☐	REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934

☒	ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

☐	TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

☐	SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

Title of each class	Trading Symbol	Name of each exchange on which registered
Common Shares, nominal value CHF 0.02 per share	ACIU	The Nasdaq Global Market

Large accelerated filer ☐	Accelerated filer ☒	Non-accelerated filer ☐
		Emerging growth company ☐

US GAAP ☐

International Financial Reporting Standards as issued by the International Accounting Standards Board ☒

Other ☐

FORWARD-LOOKING STATEMENTS			1
PART I			2
ITEM 1. IDENTITY OF DIRECTORS, SENIOR MANAGEMENT AND ADVISERS			2
	A.	Directors and senior management	2
	B.	Advisers	2
	C.	Auditors	2
ITEM 2. OFFER STATISTICS AND EXPECTED TIMETABLE			2
	A.	Offer statistics	2
	B.	Method and expected timetable	2
ITEM 3. KEY INFORMATION			2
	A.	[Reserved]	3
	B.	Capitalization and indebtedness	3
	C.	Reasons for the offer and use of proceeds	3
	D.	Risk factors	3
ITEM 4. INFORMATION ON THE COMPANY			48
	A.	History and development of the company	48
	B.	Business overview	48
	C.	Organizational structure	113
	D.	Property, plant and equipment	114
ITEM 4A. UNRESOLVED STAFF COMMENTS			114
ITEM 5. OPERATING AND FINANCIAL REVIEW AND PROSPECTS			114
	A.	Operating results	114
	B.	Liquidity and capital resources	130
	C.	Research and development, patents and licenses, etc.	132
	D.	Trend information	133
	E.	Critical Accounting Estimates	133
ITEM 6. DIRECTORS, SENIOR MANAGEMENT AND EMPLOYEES			133
	A.	Directors and senior management	133
	B.	Compensation	137
	C.	Board practices	139
	D.	Employees	142
	E.	Share ownership	142
ITEM 7. MAJOR SHAREHOLDERS AND RELATED-PARTY TRANSACTIONS			142
	A.	Major shareholders	142
	B.	Related-party transactions	144
	C.	Interests of experts and counsel	144
ITEM 8. FINANCIAL INFORMATION			144
	A.	Consolidated statements and other financial information	144
	B.	Significant changes	145
ITEM 9. THE OFFER AND LISTING			145
	A.	Offering and listing details	145
	B.	Plan of distribution	145
	C.	Markets	145
	D.	Selling shareholders	145
	E.	Dilution	145
	F.	Expenses of the issue	145
ITEM 10. ADDITIONAL INFORMATION			145
	A.	Share capital	145
	B.	Memorandum and articles of association	145
	C.	Material contracts	145
	D.	Exchange controls	145
	E.	Taxation	146
	F.	Dividends and paying agents	152

	G.	Statement by experts	152
	H.	Documents on display	153
	I.	Subsidiary information	153
ITEM 11. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK			153
ITEM 12. DESCRIPTION OF SECURITIES OTHER THAN EQUITY SECURITIES			154
	A.	Debt securities	154
	B.	Warrants and rights	154
	C.	Other securities	154
	D.	American depositary shares	154
PART II			154
ITEM 13. DEFAULTS, DIVIDEND ARREARAGES AND DELINQUENCIES			154
	A.	Defaults	154
	B.	Arrears and delinquencies	155
ITEM 14. MATERIAL MODIFICATIONS TO THE RIGHTS OF SECURITY HOLDERS AND USE OF PROCEEDS			155
ITEM 15. CONTROLS AND PROCEDURES			155
	A.	Disclosure controls and procedures	155
	B.	Management’s Annual Report on internal control over financial reporting	155
	C.	Attestation report of the registered public accounting firm	155
	D.	Changes in internal control over financial reporting	155
ITEM 16. [RESERVED]			155
ITEM 16A. Audit committee financial experts			155
ITEM 16B. Code of Ethics			156
ITEM 16C. Principal accountant fees and services			156
ITEM 16D. Exemptions from the listing standards for audit committees			156
ITEM 16E. Purchases of equity securities by the issuer and affiliated purchasers			156
ITEM 16F. Change in registrant’s certifying accountant			156
ITEM 16G. Corporate governance			156
ITEM 16H. Mine safety disclosure			157
ITEM 16I. Disclosure regarding foreign jurisdictions that prevent inspections			157
PART III			157
ITEM 17. Financial statements			157
ITEM 18. Financial statements			158
ITEM 19. Exhibits			158

•

the success of our and our collaboration partners’ clinical studies, and our and their ability to obtain and maintain regulatory approval and to commercialize ACI-35, semorinemab, ACI-7104, Morphomer Tau, ACI-24 for Alzheimer’s disease (AD) and for Down syndrome-related AD (ACI-24 for DS), crenezumab, PI-2620, our Tau-positron emission tomography (PET) imaging tracer, our alpha-synuclein (a-syn) PET tracer and to a lesser extent our preclinical candidates;

•

the preclinical and clinical safety, efficacy and utility of our product candidates;

•

the ability of our competitors to discover, develop or commercialize competing products before or more successfully than we do;

•

our plans to research, develop and commercialize our product candidates;

•

the identification of serious adverse, undesirable or unacceptable side effects related to our product candidates;

•

our ability to maintain our current strategic relationships with our collaboration partners;

•

our ability to protect and maintain our, and not infringe on third parties’, intellectual property rights throughout the world;

•

our ability to raise capital when needed in order to continue our product development programs or commercialization efforts;

•

our ability to attract and retain qualified employees and key personnel;

•

the acceptance by the Food and Drug Administration (FDA) and applicable foreign regulatory authorities of data from studies that we and our collaboration partners conduct within and outside the US now and in the future;

•

our foreign private issuer status, the loss of which would require us to comply with the Exchange Act’s domestic reporting regime, and cause us to incur significant legal, accounting and other expenses;

•

our incorporation in Switzerland, the laws of which govern our corporate affairs and may differ from those applicable to companies incorporated in the US; and

•

the other risk factors discussed under “Item 3. Key information—D. Risk factors.”

•

completing preclinical and clinical studies that demonstrate the efficacy, safety and clinical utility of our preclinical and clinical product candidates;

•

receiving marketing approvals from applicable regulatory authorities;

•

establishing commercial manufacturing capabilities;

•

launching commercial sales, marketing and distribution operations;

•

acceptance of our product candidates by patients, the medical community and third-party payors;

•

a continued acceptable safety profile following approval;

•

competing effectively with other therapies or diagnostic approaches; and

•

obtaining, maintaining, enforcing and defending our intellectual property rights and claims and not infringing on third parties’ intellectual property rights.

•

be delayed in obtaining marketing approval for our product candidates;

•

not obtain marketing approval;

•

obtain approval for indications or patient populations that are not as broad as intended or desired;

•

obtain approval with labeling that includes significant use or distribution restrictions or significant safety warnings, including boxed warnings;

•

be subject to conditional approval or otherwise to additional post-marketing studies or other requirements; or

•

remove the product from the market after obtaining marketing approval.

•

how clinicians and potential patients perceive our novel products;

•

the timing of market introduction;

•

the number and clinical profile of competing products;

•

our ability to provide acceptable evidence of safety and efficacy or clinical utility;

•

the prevalence and severity of any side effects;

•

relative convenience and ease of administration;

•

cost-effectiveness;

•

patient diagnostics and screening infrastructure in each market;

•

marketing and distribution support;

•

availability of coverage, reimbursement and adequate payment from health maintenance organizations and other third-party payors, both public and private; and

•

other potential advantages over alternative treatment methods.

•

regulatory authorities may withdraw approvals of such product and require us or our collaboration partners to take any approved products off the market;

•

regulatory authorities may require the addition of labeling statements, specific warnings, a contraindication or field alerts to physicians and pharmacies;

•

we may be required to create a medication guide outlining the risks of such side effects for distribution to patients;

•

we may be required to change the way the product is administered, to conduct additional studies or to change the labeling of the product;

•

we or our collaboration partners may be subject to limitations in how we promote the product;

•

sales of the product may decrease significantly;

•

we could be sued and held liable for harm caused to patients; and

•

our reputation and physician or patient acceptance of our products may suffer.

•

develop and commercialize products that are safer, more effective, less expensive, or more convenient or easier to administer;

•

obtain quicker FDA or other regulatory approval for their products;

•

establish superior intellectual property and proprietary positions;

•

have access to more manufacturing capacity;

•

implement more effective approaches to sales, marketing and distribution; or

•

form more advantageous strategic alliances.

•

economic weakness, including inflation, or political instability in particular non-US economies and markets;

•

differing regulatory requirements for drug approvals in non-US countries;

•

potentially reduced protection for intellectual property rights;

•

difficulties in compliance with non-US laws and regulations;

•

changes in non-US regulations and customs, tariffs and trade barriers;

•

changes in non-US currency exchange rates and currency controls;

•

changes in a specific country’s or region’s political or economic environment;

•

trade protection measures, import or export licensing requirements or other restrictive actions such as sanctions by US or non-US governments;

•

negative consequences from changes in tax laws;

•

compliance with tax, employment, immigration and labor laws for employees living or traveling abroad;

•

workforce uncertainty in countries where labor unrest is more common than in the US;

•

difficulties associated with staffing and managing international operations, including differing labor relations;

•

production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and

•

business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters including earthquakes, typhoons, floods and fires.

•

delays or difficulties in conducting preclinical research and clinical trials;

•

interruption in global manufacturing and shipping that may affect the manufacturing and/or transport of clinical trial materials and other materials, including testing equipment and personal protective equipment, used at our or our contract research organizations’ (CROs’) and contract manufacturing organizations’ (CMOs’) facilities;

•

changes in local regulations as part of a response to the Covid-19 coronavirus outbreak which may require us to change the way in which clinical trials are conducted and may result in unexpected costs; and

•

impact our ability to secure additional financing.

•

we may not be able to control the amount and timing of resources that the collaboration partner devotes to the product development program;

•

the collaboration partner may experience financial difficulties;

•

we may be required to grant or otherwise relinquish important rights such as marketing, distribution and intellectual property rights;

•

a collaboration partner could move forward with a competing product developed either independently or in collaboration with third parties, including our competitors; or

•

business combinations or significant changes in a collaboration partner’s business strategy may adversely affect our willingness to continue any arrangement.

•

the scope of rights granted under the agreement, any restrictions in licensed fields and other interpretation-related issues;

•

the extent to which our technology and processes infringe or otherwise violate the intellectual property of the licensor, the licensee or partner that is not subject to the agreement;

•

the sublicensing of patent and other rights;

•

the diligence, development and commercialization obligations under the agreement and what activities satisfy those obligations;

•

the ownership of inventions and know-how resulting from the joint or mutual creation or use of intellectual property by our licensors or collaboration partners and us;

•

the priority of invention in patented technology;

•

non-compete commitments; and

•

consequences for changes in control.

•

successfully completing research and clinical development of our product candidates, by us or our collaboration partners, as the case may be;

•

obtaining marketing approvals for our clinical product candidates, including ACI-35, ACI-24 for AD and DS, ACI-7104, semorinemab, crenezumab, Morphomer Tau, PI-2620 and our a-syn PET tracer, for which we or our collaboration partners complete clinical studies;

•

developing a sustainable and scalable manufacturing process for any approved product candidates, and maintaining supply and manufacturing relationships with third parties that can conduct the process and provide adequate (in amount, quality and time) products to support clinical development and the market demand for our product candidates, if approved;

•

launching and commercializing product candidates for which we obtain marketing approval, either directly or with a collaborator or distributor;

•

obtaining market acceptance of our product candidates as viable treatment or diagnostic options;

•

addressing any competing technological and market developments;

•

identifying, assessing, acquiring and/or developing new product candidates;

•

negotiating favorable terms in any collaboration, licensing, or other similar arrangements into which we may enter;

•

maintaining, protecting, acquiring and expanding our portfolio of intellectual property rights, including patents, trade secrets and know-how; and

•

attracting, hiring and retaining qualified personnel.

•

the FDA, EMA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical studies;

•

the population studied in the clinical program may not be sufficiently broad or representative to assure safety in the full population for which we seek approval;

•

the FDA, EMA or comparable foreign regulatory authorities may disagree with our interpretation of data from nonclinical or clinical studies;

•

the data collected from clinical studies of our product candidates may not be sufficient to support the submission of an NDA or other submission or to obtain regulatory approval in the US or elsewhere;

•

we may be unable to demonstrate to the FDA, EMA or comparable foreign regulatory authorities that a product candidate’s benefit-risk ratio for its proposed indication is acceptable;

•

the FDA, EMA or other regulatory authorities may fail to approve the manufacturing processes, test procedures and specifications, or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and

•

the approval policies or regulations of the FDA, EMA or comparable foreign regulatory authorities may change significantly in a manner rendering our clinical data insufficient for approval.

•

the delay or refusal of regulators or IRBs to authorize us to commence or amend a clinical study at a prospective study site or changes in regulatory requirements, policies and guidelines;

•

delays or failure to reach agreement on acceptable terms with prospective CROs and clinical study sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and study sites;

•

delays in patient enrollment and variability in the number and types of patients available for clinical studies;

•

the inability to enroll a sufficient number of patients in studies to ensure adequate statistical power to detect statistically significant treatment effects;

•

negative or inconclusive results, which may require us to conduct additional preclinical or clinical studies or to abandon projects that we expected to be promising;

•

safety or tolerability concerns, which could cause us to suspend or terminate a study if we find that the participants are being exposed to unacceptable health risks;

•

regulators or IRBs requiring that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements or safety concerns, among others;

•

lower than anticipated retention rates of patients and volunteers in clinical studies;

•

our CROs or clinical study sites failing to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all, deviating from the protocol or dropping out of a study;

•

delays relating to adding new clinical study sites;

•

difficulty in maintaining contact with patients after treatment, resulting in incomplete data;

•

delays in establishing the appropriate dosage levels;

•

the quality or stability of the product candidate falling below acceptable standards;

•

the inability to produce or obtain sufficient quantities of the product candidate to complete clinical studies; and

•

exceeding budgeted costs due to difficulty in accurately predicting costs associated with clinical studies.

•

restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, or voluntary or mandatory product recalls;

•

fines, warning letters or holds on clinical studies;

•

refusal by the FDA or an applicable foreign regulatory authority to approve pending applications or supplements to approved applications filed by us or our collaborations partners, or suspension or revocation of product license approvals;

•

regulatory constraints in promotion and distribution of drug products in various markets;

•

product seizure or detention, or refusal to permit the import or export of products; and

•

injunctions or the imposition of civil or criminal penalties.

•

the US healthcare Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under US government healthcare programs such as Medicare and Medicaid;

•

the US False Claims Act imposes criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the US government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;

•

the US HIPAA imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

•

the HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;

•

the transparency requirements under the Health Care Reform Law require manufacturers of drugs, devices, biologics and medical supplies to report to the US Department of Health and Human Services information related to payments and other transfers of value made by such manufacturers to physicians and teaching hospitals, and ownership and investment interests held by physicians or their immediate family members; and

•

analogous laws and regulations, such as state anti-kickback and false claims laws, will apply to sales or marketing arrangements, consultancy and service agreements, and claims involving healthcare items or services reimbursed by nongovernmental third-party payors, including private insurers, and some state laws require pharmaceutical and biopharmaceutical companies to comply with the pharmaceutical and biopharmaceutical industries’ voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, in addition to requiring manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures.

•

positive or negative results of testing and clinical studies by us, strategic partners, or competitors;

•

delays in entering into strategic relationships with respect to development and/or commercialization of our product candidates or entry into strategic relationships on terms that are not deemed to be favorable to us;

•

the sentiment of retail investors, including the perception of our clinical trial results by such retail investors, which investors may be subject to the influence of information provided by social media, third party investor websites and independent authors distributing information on the internet;

•

technological innovations or commercial product introductions by us or our collaboration partners or competitors;

•

changes in government regulations;

•

developments concerning proprietary rights, including patents and litigation matters;

•

public concern relating to the commercial value or safety of any of our product candidates;

•

financing or other corporate transactions;

•

publication of research reports or comments by securities or industry analysts or key opinion leaders;

•

general market conditions in the pharmaceutical or biopharmaceutical industry or in the economy as a whole; or

•

other events and factors beyond our control.

•

the non-Swiss court had jurisdiction pursuant to the Swiss Federal Act on Private International Law;

•

the judgment of such non-Swiss court has become final and non-appealable;

•

the judgment does not contravene Swiss public policy;

•

the court procedures and the service of documents leading to the judgment were in accordance with the due process of law; and

•

no proceeding involving the same parties and the same subject matter was first brought in Switzerland, or adjudicated in Switzerland, or was earlier adjudicated in a third state for which the decision is recognizable in Switzerland.

•

The World Health Organization recognizes dementia as a global public health priority. Worldwide, there is a new case of dementia every 3 seconds, with an estimated global patient population of greater than 50 million in 2020. This is predicted to increase to 139 million by 2050 (Alzheimer’s Disease International).

•

The estimated total healthcare costs for the treatment of Alzheimer disease in the United States in 2021 is estimated to be USD 355 billion per the Alzheimer’s Association, with the worldwide cost for dementia expected to increase to approximately USD 2.8 trillion annually by 2050 as the population ages. In fact, if the estimated global costs of dementia were a country, it would be the 14th largest economy in the world.

•

ACI-35.030. Janssen and AC Immune are evaluating the anti-phosphorylated-Tau (anti-pTau) vaccine candidate ACI-35.030 in a Phase 1b/2a study in subjects with early AD. 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. No clinically relevant safety concerns related to the vaccine candidate were observed. Based on these results, the second highest dose cohort was expanded in Q2 2021 to facilitate plans for further late-stage development. ACI-35.030 specifically targets pathological pTau species and is eventually intended as a disease-modifying treatment for AD and other Tauopathies.

•

ACI-24 for AD. A first Phase 1/2 study was completed and finalized in 2019. The subsequent Phase 2 study in AD assessed the safety, tolerability, immunogenicity and target engagement of ACI-24 using intramuscular immunizations and analyzed the effects of ACI-24 on brain amyloid as assessed by PET imaging. This trial was completed and finalized in November 2021. ACI-24 was safe and well tolerated and triggered a clear IgM response with lower Abeta-specific IgG titers. While no apparent effect in amyloid-PET was observed in this limited study population, there was evidence of a pharmacodynamic effect observed by an increase of CSF Aβ1-40 and Aβ1-42 levels compared to the placebo, thus suggesting target engagement. These results support the clinical development of the optimized formulation of ACI-24 (i.e. ACI-24.060) with Abeta unrelated T-helper cell epitopes to increase the magnitude and the boost-ability of the antibody response.

•

ACI-24 for DS. Our Phase 1b clinical study of ACI-24 for individuals with DS, intended to assess safety, tolerability and immunogenicity at two doses, was completed and results reported in Q1 2021. The results support a favorable safety and tolerability profile of ACI-24 and show a pharmacodynamic response in this vulnerable patient population and the advancement of this program with the optimized formulation of ACI-24. The Clinical Trial Application (CTA) for the next study evaluating the optimized formulation of ACI-24 in AD and Down syndrome populations was submitted in Q4 2021. The trial initiation is planned in H1 2022.

•

ACI-7104. ACI-7104, the optimized formulation of the clinically-validated PD vaccine candidate PD01, will advance into an adaptive, biomarker-based Phase 2 study. This trial will evaluate an initial dose-response of the optimized formulation focusing on 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 planned in H2 2022.

•

Semorinemab. Our collaboration partner, Genentech, a member of the Roche Group, completed a first Phase 2 study (Tauriel) conducted in patients with prodromal-to-mild AD in Q3 2020. This trial did not meet its primary efficacy endpoint of reducing decline on Clinical Dementia Rating-Sum of Boxes (CDR-SB) compared to placebo; the primary safety endpoint was met. A second Phase 2 study (Lauriet) conducted in patients with mild-to-moderate AD was completed in Q3 2021 and top-line data from 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. 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 prion-like propagation of Tau pathology, which coincides with both clinical symptoms and disease progression in AD.

•

Crenezumab. Roche announced in 2019 the discontinuation of the Phase 3 clinical trials in AD but is continuing in a landmark prevention trial in Colombia, in a population of genetically predisposed people at risk of developing familial AD. The overall beneficial safety profile was confirmed in the CREAD studies, supporting use of crenezumab in healthy individuals with risk of developing AD. Top-line results from this Phase 2 Prevention trial are expected in H1 2022.

•

Morphomer Tau aggregation inhibitors. In collaboration with our partner, Lilly, we are researching and developing small molecule Tau aggregation inhibitors with plans to evaluate candidates in AD and NeuroOrphan indications. We 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. In addition to AD, the program was expanded to NeuroOrphan indications and ACI-3024 will be further evaluated for efficacy in models of rare Tauopathies. Continued candidate characterization across the research program has also identified new and highly differentiated candidates with excellent cerebrospinal fluid exposure and selectivity for pathological aggregated Tau. These will be broadly developed in Tau-dependent neurodegenerative diseases.

•

Tau-PET tracer. PI-2620 is our Tau-PET imaging agent. We are working with our 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. PI-2620 completed a Phase 2 clinical trial in AD in Q4 2021.

•

A-syn-PET tracer. Our next-generation PET imaging tracer, derived from our 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), a first-in-human study and an investigator-initiated study of our latest diagnostic agent targeting a-syn were initiated in Q1 and Q3 2021, respectively. The readouts of these trials in patients with PD, multiple system atrophy (MSA) and other synucleinopathies are anticipated by Q2 2022.

3.

Accelerating the advancement of our diagnostic portfolio

4.

Continuing to optimize our long-term growth by selectively partnering product candidates for global development and commercialization

•

ACI-35 is composed of a human pTau synthetic peptide T3 as the antigen, derived from Tau sequence 393-408 and phosphorylated at serine residues S396 and S404. Lipidation of the peptide enables it to embed itself into the lipid bi-layer of the liposome and confers a specific conformation to the peptide (Theunis et al., PLoS ONE 2013).

•

In wild-type and transgenic mice, immunization with ACI-35 generated a specific antibody response to phosphorylated vs. non-phosphorylated Tau protein (Vukicevic et. al. AAT-AD/PD 2020).

•

In transgenic mice, immunization with ACI-35 led to a significant decrease of soluble and insoluble total Tau protein and insoluble pTau species in brain (Figure 13).

•

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.

•

In rhesus monkeys, ACI-35.030 induced a specific response to pTau over non-phosphorylated Tau, similar to that observed with ACI-35 (Vukicevic et. al. AAT-AD/PD 2020). This is meaningful as Tau hyper-phosphorylation is considered an early event in the development of Tau pathology, occurring even several decades before the onset of Tau deposits.

•

Sera from rhesus monkeys immunized with ACI-35.030 binds specifically to pathological Tau in brain sections with AD as compared to healthy human brain tissue (Kosco-Vilbois, KOL event ‘Untangling’ Tau Pathology to Treat Alzheimer’s and Neurodegenerative Diseases NYC, Nov 2019)

•

In preclinical studies, immunization of non-human primates (NHPs) with ACI-35.030 lead to  enhanced and more uniform anti-pTau IgG -specific antibody titers with boosting effect compared to ACI-35 (Figure 14).

•

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.

•

Immunization of rhesus macaques with JACI-35.054 generates an antibody response that binds to pathological Tau structures in human AD brain.

•

ACI-24.060’s mechanism of action is similar to the one described with the original formulation of ACI-24. The incorporation of T-cell help epitopes in this optimized formulation is intended to prime, boost and maintain a strong antibody response against key pathological Abeta species (including oligomeric and pyroglutamate Abeta). The antibodies elicited by the vaccine in NHPs showed clear target engagement by binding to human Abeta plaques on AD patient-derived brain tissue.

•

ACI-7104 is composed of a short engineered antigenic a-syn peptide. This peptide coupled to a carrier protein facilitates the induction of an a-syn-specific antibody response that binds to toxic aggregated a-syn species with high selectivity (Mandler-M et al., Acta Neuropathol. 2014).

•

Vaccination of wild-type and transgenic mice, resulted in high antibody titres in plasma, which crossed into the cerebrospinal fluid (CSF) (Mandler-M et al., Acta Neuropathol. 2014) and recognized a-syn aggregates. Vaccination resulted in a decreased aggregation and accumulation of a-syn oligomers in brains of transgenic animals (Figure 16).

•

Clearance of a-syn was accompanied by reduced neurodegeneration and by improvements in motor and memory deficits in both in vivo models (Mandler-M et al., Acta Neuropathol. 2014).

•

In vivo target engagement of induced antibodies was demonstrated by lowering of oligomeric a-syn in CSF of vaccinated subjects (Figure 18B).

•

A highly significant correlation between oligomeric a-syn concentration in CSF and MDS-UPDRS 3 score (motor-symptoms) in PD patients at baseline was shown for the first time.

•

The reduction of oligomeric a-syn in CSF correlated significantly with clinical improvement, the changes in MDS-UPDRS 3 score over time (Figure 18C).

•

Crenezumab binds to multiple forms of Abeta, particularly oligomeric forms, which it binds to with ten times higher affinity than to monomers. This is a desirable property since oligomeric forms of Abeta are believed to be principally responsible for neurotoxicity in AD.

•

Crenezumab localizes to brain regions rich in oligomers, including the halo around plaques and hippocampal mossy fibers, but not to vascular Abeta (Maloney et al., 2019).

•

Crenezumab has been designed with an IgG4 backbone to reduce effector function on microglia compared with an IgG1 backbone, and to clear Abeta from the brain while limiting inflammation by minimizing FcγR-mediated inflammatory activation of microglia (Adolfsson et al., J. Neurosci 2012).

•

Due to its capacity to bind to multiple forms of Abeta, with 10-fold higher specificity to oligomers, which are thought to be the most toxic species, crenezumab also protects against oligomer-induced neurotoxicity.

•

Linked to its unique epitope, crenezumab has been shown to promote disaggregation of existing Abeta aggregates and to disrupt their assembly, preventing amyloid plaque formation. The crystal structure reveals binding interactions that are consistent with this flexible binding profile and provides further explanation for crenezumab’s ability to block aggregation and to promote disaggregation.

•

In the proof-of-concept Phase 2 studies of crenezumab, a positive trend in cognition was observed, with a greater effect on cognition in patients with a milder stage of AD (MMSE 22–26).

•

In the ABBY cognition study, there, was a statistically significant 35% reduction in the rate of cognitive decline in the non-pre-specified milder AD patient population (MMSE 22–26) for the high-dose arm.

•

In the BLAZE biomarker study, the high-dose arm showed a consistent trend of reduced Abeta accumulation in the brain over time, as shown in two independent exploratory analyses of florbetapir-PET data. In addition, results have shown that crenezumab has the ability to enhance the removal of these proteins from the brain as evidenced by a significant increase in CSF Abeta, confirming target engagement by crenezumab.

•

Phase 2 data from ABBY and BLAZE studies suggested that there were no imbalances in overall rate of AEs, and these were not dose-related, with only one case of asymptomatic ARIA-E (0.4% in ABBY, 0.3% on active pooled) in patients treated with crenezumab. AEs also included inflammation of the throat and nasal passages, urinary tract infections and upper respiratory infections. However, no patients in the studies experienced SAEs that were believed related to the administration of crenezumab.

•

A Phase 1 study with higher doses of crenezumab up to 120 mg/kg showed good tolerability with no investigator assessed drug-related SAEs and no events of ARIA-E, supporting the dose of 60 mg/kg in the Phase 3 CREAD clinical trials.

•

The good safety profile and lack of induction of ARIA-E was confirmed in the Phase 3 CREAD and CREAD 2 studies, in which there was no increase in incidence of SAEs compared with placebo.

•

Crenezumab is currently being evaluated in a Phase 2 clinical prevention trial in Colombia, which has enrolled 300 cognitively healthy individuals of whom 200 are genetically predisposed to develop early AD. As of January 2019, two Phase 3 clinical trials, CREAD and CREAD 2, in patients with prodromal-to-mild AD were discontinued after an interim analysis of the CREAD study conducted by our collaboration partner Genentech.

Product candidate	Target	Lead application	Partner	Platform
a-syn antibody	a-syn	PD, NeuroOrphan	Proprietary	SupraAntigen
Morphomer a-syn	a-syn	PD, NeuroOrphan	Proprietary	Morphomer
Anti-TDP-43 antibody	TDP-43	NeuroOrphan	Proprietary	SupraAntigen
Morphomer inflammasome	NLRP3-ASC	CNS, non-CNS	Proprietary	Morphomer
Anti-inflammasome antibody	NLRP3-ASC	CNS	Proprietary	SupraAntigen

•

a worldwide licensing agreement with Genentech signed in November 2006 (and amended in March 2009, January 2013, May 2014 and May 2015) for crenezumab for AD, under which we may become eligible to receive payments potentially greater than USD 340 (CHF 314) million, excluding royalties;

•

a worldwide licensing agreement with Genentech signed in June 2012 (and amended in December 2015) for anti-Tau antibodies to treat AD and potentially other indications, under which we may become eligible to receive payments potentially greater than CHF 400 million, excluding royalties;

•

a worldwide licensing agreement with Janssen signed in December 2014 (and amended in April 2016, July 2017, January 2019 and November 2019) for therapeutic anti-Tau vaccines for AD, and potentially other Tauopathies, under which we may become eligible to receive payments totaling up to CHF 500 million, excluding royalties;

•

a worldwide licensing and collaboration agreement (LCA) with LMI (formerly Piramal Imaging SA) signed in May 2014 for small-molecule Tau ligands for use as PET tracers under which we may become eligible to receive payments totaling up to EUR 160 (CHF 167) million, excluding royalties; and

•

a worldwide license agreement with Lilly to research and develop Morphomer Tau small molecules for the treatment of AD and other neurodegenerative diseases, which was entered into in December 2018 (and amended in September 2019 and March 2020). The agreement was deemed effective on January 23, 2019. Under this, we may become eligible to receive payments up to approximately CHF 1.9 billion, excluding royalties.

•

provide constructive regulatory input for development products;

•

ensure smooth regulatory approvals by anticipating hurdles; and

•

build confidence with regulators by continuous communication.

•

create and maintain a corporate quality management system; and

•

ensure cGCP, cGMP, cGLP and current Good Distribution Practice (cGDP) compliance.

•

the completion of preclinical laboratory tests and animal tests conducted under cGLP regulations;

•

the submission to the FDA of an IND application for human clinical testing, which must become effective before human clinical studies commence;

•

obtaining a positive opinion from the ethics committee (Europe)/institutional review board (US) to commence study on human subjects;

•

the performance of adequate and well-controlled human clinical studies to establish the safety and efficacy of the product candidate for each proposed indication and conducted in accordance with cGCP requirements;

•

pre-NDA submission meeting with FDA (highly recommended);

•

the submission to the FDA of an NDA;

•

the FDA’s acceptance of the NDA;

•

satisfactory completion of an FDA Pre-Approval Inspection (PAI) of the manufacturing facilities at which the product is made to assess compliance with cGMP requirements;

•

the FDA’s review and approval of an NDA prior to any commercial marketing or sale of the drug in the US; and

•

having parallel scientific advice from the EMA or Health Technology Assessment body whereby the payors are involved at the outset (Phase 2), which is intended to facilitate the design of clinical studies to target primarily populations with a high chance of obtaining reimbursement and accelerate the process of time to reimbursement.

•

restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;

•

fines, warning letters or holds on post-approval clinical studies;

•

refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product license approvals;

•

product seizure or detention, or refusal to permit the import or export of products; or

•

injunctions or the imposition of civil or criminal penalties.

•

that it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than 5 in 10,000 persons in the EU when the application is made, or that it is intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition in the EU and that without incentives it is unlikely that the marketing of the drug in the EU would generate sufficient return to justify the necessary investment; and

•

that there exists no satisfactory method of diagnosis, prevention or treatment of the condition in question that has been authorized in the EU or, if such method exists, that the drug will be of significant benefit to those affected by that condition.

•

the holder of the marketing authorization for the original orphan drug has given its consent to the second applicant;

•

the holder of the marketing authorization for the original orphan drug is unable to supply sufficient quantities of the drug; or

•

the second applicant can establish in the application that the second drug, although similar to the orphan drug already authorized, is safer, more effective or otherwise clinically superior.

•

Manufacturing and batch release—MAHs should guarantee that all manufacturing operations comply with relevant laws and regulations, applicable GMPs, and the product specifications and manufacturing conditions set out in the marketing authorization, and that each batch of product is subject to appropriate release formalities.

•

Availability and continuous supply—Pursuant to Directive 2001/83/EC, as transposed into the national laws of the Member States, the MAH for a medicinal product and the distributors of the said medicinal product actually placed on the market in a Member State shall, within the limits of their responsibilities, ensure appropriate and continued supplies of that medical product to pharmacies and persons authorized to supply medicinal products so that the needs of patients in the Member State in question are covered.

•

Pharmacovigilance—MAHs are obliged to establish and maintain a pharmacovigilance system, including a qualified person responsible for oversight, to submit safety reports to the regulators and to comply with the good pharmacovigilance practice guidelines adopted by the EMA.

•

Advertising and promotion—MAHs remain responsible for all advertising and promotion of their products, including promotional activities by other companies or individuals on their behalf, and in some cases must conduct internal or regulatory pre-approval of promotional materials. Regulation in this area also covers interactions with healthcare practitioners and/or patient groups, and in some jurisdictions legal or self-regulatory obligations to disclose such interactions exist.

•

Medical affairs/scientific service—MAHs are required to disseminate scientific and medical information on their medicinal products to healthcare professionals, regulators and patients.

•

Legal representation and distributor issues—MAHs are responsible for regulatory actions or inactions of their distributors and agents.

•

Preparation, filing and maintenance of the application and subsequent marketing authorization— MAHs must maintain appropriate records, comply with the marketing authorization’s terms and conditions, fulfill reporting obligations to regulators, submit renewal applications and pay all appropriate fees to the authorities. We may hold any future marketing authorizations granted for our product candidates in our own name, or appoint an affiliate or a collaboration partner to hold marketing authorizations on our behalf. Any failure by an MAH to comply with these obligations may result in regulatory action against an MAH and ultimately threaten our ability to commercialize our products.

Location		Primary Function		Approximate Size
École Polytechnique Fédérale Lausanne (EPFL) Innovation Park Building B, 1015 Lausanne, Vaud, Switzerland		Headquarters   Research, discovery, preclinical and clinical development   Chemistry manufacturing and control		27,000 square feet
1230 Avenue of the Americas Suite 1634 New York, New York 10020		US operations		1,600 square feet

•

A right-of-use license;

•

Clinical milestone payments: payable upon commencement of each of Phase 1 and Phase 2 of clinical developments, and upon the earlier of Genentech’s decision to authorize Phase 3 or the commencement of Phase 3 of clinical developments. In addition, for a second indication, clinical milestone payments would be payable upon commencement of Phase 2 of clinical developments and upon the earlier of Genentech’s decision to authorize Phase 3 or the commencement of Phase 3 of clinical developments;

•

Regulatory milestone payments: payable upon making regulatory filings in the US and Europe, respectively, and milestone payments upon obtaining marketing approval in each of the US and Europe. In addition, for a second indication, additional regulatory and approval milestones would be payable.

•

Royalties: payable on sales, with different royalty rates applicable in the US and Europe. Royalty levels are tied to annual sales volumes. We may receive royalties on sales of crenezumab with the percentage rates ranging from the mid-single digits to mid-teens.

•

A right-of-use license.

•

Preclinical and clinical milestone payments: payable upon selection of a lead candidate and commencement of each of Phase 1, 2 and 3 of clinical development. In addition, for a second indication, clinical milestone payments would be payable upon commencement of each of Phase 2 and 3 of clinical development.

•

Regulatory milestone payments: payable upon making regulatory filings for marketing approvals in each of the US, Europe and Japan. In addition, for a second indication, similar regulatory milestones would be payable.

•

Commercialization milestones: payable upon making a first commercial sale in each of the US, Europe and Japan. For a second indication, commercialization milestones exist for each of the US, Europe and Japan, which are triggered by the first commercial sale for the second indication in each of those jurisdictions.

•

Royalties: payable on sales with royalty rates differing based on the source of the intellectual property underlying the commercial product. We may receive royalties on sales at a percentage rate ranging from the mid-single digits to low-double digits

•

A right-of-use license.

•

Clinical milestone payments: payable upon reaching certain milestones in the Phase 1b study, commencement of the first Phase 2b or 2b/3 of clinical development, upon reaching enrollment thresholds in the first Phase 2b or Phase 2b part of the first Phase 2b/3, commencement of the first Phase 3 or Phase 3 part of a Phase 2b/3 study. In addition, for a second indication, clinical milestone payments would be payable upon commencement of a Phase 3 clinical study, which would be payable concurrently with the first regulatory milestone, if Janssen were to file for regulatory approval based on Phase 2 clinical data.

•

Regulatory milestone payments: payable upon making regulatory filings in the US, Europe, and Japan, respectively. In addition, for a second indication, similar regulatory milestones would be payable. For a second indication, additional regulatory milestone payments are payable by Janssen to us upon receipt of each of the regulatory approvals in the US, Europe and Japan.

•

Commercialization milestones: payable upon making a first commercial sale in each of the US, Europe and Japan, and upon achieving certain commercial milestones.

•

Royalties: payable on sales, with royalty rates differing based on the level of annual sales. We may receive royalties on sales at a percentage rate ranging from the high-single digits to the mid-teens for the phospho-tau vaccine program.

•

A right-of-use license.

•

Clinical milestone payments: payable upon the commencement of the Phase 1, 2 and 3 studies for generation of data intended to support a regulatory submission in the US or the EU. We would be entitled to further clinical milestone payments for the commencement of a Phase 2 and 3 study for a second indication.

•

Regulatory milestone payments: payable upon acceptance of Regulatory filing (NDA) and Regulatory approval for Commercialization in the US or the EU.

•

Commercialization milestones: tied to specific annual net sales amounts.

•

Royalties: payable on sales, with royalty rates differing based on the level of annual sales. We may receive royalties on sales at a percentage rate ranging from the mid-single digits to the low-teens.

•

An exclusive license: granted by us to Lilly under certain of our intellectual property to develop,

•

Clinical milestone payments: payable upon completion of the Lilly preclinical activities period and following the first patient dosed in a Phase 2 and Phase 3 clinical study of a licensed product in the US or the EU.

•

Regulatory milestone payments: payable within 60 days after obtaining regulatory approval for any licensed product in the first indication and any licensed product in certain additional indications in the US, Europe and Japan, respectively.

•

Commercialization milestones: payable upon achieving certain commercial sales milestones.

•

Royalties: payable on sales with royalty rates differing based on the level of annual sales of licensed products. We may receive royalties on sales at a percentage rate ranging from the low double-digits to the mid-teens.

•

communicating with our applicable personnel to identify services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of actual costs;

•

estimating and accruing expenses in our consolidated financial statements as of each balance sheet date based on facts and circumstances known to us at the time; and

•

periodically confirming the accuracy of our estimates with selected providers and adjusting, if necessary.

•

fees paid to CROs in connection with preclinical and toxicology studies and clinical studies;

•

fees paid to investigative sites in connection with clinical studies;

•

fees paid to CMOs in connection with the production of our product candidates prior to qualifying for capitalization as inventory; and

•

professional service fees for consulting and related services.

	Assumption		Method of estimation
●	Estimated expected term of options	●	Simplified method
●	Expected volatility	●	Estimate based on average historical volatilities of common shares of comparable publicly traded companies. We will continue to apply this process to grants made as a public company until a sufficient amount of historical information regarding the volatility of our own stock price becomes available
●	Risk-free interest rate	●	Yields of long-dated Swiss government zero coupon bond issues
●	Expected dividends	●	Zero percent as dividends have not been paid
●	Forfeiture rates	●	Historical and expected forfeiture data

•

AD;

•

focused non-AD NDD including Parkinson’s disease, ALS and NeuroOrphan indications; and

•

diagnostics.

		For the Years Ended December 31,
In CHF thousands		2021				2020				Change
Contract revenue			—				15,431				(15,431	)
Total revenues			—				15,431				(15,431	)

•

a decrease of CHF 14.3 million in our agreement with Lilly. The Company recognized a CHF 10 million milestone as well as CHF 4.3 million for R&D activities in 2020; and

•

a decrease of CHF 1.1 million in our collaboration with Janssen.

		For the Years Ended December 31,
In CHF thousands		2021				2020				Change
Discovery and preclinical expenses			19,963				20,408				(445	)
Clinical expenses			14,872				17,124				(2,252	)
Group function expenses			929				904				25
Total Direct R&D			35,764				38,436				(2,672	)
Payroll expenses			16,465				14,424				2,041
Share-based compensation			1,528				1,276				252
Other non-allocated			8,525				5,351				3,174
Total R&D			62,282				59,487				2,795

		For the Years Ended December 31,
In CHF thousands		2021				2020				Change
Operating expenses1			44,289				43,787				502
Salaries and related costs2			17,993				15,700				2,293
Total research and development expenses			62,282				59,487				2,795

•

a decrease of CHF 2.0 million for the research of alpha-synuclein antibodies.

•

an increase of CHF 0.7 million for the expansion of our Morphomer Tau program into NeuroOrphan indications and the further characterization of our preclinical candidates, CHF 0.5 million for the optimization and development of our anti-TDP-43 antibody, CHF 0.1 million for our diagnostic imaging agents and CHF 0.4 million in other discovery programs,

•

a decrease of CHF 2.2 million for Phase 1 activities for our Morphomer Tau compound which completed in 2020, CHF 2.0 million for ACI-24 for DS as a result of prior period scaling up activities for a Phase 2 clinical trial which were not repeated in the current period and CHF 1.8 million for ACI-24 for AD as the six-month safety period completed,

•

an increase of CHF 3.5 million for ACI-35.030 driven by R&D cost sharing, increased patient enrollment into the Phase 1b/2a study and increased frequency of interim analysis testing and CHF 0.2 million for other clinical programs.

•

an increase in salary and benefit related costs of CHF 2.0 million primarily related to the internal reallocation of certain employees’ personnel cost from general and administrative expenses to research and development personnel expenses in 2021 and the annualization of 2020 hires; and

•

higher share-based compensation expense of CHF 0.3 million related predominantly to an increase of stock options issued to employees.

•

an increase of CHF 2.8 million associated with the reallocation of certain IT and facilities expenditures made in 2021 that were not reclassified in the prior period, CHF 0.3 million in depreciation expense and CHF 0.1 million in other items.

		For the Years Ended December 31,
In CHF thousands		2021				2020				Change
Operating expenses1			7,031				7,471				(440	)
Salaries and related costs2			10,879				11,086				(207	)
Total general and administrative expenses			17,910				18,557				(647	)

•

CHF 2.8 million associated with the reallocation of certain IT and facilities expenditures made in 2021 that were not reclassified in the prior period,

•

a CHF 1.1 million for transaction costs associated with our asset acquisition for a portfolio of therapeutics targeting alpha-synuclein from Affiris,

•

a CHF 0.9 million increase in our directors’ and officers’ insurance for the period; and

•

CHF 0.3 million increase in other administrative expenses.

		For the Years Ended December 31,
In CHF thousands		2021				2020				Change
Other operating income/(expense)			1,182				1,353				(171	)
Total other operating income/(expense)			1,182				1,353				(171	)

•

a decrease of CHF 0.3 million in grant income related to activities completed prior to the start of the current period related to our MJFF awards in 2021,

•

an increase of CHF 0.1 million in grant income for activities completed for our Target ALS Foundation award.

		For the Years Ended December 31,
In CHF thousands		2021				2020				Change
Financial income			6,485				78				6,407
Financial expense			(581	)			(184	)			(397	)
Exchange differences			113				(555	)			668
Finance result, net			6,017				(661	)			6,678

•

an increase of CHF 6.4 million in financial income, predominantly related to a CHF 6.5 million gain on the change in fair value of derivative financial assets associated with two convertible notes sold to certain Affiris affiliated entities as a result of fair value remeasurements; and

•

a CHF 0.7 million increase in favorable foreign currency exchange differences related to movement in the CHF versus foreign currencies, predominantly the US Dollar and Euro,

•

a CHF 0.4 million increase in financial expense, of which CHF 0.4 million relates to interest expense as many of our CHF-denominated deposit accounts bear negative interest as well as our lease liabilities in accordance with IFRS 16.

		For the Years Ended December 31,
(In CHF thousands, except for share and per share data)		2021				2020				2019
Income/(loss)			(72,996	)			(61,921	)			45,442
Adjustments:
Non-cash share-based payments1			4,126				4,088				2,834
Foreign currency (gains)/losses2			70				703				826
Change in fair value of derivative financial assets3			(6,459	)			—				—
Transaction costs4			1,144				—				—
Effective interest expenses5			—				—				1,355
Change in fair value of conversion feature6			—				—				(4,542	)
Adjusted income/(loss)			(74,115	)			(57,130	)			45,915
Earnings/(loss) per share – basic			(0.97	)			(0.86	)			0.64
Earnings/(loss) per share – diluted			(0.97	)			(0.86	)			0.64
Adjustment to earnings/(loss) per share – basic			(0.02	)			0.07				0.01
Adjustment to earnings/(loss) per share – diluted			(0.02	)			0.07				0.00
Adjusted earnings/(loss) per share – basic			(0.99	)			(0.79	)			0.65
Adjusted earnings/(loss) per share – diluted			(0.99	)			(0.79	)			0.64
Weighted-average number of shares used to compute adjusted loss per share – basic			74,951,833				71,900,212				70,603,611
Weighted-average number of shares used to compute adjusted loss per share – diluted			74,951,833				71,900,212				71,103,341

		For the Years Ended December 31,
In CHF thousands		2021				2020				Change
Net cash provided by (used in):
Operating activities			(65,689	)			(59,517	)			(6,172	)
Investing activities			(53,664	)			28,329				(81,993	)
Financing activities			40,746				(803	)			41,549
Net change in cash and cash equivalents			(78,607	)			(31,991	)			(46,616	)