20-F: AC Immune Reports 2025 Losses Amid R&D Investment & Pipeline Progress

AC Immune SA reported a net loss of CHF 70.4 million for 2025, driven by significant R&D investments and strategic pipeline advancements in neurodegenerative diseases, while maintaining sufficient liquidity until Q3 2027.

Summary

• Net loss increased to CHF 70.4 million for the year ended December 31, 2025, compared to CHF 50.9 million in 2024.
• Contract revenues decreased significantly to CHF 3.6 million in 2025 from CHF 27.3 million in 2024.
• Research and development expenses decreased to CHF 56.4 million in 2025 from CHF 62.6 million in 2024, primarily due to reduced manufacturing activities and completed preclinical work in some programs, offset by increased costs in others.
• General and administrative expenses decreased to CHF 16.1 million in 2025 from CHF 17.3 million in 2024, mainly due to lower legal fees.
• The liquidity position (cash and cash equivalents plus short-term financial assets) was CHF 91.4 million as of December 31, 2025, a decrease from CHF 165.5 million in 2024.
• Existing capital resources are believed to be sufficient to meet projected operating requirements until the end of Q3 2027, assuming no other milestone payments.
• Interim analyses for ACI-7104.056 (anti-a-syn active immunotherapy for Parkinson's disease) Phase 2 VacSYn trial in H2 2025 showed strong anti-a-synuclein antibody levels, good tolerability, and trends toward disease modification.
• ACI-24.060 (anti-Abeta active immunotherapy for Alzheimer's disease and Down Syndrome) Phase 1b/2 trial demonstrated good tolerability and immunogenicity with no Amyloid-Related Imaging Abnormalities-vasogenic edema (ARIA-E) reported.
• Enrollment for ACI-35.030/JNJ-2056 (anti-pTau active immunotherapy for preclinical Alzheimer's disease) Phase 2b ReTain study has been temporarily paused by Johnson & Johnson to evaluate trial aspects, not due to new safety findings.
• ACI-19764 (NLRP3 inhibitor) First-In-Human study initiated in February 2026, with data for singleand multiple-ascending doses expected in Q4 2026.
• PI-2620 (Tau-PET imaging agent) received FDA Fast Track Designation in August 2024 for Alzheimer's disease, Progressive Supranuclear Palsy (PSP), and Corticobasal Degeneration (CBD).
• ACI-19626 (TDP-43 PET tracer), a first-in-class agent, initiated its First-In-Human study in Q1 2025, with initial results suggesting higher brain uptake in genetic Frontotemporal Lobar Degeneration (FTLD) cases.
• The company regained global rights to Semorinemab and Crenezumab in February 2025 following the termination of collaboration agreements with Genentech.

Sentiment

Score: 6

Explanation: StockSavvy.ai views this as a mixed filing. While financial performance shows increased losses and decreased revenue, significant clinical pipeline progress and strategic partnerships, including new Fast Track designations and the initiation of multiple Phase 1/2/3 trials, provide a positive long-term outlook for a clinical-stage biopharmaceutical company. The temporary pause in one trial is noted but not attributed to safety.

Positives

• ACI-7104.056 (anti-a-syn active immunotherapy for PD) Phase 2 interim results show strong antibody responses, good safety, and trends toward disease modification, including stabilization of CSF a-syn, neurofilament light chain (NfL), dopamine transporter (DaT) SPECT imaging, and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III scores.
• ACI-24.060 (anti-Abeta active immunotherapy for AD/DS) Phase 1b/2 trial demonstrates good tolerability and immunogenicity at all tested doses in AD and DS subjects, with no ARIA-E reported, and preliminary insights show increased anti-Abeta1-42 IgG titers and durable immune response.
• ACI-24.060 is subject to an exclusive option and license agreement with Takeda Pharmaceuticals USA, Inc., including an upfront payment of USD 100.0 million (CHF 92.3 million) and potential future payments up to approximately USD 2.1 billion (CHF 1.7 billion) plus tiered royalties.
• ACI-35.030/JNJ-2056 (anti-pTau active immunotherapy for AD) received FDA Fast Track designation in July 2024, potentially accelerating its regulatory pathway.
• PI-2620 (Tau-PET imaging agent) received FDA Fast Track Designation in August 2024 for AD, PSP, and CBD, highlighting its potential diagnostic utility across multiple neurodegenerative conditions.
• ACI-19764 (NLRP3 inhibitor) First-In-Human study initiated in February 2026, with preclinical data suggesting it is a potent, selective, and highly brain-penetrant compound.
• Identification of several lead Morphomer Tau aggregation inhibitors in 2025, with IND/CTA-enabling activities planned for 2026, indicating pipeline progression.
• Identification of a customized Tau PET ligand for early clinical development of Morphomer Tau, offering a unique tool for target engagement assessment.
• ACI-12589 (a-syn-PET tracer) is clinically validated for Multiple System Atrophy (MSA), and ACI-15916 (next-generation a-syn PET tracer) Phase 1 trial in PD initiated in Q1 2025.
• ACI-19626 (TDP-43 PET tracer) is a first-in-class tracer in its FIH study, showing initial promising results in genetic FTD cases, addressing a high unmet medical need.
• Regained global rights to Semorinemab and Crenezumab in February 2025, providing potential for future development or partnering opportunities.
• The company has a strong track record of establishing value-driving collaboration agreements with leading pharmaceutical companies, leveraging external expertise and non-dilutive capital.

Negatives

• Net loss increased to CHF 70.4 million for the year ended December 31, 2025, compared to CHF 50.9 million in 2024, indicating a worsening financial performance.
• Contract revenues significantly decreased to CHF 3.6 million in 2025 from CHF 27.3 million in 2024, reflecting a substantial drop in revenue generation.
• Accumulated losses reached CHF 439.0 million as of December 31, 2025, highlighting a continued history of unprofitability.
• Total liquidity decreased from CHF 165.5 million in 2024 to CHF 91.4 million in 2025, representing a significant reduction in available capital.
• Enrollment for the ACI-35.030/JNJ-2056 Phase 2b ReTain trial has been temporarily paused by Johnson & Johnson, which could delay the development timeline.
• Two serious adverse events (SAEs) in subjects with Alzheimer's disease in the ACI-24.060 trial were considered possibly related to the study treatment.
• The company has no products approved for commercial sale and has never generated any revenues from product sales, indicating a high-risk profile for a clinical-stage biopharmaceutical company.
• Tax loss carry-forwards of CHF 362.3 million as of December 31, 2025, will expire in 7 years if not utilized, posing a risk to future tax benefits.

Risks

• Heavy dependence on the success of clinical and preclinical products, with low probabilities of success in the central nervous system (CNS) space.
• Results of early preclinical and clinical studies may not be predictive of future results, potentially leading to failure in later-stage clinical studies or regulatory approval.
• Products may not gain market acceptance or may be preempted by competitors, including generic versions of approved innovator products.
• Inability to successfully use and expand Morphomer and SupraAntigen proprietary technology platforms to build additional product candidates.
• Operating in highly competitive and rapidly changing industries, which may result in others discovering, developing or commercializing competing products more successfully.
• Future growth and ability to compete depends on retaining key personnel and recruiting additional qualified personnel, including members of the Executive Committee.
• A breakdown or breach of information technology systems and cybersecurity efforts, or those of key business partners, contract research organizations (CROs), or service providers, could subject the company to liability or reputational damage.
• Failure to maintain, or realize the benefits from, current strategic relationships with license and collaboration partners (Eli Lilly and Company, Janssen Pharmaceuticals Inc., Lantheus Holdings, Inc., Takeda Pharmaceuticals, USA, Inc.) could materially adversely affect financial condition.
• Collaboration agreements may make the company an attractive acquisition target under certain circumstances, potentially bringing additional uncertainties to business development.
• Insufficient patent terms to protect products and business effectively, or failure to comply with intellectual property agreements, could adversely affect product sales and technology development.
• Potential for claims challenging the inventorship of patents and other intellectual property.
• History of operating losses and anticipation of incurring losses for the foreseeable future, requiring additional funding to avoid delaying, reducing, or eliminating product development programs.
• Inability to obtain regulatory approval for any product candidates, which is necessary for commercialization.
• Even if regulatory approvals are obtained in one jurisdiction, there is no assurance of obtaining approval in other jurisdictions, limiting market opportunities.
• Ongoing obligations and review post-approval may result in significant additional expenses, labeling restrictions, or market withdrawal.
• FDA and applicable foreign regulatory authorities may not accept data from clinical studies conducted outside the U.S.
• Enacted and future legislation (e.g., Inflation Reduction Act of 2022) may increase the difficulty and cost of obtaining marketing approval and commercializing product candidates, and may affect pricing policies.
• Limited free float in common shares may have a negative impact on liquidity and market price.
• Certain existing shareholders exercise significant control, and their interests may conflict with the interests of other shareholders.
• Rights of shareholders may differ from those in companies governed by U.S. jurisdictions due due to Swiss incorporation.
• Potential Passive Foreign Investment Company (PFIC) status for U.S. investors, leading to adverse U.S. federal income tax consequences.
• Exposure to costly and damaging liability claims, either during clinical testing or at the commercial stage, or as a result of claims against directors and officers.
• Orphan-drug designation may not ensure market exclusivity in a particular market, potentially leading to earlier competition.
• Limited resources and access to capital necessitate prioritization of development for certain product candidates, potentially diverting resources away from better opportunities.
• Research and development activities could be affected or delayed as a result of possible restrictions on animal testing.
• Business disruptions from natural disasters, geopolitical actions (e.g., Russia-Ukraine conflict, Israel-Hamas conflict), or public health crises (e.g., Covid-19 pandemic) could seriously harm future revenue and financial condition.
• Inability to effectively monitor and respond to rapid and ongoing developments and expectations relating to environmental, social, and governance (ESG) and climate change matters, potentially imposing costs or reputational harm.
• Lack of history in commercializing biologics or pharmaceutical products, making it difficult to evaluate prospects for future viability.
• Risks from the improper conduct of employees, agents, contractors, or collaborators could adversely affect reputation and business.
• Business activities may be subject to the Foreign Corrupt Practices Act (FCPA) and similar anti-bribery and anti-corruption laws, with potential for fines and sanctions for violations.
• The use of new and evolving technologies, such as artificial intelligence (AI), may require material resources and present risks and challenges, including intellectual property, security, inaccuracy, bias, and data privacy issues.

Future Outlook

The company anticipates incurring significant operating losses for the foreseeable future as it continues its research and development efforts for current and future product candidates. Product revenues are not expected for at least several years, if ever. Existing capital resources of CHF 91.4 million are projected to be sufficient until the end of Q3 2027, assuming no other milestone payments. The company expects to require substantial additional funding to develop and commercialize certain product candidates. Research and development costs are expected to increase for advancing ACI-24.060 and ACI-7104.056, and for investing in intracellular programs like ACI-19764, though total R&D costs are expected to be lower than previous years following a September 2025 reorganization. Regulatory feedback will be sought for ACI-7104.056 to potentially accelerate towards registration. IND/CTA-enabling activities for Morphomer Tau aggregation inhibitors and a customized Tau PET ligand are planned for 2026. Data for ACI-19764's SAD and MAD studies are expected in Q4 2026, and the readout from ACI-15916's Phase 1 study is expected in H1 2026. The company aims to carry forward its PET tracer programs in collaboration with partners after Phase 1 results and intends to retain selected promising product candidates in-house for longer to generate greater value before partnering. Initial commercial efforts, if marketing approval is granted, would focus on the U.S. and certain European markets.

Management Comments

• Our goal is to continue leveraging our proprietary discovery platforms, SupraAntigen and Morphomer, to shift the treatment paradigm for neurodegenerative disease towards Precision Medicine.
• We believe our clinically validated technology platforms and multi-target, multimodal approach will enable AC Immune to revolutionize the treatment paradigm for neurodegenerative disease by shifting it towards Precision Medicine and disease prevention.
• The consistent signs of efficacy, together with the continued strong safety profile, provide a compelling rationale to progress ACI-7104.056 into more advanced clinical development.
• We believe that these antibodies will modify the course of disease by supporting clearance of toxic protein aggregates, or by preventing their spreading and accumulation, thereby preserving neuronal health and function.
• The Company will continue to review and evaluate available data sets, before decisions are made on potential further development and other opportunities (regarding Semorinemab and Crenezumab).
• AC Immune aims to see these programs carried forward in collaboration with partners after Phase 1 results (regarding PET tracers).
• We are committed to working closely with global regulatory authorities to adhere to and achieve the highest levels of safety and quality of our product candidates in the most timely and efficient manner.
• Our management takes the position that cybersecurity is owned companywide as a collective team, not just by the EVP Artificial Intelligence and Information Systems.

Industry Context

StockSavvy.ai notes that the neurodegenerative disease market is large and growing, with an estimated global patient population of over 50 million in 2020, projected to reach 139 million by 2050. Total healthcare costs for Alzheimer's disease in the U.S. were USD 321 billion in 2022, with worldwide dementia costs expected to reach USD 2.8 trillion annually by 2030. This highlights a significant unmet medical need that AC Immune is addressing with its Precision Medicine approach. The industry is shifting towards early-stage diagnosis and disease-modifying treatments, which aligns with AC Immune's focus on PET imaging agents for early detection and active immunotherapies for prevention. The competitive landscape includes large pharmaceutical companies, but AC Immune differentiates itself through its dual proprietary technology platforms (SupraAntigen and Morphomer) and multi-target, multimodal approach, aiming for combination therapies tailored to individual patient pathologies.

Comparison to Industry Standards

• **Lecanemab (Eisai Co., Ltd. and Biogen Inc.)**: Approved for AD, provides incomplete clinical efficacy, non-negligible safety risks (ARIA-E), and requires frequent intravenous infusion every 2 weeks. AC Immune's ACI-24.060 (anti-Abeta active immunotherapy) has shown good tolerability with no ARIA-E reported in its Phase 1b/2 trial, suggesting a potentially improved safety profile compared to existing monoclonal antibodies.
• **Donanemab**: Approved for MCI and mild dementia due to AD, administered every 4 weeks, but also presents similar non-negligible safety risks (ARIA severity might require treatment interruption/discontinuation). AC Immune's active immunotherapies aim for potentially improved safety and efficacy profiles by stimulating the patient's own immune system, avoiding repeated large doses of externally manufactured antibodies, and potentially offering less burdensome annual or biannual dosing for maintenance therapy.
• **TAUVID (Eli Lilly)**: FDA-approved Tau-PET tracer, but only for pathology indication (correlation with histopathology findings in Braak 5 and 6 patients), not for prognosis. AC Immune's PI-2620 (Tau-PET imaging agent) is a next-generation tracer with high binding affinity and selectivity for aggregated Tau, suitable for measuring accumulation over time, and importantly, binds to 4R Tau isoforms seen in PSP and CBD, which most other tracers (including TAUVID) cannot. This provides a significant differentiator for broader diagnostic utility.
• **ACI-7104.056 (anti-a-syn active immunotherapy)**: The predecessor was the first active immunotherapy candidate against pathological a-syn tested in a clinical study for early PD. Interim Phase 2 results show trends for disease modification, which is a significant step in a field with limited disease-modifying treatments. Competitors like Vaxxinity's UB-312 have completed Phase 1b studies, indicating AC Immune is at a comparable or more advanced stage in this specific active immunotherapy.
• **ACI-19764 (NLRP3 inhibitor)**: Positioned as a 'best-in-class compound' with high brain penetrance (brain/plasma ratio of 0.7 in rats, CSF/plasma ratio of 1.0 in dogs) and potent efficacy (2nM in human macrophages, 20.5nM in human whole blood). Competitors like VTX3232 (Ventyx-Eli Lilly), NT-0796 (NodThera), and selnoflast (Roche) are also in various clinical stages for NLRP3 inhibition, but AC Immune highlights its compound's superior efficacy and brain penetrance.
• **TDP-43 PET tracer (ACI-19626)**: Stated as 'first-in-class' with no known competitors in the clinic, indicating a pioneering position in diagnosing TDP-43 proteinopathies.

Management Changes

Corporate Governance

Legal Proceedings

• No material adverse legal proceedings reported as of the date of this Annual Report.

Related Party Transactions

• No related party transactions disclosed other than compensation of directors and executive management.

Stakeholder Impact

• **Shareholders**: Face increased net losses and decreased revenue, alongside a reduction in total liquidity. However, significant pipeline advancements, new Fast Track designations, and a major licensing deal with Takeda offer potential long-term value. Risks include potential dilution from future capital raises, share price volatility, and the inherent uncertainties of drug development. No dividends are expected in the foreseeable future.
• **Employees**: The company underwent a restructuring in September 2025, resulting in termination benefits for impacted employees. Compensation plans, including stock options and restricted share units, are in place to incentivize and retain talent. The company's cybersecurity program emphasizes employee awareness and training.
• **Customers/Patients**: The company's focus on Precision Medicine for neurodegenerative diseases aims to deliver new disease-modifying treatments and diagnostics for conditions like Alzheimer's, Parkinson's, MSA, and FTD. Successful development could significantly improve patient outcomes, but risks of product failure or side effects remain.
• **Collaboration Partners**: Existing and new strategic alliances with companies like Takeda, Janssen, Lilly, and Lantheus are crucial for funding, development, and commercialization. These partnerships leverage external expertise and resources, but partners may terminate agreements or pursue competing products, impacting the company's pipeline.
• **Creditors**: The company's liquidity position of CHF 91.4 million is projected to cover operating requirements until Q3 2027, providing a degree of financial stability in the short to medium term. However, continued losses and the need for future capital raises present ongoing risks.

Next Steps

• Seek regulatory feedback on the ACI-7104.056 clinical development plan to potentially accelerate towards registration.
• Expect final data from Part 1 of the VacSYn trial (ACI-7104.056) in mid-2026.
• Initiate IND/CTA-enabling activities for Morphomer Tau aggregation inhibitors in 2026.
• Initiate IND/CTA enabling studies for a customized Tau PET ligand in 2026.
• Expect data for Single-Ascending Dose (SAD) and Multiple-Ascending Dose (MAD) of ACI-19764 in Q4 2026.
• Expect readout from the ACI-15916 Phase 1 study in H1 2026.
• Continue to review and evaluate available data sets for crenezumab and semorinemab to make decisions on potential further development and other opportunities.
• Retain selected promising product candidates in-house for a longer period to generate greater value before partnering.
• Focus initial commercial efforts in the U.S. and certain European markets if product candidates are granted marketing approval.
• Require further training for employees that fail simulated phishing campaigns and encourage reporting of suspicious activity as part of the cybersecurity program.

Key Dates

Recommendation

The company is in a high-risk, high-reward clinical stage, characterized by significant R&D investments and a history of losses. While the financial results for 2025 show increased losses and decreased revenue, the substantial progress in its diverse pipeline, including multiple Fast Track designations and promising interim clinical data for several candidates, provides a strong long-term growth narrative. The Takeda licensing deal for ACI-24.060 is a significant validation and source of potential future non-dilutive capital. However, the temporary pause in the ACI-35.030 trial and the inherent uncertainties of drug development, coupled with the need for future capital raises, suggest a 'Hold' recommendation. Investors should monitor clinical trial readouts and financial stability closely.

Keywords

Neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, Active immunotherapy, Small molecule drugs, Diagnostics, PET tracers, Clinical trials, Biopharmaceutical, Drug development, Corporate governance, SEC filing, ACIU, Switzerland, IFRS, Abeta, Tau, Alpha-synuclein, NLRP3 inhibitor, Precision Medicine