On March 23, 2021 AC Immune SA (NASDAQ: ACIU), a clinical-stage biopharmaceutical company pioneering precision medicine for neurodegenerative diseases, reported its financial results for the year ended December 31, 2020 (Press release, AC Immune, MAR 23, 2021, View Source [SID1234577010]). The Company also provided an overview of its execution strategy and anticipated clinical and preclinical milestones for 2021, as well as the strong progress being made across its broad portfolio of therapeutic and diagnostic product candidates.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Prof. Andrea Pfeifer, CEO of AC Immune SA, commented: "We began 2021 with strong momentum based on the effective execution of our multi-pronged clinical development growth strategy. This is exemplified by our anti-pTau vaccine, which recently demonstrated highly potent immune responses against pathological Tau and remarkable safety in patients with early Alzheimer’s disease (AD). We are also creating future value by accelerating development of our proprietary, first-in-class candidates addressing novel targets in neurodegeneration, such as our promising alpha-synuclein PET tracer, which will generate initial clinical results this year, and our highly valued programs targeting the NLRP3 inflammasome. Our strong track record shows that expanding our efforts to advance these key early-stage programs may lead to multiple future opportunities for strategic partnership as well as in-house clinical development for select indications. In parallel, we continue to collaborate with our global partners to advance our later-stage clinical programs toward key inflection points. Looking forward in 2021, we expect to build upon our successes and continue innovating as a leader in precision medicine for neurodegenerative disease."

2020 and Q1 2021 Research & Development Highlights

Clinical Pipeline advancement

Reported promising interim Phase 1b/2a results for ACI-35.030, a novel anti-phospho-Tau (pTau) vaccine candidate showing strong safety and high titers of antigen-specific antibodies in 100% of older patients with early AD. The study is currently enrolling patients into the highest dose group, with further clinical readouts expected this year.
Advanced next-generation alpha-synuclein positron emission tomography (PET) tracer candidate, ACI-12589, into a first-in-human clinical study, with an expected data readout in Q3 2021
Reported topline Phase 2 results for semorinemab, the Company’s investigational monoclonal anti-Tau antibody candidate for the treatment of prodromal to mild AD, partnered with Genentech, a member of the Roche Group. These represent the first-ever Phase 2 results for an anti-Tau antibody therapeutic in AD. Primary completion of the second Phase 2 study in moderate AD patients is expected in Q2 2021.
Completed a Phase 1 clinical study in healthy volunteers for ACI-3024, an oral small molecule Morphomer Tau aggregation inhibitor, which achieved target brain exposure. The Companies have decided to pursue other promising Tau Morphomer candidates from AC Immune’s research platform for potential clinical development in AD. ACI-3024 will be further evaluated for efficacy in models of rare Tauopathies.
Partnership milestone payments and grants

Received a CHF 10 million milestone payment from Eli Lilly and Company related to ACI-3024
Amended the collaboration agreement with Lilly for Tau Morphomers to include a new CHF 60 million Phase 2 milestone payment, which increased the total potential deal value by CHF 40 million to CHF 1.86 billion
Received multiple prestigious and highly competitive grants in 2020 focused on acceleration of the Company’s proprietary and potentially game-changing diagnostic programs
Won Ken Griffin Alpha-synuclein Imaging Competition from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and is able to receive together with its clinical partner USD 3.2 million (CHF 3.1 million) to support AC Immune’s alpha-synuclein-PET tracers
Awarded a EUR 1.45 million grant to support the partnership between AC Immune and the EU Joint Programme – Neurodegenerative Disease Research (JPND) ImageTDP-43 Consortium to advance its first-in-class TAR DNA-binding protein 43 (TDP-43) PET tracers
Awarded a USD 600,000 grant from Target ALS to develop novel immuno-assays to detect pathological TDP-43 in cerebrospinal fluid (CSF) and blood based on AC Immune’s SupraAntigen-derived anti-TDP-43 antibodies
Strengthening of Management and Board

Appointed Prof. Johannes R. Streffer, former UCB Biopharma Head of Translational Neuroscience, to the new role of Chief Medical Officer
Welcomed Prof. Carl H. June, world authority on immune tolerance and adoptive immunotherapy, to the Company’s Board of Directors
Appointed renowned Neurologist with a specific focus in the emerging field of Down syndrome (DS)-related Alzheimer’s disease, Dr. Juan Fortea to AC Immune’s Clinical Advisory Board
Future Value Creation

Reported key advancements for several therapeutic programs targeting the NLRP3 inflammasome, including small molecule inhibitors, which showed the first evidence of in vivo activity in a model of peripheral inflammation, as well as high-affinity monoclonal antibodies that bind extracellular components of the (NOD)-like receptor protein 3 (NLRP3) pathway and inhibit inflammasome-mediated immune response in vitro
Identified and characterized the first biologically active small molecule Morphomer alpha-synuclein aggregation inhibitors, which significantly decreased alpha-synuclein aggregate formation in cellular assays by interfering with the fibrillation process
Strengthened strategic partnership with WuXi Biologics to accelerate advancement of TDP-43 antibody into clinical development for NeuroOrphan indications
2021 execution strategy to maximize value creation

AC Immune’s execution strategy is focused on three key initiatives, which support the Company’s overarching goal of enabling precision medicine for neurodegenerative diseases:

The Company plans to accelerate the development of its late-stage therapies in AD in collaboration with its strategic partners, including its novel pTau vaccine with Janssen Pharmaceuticals Inc., which continues to show great promise.
AC Immune is sharpening its strategic focus on non-AD indications with high unmet need. Currently this includes its anti-Abeta vaccine in people with DS, as well as its therapeutic and diagnostic candidates targeting TDP-43 and alpha-synuclein, where the Company may focus in-house efforts on select NeuroOrphan indications while seeking potential partnerships for larger indications like LATE (limbic-predominant age-related TDP-43 encephalopathy) and Parkinson’s disease (PD). Furthermore, AC Immune’s NLRP3 inflammasome-targeted programs have broad applicability both within central nervous system (CNS) and non-CNS indications.
The Company plans to accelerate advancement of its diagnostic candidates to late-stage development, as continued leadership in precision medicine is a key differentiator for AC Immune. These candidates include its Tau, alpha-synuclein, and TDP-43 PET tracers, which potentially enable earlier disease diagnosis, improved clinical trial outcomes and additional revenue generation for the Company.
Anticipated 2021 milestones
Clinical Milestones

ACI-35.030 anti-pTau vaccine: reported Phase 1b/2a in AD interim results in Q1 (second highest dose); further Phase 1b/2a interim analysis in Q4 (highest dose)
JACI-35.054 alternative anti-pTau vaccine: Phase 1b/2a in AD interim analysis in Q2 (low dose)
Alpha-synuclein imaging agent: advanced third-generation candidate to first-in-human clinical study in Q1; readout expected in Q3
ACI-24 anti-Abeta vaccine in DS: reported Phase 1b top line results in Q1; to present further study results at the Alzheimer’s Association International Conference 2021 in Q2
ACI-24 in AD: reported Phase 2, 12-month interim analysis in Q1; 18-month interim analysis in Q2
Semorinemab anti-Tau antibody: Phase 2 trial primary completion (estimated last patient, last visit) in moderate AD in Q2
ACI-3024 small molecule Morphomer Tau aggregation inhibitor: select NeuroOrphan indication for further development in Q2
ACI-24 in DS: submit investigational new drug (IND) application for optimized vaccine formulation in Q4
Preclinical Milestones

Alpha-synuclein small molecule inhibitor: identified first biologically active small molecule in Q1; start in vivo proof-of-concept studies in Q3
TDP-43 imaging agent: initiate investigational new drug (IND)-enabling studies in Q3
Morphomer NLRP3-ASC: report in vivo proof-of-concept results in a non-CNS disease model and begin in vivo proof-of-concept studies with validated candidate in CNS in Q4
Anti NLRP3-ASC antibody: begin in vivo proof-of-concept studies in Q4
Anti-TDP-43 antibody: initiate IND-enabling toxicology studies in Q4
TDP-43 biofluid diagnostic: establish validation-ready assay in Q4
Therapeutic and Diagnostic Pipeline Overview

AC Immune also provided a comprehensive overview highlighting strong progress across its clinical and preclinical development pipeline. This supplemental material can be viewed and downloaded in the investor section of the Company’s website.

Analysis of Financial Statements for the year ended December 31, 2020

Cash Position: The Company had a total cash balance of CHF 225.9 million, comprised of CHF 160.9 million in cash and cash equivalents and CHF 65 million in short-term financial assets. This compares to a total cash balance of CHF 288.6 million as of December 31, 2019. The decrease of CHF 62.7 million is principally due to continued investments in our R&D pipeline. The total shareholders’ equity position decreased to CHF 215.5 million from CHF 272.4 million as of the prior year. The Company’s cash balance provides enough capital resources to progress through at least Q1 2024 without potential incoming milestone payments.
Contract Revenues: Contract revenues for the year ended December 31, 2020 totaled CHF 15.4 million compared to CHF 110.5 million in 2019, representing a CHF 95 million decrease. The Company recognized a CHF 10 million milestone and CHF 4.3 million for research and development activities in 2020 from its Lilly agreement compared to CHF 103.1 million for an upfront payment and milestone and CHF 2.6 million for research and development activities in 2019.
R&D Expenditures: R&D expenses increased by CHF 9.1 million for the year ended December 31, 2020.
Discovery and preclinical expenses: The Company increased expenditures across a variety of its discovery and preclinical programs. These include investments to advance the second generation of our ACI-24 for Down Syndrome project, the initiation of IND-enabling studies of our anti-TDP-43 antibody project and various other investments across our alpha-synuclein and neuroinflammation programs.
Clinical expenses: The Company also increased expenditures across multiple Clinical programs. These include investments to prepare a follow-on trial for our Abeta vaccine for Down Syndrome project, additional enrollment costs for the Phase 1b/2a study for ACI-35.030 and a full year of clinical activities to complete the Phase 1 of our Morphomer Tau asset in partnership with Lilly.
Salary- and benefit-related costs: The Company’s salary- and benefit-related costs increased by CHF 2.7 million, primarily due to the addition of 13 FTEs, annualization of 2019 hires and increases in share-based compensation.
G&A Expenditures: For the year ended December 31, 2020, G&A increased by CHF 2.5 million to 18.6 million. Of this increase, CHF 1.7 million is due to salary- and benefit-related costs, primarily due to the addition of 3 FTEs, annualization of 2019 hires and increases in share-based compensation. Additionally, the Company incurred a CHF 0.8 million increase in other G&A expenses, predominantly associated with depreciation expense, insurance and professional fees
IFRS Income/(Loss) for the Period: The Company reported a net loss after taxes of CHF 61.9 million for the year ended December 31, 2020, compared with net income of CHF 45.4 million for 2019
2021 Financial Guidance

For the full year 2021, the Company expects its total cash burn to range between CHF 65 million ‒75 million.