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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Investor Presentation NASDAQ: ACIU | May 2025 PIONEERING PRECISION MEDICINE TARGETED THERAPEUTICS FOR NEURODEGENERATIVE DISEASES ver. 30.04.2025
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Disclaimer 2 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 statements that address future operating, financial or business performance or AC Immune’s strategies or expectations. In some cases, you can identify these statements by forward- looking words such as “may,” “might,” “will,” “should,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “projects,” “potential,” “outlook” or “continue,” and other comparable terminology. Forward-looking statements are based on management’s current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include those described under the captions “Item 3. Key Information – Risk Factors” and “Item 5. Operating and Financial Review and Prospects” in AC Immune’s Annual Report on Form 20-F and other filings with the Securities and Exchange Commission. These include: the impact of Covid-19 on our business, suppliers, patients and employees and any other impact of Covid-19. Forward-looking statements speak only as of the date they are made, and AC Immune does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law. All forward-looking statements are qualified in their entirety by this cautionary statement. SupraAntigen® is a registered trademark of AC Immune SA in the following territories: AU, CH, EU, GB, JP, RU, SG and USA. Morphomer® is a registered trademark of AC Immune SA in CH, CN, EU, GB, JP, KR, NO and RU.
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Cash reserves on Balance sheet Funding into Q1 2027 AC Immune today – an overview 3 Pioneering next generation Precision Medicine for neurodegenerative diseases ■ Based in Lausanne, Switzerland ■ ~170 employees ■ Listed September 2016 (NASDAQ: ACIU) ■ 100.6 million shares outstanding1 ■ Cash resources of CHF 145.7 million2 Diverse and balanced pipeline with a large number of wholly-owned assets Key differentiation: Precision Medicine Enabled by leadership in Active Immunotherapy New breakthroughs, e.g. morADC3: our platforms have repeatedly created potentially transformative innovations Partnering: strategic, risk-mitigating, timely, monetization with >CHF 4 billion in potential milestones (1) As of March 31, 2025; excluding treasury shares; (2) As of March 31, 2025; (3) Morphomer-antibody drug conjugate
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Neurodegenerative diseases Prevention as the best approach to long-term preservation of neurological health 4 (1) Alzheimer’s disease; (2) Gustavsson et al. Alzheimer’s and Dement. 2023 19:658-670. https://doi.org/10.1002/alz.12694; (3) Monoclonal antibody; (4) Neurodegenerative disease; (5) alpha-synuclein; (6) TAR DNA-binding protein 43; (7) Amyotrophic lateral sclerosis; (8) Limbic-predominant age-related TDP-43 encephalopathy mAb 3 treatment Global Prevalence of AD1 Stages2 (million) 315 69 32 Active immunotherapy for treatment and prevention Diagnostics enable earlier intervention Preclinical AD Prodromal AD AD Dementia Abeta Tau a-syn5 TDP-436 Neuro- inflammation ALS7 LATE8 Parkinson’s Disease / Lewy body dementia Alzheimer’s disease ■ AD prevention through combination of advanced diagnosis and early active immunotherapy ■ Global disease prevention market potentially over 300 million people Co-pathologies in NDD4
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission SupraAntigen® and Morphomer® platforms Deliver conformation-specific candidates for integrated Precision Medicine in CNS 5 Clinically validated CNS-optimized Precision medicine enabling Conformation- specific SupraAntigen® Morphomer® Active immunotherapies & Antibodies Small Molecules morADC
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Indication Candidate Partner Modality Discovery Preclinical Phase 1 Phase 2 Phase 3 Parkinson’s disease ACI-7104.056 anti-a-syn1 active immunotherapy Morphomer® a-syn anti-a-syn small molecule Neuro- inflammation ACI-19764 anti-NLRP3 3 small molecule inhibitor Anti-NLRP3-ASC4 anti-ASC monoclonal antibody ALS5 ACI-5891.9 anti-TDP-43 6 monoclonal antibody NDDs7 morADC Morphomer-antibody drug conjugate Alzheimer’s disease ACI-24.060 anti-Abeta active immunotherapy ACI-35.030 (JNJ-2056) anti-pTau active immunotherapy Morphomer Tau anti-Tau small molecule inhibitor Broad and robust pipeline in neurodegenerative diseases Driven by validated proprietary technology platforms for sustained growth 6 Wholly-ownedPartnered DS9 FDA Fast Track AD8 FDA Fast Track small molecule (1) alpha-synuclein; (2) Parkinson’s disease; (3) (NOD)-like receptor protein 3; (4) Apoptosis-associated speck-like protein containing a CARD, also PYCARD; (5) Amyotrophic lateral sclerosis; (6) TAR DNA- binding protein 43; (7) Neurodegenerative diseases; (8) Alzheimer’s disease; (9) Down syndrome
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Active immunotherapies H1’25 H2’25 ACI-24.060 (Takeda) Abeta ABATE Phase 2 trial interim results (AD1; DS2) ACI-7104.056 a-syn3 Phase 2 VacSYn trial in PD4: Part 1 interim results, pharmacodynamics, biomarkers Phase 2 VacSYn trial in PD: Part 2 Initiation5 Monoclonal antibodies and small molecule drugs Monoclonal antibody TDP-436 Validated pharmacodynamic assay for clinical readout Morphomer-NLRP3 (ACI-19764) NLRP37 Lead candidate declaration and initiation of IND-enabling studies IND8/CTA9 filing Morphomer-Tau Tau Lead candidate declaration and initiation of IND-enabling studies Morphomer a-syn a-syn Lead candidate declaration morADC Platform (a-syn) In vivo PoC study of proprietary brain delivery platform Diagnostics TDP-43-PET10 tracer TDP-43 Phase 1 initial readout in genetic FTD11 a-syn-PET tracer (ACI-15916) a-syn Phase 1 readout Key milestones Multiple catalysts across pipeline including selected 2025 milestones (1) Alzheimer’s disease; (2) Down syndrome; (3) alpha-synuclein; (4) Parkinson’s disease; (5) IND/CTA approval; (6) TAR DNA-binding protein 43; (7) (NOD)-like receptor protein; (8) Investigational new drug; (9) Clinical Trial Application; (10) Positron emission tomography; (11) Frontotemporal dementia 7 Readouts Other development events
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission AC Immune strong Balance Sheet 8 Operations well-funded into 2027 Astute investment strategy focused on major value drivers and near- term catalysts Strong Balance Sheet2 Cash runway into Q1 2027 2025 annual cash burn guidance CHF 75m – 85m Cash of CHF 145.7 million1 (1) As of March 31, 2025; (2) Assumes no other milestones or deals included
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission AC Immune’s four core value-driving pillars 9 Combining biomarker-based clinical development, validated targets and strong collaborations The only active immunotherapy in a prevention study for pre-symptomatic Alzheimer’s disease ACI-35.030 anti-pTau Biomarker-driven development targeting the hallmark protein in Alzheimer’s disease and Alzheimer’s in Down syndrome ACI-24.060 anti-Abeta A unique suite of disease- modifying therapeutics and diagnostics targeting pathological a-syn a-syn-targeted programs for PD Inhibiting neuroinflammation to alleviate disease pathology and disrupt the negative feedback loop NLRP3 inflammasome
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission AC Immune’s four core value-driving pillars 10 Combining biomarker-based clinical development, validated targets and strong collaborations The only active immunotherapy in a prevention study for pre-symptomatic Alzheimer’s disease ACI-35.030 anti-pTau Biomarker-driven development targeting the hallmark protein in Alzheimer’s disease and Alzheimer’s in Down syndrome ACI-24.060 anti-Abeta A unique suite of disease- modifying therapeutics and diagnostics targeting pathological a-syn a-syn-targeted programs for PD Inhibiting neuroinflammation to alleviate disease pathology and disrupt the negative feedback loop NLRP3 inflammasome
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targeting neurodegenerative diseases Long-lasting specific immunity for pathological target, consistent, boostable Limited annual dosing (once or twice) after priming year No observed ARIA-E1 to date (safety profile well suited to long-term use) Cost-effective (attractive healthcare economics across global populations) Ease of administration and simple logistics for global access Active immunotherapy Stimulates the patient's immune system to produce their own antibodies Passive immunotherapy Externally generated mAb requires administration every two to four weeks Major advantages (1) Amyloid-related imaging abnormalities-edema 11
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Disruptive potential of SupraAntigen® Active immunotherapies delivering superior results in neurodegenerative diseases 12 For ACI-35.030: (1) 100% response after 1st injection; (2) Increases over time ■ Robust immunogenicity and strong safety demonstrated in humans ■ Evidence for lasting immune response supporting a disease prevention approach Immunogenicity Target & conformation specificity Avidity increase over time Sustainable response Boostable response Unprecedented Clinical PerformanceLiposomal anchor (Palmitic chains) Liposomal bilayer (Cholesterol and phospholipids) Adjuvant 1 T-cell Peptide (non-target) Adjuvant 2 Target-specific antibody response Helper T-cells safely engaged (target-unrelated) Target antigen
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission 13 ACI-35.030 and JACI-35.054 utilized the same pTau1 epitope – compared head-to-head in Phase 1b/2a trial in AD2 patients ACI-35.030 induced anti-ePHF Ab5 responses in 100% of patients after 1st injection ACI-35.030-inducedAbs against normal Tau returned to baseline levels as Ab response matured 103 104 105 0 8 16 24 32 40 48 56 64 72 Weeks Antibody Titers (Geometric Mean) Anti-ePHF3 IgG Titers4 Injection 102 103 104 105 106 0 8 16 24 32 40 48 56 64 72 Weeks Antibody Titers (Geometric Mean) Anti-Tau IgG Titers4 Injection ACI-35.030 JACI-35.0540 (1) Phosphorylated Tau; (2) Alzheimer’s disease; (3) Enriched paired helical filaments; (4) ACI-35.030 original sub-cohort 1.2 data; (5) Antibody Follows data showingACI-35.030’s superior specificity for pathological T auvs. JACI-35.054 ACI-35.030 selected for further development by partner Janssen
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission A randomized, multicenter, double-blind, placebo-controlled Phase 2b study Study population Biomarker readouts Primary cognitive endpoint Reain: Phase 2b study of ACI-35.030 (JNJ-2056) in preclinicalAD1 14 ▪ ~500 participants with preclinicalAD: ▪ Cognitively normal ▪ TauPET positive ▪ Amyloid positive2 ▪ Prior to appearance of clinical symptoms ▪ Taupathology compared with placebo: ▪ Tau-PET imaging3 ▪ Baseline and annually for 4 years ▪ Potential BLA filing and acceleratedapproval ▪ PreclinicalAD Cognitive Composite 54: ▪ Episodic memory ▪ Timed executive function ▪ Global cognition ▪ Potential traditional approval anti-pTau active immunotherapy (249 patients) Placebo (249 patients) Follow up Open-label extensionRandomization 1:1Screening 0 2 6 12 18 then every 6 months (1) Alzheimer’s disease; (2) Implied Abeta positivity (A+) because of Tau positivity (T+), but not part of the inclusion criteria; (3) Tau-PET measured in the Tau-naïve composite region; (4) PACC-5 Dosing scheme: Treatment period of 4 years
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission AC Immune’s four core value-driving pillars 15 Combining biomarker-based clinical development, validated targets and strong collaborations The only active immunotherapy in a prevention study for pre-symptomatic Alzheimer’s disease ACI-35.030 anti-pTau Biomarker-driven development targeting the hallmark protein in Alzheimer’s disease and Alzheimer’s in Down syndrome ACI-24.060 anti-Abeta A unique suite of disease- modifying therapeutics and diagnostics targeting pathological a-syn a-syn-targeted programs for PD Inhibiting neuroinflammation to alleviate disease pathology and disrupt the negative feedback loop NLRP3 inflammasome
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission ACI-24 active immunotherapy reduces Abeta plaque burden 16 ■ ACI-24 treatment significantly reduces Abeta plaque burden in aggressive APPxPS1 model ■ Similar plaque reductions seen with lecanemab and donanemab in less aggressive APP models Control ACI-24 * p<0.05 0.0 0.5 1.0 1.5Abeta coverage (% of the area) Area ✱ Control ACI-24 0 5 10 15 20 25 Plaques (number/μm2) Number ✱ ✱ ** p<0.01 Ref: Njavro, et al., Cells 2023 54% ↓ 48% ↓ Abeta Plaque Staining in Control and ACI-24-treated Mice ACI-24 (1) Alzheimer’s disease mouse model: APPxPS-1 double transgenic mice; (2) Alzheimer’s disease; (3) Antibodies Control Quantificationof Abeta Plaques Significant Abeta plaque reduction in vivo in preclinical APPxPS1 model1
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Treatment in AD4 (up to 4 dose/regimen cohorts) (12 months) : Biomarker-based Phase 1b/2 study of ACI-24.060 in AD1 and DS2 17 Placebo-controlled Phase 1b/2 Study Overview Trial Schematic Adaptive Study Design Follow up (6 months) Outcome measures ▪ Safety/tolerability ▪ Pharmacodynamics: Serum anti-Abeta antibody titers ▪ Abeta-PET imaging ▪ Exploratory biomarkers and clinical endpoints Both BothADDS ▪ Interim analyses of safety/tolerability & immunogenicity ▪ Biomarker analyses includingAbeta PET3 and others ▪ Initiation using selected dose identified in AD (based on safety/tolerability and immunogenicity) ▪ Up to 4 different doses and/or dose regimens ▪ Expansion of one cohort to assess effect on Abeta PET Dose selection (safety / immunogenicity) Dose escalation in AD Follow up / expansion phase in AD Follow up (6 months) Expansion in AD (12 months) Follow up (6 months) Treatment in DS5 (18 months) (1) Alzheimer's disease; (2) Down syndrome-related AD; (3) Positron emission tomography; (4) AD participants must between 50 – 85 years of age and have prodromal AD with Clinical Dementia Rating Global Score of 0.5 and Abeta pathology confirmed by PET scan; (5) Cohort comprised of non-demented people living with DS (age 35 – 50 years) and Abeta pathology confirmed by PET scan
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Placebo-controlled Phase 1b/2 study: no safety concerns to date Patient baseline characteristics and interim safety/tolerability findings 18 Baseline profile1 Unit Part 1: AD Part 2: DS Number of patients n 74 15 Age Years mean std 70.7 6.14 45.0 3.95 Sex Male Female n (%) n (%) 34 (45.9%) 40 (54.1%) 6 (40.0%) 9 (60.0%) Race White Black / African American Asian n (%) n (%) n (%) 71 (95.9%) 2 (2.7%) 1 (1.4%) 15 (100%) 0 0 Cognitive performance MMSE 2 ADAS-Cog-13 3 KBIT-2 4 mean (std) mean (std) mean (std) 24.5 (3.6) 25.3 (9.0) - - - 53.8 (10.6) (1) Data cut-off date: 23 Jan. 2025; (2) Mini-mental state examination, interim data; (3) Alzheimer's Disease Assessment Scale, Cognitive part, interim data; (4) Kaufman Brief Intelligence Test Second Edition, interim data based on 14 out of 15 subjects with DS; (5) Treatment Emergent Adverse Events To date, no death; one serious adverse event related to study treatment (vomiting and headache in AD)2 Most frequent TEAEs5 are injection site reactions of mild or moderate intensity 3 ▪ No ARIA-H in subjects with DS ▪ In AD, all events were asymptomatic and their frequency in line with expected placebo incidence5 Overall good safety and tolerability in both, AD and DS, study populations1 ▪ No ARIA-E ▪ No evidence of CNS inflammation4
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission 19 Preliminary insights from blinded cohorts AD1, AD2 and AD3 ACI-24.060 exhibits a dose-dependent immune response against toxic species of Abeta Trend towards increase in the magnitude of anti-Abeta1-42 IgG titers with increasing dose2 Increase in the responder rate with increasing dose and repeated immunizations3 Immunogenicity observed in AD subjects at all tested doses1 Boosting effect for all dose levels observed after repeated immunizations with ACI-24.0604 More durable and sustained immune response were observed in cohorts AD2 and AD35 ■ 12-month treatment time point for AD1, AD2 and AD3 reached in late 2025
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission 20 Active immunotherapy: a new class of treatment for neurodegenerative disease Potential for profound social and economic impact Treatment Maintenance Prevention for global treatment and prevention of neurodegenerative diseases
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission AC Immune’s four core value-driving pillars 21 Combining biomarker-based clinical development, validated targets and strong collaborations The only active immunotherapy in a prevention study for pre-symptomatic Alzheimer’s disease ACI-35.030 anti-pTau Biomarker-driven development targeting the hallmark protein in Alzheimer’s disease and Alzheimer’s in Down syndrome ACI-24.060 anti-Abeta A unique suite of disease- modifying therapeutics and diagnostics targeting pathological a-syn a-syn-targeted programs for PD Inhibiting neuroinflammation to alleviate disease pathology and disrupt the negative feedback loop NLRP3 inflammasome
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission 22 Pioneering a-syn 1 modalities to address Parkinson’s disease ▪ Active immunotherapy targeting pathological oligomeric a-syn to prevent spreading and neurodegeneration ▪ In Phase 2 trial in early PD2 with safety and immunogenicity data reported in H2 2024 ▪ Morphomer® diagnostic PET4 tracers for pathological a-syn aggregates to detect and differentiate a-synucleinopathies ▪ Excellent selectivity with IND5-enabling studies6 completed in H2 2024 ▪ Small molecule Morphomer® targets intracellular pathological a-syn aggregates to treat and prevent Parkinson’s disease ▪ Lead candidate decision anticipated in 2025 Unique pipeline assets: 3 therapeutics and 2 diagnostics (1) alpha-synuclein; (2) Parkinson’s disease; (3) Antibody drug conjugate; (4) Positron emission tomography; (5) Investigational New Drug; (6) IND-enabling studies for ACI-15916 ▪ Small molecule Morphomer® ADC3 with enhanced brain penetration and potency compared to either parent molecule ▪ New Platform technology: Lead discovery ACI-7104.056 Mor-a-syn ACI-12589 ACI-15916 morADC ▪ Parkinson’s disease affects over 6 million people worldwide ▪ Challenges remain in diagnosis and there are substantial unmet needs for effective therapeutic interventions
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Placebo-controlled Phase 2 Study Overview – Interim data in H2 ‘24 ▪ Key immunogenicity measures ▪ Measures of pathological a-syn (a-syn oligomers and aggregates) (1) Participants must have idiopathic PD and be stable on up to 300 mg of L-Dopa treatment and dopaminergicdeficit determined by Dopamine Transporter Single Photon Emission Computed Tomography; (2) Unified Parkinson’s disease rating scale; (3) Dopamine Transporter Single Photon Emission Computed Tomography; (4) Arterial spin labeling; (5) Diffusion tensor imaging Treatment in PD1 (18 months) Cohort 1 in PD – Dose A Cohort 2 in PD – Dose B Interim analyses Safety Antibody titers A-syn assay Pharmacodynamics Follow up (6 months) Part 2: Proof of Concept in Early PD ▪ Motor and Non-Motor Functioning (UPDRS2 based) ▪ Degeneration of dopaminergic terminals (DaT SPECT3 imaging) ▪ Advanced MRI (includingASL4 and DTI5) ▪ Digital biomarkers of motor and non-motor function ▪ Functional and patient reported outcomes Expansion cohort (up to 150 subjects) Dose previously tested in Part 1 Treatmentin PD (18 months) Follow up (6 months) ▪ Seamless transition ▪ ▪ All participants from Part 1 will contribute to final analysis Biomarker based interim analyses ▪ Early immunogenicity to tailor dose and/or dose regimen ▪ Apply disease-relevant biomarkers for early transition to filing Part 1: Safety & PK/PD : Adaptive biomarker-based Phase 2 study of ACI-7104 in early PD 23
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Placebo-controlled Ph 2 Study: No safety concerns raised by DSMB4 : Patient baseline characteristics and interim safety/tolerability findings 24 Baseline profile Unit Total1 Total number of patients n 34 Age Years mean (std) 62.1 (6.7) Sex Male Female n (%) n (%) 22 (65%) 12 (35%) Hoehn and Yahr stage Stage I Stage II n (%) n (%) 16 (47%) 18 (53%) MDS-UPDRS scores Part 1: Non-motor experiences of daily living Part 2: Non-motor experiences of daily living Part 3: Motor examination mean (std) mean (std) mean (std) 4.09 (3.1) 4.09 (3.2) 21.09 (9.8) PD Treatment treatment-naïve L-Dopa 300mg/day n (%) n (%) 11 (32%) 23 (68%) (1) cut-off date November 08, 2024; (2) Worsening of preexisting generalized anxiety disorder unrelated to study drug; (3) incidence in the pooled active and placebo subjects; (4) Data Safety Monitoring Board; (5) Adverse Event; (6) Magnetic Resonance Imaging; (7) Electrocardiogram No death or severe adverse event observed to date; no serious adverse event considered related to the study drug2 One AE5 leading to discontinuation from the study2 considered unrelated to study drug3 Most common AEs are transient and generally of mild severity: Injection Site Reactions (50%) and headaches (14.7%)34 No significant MRI6, lab, ECG7 abnormalities5 Overall good safety/tolerability to date 1
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission ACI-7104.056 VacSYn Ph 2 trial: Interim results (week 26) 25 Weeks Mean IgG antibody titers AU/ml (± SEM) Anti-a-syn1 antibody titers Strong and boostable anti-a-syn antibody response (after four immunizations) ▪ Anti-a-syn antibody titers evident after 2 injections ▪ ACI-7104.056 induces anti-a-syn antibody levels on average over 20-fold higher2 than placebo after 4 immunizations ▪ Repeated immunizations showed boostability and potential for further amplification of the response ▪ No anti-a-syn antibody responses were observed in placebo-treated subjects ▪ To date, no clinically relevant safety issue reported Key results (1) alpha-synuclein (peptide aa 115-121); (2) assay background level defined by signal in the placebo group Immunizations ACI-7104.056 Placebo 20000 10000 0 30000 40000 0 5 10 15 20 25
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission AC Immune’s four core value-driving pillars 26 Combining biomarker-based clinical development, validated targets and strong collaborations The only active immunotherapy in a prevention study for pre-symptomatic Alzheimer’s disease ACI-35.030 anti-pTau Biomarker-driven development targeting the hallmark protein in Alzheimer’s disease and Alzheimer’s in Down syndrome ACI-24.060 anti-Abeta A unique suite of disease- modifying therapeutics and diagnostics targeting pathological a-syn a-syn-targeted programs for PD Inhibiting neuroinflammation to alleviate disease pathology and disrupt the negative feedback loop NLRP3 inflammasome
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission NLRP31 Inflammasome is a promising therapeutic target Key disease driver in multiple CNS and other diseases 27 ■ Mechanism of action can be applied across a broad range of neuroinflammatory and other diseases ■ Pharmacological inhibition of NLRP3 lowers aberrant cytokine release and reduces disease pathology 13,14,15 (1) Nod-Like Receptor protein containing Pyrin 3; (2) Apoptosis-associated speck-like protein containing a CARD, also called PYCARD; (3) monoclonal antibody; (4) TAR DNA binding protein-43; (5) Venegas et al., 2017; (6) phosphorylated Tau; (7) alpha-synuclein; (8) Interleukin-1 beta; (9) Interleukin-18; (10) Central nervous system; (11) neurodegenerative diseases; (12) Inflammatory bowel disease; (13) Stancu et al., 2019; (14) Dempsey et al., 2018; (15) Gordon et al., 2018 TDP-434 Fibrillar Abeta pTau 6 neurofibrillary tangles Neuronal atrophy Fibrillar a-syn7 Nucleus ASC Speck Microglia NLRP3 Inflammasome activation anti-ASC2 mAb3 Inhibition of propagation NLRP3 small molecules Inhibition of activation ASC specks in Abeta plaques5 Lysosome IL-1 8 IL-18 9 ▪ Potential best-in-class compounds ▪ Small molecule therapeutics ▪ Monoclonal antibody diagnostics ▪ Multiple substantial indications AC Immune’s unique positioning CNS10 ▪ Parkinson’s disease ▪ Alzheimer’s disease ▪ Multiple sclerosis ▪ Other NDDs11 Other ▪ Obesity ▪ Type 2 diabetes ▪ Rheumatoid arthritis ▪ IBD12
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission ACI-19764 small molecule candidate targeting NLRP3 1 Preclinical efficacy demonstrated in mouse models of neuroinflammation 28 Multiple sclerosis model (EAE2)Human whole blood IL-1Brain penetration 0 4 8 12 16 20 24 1 10 100 1000 Time (h) Plasma Brain CSF Highly brain penetrant molecule with a brain/plasma4 ratio of 0.7 after a single oral dose in rats (5 mg/kg)Unbound concentration (nM) Potent NLRP3 inhibition leads to reduction in pro-pyroptotic caspase-1 (1) (NOD)-like receptor protein 3; (2) Experimental autoimmune encephalomyelitis; (3) Dosed at 5mg/kg in medicated chow; (4) Kp,uu – unbound partition coefficient; (5) Alzheimer’s disease; (6) Parkinson’s disease; (7) Amyotrophic lateral sclerosis; (8) Frontotemporal dementia; (9) Multiple sclerosis ■ Mechanism of action can be applied across a broad range of neuroinflammatory diseases including: AD5, PD6, ALS7, FTD8, MS9 and traumatic brain and spinal cord injury naïve EAE+vehicle EAE+ACI-19764 5mpk 0 2 4 6 8 10 Caspase-1 levels in spinal cord (fold-change vs naive group) ✱✱✱ ✱✱✱ naïve EAE+vehicle EAE+ACI-19764 5mpk 0 2 4 6 8 GSDM-D levels in spinal cord (fold-change vs naïve group) ✱✱✱✱ ✱ Caspase-1 levels in spinal cord (fold-change vs. naïve group) Naïve EAE + vehicle EAE + ACI-19764 3 IL-1 ( of control) ACI-19764 concentration [log nM] ATP 3 mM ACI-19764 IC50 = 20.5 nM MCC950 IC50 = 363 nM ACI-19764 exhibits low nM efficacy in translationally relevant in vitro assays
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission ACI-19764 small molecule candidate targeting NLRP3 Excellent brain penetrance, safety and efficacy (preclinical tox / PK data) 29 ▪ Mouse brain Kp,uu1 : 0.3 ▪ Rat brain Kp,uu : 0.7 ▪ Dog CSF2 Kp,uu : 1 ▪ BCS3 class 1 ▪ Predicted human oral dose below 100mg/day Optimal brain PK and developability ▪ Strong IL-1β4 inhibition ▪ Human macrophages IC50 : 2nM ▪ Human WB5 IC50 : 20.5nM ▪ Mouse WB IC50 : 84.4nM ▪ Mouse microglia IC50 : 5.6nM ▪ In vivo (EAE6 model) inhibition of inflammation (IL-1β; caspase-1; GFAP7; CD48) ▪ No inhibition of other types of inflammasome9 High potency and selectivity ▪ No adverse findings up to 400 mg/kg in short toxicology rat study ▪ No adverse effects upon chronic treatment in several in vivo studies ▪ Tg83 mice (3 months) ▪ EAE mice (30 days) ▪ DIO mice (28 days) Excellent safety and tolerability ▪ ACI-19764 shows excellent brain penetration, efficacy, safety, and developability profile ▪ IND-enabling studies to be completed in 2025 (1) Optimal brain to plasma ration (Kp,uu) = 1.0; (2) cerebrospinal fluid; (3) Biopharmaceutics Classification System; class 1 defines high soluble and high permeable drugs(4) interleukin-1 beta; (5) whole blood; (6) Experimental autoimmune encephalomyelitis; (7) Glial fibrillary acidic protein; (8) cluster of differentiation 4, marker of T helper cells; (9) AIM2, NLRP1, NLRC4 29
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Tracers from the Morphomer® platform
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Indication Candidate Partner Modality Discovery Preclinical Phase 1 Phase 2 Phase 3 Parkinson’s disease ACI-15916 a-syn-PET3 tracer (diagnostic) MSA4 ACI-12589 a-syn-PET tracer (diagnostic) ALS5 ACI-19626 TDP-43-PET tracer (diagnostic) Alzheimer’s disease PI-2620 Tau-PET tracer (diagnostic) Precision medicine approach enabled by the Morphomer® platform Developing a suite of tracers against emerging targets in neurodegenerative diseases 31 (1) alpha-synuclein; (2) TAR DNA-binding protein 43; (3) Positron emission tomography; (4) Multiple system atrophy; (5) Amyotrophic lateral sclerosis; (6) Alzheimer’s disease Wholly- owned Partnered TDP-432 inclusions A B C a-syn1 Lewy bodies ACI-12589 Tau neurofibrillary tangles PI-2620 FDA Fast Track
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission Technology platforms driving value-creating pharma deals Strategy: optimize value to risk ratio and retain significant upside 32 ■ Over CHF 400 million in upfront payments from deals; further >CHF 4.3 billion possible ■ Considerable additional potential value in our unpartnered clinical and preclinical programs (1) Monoclonal antibody Platform Wholly- owned Programs SupraAntigen® Morphomer® ■ a-syn active immunotherapy ■ Anti-TDP-43 mAb1 ■ Anti-NLRP3-ASC mAb ■ Mor-a-syn ■ Mor-TDP-43 PET / Mor -a-syn PET ■ Mor-NLRP3-ASC ■ morADC
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission AC Immune’s leadership in Precision Medicine 33 (1) Neurodegenerative disease; (2) assumes no other milestones Multiple unpartnered high-value assets Strong Balance Sheet with cash runway into 20272 Scientific excellence drives landmark partnering deals and shareholder value Confirmed leadership in active immunotherapies in NDD1
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission 34 Shifting the treatment paradigm for neurodegenerative disease towards precision medicine and disease prevention AC Immune: Pioneering science and precision medicine
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Supplementary information
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission AC Immune’s strong track record in deals1 with leading pharma companies Strategy: optimize value to risk ratio and retain significant upside 36 (1) Disclosure limited due to confidentiality agreements with collaboration partners; (2) In millions; (3) Total payments received from partner until termination of agreement; (4) Positron emission tomography; (5) In Alzheimer’s disease; (6) Phase 1 completed; (7) Equity investment; (8) Converted to CHF on date of receipt; (9) Excludes convertible note agreement of USD 50 million ; * previously licensed to Genentech (a member of the Roche Group) Program Phase Total value2 Upfront2 Milestones received2 Royalties Partner ACI-24.060 (anti-Abeta active immunotherapy) Phase 1b/2 >USD 2,100 USD 100 Mid-to-high teens ACI-35.030 (anti-pTau active immunotherapy) Phase 2b CHF 500 CHF 26 CHF 45 Low-double digits to mid-teens Tau Morphomer® drugs Phase 1 6 CHF 1,860 CHF 80 +USD 50 7 CHF 40 Low-double digits to mid-teens PI-2620 (Tau PET4 tracer) Phase 3 5 EUR 160 EUR 0.5 EUR 7 Mid-single digits to low-teens Crenezumab (anti-Abeta antibody) Phase 2 USD 65 3 USD 25 USD 40 * Semorinemab (anti-Tau antibody) Phase 2 CHF 59 3 CHF 17 CHF 42 * Total (millions)8 CHF ~4,750 CHF 255.2 9 CHF 172 ■ Outstanding potential milestone payments exceed ~CHF 4.3 billion
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NASDAQ: ACIU | Investor Presentation, May 2025 © 2025 AC Immune. Not to be used or reproduced without permission morADC platform offers enhanced targeting of brain proteinopathies 37 Enables single or dual targeting strategies to deliver combination therapy in a single agent Single targeted morADC (a-syn/a-syn) shows up to 80x higher anti-aggregation effects than parental molecules Dual targeted morADC (Abeta/Tau) shows 3x and 15x higher anti-aggregation effects than parental molecules ■ morADCs: important synergistic effects on targeted proteinopathies Additionally, enhanced brain exposure (up to 8x higher) was observed for the monoclonal antibody within the morADC AC Immune unpublished data pS129 a-syn Control Control a-syn a-syna-syn Seeding inhibition Aggregation inhibition Synergistic inhibition of aggregation and seeding and increased brain penetration 0 20 40 60 80 100 A-syn ThT flluorescence (% of vehicle control) Antibody Morphomer Compound mixture morADC 3 1.5 10 5 10 5 3 1.5+ + 3 1.5 A-syn ThT fluorescence