Ac Immune Sa · NASDAQ:ACIU
Ac Immune Sa — AD/PD 2024
13 slides from Ac Immune Sa's conference presentation, Mar 6, 2024
Slide 1: Targeting the Inflammasome Pathway with an Anti-ASC Immunotherapy in Alzheimer's Disease
TARGETING THE INFLAMMASOME PATHWAY WITH AN ANTI-ASC IMMUNOTHERAPY IN ALZHEIMER’S DISEASE Davide Basco, PhD – AD/PD 2024 March 6th, 2024 www.acimmune.com
Slide 2: Disclaimer
Disclaimer This presentation may contain statements that constitute “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are statements other than historical fact and may includ
Slide 3: Inflammation is a central mechanism in Alzheimer's disease (AD)
Inflammation is a central mechanism in Alzheimer’s disease (AD) In addition to amyloid beta deposition, activation of immune cells manifests early in the pathology Microglia and astrocyte activation Long and Holtzman, 2019 1 2 ▪ Aim: target immune cell-mediated pathology via the NLRP3 /ASC inflammas
Slide 4: The target: Apoptosis-associated speck-like protein containing CARD (ASC)
The target: Apoptosis-associated speck-like protein containing CARD (ASC) A sensor protein part of the pro-inflammatory inflammasome complex Two globular domains Part of the inflammasome complex Assembled in specks CARD ASC Caspase-1 NLRP3 PYD PDB : 2KN6 Hochheiser et al, 2022 ASC-GFP ▪ Pro-inflamma
Slide 5: The role of ASC specks in AD as propagators of amyloid pathology
The role of ASC specks in AD as propagators of amyloid pathology ASC in seeding amyloid beta protein aggregates Alzheimer’s disease Human brain Modified from Hulse and Bhaskar, 2022 Venegas et al. 2017 ASC Aβ ▪ Extracellular ASC specks are detectable in brain of AD patients and seed amyloid beta pla
Slide 6: Generating a highly potent anti-ASC mAb: ACI-6635
Generating a highly potent anti-ASC mAb: ACI-6635 Cross-reactive on human and mouse ASC SupraAntigen® vaccine platform Affinity (SPR1) Target engagement (WB & IHC) 100 Human ASC units)Unit (RU) KD: 1.12 nM Basco, ITS 2023 50 Response 25 (Relative 20 0 0 1000 2000 3000 15 Time (s) Response UnitRespon
Slide 7: ACI-6635: mechanism of action in phagocytosis
ACI-6635: mechanism of action in phagocytosis Accelerate ASC aggregate uptake with immune complexes using IgG effector function 2.5×10 6 ✱✱ Phagocytosis index at peak (3h) 1250 ACI-6635 (IC50=4.5nM) 2×10 6 hASC-pHrodo + ACI-6635 ✱✱✱✱ ✱✱✱ Phagocytosis index (AU) IL-1 release (pg/mL) ACI-6635_ER1 (IC
Slide 8: ACI-6635: efficacy in a mouse model of AD
ACI-6635: efficacy in a mouse model of AD Reduces neuroinflammation in the ARTE10 amyloidosis mouse model ARTE10 Treatment start Treatment stop ARTE10 Isotype ctrl ACI-6635 (Age: 3 months) (Week 14) WT Treatment ACI-6635 or isotype ctrl, 60 Readouts Iba1 mg/kg weekly i.p. Biochemistry Histology AC I
Slide 9: ACI-6635 decreases neuroinflammation via reduction of ASC spreading
ACI-6635 decreases neuroinflammation via reduction of ASC spreading mAb-mediated ASC removal mitigates gliosis and plaque engulfment DAPI Aβ DAPI Aβ ASC DAPI Aβ IBA1 DAPI Aβ GFAP Isotype ctrl pa ASC, IBA1 ASC, GFAP 0.020 0.10 AC Immune unpublished data pl r = 0.9047 r = 0.8285 pl p < 0.0001 p < 0.00
Slide 10: ACI-6635: efficacy in a mouse model of AD
ACI-6635: efficacy in a mouse model of AD Reduces cortical amyloid plaque load amyloidosis ofc ARTE10 aon Aβ plaque area WT Isotype ctrl ACI-6635 4000 **** * AC Immune unpublished data DAPI Aβ 3000 Area (μm2) 2000 1000 0 *p<0.05; ****p<0.0001 vs ARTE10, Isotype ctrl. One-Way ANOVA ▪ ACI-6635 signifi
Slide 11: Summary and conclusions
Summary and conclusions ▪ A broad panel of ASC mAbs were generated using our proprietary SupraAntigen® vaccine platform 1 ▪ ACI-6635 identified as lead mAb with pM binding affinity, potent in in vitro assays and cross-reactive to human and mouse ASC ▪ Using mAb, ACI-6635, demonstrates that immunothe
Slide 12: Acknowledgements
Acknowledgements Alessio Mylonas Alexandra Casel Chantal Alliod Roger Moser Romain Ollier Gabrielle Bodley Monisha Ratnam Florence Gauye Léa Champion Madiha Derouazi Andrea Pfeifer Marie Kosco-Vilbois Tamara Seredenina
Slide 13: AC Immune
AC Immune We continue to shape the future of neurodegeneration by discovering and developing breakthrough therapies through pioneering science and precision medicine Web: https://www.acimmune.com/ Social media: www.linkedin.com/company/ac-immune Presenter: [email protected] Business developm