygous Carrier 6 (12.5) 2 (14.3) CDR-GS, mean (SD) 0.6 (0.3) 0.6 (0.2) CDR-SB, mean (SD) 3.6 (1.9) 3.2 (1.8) MMSE, mean (SD) 2
Slide 12: Summary
Summary • Screen failure rates are similar to other studies requiring amyloid positivity • The amyloid plaque load in INTERCEPT-AD tends to be lower compared to other studies in this population • Sites can successfully recruit patients with MCI and early AD into a Phase 1 trial that incorporates man
Slide 13: Thank you!
Thank you!
Slide 14: Recruitment strategies and tactics for INTERCEPT-AD
Recruitment strategies and tactics for INTERCEPT-AD: A phase I trial of Aβ oligomer- targeting ACU193 in early Alzheimer’s disease Robyn Moxon Acumen Pharmaceuticals, Inc
Slide 15: Author Disclosures
Author Disclosures Robyn Moxon is an employee of Acumen Pharmaceuticals.
Slide 16: 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 17: Recruitment for AD Trials
Recruitment for AD Trials • Clinical trials are essential but recruitment is often difficult • Recruitment tactics often include: o Media advertising o Physician referrals o Patient registries o Referral campaigns o Social media/digital ads o Targeted community outreach • Not all recruitment tactics
Slide 18: INTERCEPT-AD Participants
INTERCEPT-AD Participants • INTERCEPT-AD is a phase 1 randomized, placebo-controlled, double-blind study of ACU193 in mild cognitive impairment or mild dementia due to AD • Seventeen study sites in the U.S. • Eligible vs Randomized Participants
Slide 19: Recruitment Categories
Recruitment Categories Ey SITE : DATABASE @) EXTERNAL rok REFERRAL PHYSICIAN SITE REFERRAL CAMPAIGN Patients in Patients Patients site’s referred by referred by database or friends, physicians not referred by family, or affiliated with clinic staff self-referrals study site Site-led ads, events, and
Slide 20: Referral Source Use by Sites for Screening
Referral Source Use by Sites for Screening • Site databases o Used by most sites 13 (76%) o Accounted for most screenings 107 (41%) o Identified more eligible participants 32 (46%) • Recruitment tactics customized for successful site enrollment • Selection was based on site-specific needs
Slide 21: Referral Sources for Screened and Eligible Participants
Referral Sources for Screened and Eligible Participants Screened Participants (n=260) Eligible Participants (n=70) *Campaign C had 0 Eligible Participants
Slide 22: Screening and Eligibility Rate by Referral Source
INTERCEPT-AD Screening and Eligibility Rate by Referral Source Campaign A Site Database Site Campaign Campaign B Physician Referral Campaign C External Referral Screening Rate per Site by Referral Source Eligibility Rate per Site by Referral Source
Slide 23: Participant Funnels by Source
Participant Funnels by Source * Includes 43 Pre-screened patients with unknown referral source
Slide 24: Summary
Summary • Sites with robust internal patient databases contributed higher numbers of screening and eligibility • Digital advertising can be a successful source for recruiting for Alzheimer’s trials • Recruitment strategies may find success with a customized approach addressing unique capabilities of
Slide 25: Topline results of INTERCEPT-AD
Topline results of INTERCEPT-AD: A phase I trial of Aβ oligomer-targeting ACU193 in early Alzheimer’s disease Eric Siemers, MD Chief Medical Officer Acumen Pharmaceuticals, Inc
Slide 26: Disclosures
Disclosures Chief Medical Officer • Acumen Pharmaceuticals Inc. Consulting Agreements (2021 or later) • Cogstate Ltd. • Cortexyme Inc. • Gates Ventures LLC • Hoffman La-Roche Ltd. • Indiana University • LuMind Research Down Syndrome Foundation • Partner Therapeutics Inc. • Vaccinex, Inc. Stock posit
Slide 27: 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 28: Treatment Emergent SAEs: Participants dosed with ACU193
Treatment Emergent SAEs: Participants dosed with ACU193 Subject Treatment Action SAE Verbatim Severity Relationship Outcome ID Assignment Taken 112- 10mg/kg Dose Not Ovarian Fibroma 3 Not Related Resolved 1002 (Cohort 5, MAD) Changed 10mg/kg Dose Not 112- Pneumonia 3 Unlikely Related Resolved (Cohor
Slide 29: TEAEs >3% and ACU193>Placebo
TEAEs >3% and ACU193>Placebo ACU193 (N=48) Placebo (N=14) TEAE 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 29
Slide 30: ARIA-E Summary for INTERCEPT-AD
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 2,3 3,3 3,4 4,4 3,3 3,4 3,3 PBO PBO 3,4 PBO PBO 3,4 PBO P
Slide 31: ARIA-E: Patient Details
ARIA-E: Patient Details 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 - Symptomatic C6 Hete
Slide 32: ACU193 Serum PK
ACU193 Serum PK Single Dose Cohorts Multiple Dose Cohorts Serum exposure is dose proportional without accumulation 32
Slide 33: ACU193 CSF PK
ACU193 CSF PK 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 (discontinued after lacunar infarct) 33
Slide 34: Target Engagement Assessed by Measuring ACU193-AbO Complex in CSF
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 tailored to selectivel
Slide 35: Target Engagement of ACU193 with AβOs is Dose Proportional
Target Engagement of ACU193 with AβOs is Dose Proportional Single Dose Cohorts Multiple Dose Cohorts* p = 0.0007 No significant differences p = 0.03 p = 0.001 Dose-related target engagement *One patient from Cohort 5 (10 mg/kg Q4W) excluded because only received one administration of drug (discontin
Slide 36: ACU193 CSF Target Engagement vs. Drug Exposure, Emax Model
ACU193 CSF Target Engagement vs. Drug Exposure, Emax Model Single & Multiple Dose Cohorts - Exposure Response Relationship (Emax Model) Emax: 23.2 AU/mL EC50: 1.43 x 105 pg/mL Approaching maximal TE response at doses of 25 mg/kg Q2W and 60 mg/kg Q4W 36 *One patient from Cohort 5 (10 mg/kg Q4W) exclu
Slide 37: Ab PET: Mean Changes in Amyloid Plaque in SAD and MAD Cohorts
Ab PET: Mean Changes in Amyloid Plaque in SAD and MAD Cohorts Single Dose Cohorts Multiple Dose Cohorts Mean + SD Error bars shown only for pooled placebo group. Mean + SD Small changes in plaque load based on florbetapir PET appeared to be present in 60 mg/kg Q4W and 25 mg/kg Q2W cohorts Note: Plac
Slide 38: Ab PET: Individual Patient Changes in Amyloid Plaque
Ab PET: Individual Patient Changes in Amyloid Plaque in Cohort 6 at 60 mg/kg Q4W and Cohort 7 at 25 mg/kg Q2W Some but not all individual participants in 60 mg/kg Q4W and 25 mg/kg Q2W cohorts showed small reductions in plaque load after 63 or 70 days 38
Slide 39: Exploratory Computerized Cognitive Testing
Exploratory Computerized Cognitive Testing Single Dose Cohorts Multiple Dose Cohorts Cogstate Cognitive Z-score SAD Cogstate Cognitive Z-score MAD Change from Baseline Change from Baseline 1.0 1.5 Change from Baseline 2 mg/kg 10 mg/kg Q4W Change from Baseline 1.0 10 mg/kg 0.5 60 mg/kg Q4W 25 mg/kg 0
Slide 40: Exploratory Arterial Spin Labeling
Exploratory Arterial Spin Labeling (Siemens MRI scanners only) Single Dose Cohorts Multiple Dose Cohorts SAD Normalized Cortical Composite ASL MAD Normalized Cortical Composite ASL Change from Baseline Change from Baseline Change in Normalized Cortical ASL Change in Normalized Cortical ASL 0.30 0.2
Slide 41: Conclusions
Conclusions • No unexpected safety signals found; rates of ARIA-E appear to be manageable and no cases of ARIA-E occurred in 6 participants who were ApoE e4 homozygotes and received ACU193 • PK is generally consistent with Q4W dosing; INTERCEPT-AD provides data that will inform doses for the subsequ
Slide 42: Acknowledgements
Acknowledgements Participants and their Study Partners • We acknowledge with thanks the individuals who enrolled in INTERCEPT-AD trial as well as their family, study partners, and friends who supported them Site Staff and Study Team Members • We would also like to acknowledge the Site Staff, CRO, an
Slide 43: Thank you!
Thank you!
Acumen Pharmaceuticals — Technical Presentation (2023) on 6ix