Slide 1: Tau Morphomer Therapeutics and ACI-35 Anti-pTau Therapeutic Vaccine
© 2019 AC Immune. Not to be used or reproduced without permission. Tau Morphomer TM Therapeutics and ACI - 35 A nti - pTau Therapeutic V accine Marie Kosco - Vilbois, Ph.D , CSO AC Immune Version Nov 4
Slide 2: Disclaimer
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 2 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 Secu
Slide 3: ACI-3024: Potential First in Class Small Molecule Tau Aggregation Inhibitor
www.acimmune.com © 2019 AC Immune. Not to be used or reproduced without permission. ACI - 3024: Potential First in Class Small Molecule Tau Aggregation Inhibitor
Slide 4: Morphomers address spreading hypothesis of misfolded Tau in neurodegenerative diseases
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 4 Nucleus Nucleus Affected cell Healthy cell Recipient cell Misfolded proteins Normally folded proteins Reverse misfolding Promote disaggregation Prevent seeding Morphomer target Nucleus Morph
Slide 5: Morphomer platform: discovery of ACI-3024
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 5 ▪ Conformation - specific, non - peptidic , small molecules with drug like properties ▪ Protein propagation inhibitors ( Kroth et al . , 2012 ) ▪ Robust library contains > 7000 compounds wit
Slide 6: ACI-3024: lead characterization, summary of in vitro results
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 6 Summary of in vitro results ACI - 3024: l ead characterization Tau aggregation inhibition ▪ Potent reduction of Tau aggregation ▪ Effect independent of Tau and FTDP - 17 1 isoform mutants Ta
Slide 7: ACI-3024: in vitro pharmacology
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 7 ACI - 3024: i n vitro pharmacology Ref.: Poli S, et al., CTAD 2018 Intracellular Tau misfolding in in vitro differentiated neuroblastoma cells expressing Tau P301L Undifferentiated cells Ret
Slide 8: ACI-3024: target engagement and functional selectivity
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 8 [3H] - ACI - 3024 [3H] - ACI - 3024 Cold ACI - 3024 High resolution autoradiography on human AD 1 brain sections Ex vivo disaggregation on Tau NFT 2 on human AD brain sections A CI - 3024: t
Slide 9: ACI-3024: in vivo evaluation in rTg4510 mice
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 9 ACI - 3024: in vivo evaluation in rTg4510 mice Treatment study in aged transgenic mice ▪ rTg4510 T auopathy mouse model expressing repressible (Tet promotor Tau on/off) human 4R0N Tau carryi
Slide 10: ACI-3024: decrease in misfolded Tau
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 10 Immunohistochemistry: analysis of misfolded Tau (MC1) in rTg4510 brain section Misfolded Tau levels in brain sections Representative staining (MC1 in red , DAPI in blue ) 50 µm Mean + SEM A
Slide 11: ACI-3024: effect on neuroinflammation
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 11 Activation of microglial cells Inflammatory marker release from microglial cells Human AD - brain derived Tau activation of rat primary microglial cells ACI - 3024: e ffect on neuroinflamma
Slide 12: ACI-3024 pharmacology, ADME and toxicology profile
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 12 • Active and selective in multiple in vitro pharmacology assays • Good selectivity as assessed on 138 targets ( Cerep Bioprint profile) In vitro on - and off - target activity • Good in vit
Slide 13: ACI-3024: First in Human study
ACI - 3024: First in Human study
Slide 14: Escalation scheme SAD (ongoing)
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 14 Escalation scheme SAD 1 (ongoing) Cohort 2 Dose 2 Cohort 3 Dose 3 Cohort 4 Dose 4 Cohort 5 Dose 5 Cohort 1 Dose 1 Dosing Dose Escalation Meeting: evaluate safety, tolerability, pharmakineti
Slide 15: Escalation scheme MAD (next)
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 15 Escalation scheme MAD 1 (next) MAD - HV1 2 Dose 1 MAD - HV2 Dose 2 MAD - HV3 Dose 3 MAD - HV4 Dose 4 Dosing Dose Escalation Meeting: evaluate safety, tolerability, pharmacokinetics data (st
Slide 16: ACI-3024: selective Tau aggregation inhibitor summary
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 16 ▪ The Morphomer TM platform has enabled identification of a new class of low molecular weight compounds, which specifically target misfolded and aggregated Tau 1 2 3 ▪ ACI - 3024 has shown
Slide 17: ACI-35 and ACI-35.030 1st and 2nd Generation Anti-pTau Vaccines
© 2019 AC Immune. Not to be used or reproduced without permission. ACI - 35 1st and 2nd Generation Anti - pTau Vaccines
Slide 18: 1st generation vaccine: ACI-35 structure
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 18 1 st generation vaccine: ACI - 35 structure Anti - pTau therapeutic vaccine Liposomal anchor (Palmitic chains) Liposomal bilayer (Cholesterol and phospholipids) Adjuvant ( MPLA) ACI - 35 is
Slide 19: ACI-35: proof-of-concept
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 19 Key preclinical results ACI - 35: proof - of - concept **** p<0.0001; ANOVA Improvement of behavior (hTauP301S mice) Immune response specific to phosphorylated Tau ( pTau ) ACI - 35 vaccina
Slide 20: ACI-35: proof-of-concept key preclinical results
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 20 ACI - 35: proof - of - concept * * PBS ACI - 35 AT - 100 Anti - pS396 * p <0.05 AC Immune, unpublished data Key preclinical results ▪ Specific antibody response to pathogenic Tau; Decrease
Slide 21: ACI-35 Phase 1b study - overview of clinical data
ACI - 35 Phase 1b study - overview of clinical d ata
Slide 22: Clinical study design: ACI-35 Phase 1b study in AD
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 22 Clinical study design ACI - 35 Phase 1 study in AD 1 Cohort 1 (Dose 1: ACI - 35 or placebo) Cohort 2 (Dose 2: ACI - 35 or placebo) Cohort 3 (Dose 2: ACI - 35 or placebo) Cohort 4 (Dose 3: A
Slide 23: Immunogenicity results
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 23 Responder analysis ( MSD 1 assay in serum) Immunogenicity results ▪ Essentially all actively treated patients were anti - pTau responders ▪ No anti - pTau response observed with placebo ▪ E
Slide 24: Safety results
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 24 Safety results ▪ Injection site reactions and fatigue were the most common study adverse events ▪ Except for injection site reactions, no pattern of adverse events (AE) compared to placebo
Slide 25: ACI-35: Phase 1b study in AD patients key clinical observations
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 25 ACI - 35: Phase 1b study in AD patients Key clinical observations ▪ Safe at all doses tested ▪ Early target - specific antibody response against pTau after the first injection in the vast m
Slide 26: 2nd generation vaccine: ACI-35.030 structure
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 26 2 nd generation vaccine: ACI - 35.030 structure Anti - pTau optimized therapeutic vaccine and ▪ Aim: An optimized liposomal vaccine comprising a tau peptide and a T cell epitope capable of
Slide 27: ACI-35.030: rationale
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 27 pTau-specific IgG titers -14 8 22 36 50 64 78 92106120134148162176190 10 100 1000 10000 100000 1000000 Time (days) E n d p o i n t t i t e r ACI-35.030 ACI-35 ACI - 35.030: r ationale pTau
Slide 28: ACI-35.030: results from rhesus immunization
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 28 ACI - 35.030: r esults from rhesus immunization B inding to Tau from human AD 1 brain Healthy brain tissue AD Braak Stage V/VI ▪ Sera from rhesus monkeys immunized with ACI - 35.030 binds t
Slide 29: ACI-35.030 non-clinical studies key learnings
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 29 ACI - 35.030 non - clinical studies Key learnings ▪ Demonstrates an excellent nonclinical safety profile ▪ Produces an enhanced homogeneous antibody response with boosting effect ▪ No Tau -
Slide 30: ACI-35.030: Phase 1b/2a study
ACI - 35.030: Phase 1b/2a study
Slide 31: ACI-35.030 Phase 1b/2a study in AD
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 31 ACI - 35.030 Phase 1b/2a study in AD 1 ▪ A randomized, multicenter, double - blind, placebo - controlled clinical study ▪ Ratio of 3:1 active (ACI - 35.030) versus placebo per cohort ▪ Prim
Slide 32: AC Immune: pioneers in anti-Abeta and anti-Tau vaccines
© 2019 AC Immune. Not to be used or reproduced without permission. NASDAQ: ACIU | KOL Lunch | November 2019 32 AC Immune: pioneers in anti - Abeta 1 and anti - Tau vaccines 2008 ACI - 24 - 0701 study Dose escalation in mild to moderate AD 2 2013 ACI - 35 - 1201 study Dose escalation and exploration