Ac Immune Sa · NASDAQ:ACIU

Ac Immune Sa — AAIC 2023

16 slides from Ac Immune Sa's conference presentation, Jul 18, 2023

  1. Slide 1: Discovery and initial clinical evaluation of [18F]ACI-12589, a novel PET-tracer for a-synuclein

    Discovery and initial clinical evaluation of [18F]ACI-12589, a novel and promising PET-tracer for a-synuclein …..and beyond Francesca Capotosti, PhD | AAIC 2023 | July 18th

  2. Slide 2: Disclaimer

    Disclaimer This presentation contains 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 include s

  3. Slide 3: Precision medicine approach enabled by the Morphomer platform

    Precision medicine approach enabled by the Morphomer® platform Developing a suite of PET1 tracers against emerging targets in NDD2 B C Tau NFTs3 a-syn4 Lewy bodies TDP-435 inclusions PI-2620 ACI-12589 Leverage the Morphomer® small molecule platform: ▪ Non-peptidic, small molecules with CNS-drug prop

  4. Slide 4: ACI-12589: a promising a-syn PET tracer

    ACI-12589: a promising a-syn1 PET2 tracer [3H]ACI-12589 specific binding on brain tissue from different a-synucleinopathy cases Familial PD PDD6 PD MSA LBV7 Non-diseased controls 3 FC8 AMG9 AMG CBM10 AMG FC AMG CBM Familial PD a-syn pS129 (nM) 150 (Frontal Cortex) Ratio of specific signal in 5 IHC S

  5. Slide 5: [18F]ACI-12589: the first PET tracer to image a-syn in humans

    [18F]ACI-12589: the first PET1 tracer to image a-syn2 in humans Demographics of FiH3 study Control PD4 MSA5 DLB6 AD7 PSP8 Ataxias n (43) 8 8 13 2 5 3 3 5/3 7/1 7/6 2/0 4/1 3/0 2/1 Sex (M/F) In collaboration with Prof. O. Hansson Ref.: Smith et. al, submitted 63±11 68±6 61±8 81±1 69±4 72±9 54±14 Age

  6. Slide 6: [18F]ACI-12589 uptake in MSA cases compared to controls

    [18F]ACI-12589 uptake in MSA cases compared to controls SUVR 60-90 min using occipital cortex as reference region Ref.: Smith et. al, submitted ■ Clear tracer retention in cerebellar white matter and cerebellar peduncles in MSA-C cases ■ Increased basal ganglia uptake in MSA-P cases in comparison to

  7. Slide 7: MSA-P and MSA-C

    MSA-P MSA-C © 2023 AC Immune. Not to be used or reproduced without permission

  8. Slide 8: MSA-P

    MSA-P © 2023 AC Immune. Not to be used or reproduced without permission

  9. Slide 9: [18F]ACI-12589 uptake discriminates MSA from other synucleinopathies

    [18F]ACI-12589 uptake discriminate MSA from other synucleinopathies Signal quantification in the cerebellar white matter Vt (Logan GA) vs BPnd (Logan Ref) SUVR 60-90 min Vt (Logan) Ref: Occipital Cortex Ref.: Smith et. al, submitted BPnd (Logan Ref) vs SUVr 60-90 min Diagnosis: Control DLB MSA-C PD

  10. Slide 10: [18F]ACI-12589 uptake in genetic PD cases

    [18F]ACI-12589 uptake in genetic PD1 cases SUVr 60-90 minutes using cerebellar grey as reference region Ref.: Smith et. al, submitted 2 3 ■ Signal retention is observed in disease-relevant brain regions in genetic PD cases (SNCA duplication carriers) ■ The retention is higher in the more advanced sy

  11. Slide 11: [18F]ACI-12589 uptake in monkey models of a-syn pathology

    [18F]ACI-12589 uptake in monkey models of a-syn pathology Longitudinal brain uptake in two different a-syn inoculation models Bi-lateral inoculation: PMCA a-syn Control1 PMCA a-syn2 AAV-a-syn A53T3 In collaboration with Olivier Barret, MIRCen CEA MRI 2.5 [18F]ACI-12589 PET SUVR 6 months post inocula

  12. Slide 12: Next generation a-syn PET tracers for patients with PD

    Next generation a-syn1 PET2 tracers for patients with PD3 Improved target occupancy on brain tissue from different a-synucleinopathy cases Saturation binding on total Target engagement PD brain homogenates by high resolution autoradiography [3H]ACI-12589 [3H]ACI-15916 [3H]ACI-12589 [3H]ACI-15916 [3H

  13. Slide 13: Next generation a-syn PET tracers: specific binding

    Next generation a-syn1 PET2 tracers for patients with PD3 Specific binding on brain tissue from different a-synucleinopathy cases Autoradiography on a-synucleinopathy tissues Total NSB4 Total NSB Total NSB Total NSB Total NSB Total NSB ACI-15916 ACI-12589 [3H]ACI-15916 [3H]ACI-12589 8 * (counts/min/

  14. Slide 14: Next generation a-syn PET tracers: selectivity in Alzheimer's tissue

    Next generation a-syn1 PET2 tracers for patients with PD3 Selectivity assessment using Alzheimer’s disease tissue Radiobinding with AD4 brain homogenates High-resolution ARG6 on Tau rich AD sections (Frontal Cortex) (Entorhinal Cortex) [3H]ACI-15916, Kd ND5 8000 [3H]ACI-Abeta Ref, Kd 30 nM Ref: AC I

  15. Slide 15: [18F]ACI-12589 will improve MSA diagnosis and support Precision Medicine

    [18F]ACI-12589 will improve MSA1 diagnosis and support Precision Medicine ▪ Preclinically, ACI-12589: ✓ binds specifically and selectively to a-synuclein inclusions in different human synucleinopathy cases ✓ shows longitudinally increasing uptake in different a-syn monkey models ▪ [18F]ACI-12589 is

  16. Slide 16: Acknowledgements

    Acknowledgements Efthymia Vokali Jerome Molette Myriam Ravache Christophe Delgado Jaqueline Kocher Laure Pittet Elpida Tsika Kasia Piorkowska Heiko Kroth Coralie Vallet Ruth Luthi-Carter Valerie Hliva Olivier Sol Andrea Pfeifer Johannes Streffer Marie Kosco-Vilbois Oskar Hansson Ruben Smith Olivier

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