Acumen Pharmaceuticals, Inc. · NASDAQ:ABOS
Acumen Pharmaceuticals — Clinical Trials on Alzheimer's Disease (CTAD) 2023
50 slides from Acumen Pharmaceuticals's conference presentation, Oct 27, 2023
Slide 1: INTERCEPT-AD phase 1 insights and findings from the investigation of ACU193
INTERCEPT-AD phase 1 insights and findings from the investigation of ACU193, a monoclonal antibody targeting soluble Aβ oligomers Clinical Trials on Alzheimer’s Disease Boston, Massachusetts October 27, 2023
Slide 2: Symposium agenda and speakers
INTERCEPT-AD phase 1 insights and findings from the investigation of ACU193, a monoclonal antibody targeting soluble Aβ oligomers Chair: Diana Kerwin, Kerwin Medical Center, Dallas, TX Determination of target engagement at various doses of ACU193 in INTERCEPT-AD Mirjam Trame, Certara, Boston, MA Red
Slide 3: 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, a
Slide 4: Determination of Target Engagement at Various Doses of ACU193 in INTERCEPT-AD
Determination of Target Engagement at Various Doses of ACU193 in INTERCEPT-AD Mirjam N Trame, PharmD, PhD Vice President, Certara Drug Development Solutions Clinical Trials on Alzheimer’s Disease Boston, Massachusetts October 27, 2023 © Copyright 2020 Certara, L.P. All rights reserved. 4 4
Slide 5: Disclosure
Disclosure • Dr. Trame is an employee of Certara and consulting for Acumen Pharmaceuticals. © Copyright 2020 Certara, L.P. All rights reserved. 5 5
Slide 6: 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 7: INTERCEPT-AD Phase 1 Study
INTERCEPT-AD Phase 1 Study © Copyright 2020 Certara, L.P. All rights reserved. 7 7
Slide 8: Target Engagement: Measuring ACU193-AβO Complex in CSF
Target Engagement: Measuring ACU193-AβO Complex in CSF MSD S-Plex (Turbo) Immunoassay ACU193-AbO Complex AbO selective detection (anti-AbO mAb) Only drug/AbO complex is measurable ACU193 drug specific capture (anti-ACU193 idiotype mAb) Novel assay configuration tailored to selectively detect ACU193-
Slide 9: Clear ACU193 Concentration Target-Engagement Profile in the CSF
Clear ACU193 Concentration Target-Engagement Profile in the CSF • Clear concentration- response profile in CSF Predicted EC50 • These lumbar samples Predicted Emax were taken while drug levels were falling, so they represent the lowest target engagement levels (something like “trough levels”); withi
Slide 10: PK/PD Model for ACU193 Target Engagement
PK/PD Model for ACU193 Target Engagement • CSF concentrations defined by a two-compartment model, then linked to target engagement in the CSF and Amyloid PET Centiloid reduction using a Michaelis-Menten (Emax) model CSF CSF Target 𝐸𝑚𝑎𝑥 ∙ [𝐶𝑆𝐹] Serum = (Periphery) Engagement, AU/mL [𝐶𝑆𝐹] +…
Slide 11: Simulated CSF Target Engagement at Steady-State
Simulated CSF Target Engagement at Steady-State CSF target engagement was simulated at a candidate list of doses given Q4W at steady-state Ph2/3 Dosing Strategy (ALTITUDE-AD) lower dose: 35 mg/kg Q4W upper dose: 50 mg/kg Q4W • Notable diminishing differentiation as dose increases • Doses were select
Slide 12: Simulated CSF Target Engagement for Doses Chosen for ALTITUDE-AD
Simulated CSF Target Engagement for Doses Chosen for ALTITUDE-AD CSF target engagement was simulated for doses chosen for the subsequent Phase 2/3 study Ph2/3 Dosing Strategy (ALTITUDE-AD) lower dose: 35 mg/kg Q4W upper dose: 50 mg/kg Q4W • Doses were selected with accumulation in mind: ACU193 conce
Slide 13: Positive Effect and Significant Reduction in Amyloid PET Centiloids
Positive Effect and Significant Reduction in Amyloid PET Centiloids The PET data signal-to-noise is challenging, but dose and schedule dependence is evident in plaque reduction Ph2/3 Dosing Strategy (ALTITUDE-AD) lower dose: 35 mg/kg Q4W upper dose: 50 mg/kg Q4W Ph 2/3 Dosing • Centiloid data suppor
Slide 14: Summary and Conclusions
Summary and Conclusions • A CSF measure of target engagement (ACU193-Aβ-oligomer complex) was developed showing clear dose-related increases in target engagement across all cohorts • A PK/PD model was utilized and demonstrated that the highest doses used in INTERCEPT-AD (60 mg/kg Q4W and 25 mg/kg Q2
Slide 15: Thank you!
Thank you! © Copyright 2020 Certara, L.P. All rights reserved. 15 15
Slide 16: Reduction in amyloid plaque load using higher doses of ACU193 in INTERCEPT-AD
Reduction in amyloid plaque load using higher doses of ACU193 in INTERCEPT-AD Eric R Siemers, MD Chief Medical Officer, Acumen Pharmaceuticals Clinical Trials on Alzheimer’s Disease Boston, Massachusetts October 27, 2023
Slide 17: Disclosures
Disclosures Dr. Siemers is an employee and shareholder at Acumen Pharmaceuticals. Consulting Agreements (2021 or later) • Cogstate Ltd. • Gates Ventures LLC • Hoffman La-Roche Ltd. • Vaccinex, Inc. 17
Slide 18: 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 19: Relationship between florbetapir SUVr and Centiloids
Relationship between florbetapir SUVr and Centiloids SUVr = 1.6 -> Centiloids = 96.05 SUVr = 1.2 -> Centiloids = 26.24 Visual read range SUVr = 1.0 -> Centiloids = -8.67 Centiloids = (174.54 * SUVr) – 183.21 19
Slide 20: Results from hybrid SUVr/visual read assessments
Results from hybrid SUVr/visual read assessments • Of 194 amyloid PET scans obtained during screening: ➢ 49 (25%) had a global cortical SUVr of <1.0 ➢ 81 (42%) had a global cortical SUVr of 1.0 – 1.2 ➢ 64 (33%) had a global cortical SUVr of >1.2 • Of the 81 scans with a global SUVR of 1.0 – 1.2, 14
Slide 21: All amyloid plaques are not created equal
All amyloid plaques are not created equal Boon et al. Acta Neuropathologica (2020) 140:811-830 https://doi.org/10/1007/s00401-020-02198-8 21
Slide 22: INTERCEPT-AD Individual Cohort Results
INTERCEPT-AD Individual Cohort Results
Slide 23: Mean Centiloid changes by cohort
Mean Centiloid changes by cohort
Slide 24: SAD and MAD placebo Centiloid changes
SAD placebo MAD placebo 160 160 140 140 120 120 Centiloids Centiloids 100 100 80 80 60 60 40 40 20 20 0 0 -20 -20 0 10 20 30 40 0 10 20 30 40 50 60 70 Days Days 001 003 005 007 009 011 013 002 004 006 008 010 012 014 Baseline mean = 48.5 Centiloids Baseline mean = 48.6 Centiloids Endpoint mean = 50.
Slide 25: SAD cohorts Centiloid changes by participant
Cohort 1 Cohort 2 2 mg/kg SAD 10 mg/kg SAD 160 160 015 140 140 016 021 120 120 022 Centiloids Centiloids 100 017 100 80 018 80 023 60 60 024 019 40 40 020 025 20 20 0 0 -20 -20 0 10 20 30 40 0 10 20 30 40 Days Days Cohort 3 Cohort 4 25 mg/kg SAD 60 mg/kg SAD 160 160 140 026 140 032 120 027 120 033 C
Slide 26: Cohort 5 MAD Centiloids
Cohort 5: 10 mg/kg Q4W MAD 160 038 140 Centiloids 120 039 100 040 80 041 60 042 40 043 20 0 -20 0 10 20 30 40 50 60 70 Days Baseline mean = 55.8 Centiloids Endpoint mean = 53.4 Centiloids
Slide 27: Cohort 6 MAD Centiloids
Cohort 6: 60 mg/kg Q4W MAD 160 044 140 Centiloids 120 045 100 046 SYMPTOMATIC 80 047 60 048 40 049 20 0 050 -20 051 0 10 20 30 40 50 60 70 Days Baseline mean = 71.9 Centiloids Endpoint mean = 53.7 Centiloids
Slide 28: Cohort 7 MAD Centiloids
Cohort 7: 25 mg/kg Q2W MAD 160 052 140 120 053 Centiloids 100 054 80 055 60 056 40 057 20 0 058 -20 0 10 20 30 40 50 60 70 059 Days Baseline mean = 66.8 Centiloids Endpoint mean = 53.0 Centiloids
Slide 29: All cohorts: Plaque reduction vs target engagement
All cohorts: Plaque reduction vs target engagement R2 = 0.1577 Change in Plaque Burden 20 2 mg/kg SAD p = 0.0323 10 mg/kg SAD (Δ Centiloids) 25 mg/kg SAD 0 60 mg/kg SAD 10 mg/kg Q4W -20 25 mg/kg Q2W 60 mg/kg Q4W -40 5 10 15 20 25 30 ACU193-AβO Complex (AU/mL)
Slide 30: ApoE4 homozygotes
ApoE4 homozygotes 160 C5 - 040 140 120 C5 - 041 Centiloids 100 C6 - 050 80 C7 - 057 60 C3 - 028 40 20 C7 - 059 0 -20 0 10 20 30 40 50 60 70 Days Baseline mean = 78.3 Centiloids Endpoint mean = 70.2 Centiloids
Slide 31: Slowing of CDR-SB progression versus reduction in plaque load
Slowing of CDR-SB progression versus reduction in plaque load 120 Amyloid PET load (Centiloids) 100 80 60 6% slowing 40 -2% slowing 8% slowing 22% slowing 20 27% slowing 23% slowing 36% slowing 0 0 5 10 15 20 25 30 Months ENGAGE EMERGE Clarity Graduate 1 Graduate 2 Trailblazer-Alz Trailblazer-Alz2 C
Slide 32: Summary and conclusions
Summary and conclusions • Hybrid quantification/visual read system was used in Phase 1 trial of early AD ➢ Relatively few patients entered the trial on the basis of the visual read ➢ Given the SUVr cut-off used in this study, somewhat lower baseline Centiloid values were seen compared to other studi
Slide 33: Thank you!
Thank you!
Slide 34: Characteristics of participants in INTERCEPT-AD who did or did not develop ARIA
Characteristics of participants in INTERCEPT-AD who did or did not develop ARIA
Slide 35: Disclosures
Disclosures Stephen Salloway, MD, MS • Butler Hospital receives research support for clinical trials from Janssen, Lilly, Eisai, Genentech, Roche, and Biogen • Dr. Salloway has provided consultation to Eisai, Biogen, Lilly, Roche, Genentech, Bolden, Novo Nordisk, Prothena, Acumen, Labcorp, Alector,
Slide 36: 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 37: INTERCEPT-AD: MRI-related protocol information
INTERCEPT-AD: MRI-related protocol information • Exclusion Criteria: MRI at screening has more than four ARIA-H, presence of ARIA-E, or superficial siderosis • The investigator may request a safety MRI at any time based on clinical findings or suspicion • Medical management will be determined by loc
Slide 38: MRI and ACU193 dosing schedule
MRI and ACU193 dosing schedule SAD Cohorts 1-4 (2,10, 25 and 60 mg/kg) Day 1 Day 21 Day 140 ACU193 (or placebo) X MRI X X MAD Cohort 5 (25 mg/kg Q4W) MAD Cohort 6 (60 mg/kg Q4W) Baseline Day 28 Day 56 Day 63 Day 70 Day 126 Day 196 ACU193 (or placebo) X X X MRI – cohort 5 X X X MRI results for MRI –
Slide 39: INTERCEPT-AD: ARIA-E summary
INTERCEPT-AD: ARIA-E summary 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 PBO
Slide 40: 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 41: Cohort 4 participant (asymptomatic ARIA-E)
Cohort 4 participant (asymptomatic ARIA-E) • 58-year-old white female • History of hypothyroidism, diverticulum, diabetes mellitus, depression, and menopause • SAD Cohort 4 (ACU193 60 mg/kg) • ARIA-E found on Day 21 MRI • Asymptomatic • One infusion of ACU193 • Extensive ARIA-E leptomeningeal pariet
Slide 42: Cohort 4 participant images
Cohort 4 participant (asymptomatic ARIA-E) images Day 21 Day 140 (EOS)
Slide 43: Cohort 6 participant (symptomatic ARIA-E)
Cohort 6 participant (symptomatic ARIA-E) • 80-year-old white female subject • History of ventricular extrasystoles, essential tremor, arthritis, scoliosis, spinal osteoarthritis, rotator cuff syndrome, skin cancer, pollakiuria, allergy to arthropod sting, and drug hypersensitivity (penicillin) • MA
Slide 44: Cohort 6 participant images
Cohort 6 participant (symptomatic ARIA-E) images Day 28 Day 126 (EOS)
Slide 45: Cohort 7 participant (asymptomatic ARIA-E and superficial siderosis)
Cohort 7 participant (asymptomatic ARIA-E and superficial siderosis) • 70-year-old white female • History of GERD, osteoporosis, hyperlipidemia, urinary tract infection, and hypertension • MAD Cohort 7 (ACU193 25 mg/kg Q2W) • ARIA-E and superficial siderosis found on Day 70 MRI • Asymptomatic • All
Slide 46: Cohort 7 participant (asymptomatic ARIA-E) images
Cohort 7 participant (asymptomatic ARIA-E) images Day 28 Day 70 Day 98 (EOS) ARIA-E noted in retrospect at D70 ARIA-E first identified Resolution occurred D135 - post DBL 46
Slide 47: Cohort 7 participant (superficial siderosis) images
Cohort 7 participant (superficial siderosis) images Day 70 Day 98 (EOS)
Slide 48: Change in amyloid burden in participants with ARIA-E
Change in amyloid burden in participants with ARIA-E ∆ -30.5 (-27.4%) ∆ -9.3 (-10%) ∆ -16 (20.4%) ∆ -9.6 (-13.9%) ∆ -42.2 (-47.4%) Baseline mean = 88.2 Centiloids Endpoint mean = 66.6 Centiloids
Slide 49: Summary
Summary • Differentiated rate of ARIA-E • 5 cases of ARIA-E; 1 symptomatic from 48 on drug • No cases of symptomatic ARIA-E at 2, 10, or 25 mg/kg doses • 4 of 5 ARIA-E cases in ApoE4 heterozygotes • No ARIA-E observed in ApoE4 homozygotes (n=6) • All treatment-emergent ARIA-E showed radiographic res
Slide 50: Thank you!
Thank you!
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