AC Immune Stock

AC Immune SA (AC Immune), a clinical stage biopharmaceutical company, focuses on pioneering precision medicine for neurodegenerative diseases.

The company’s differentiated approach integrates novel therapeutics and diagnostics to overcome the fundamental challenge in this therapeutic area – the high number of co-pathologies driving disease development and progression and the urgent need for more tailored therapeutic regimens.

The company is advancing 16 therapeutic and diagnostic programs, with seven in clinical trials, targeting five different types of misfolded pathological proteins related to Alzheimer’s disease (AD), Parkinson’s disease (PD) and other neurodegenerative disorders. The company’s pipeline assets are further validated by the multiple partnerships it has established with leading global pharmaceutical companies.

The company is developing a suite of diagnostics designed to be first-in-class or best-in-class, which will enable improved diagnosis of pathologies, patient selection and assessment of clinical trial outcomes. The company has four diagnostic programs in its pipeline, developed using its proprietary technology platforms and targeting the therapeutic targets: Tau, a-syn and TDP-43.

The company has a strong track record of establishing value-driving collaboration agreements with leading pharmaceutical companies, including two collaborations with Genentech, one with Janssen and one with Lilly. Additionally, in this respect, the company established a strategic partnership with WuXi Biologics for its expertise in manufacturing biologicals in China and potential collaborations regarding AC Immune’s SupraAntigen platform.

The company’s clinical stage product candidates include:

ACI-35.030

AC Immune and Janssen Pharmaceuticals, Inc. (Janssen), part of the Janssen Pharmaceutical Companies of Johnson & Johnson, are evaluating the anti-phosphorylated-Tau (anti-pTau) vaccine candidate ACI-35.030 in a Phase 1b/2a study in subjects with early AD (NCT04445831). Interim results show that ACI-35.030 vaccination generated a strong antigen-specific antibody response against pTau in 100% of participants, achieving anti-pTau antibody levels of about two orders of magnitude higher than pre-vaccination levels, whereas anti-ePHF (enriched paired helical filaments) antibody titers increased by one order of magnitude from baseline as early as two weeks after the second injection at week 8 of the mid-dose of ACI-35.030. Based on these results, the second highest dose cohort was expanded in Q2 2021 to facilitate plans for further late-stage development. The safety and the tolerability have been good in the study, and so far the Data Safety Monitoring Board has always stated that the trial may continue without modification. ACI-35.030 specifically targets pathological pTau species and is eventually intended as a disease-modifying treatment for AD and other Tauopathies.

In Q4 2022, it was announced that, based on the Phase 1b/2a interim data, ACI-35.030 had been selected for further development. New clinical data from the Phase 1b/2a trial showed that ACI-35.030 treatment rapidly leads to the strong and durable induction of antibodies specific for pathological forms of Tau, such as pTau and its aggregated form, ePHF. The ACI-35.030-induced antibody response was sustained and could be periodically boosted over a period of 72 weeks. The decision to select ACI-35.030 follows the comparison demonstrating its strengths relative to an alternative anti-pTau protein conjugate vaccine, JACI-35.054.

ACI-24.060 for AD and for AD in DS

The original formulation of the company’s wholly owned anti-amyloid-beta vaccine candidate was shown to be safe and well tolerated along with preliminary evidence of immunogenicity and pharmacodynamic effects in patients with AD and in people with DS. Based on these results, the optimized formulation, ACI-24.060, which incorporates Abeta unrelated T-helper cell epitopes to increase the magnitude and the boost-ability of the antibody response, was advanced into the ABATE Phase 1b/2 trial.

ABATE is a multicenter, adaptive, double-blind, randomized, placebo-controlled study designed to assess the safety, tolerability, immunogenicity, and pharmacodynamic effects of ACl-24.060 in subjects with prodromal AD and subsequently in adults with DS is ongoing. The Clinical Trial Application (CTA) has been approved by the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) and by the Spanish Agency for Medicines and Health Products (AEMPS) with the first patient dosed in Q2 2022. AC Immune plans for an Investigational New Drug (IND) application in the U.S.A. in H1 2023 for the global development of the vaccine candidate.

ACI-7104.056

The optimized formulation of the clinically-validated PD vaccine candidate PD01, will advance into an adaptive, biomarker-based Phase 2 study following the recent clearance of the CTA. This trial will evaluate an initial dose-response of ACI-7104.056 focusing on safety and immunogenicity against a-syn and pathological a-syn species. Additionally, the identification or verification of disease-specific biomarkers and progression of motor and non-motor symptoms of Parkinson’s disease will be monitored, together with digital, imaging and fluid biomarkers, in the second part of the study. The trial initiation is anticipated in H1 2023.

Semorinemab

The company’s collaboration partner, Genentech, a member of the Roche Group, is developing semorinemab for the treatment of AD. A Phase 2 study (Lauriet) conducted in patients with mild-to-moderate AD was completed in Q3 2021 and data showed a statistically significant reduction on one of two co-primary endpoints, ADAS-Cog11. The second co-primary endpoint, ADCS-ADL, and secondary endpoints were not met. Safety data showed that semorinemab is well tolerated with no unanticipated safety signals. At CTAD 2022, Genentech presented CSF and plasma biomarkers. These data confirmed peripheral target engagement and reduction in CSF total Tau, pTau181 and pTau217, observed after semorinemab treatment but not with placebo. Genentech reported that the open label portion of the study will continue as planned and that further analyses are ongoing. Semorinemab is designed to slow the spreading of Tau pathology, which coincides with both clinical symptoms and disease progression in AD.

Crenezumab

In August 2022, the company provided an update on the Alzheimer’s Prevention Initiative study evaluating crenezumab in autosomal dominant Alzheimer’s disease, a specific genetic mutation which causes early-onset Alzheimer’s disease. While numerical differences favoring crenezumab over placebo were observed across the co-primary, multiple secondary and exploratory endpoints, none of these effects were statistically significant. Initial data was presented at the Alzheimer's Association International Conference (AAIC) on August 2, 2022. Further plasma biomarker analyses presented at the CTAD 2022 conference further favored crenezumab over placebo. All participants in the study were offered up to one year of continued treatment (crenezumab for all carriers and placebo for all non-carrier) following the end of the double-blind period while primary results and additional analyses were pending. Final efficacy visits have begun.

Morphomer Tau Aggregation Inhibitors

In collaboration with the company’s partner, Lilly, it is researching and developing small molecule Tau aggregation inhibitors with plans to evaluate candidates in AD and NeuroOrphan tauopathies. The company completed a Phase 1 clinical study in healthy volunteers with ACI-3024, in Q2 2020, which showed a dose-dependent exposure and brain penetration, achieving the desired levels of ACI-3024 in the CSF. Continued candidate characterization across the research program has also identified new and highly differentiated candidates with excellent cerebrospinal fluid exposure, selectivity for pathological aggregated Tau.

PI-2620

PI-2620 is the Tau-PET imaging agent discovered during the collaboration of AC Immune and LMI. The company is working with its partner, LMI, to advance PI-2620 as a highly differentiated, best-in-class Tau diagnostic for AD, as well as non-AD Tauopathies, such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Results have demonstrated PI-2620’s differentiated characteristics as a diagnostic tool for studying Tau-related diseases. Results on the use of PI-2620 in AD patients from an investigator sponsored Phase 2 trial at the Asan Medical Center (NCT03903211) were presented at the 2022 AAIC. Following these, LMI moved PI-2620 into late-stage clinical development in AD and made a milestone payment. The first Alzheimer’s patient in ADvance, the pivotal Phase 3 histopathology study in AD (NCT05641688) was imaged in January 2023.

ACI-12589

The company’s next-generation a-syn Positron Emission Tomography (PET) imaging tracer, derived from its Morphomer platform, has shown significant potential to reliably detect and map deposits of pathological alpha-synuclein protein in the brain. Supported by the Michael J. Fox Foundation for Parkinson’s Research (MJFF), ACI-12589, the company’s latest diagnostic imaging agent, completed a first-in-human study and an investigator-initiated study in 2022. The readouts of these trials in patients with PD, multiple system atrophy (MSA) and other synucleinopathies were reported at the AD/PD and AAIC 2022 conferences. These images provided the first clinical proof-of-concept for an a-syn PET tracer, as ACI-12589 clearly distinguished patients with MSA from those with other alpha-synucleinopathies and healthy controls. Moreover, the company’s Morphomer platform is delivering additional candidates with improved binding properties and the potential to image a-syn pathology in patients with PD.

Clinical Programs

Anti-pTau Vaccine

In collaboration with Janssen, the company is advancing the anti-pTau vaccine program with ACI-35.030 that is directed against a key component of the pathology of AD: phosphorylated Tau proteins, found in Tau tangles. Developed using the company’s SupraAntigen technology, its vaccine is designed to stimulate a patient’s immune system to produce antibodies against misfolded and phosphorylated, pathological Tau protein, which aggregates to create the neurofibrillary tangles that characterize AD.

Clinical Development

ACI-35.030

ACI-35.030 is an optimized liposomal anti-pTau vaccine formulation designed to elicit antibodies against extracellular pTau protein in order to prevent and reduce the spread and development of Tau pathology within the brain. In preclinical studies, ACI-35.030 showed that it retains the excellent non-clinical safety profile and the highly specific antibody response against pTau observed with the initial formulation, ACI-35, while demonstrating an enhanced and more uniform antibody response. The company is developing ACI-35.030 with Janssen in accordance with its collaboration agreement.

ACI-35.030 comprises a pTau peptide and a T-cell epitope capable of binding to human leukocyte antigen-major histocompatibility complex, class II (HLA-DR) molecules.

JACI-35.054

JACI-35.054 is an alternative pTau vaccine, which is developed with Janssen in accordance with the company’s collaboration agreement. In preclinical studies, JACI-35.054 showed good safety, and induced a strong antibody response against pTau.

JACI-35.054 is an alternative anti-pTau vaccine comprising a pTau peptide antigen conjugated to an immunogenic carrier protein CRM197, combined with adjuvants.

CRM197 is a well-defined recombinant protein that is a commercially available version of a non-toxic mutant of diphtheria toxin (DT) A chain and has been shown to be a safe carrier protein in commercial prophylactic vaccines and clinical trials for a plethora of different vaccine candidates.

In Q4 2022, it was announced that, based on the Phase 1b/2a interim data, ACI-35.030 has been selected over JACI-35.054 for further development.

The Phase 1b/2a study (NCT04445831) is a randomized, multicenter, double-blind, placebo-controlled clinical study with a primary objective to assess the safety, tolerability and immunogenicity of different dosages of ACI-35.030 and JACI-35.054 in participants with early AD. Secondary objectives assess additional immunogenicity parameters, while exploratory endpoints include notable biomarkers of progression of AD, as well as clinical assessments. This Phase 1b/2a study evaluating ACI-35.030 and JACI-35.054 was initiated in Q3 2019 and is ongoing in Europe.

ACI-24.060

ACI-24.060 derives from an original AC Immune anti-amyloid-beta vaccine, ACI-24, that was assessed in patients with AD and in subjects with down syndrome (DS). As ACI-24 was shown to be safe and well tolerated with preliminary evidence of immunogenicity and pharmacodynamic effects in these two study populations, the optimized version ACI-24.060 was created. ACI-24.060 contains additional Abeta unrelated T-helper cell epitopes and has demonstrated similar safety and tolerability in NHPs with superior immunogenicity in mouse and NHP studies as compared to the original ACI-24.

The company is pursuing clinical development of ACI-24.060 in early AD, as well as the population of people living with DS exhibiting the presence of brain amyloid pathology. ACI-24.060 is proprietarily owned.

ABATE Phase 1b/2: The ABATE clinical study (NCT05462106) is a multicenter, adaptive, placebo-controlled, dose-escalation, double-blind, randomized study containing two parts.

Study part 1 is conducted in subjects with prodromal AD to assess the effect of study treatment (ACI-24.060 or placebo) administered over 48 weeks. Study part 1 is conducted in several centers located in the U.K. and Europe. The first dosing in study part 1 occurred in Q2 2022.

Study part 2 will be conducted in up to 80 non-demented adult subjects with DS and with confirmed presence of amyloid pathology by PET scan to assess the effect of study treatment (ACI-24.060 or placebo) administered over 74 weeks. Study part 2 will be conducted in the U.K., Europe and the U.S.

ACI-24 development in AD in DS

The AD pathology that commonly develops in people with DS bears remarkable similarities to familial and sporadic forms of AD and is characterized by a progressive accumulation of brain Abeta amyloid plaques leading to the appearance of AD-related cognitive decline and a modification of other relevant biomarkers. The company is pioneering the development of its anti-amyloid-beta vaccine in AD patients and subjects with DS.

ACI-7104.056 – Anti-a-syn Vaccine

ACI-7104.056 is an optimized peptide-conjugate vaccine formulation designed to induce a-syn-specific antibodies recognizing aggregated a-syn species that have been demonstrated to be toxic to neurons. In contrast, ACI-7104.056-induced antibodies do not bind to the monomeric, physiological form of a-syn and do not cross-react with other members of the synuclein family, such as beta- and gamma-synuclein.

The safety, tolerability and immunogenicity of the ACI-7104.056 predecessor a-syn vaccine were studied over a three-and-a-half-year period in 24 early PD subjects and have been previously published (Volc et al., The Lancet Neurology 2020). There were four consecutive studies in this group of patients, with patients randomized to receive a lower or higher dose of the alpha synuclein vaccine. After four priming doses, subjects were re-randomized to receive a booster injection at one of the two doses, followed by a second booster injection at the high dose. This Phase 1 study series demonstrated a favorable long-term safety profile for PD01.

Semorinemab

Semorinemab is a humanized high-affinity IgG4 isotype antibody candidate that binds all forms of Tau. Semorinemab is designed to intercept extracellular Tau, stopping or slowing cell-to-cell spread and propagation of pathological Tau in the brain. Semorinemab is in Phase 2 clinical development for AD as part of an ongoing collaboration, which was established in 2012, with Genentech.

In November 2021, the company reported that Genentech had presented the full top-line data from the Lauriet study during a late-breaking session at the 14th Clinical Trials on Alzheimer’s Disease conference. Semorinemab’s results provide the first positive cognitive results for an anti-Tau mAb therapy in AD.

Crenezumab

Crenezumab is a humanized, conformation-specific monoclonal antibody that targets misfolded Abeta and has a broad binding profile. Crenezumab was developed using the company’s proprietary SupraAntigen platform. In 2006, the company licensed crenezumab to Genentech, a company with a long history of developing and commercializing innovative biologics.

Crenezumab has been studied in two Phase 2 clinical studies, the ABBY proof-of-concept study and the BLAZE biomarker study. Consistent trends across different endpoints and dose dependencies were considered indicators of a response in this learning phase of development, with confirmation to then be sought in Phase 3.

Morphomer Tau

Approximately 2,200 compounds have been screened thus far for the Morphomer Tau program. This has allowed for the identification of several chemical series of orally bioavailable small molecules with suitable CNS properties. The lead compounds displayed selectivity for binding to pathological Tau aggregates in preference to other protein aggregates. In addition, the lead compounds were able to prevent Tau aggregation and promote its disaggregation. Further characterization using multiple orthogonal in vitro, ex vivo and in vivo tests addressing pharmacology absorption, distribution, metabolism, and excretion (ADME), and safety properties led to the identification of the first clinical candidate ACI-3024.

ACI-3024

ACI-3024 is a potent Tau aggregation inhibitor active against the 3R and 4R human Tau isoforms, as well as the mutant forms associated with human Tauopathies, such as FTLD-Tau (e.g., progressive supranuclear palsy (PSP), Pick’s disease, corticobasal degeneration). ACI-3024 selectively binds to aggregated Tau and does not bind to the monomeric forms of Tau.

ACI-3024 has a good in vitro and in vivo absorption, distribution, metabolism, and excretion (ADME) profile, including low clearance, long half-life and good CNS disposition as assessed by brain and CSF concentrations. ACI-3024 was negative in in vitro and in vivo genotoxicity assays [Ames, micronucleus test (MNT) and mouse lymphoma cell mutagenesis (MLY)] and has undergone an extensive toxicology and safety pharmacology assessment.

ACI-3024 will not be further developed under the collaboration and the companies have decided to pursue other promising Tau Morphomer candidates from AC Immune’s research platform for potential clinical development in AD.

Tau Diagnostics

The company’s Tau-PET tracers are designed to bind specifically to the pathological forms of human Tau in AD and other Tauopathies. They have demonstrated an excellent PET tracer profile with their ability to cross the blood brain barrier and a high selectivity to pathological Tau even in the early-stage disease. The Phase 1 clinical study of the company’s clinical candidate PI-2620 in AD was completed in Q1 2018. The Phase 2 longitudinal study in AD in South Korea (Asan Medical Center, NCT03903211) was completed in Q4 2021 and results presented at AAIC 2022. The pivotal ADvance Phase 3 histopathology study in AD (NCT05641688) was initiated in December with FPFV in December 2022. The first Alzheimer’s patient was imaged with PI-2620 scan in January 2023.

PI-2620 is selective for Tau over Abeta and other ‘off-target’ binding compared with published Tau-PET agents in development, as no binding to Abeta in vivo and no ‘off-target’ retention in basal ganglia or choroid plexus was observed. In addition, PI-2620 was shown to be suitable for measuring longitudinal Tau accumulation. A major differentiator for PI-2620 is its ability to bind 4-repeat (4R) Tau isoforms, which are in varying amounts in different neurodegenerative diseases. Most Tau-PET tracers in development are not able to bind 4R Tau and are of limited use for certain diseases driven by these Tau species.

A-syn Diagnostics

The company is also developing PET imaging agents to detect a-syn, which progressively accumulates in the brains of PD patients and is believed to be central to the neurodegenerative process of PD, as well as several other disorders, including Lewy body dementia and MSA, making it a priority target for the development of therapeutics and diagnostics. The company has identified molecules leveraging its Morphomer technology that selectively bind to a-syn pathological structures from human PD brain with affinity in the low-nanomolar range.

In the same timeframe, the company has also initiated the clinical development of its third-generation candidate, ACI-12589. ACI-12589 is the first molecule capable to detect pathological a-syn in the brain of patient with MSA and to differentiate those from controls, other synucleinopathies and more generally other neurodegenerative diseases. Additionally, ACI-12589 showed some signal retention in familial PD cases in brain areas compatible with the expected distribution of pathological a-syn. The preclinical and clinical data obtained within the program were presented at AD/PD 2022 and the Alzheimer's Association International Conference (AAIC) 2022.

The FiH clinical evaluation of ACI-12589 in PD, MSA and other a-synucleinopathies was completed in 2022. In preparation to further steps in clinical development, in Q4 2022 a dosimetry study in healthy volunteers was completed.

Preclinical Programs

Using its SupraAntigen and Morphomer platforms, the company has generated additional discovery and preclinical stage molecules targeting key pathologies that drive a range of neurodegenerative diseases, including TDP-43, a-syn, and NLRP3. The company is accelerating the development of several therapeutic product candidates in preclinical development, including several programs focused on indications outside of AD as a critical part of its expansion strategy.

A-syn Antibody

The a-syn antibodies generated using the company’s SupraAntigen platform have unique binding properties allowing them to bind preferentially to the pathological forms of a-syn. Leveraging the wide collection of anti-a-syn antibodies generated with diverse binding epitopes and sub-nM binding affinities to aggregated a-syn, new immunoassays are being developed for the detection of pathological a-syn in biofluids. A-syn aggregation and spreading are established targets for PD, MSA and other synucleinopathies. Antibodies that interfere with the aggregation and spreading mechanisms of a-syn provide a therapeutic option for the treatment of PD. The a-syn antibodies were able to significantly delay the seeded aggregation of pathological a-syn in an in vitro aggregation assay, and were able to significantly decrease pathological a-syn spreading in an in vivo animal model of PD. Characterization using multiple orthogonal in vitro and in vivo tests addressing binding, specificity, functionality and pharmacological properties has led to the identification of the lead candidate ACI-5755.

ACI-5755 selectively binds to pathological forms of a-syn with low-nanomolar affinity and shows a significant preference over monomeric a-syn. Additionally, ACI-5755 shows strong recognition for pathological a-syn in patient-derived tissues in both PD and MSA. ACI-5755 showed a potent and dose-dependent reduction in the seeding capacity of pathological a-syn in a proprietary in vitro aggregation assay. Moreover, ACI-5755 substantially reduced the propagation of a-syn aggregates in a cell-based model.

Morphomer A-syn

Leveraging its Morphomer platform, the company discovered and characterized the first biologically active small molecule inhibitors targeting intracellular a-syn aggregates. Identified compounds, from several distinct chemical series, which significantly decrease a-syn aggregate accumulation in neurons by interfering with the seeding and fibrillation processes. Iterative medicinal chemistry optimization led to the identification of orally available compounds with favorable CNS-penetrant pharmacokinetic properties, which progressed into in vivo proof-of-concept study in an animal model of alpha-synucleinopathies. Treatment with hit compound resulted in significant, dose-dependent decrease of pathological a-syn aggregates in vivo, Medicinal chemistry efforts will continue on improving properties of lead chemical series, in parallel to identifying structurally diverse compounds fulfilling the target product profile.

TDP-43 Antibody

TDP-43 is a recently identified target of growing interest for NeuroOrphan indications, such as frontotemporal dementia (FTD) and ALS. Interestingly, TDP-43 also plays an important role in other significant neurodegenerative indications, such as AD or LATE.

Anti-TDP-43 antibodies binding to various regions of TDP-43 were generated by the company’s SupraAntigen platform. A subset displayed conformational selectivity to misfolded TDP-43, while others recognized all TDP-43 isoforms. Multiple antibodies were generated and characterized in vitro, from which two pan-TDP-43 antibodies (ACI-5891 and ACI-5886) were selected for the evaluation of their efficacy in mitigating TDP-43 aggregation in vitro and in vivo. ACI-5891 showed a high binding affinity for TDP-43 and ability to reduce TDP-43 aggregation in vitro and in vivo. ACI-5891 was successfully humanized and clinical lead selected (ACI-5891.9). The lead molecule shows excellent pharmacokinetics in non-human primates and good developability profile.

Strategy

The key elements of the company’s strategy include accelerating development of novel therapeutics in AD with its partners; expanding its strategic focus in Parkinson’ disease (PD) and non-AD neurodegenerative diseases, including NeuroOrphan indications and limbic-predominant age-related TDP-43 encephalopathy (LATE); and a continued focus on diagnostics enabling Precision Medicine to be an ultimate differentiator for the company.

The company’s strategy to date has been to focus on identifying partnerships for its early-stage product candidates as both a way to secure non-dilutive capital to fund its other research and development programs and also as a way to accelerate the development of these partnered products by leveraging its partners’ extensive knowledge in clinical studies, drug development, manufacturing and commercialization.

Intellectual Property

As of December 31, 2022, the company owned or co-owned with its collaboration and licensing partners, approximately 48 issued U.S. patents and 399 issued patents in other jurisdictions, as well as 34 pending U.S. patent applications and 565 pending foreign patent applications. As of December 31, 2022, the company licensed approximately 32 issued U.S. patents and 282 issued patents in other jurisdictions, as well as 16 pending U.S. patent applications and 317 pending foreign patent applications.

The patent portfolios for the company’s most advanced product candidates as of December 31, 2022 are summarized below:

Anti-Tau Vaccines

The company’s patent portfolio for anti-Tau vaccines includes a patent family with composition-of-matter claims (including claims directed to the ACI-35 antigenic peptide and a pharmaceutical composition comprising such an antigenic peptide), claims directed to treating certain indications using ACI-35 including AD, and claims directed to using ACI-35 to induce an immune response. This patent family contains approximately 28 issued patents and two pending patent applications in 27 countries. The issued patents in this patent family, if the appropriate maintenance, renewal, annuity or other governmental fees are paid, are expected to expire in 2030, excluding any additional term for patent term adjustments or patent term extensions.

The company’s patent portfolio for anti-Tau vaccines also includes a patent family relating to therapeutic Tau vaccine claims (including claims directed to a pharmaceutical composition comprising an antigenic Tau peptide), claims directed to using such vaccines to induce an immune response in a subject, and claims directed to methods for preventing or treating a neurodegenerative disease or disorder, including AD, among others. This patent family contains 1 issued patent and approximately 46 pending patent applications in 38 countries. The issued patent and any patents issuing in this patent family, if the appropriate maintenance, renewal, annuity or other governmental fees are paid, are expected to expire in 2038, excluding any additional term for patent term adjustments or patent term extensions.

ACI-24

The company’s patent portfolio for ACI-24 includes a patent family with composition-of-matter claims (including claims directed to the ACI-24 antigenic construct), claims directed to treating certain indications using ACI-24, including AD, and claims directed to using ACI-24 to induce an immune response. As of December 31, 2022, in this patent family, the company owned approximately 27 issued patents and 6 pending patent applications in 30 countries. With respect to the U.S., the company owned two issued U.S. patents. The issued patents in this patent family, if the appropriate maintenance, renewal, annuity or other governmental fees are paid, are expected to expire in 2026, excluding any additional term for patent term adjustments or patent term extensions.

The company’s patent portfolio for ACI-24 also includes a patent family directed to the use of the ACI-24 vaccine in the treatment and/or prevention of memory and/or cognitive impairments or abnormalities in the DS population, among others. As of December 31, 2022, in this patent family, the company owned approximately 14 issued patents and 4 pending patent applications in 18 countries. Issued patents in this patent family, if the appropriate maintenance, renewal, annuity or other governmental fees are paid, are expected to expire in 2032, excluding any additional term for patent term adjustments or patent term extensions.

The company’s patent portfolio for ACI-24 also includes a patent family relating to therapeutic anti-Abeta vaccine claims (including claims directed to a pharmaceutical composition comprising an antigenic peptide), and claims directed to using such vaccines in treating, preventing, inducing a protective immune response against or alleviating the symptoms associated with an Abeta-associated disease in a subject, among others. As of December 31, 2022, in this patent family, the company owned one issued U.S. patent and approximately 33 pending patent applications in 32 countries. Any issued patents in this patent family, if the appropriate maintenance, renewal, annuity or other governmental fees are paid, are expected to expire in 2039, excluding any additional term for patent term adjustments or patent term extensions.

ACI-7104

The company’s patent portfolio relating to ACI-7104 includes patents and patent applications with composition-of-matter claims (including claims directed to the peptide, as well as pharmaceutical formulations comprising the peptide), and claims directed to the use of compounds comprising the peptide in treating or preventing synucleinopathies, including PD and MSA.

The company’s patent portfolio relating to ACI-7104 includes patents and patent applications that it owns in two different patent families. As of December 31, 2022, in these patent families, the company owned approximately 13 issued patents and 17 pending patent applications, in 11 countries. With respect to the U.S., the company owned two issued U.S. patents. Issued patents in the basic patent family, if the appropriate maintenance, renewal, annuity or other governmental fees are paid, are expected to expire in 2029, excluding any additional term for patent term adjustments or patent term extensions.

Semorinemab

The company’s global patent portfolio relating to semorinemab includes patents and patent applications with claims directed to compositions of matter, methods of treatment for certain indications, including AD, and methods of use, among others.

Crenezumab

The company’s patent portfolio relating to crenezumab includes patents and patent applications with claims directed to composition of matter (including claims directed to the crenezumab antibody or a fragment thereof, a polynucleotide encoding the crenezumab antibody or a fragment thereof, a cell line used to produce the crenezumab antibody, as well as pharmaceutical compositions comprising the crenezumab antibody), claims directed to treating certain indications using the crenezumab antibody, including AD, claims directed to a method of manufacturing the crenezumab antibody and claims directed to diagnostic and prognostic uses of the crenezumab antibody.

The company’s patent portfolio relating to crenezumab includes patents and patent applications that it owns or co-owns in four different patent families. As of December 31, 2022, the company owned or co-owned approximately 50 patents (not including the patents in the individual countries where the issued European patent was validated) and 12 patent applications in 34 countries in its main patent family directed to the crenezumab antibody and methods of using the crenezumab antibody to treat certain indications, including AD. This patent portfolio includes three issued U.S. patents and one pending U.S. patent applications, which, if the appropriate maintenance or other governmental fees are paid, are expected to expire in 2027, excluding any additional term for patent term adjustments or patent term extensions. This patent portfolio also includes a PCT patent application that was filed on July 13, 2007. If the appropriate maintenance, renewal, annuity, or other governmental fees are paid, national-stage applications claiming priority from this PCT patent application, if issued, are expected to expire in 2027, excluding any additional term for patent term adjustments or patent term extensions, as applicable.

Morphomer Tau

The company’s patent portfolio relating to Morphomer Tau therapeutics includes patent applications with claims directed to composition of matter (including claims directed to the molecule, a pharmaceutical composition comprising such molecule and a mixture comprising such molecule), and claims directed to prevention and treatment of certain indications using such molecules, including AD and PSP, among others.

The company’s patent portfolio relating to the Morphomer Tau therapeutic program includes patent applications that it owns or co-owns in four different patent families. As of December 31, 2022, the company owned or co-owned approximately 48 pending patent applications and 4 issued patents, including one U.S. issued patent in the company’s main patent family directed to the ACI-3024 small molecule Tau aggregation inhibitor. If the appropriate maintenance, renewal, annuity, or other governmental fees are paid, national-stage applications claiming priority from this PCT patent application, if issued, are expected to expire in 2039, excluding any additional term for patent term adjustments or patent term extensions, as applicable.

PI-2620

The company’s patent portfolio relating to PI-2620 includes patent applications with claims directed to composition of matter (including claims directed to the molecule, its precursor and a diagnostic composition comprising such molecule), claims directed to diagnosis of certain indications using PI-2620, including AD and PSP, and claims directed to a method of manufacturing PI-2620, among others.

The company’s patent portfolio relating to PI-2620 includes patent applications that it owns or co-owns in three different patent families. As of December 31, 2022, the company owned or co-owned 6 patents and approximately 12 patent applications in 16 countries in its main patent family directed to the PI-2620 molecule, its precursor and methods of using the PI-2620 to diagnose certain indications, including AD and PSP. This main patent family includes one issued U.S. patent. If the appropriate maintenance, renewal, annuity, or other governmental fees are paid, national-stage applications claiming priority from this PCT patent application, if issued, are expected to expire in 2037, excluding any additional term for patent term adjustments or patent term extensions, as applicable.

ACI-12589

The company’s patent portfolio relating to a-syn diagnostics includes composition of matter claims (including claims directed to the ACI-12589 molecule, its precursor, and diagnostic compositions comprising the molecule), and claims directed to use of the molecule in imaging and in diagnostics of a-synucleinopathies, including PD and MSA.

The company’s patent portfolio relating to a-syn diagnostics includes patents and patent applications that it owns in three different patent families. As of December 31, 2022, the company owned or co-owned approximately 17 patent applications in 17 countries in its main patent family directed to the ACI 12589 molecule, its precursor, diagnostic compositions, and methods of using ACI-12589 for imaging and diagnostics of a-synucleinopathies, including PD and MSA. If the appropriate maintenance, renewal, annuity or other governmental fees are paid, any issued patents are expected to provide protection up to 2041, excluding any additional term for patent term adjustments or patent term extensions, as applicable.

Manufacturing and Supply

The company has established relationships with contract manufacturing organizations (CMOs), such as WuXi AppTec (WuXi STA), WuXi Biologics, Avecia, Almac Clinical Services, Bachem AG, Evonik Industries AG, Polymun Scientific Immunbiologische Forschung GmbH, piCHEM Forschungs-und Entwicklungs GmbH, Baccinex SA, Solvias AG and Pfenex Inc. among others.

Research and Development

The company’s research and development expenses were CHF 60.3 million for the year ended December 31, 2022.

Government Regulation

Besides informal conversations with the authorities, the company’s regulatory department has conducted several pre-Investigational New Drug (pre-IND), Type B and Type C meetings with the Food and Drug Administration (FDA) (ACI-24.060 for AD and DS, ACI-7104.056 and PI-2620) and Scientific Advice meetings, which are the European equivalent of pre-IND meetings (with the German Paul-Ehrlich-Institut, Swedish Medical Products Agency; the U.K. Medicine & Healthcare Products Regulatory Agency, Finnish Medicines Agency, the Spanish Agency of Medicines and Medical Devices and the European Medicines Agency).

History

AC Immune SA was founded in 2003. The company was incorporated as a Swiss limited liability company (societe à responsabilite limitee) in February 2003 and transformed into a Swiss stock corporation (societe anonyme) under the laws of Switzerland in August 2003.