On March 22, 2022 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, 2021, and provided a corporate update, highlighting progress in its broad pipeline of products to treat and diagnose neurodegenerative diseases (Press release, AC Immune, MAR 22, 2022, View Source [SID1234610557]).
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Prof. Andrea Pfeifer, CEO of AC Immune SA, commented: "We are off to a strong start in 2022 with the second of seven clinical data readouts presented last week at the AD/PD 2022 conference. The first-in-human study of our alpha-synuclein diagnostic, ACI-12589, showed it has strong potential to become the first reliable and accurate PET tracer for alpha-synucleinopathies (e.g. multiple system atrophy, MSA)."
"Pairing cutting-edge diagnostics with highly targeted and selective therapeutic agents, such as our vaccines targeting alpha-synuclein, phosphorylated-Tau, and Abeta, which are all advancing into later-stage development this year, we aim to shift the therapeutic paradigm of neurodegenerative diseases towards earlier, more accurate diagnosis, treatment, and prevention," Prof. Pfeifer said.
2021 and Subsequent Highlights
Pipeline progress
Tau
▪Expanded the Phase 1b/2a trial evaluating the first-in-class anti-phosphorylated-Tau (pTau) vaccine candidate ACI-35.030 for the treatment of AD in collaboration with Janssen Pharmaceuticals, Inc. The decision to expand the trial, which was made to support plans to advance ACI-35.030 into late-stage development, was based on encouraging interim safety, tolerability, and immunogenicity results. These showed that ACI-35.030 treatment was well tolerated and led to the strong induction of antibodies specific for pathological forms of Tau such as pTau and its aggregated form, enriched paired helical filaments (ePHF).
▪Top line data from the Phase 2 Lauriet trial of semorinemab in mild-to-moderate AD presented at CTAD 2021 showed a statistically significant (p=0.0008) 42.2% reduction in cognitive decline vs. placebo as measured by ADAS-Cog11 at week 49, one of the trial’s co-primary endpoints. There were no statistically significant differences between semoribemab and placebo arms in the other co-primary endpoint, ADCS-ADL, or in the secondary endpoints (MMSE and CDR-SB). AC Immune’s partner Genentech, a member of the Roche Group, is continuing with the trial’s open-label extension. Additional fluid biomarker data are expected in H2 2022.
Abeta
▪Presented full results from the landmark Phase 1b clinical trial evaluating the anti-Abeta vaccine ACI-24 in subjects living with Down syndrome (DS) at the Alzheimer’s Association International Conference (AAIC) 2021. These results showed evidence of immunogenicity and pharmacodynamic response following ACI-24 treatment and demonstrated its favorable safety and tolerability profile.
▪Presented at CTAD 2021 full results of the Phase 2 study evaluating ACI-24 in patients with mild AD. This assessment confirmed earlier results showing no safety concerns nor evidence of inflammation or ARIA (amyloid-related imaging abnormalities) related to ACI-24 in any subject.
▪New data on the optimized formulation of ACI-24 were published in a peer reviewed journal Brain Communications. The optimized formulation was well tolerated in preclinical models and generated a broad polyclonal anti-Abeta response with high titers of antibodies against neurotoxic pyroglutamate Abeta (pyroGlu-Abeta), a major component of Abeta plaques. Additional preclinical data on optimized ACI-24 were presented at AD/PD 2022 confirming its enhanced and sustained immunogenicity against another key pathological Abeta species, oligomeric Abeta.
A-syn
▪Clinical PET image analyses and preclinical studies were presented at AD/PD 2022 suggest that ACI-12589 was retained in brain areas affected by disease processes involving a-synuclein (a-syn) aggregation, indicating the product-candidate has potential as the first non-invasive diagnostic for alpha-synucleinopathies (e.g. MSA).
▪Completed all-stock acquisition of Affiris’ portfolio of therapeutics targeting a-syn, notably PD01, a clinically validated active vaccine candidate that places AC Immune at the forefront of Parkinson’s disease (PD) drug development. ACI-7104, the optimized formulation of PD01, is on track to enter Phase 2 testing in early PD patients in H2 2022.
▪Identified and characterized the first biologically active small molecule Morphomer a-syn aggregation inhibitors, showing that they significantly decreased a-syn aggregate formation in cellular assays by interfering with the fibrillation process.
NLRP3
▪Reported key advancements for several therapeutic discovery programs targeting the (NOD)-like receptor protein 3 (NLRP3) inflammasome. Small molecule Morphomer inhibitors of NLRP3 showed the first evidence of in vivo activity in a model of peripheral inflammation, while high-affinity SupraAntigen monoclonal antibodies were shown to bind extracellular components (ASC) of the NLRP3 pathway and inhibit inflammasome-mediated immune responses in vitro.
Strenthening Financial Position and Extend Shareholder Base
▪Strengthened cash position via an equity financing, adding the three lead investors in Covid-19 vaccine innovator BioNTech SE, Athos Service GmbH (Strüngmann family office), First Capital Partner GmbH (Egger Family Office), and MIG Fonds, as part of the Affiris deal.
Strengthening of Board
▪Appointed Alan Colowick, M.D., Monica Shaw, M.D., and Prof. Monika Bütler, Dr. oec., to the Company’s Board of Directors. Dr. Colowick is a biotech and investment executive with more than 20 years of experience in large and emerging biotech companies. Dr. Shaw is a pharmaceutical industry expert who has been involved in advancing more than 15 therapeutic products from first-in-human studies through commercialization. Prof. Bütler is a leading Swiss economist and former Vice President of the independent Swiss COVID-19 Science Taskforce.
Thought Leadership and Collaborations
▪Swiss Economic Forum (SEF) awarded AC Immune Co-Founder and CEO Prof. Andrea Pfeifer with the first SEF.WomenAward for CEO of the Year. This award recognizes women with an excellent entrepreneurial track record, giving greater prominence to role models who can inspire the next generation of businesswomen.
▪Expanded the Company’s research collaboration with leading scientists at the Center for Neurodegenerative Disease Research at the Perelman School of Medicine at the University of Pennsylvania. This partnership aims to advance therapeutic strategies targeting TAR DNA-binding protein 43 (TDP-43), a major driver of neurodegenerative diseases.
▪Received two Michael J. Fox Foundation grants to accelerate the development of first-in-class brain penetrant small molecules to inhibit alpha-synuclein aggregation and NLRP3 inflammasome activation in PD.
Our strategy for 2022
AC Immune’s execution strategy is to advance late-stage AD programs with partners, accelerate its non-AD and NeuroOrphan programs in-house, and advance development of its suite of potentially best-in-class diagnostics to enable precision medicine. The Company intends to maintain program leadership over its wholly-owned AD and PD vaccine programs until Phase 3 or beyond, and expects to initiate two mid-stage clinical trials in 2022:
▪ACI-7104 anti-a-syn vaccine candidate is on track to enter an adaptive, placebo-controlled, and biomarker-based Phase 1b/2 study in patients with early PD in H2 2022. The two part study will evaluate safety, immunogenicity, and measure biomarkers of pathological alpha-synuclein in Part 1, with a seamless transition to Part 2, which will aim to establish clinical proof-of-concept by monitoring progression of PD symptoms and biomarkers.
▪Optimized ACI-24 Abeta vaccine is on track to enter a placebo-controlled Phase 1b/2 study evaluating different dosing regimens vs. placebo in up to four cohorts of patients with AD before being expanded to a separate cohort of people living with DS to address DS-related AD. Key outcome measures for the study will include assessments of safety, immunogenicity, pharmacodynamics, target engagement, Abeta-PET and clinical outcomes.
2022 Clinical Milestones
ACI-12589
a-syn-PET tracer
Reported results from first-in-human study at AD/PD 2022 conference
ACI-35.030
anti-pTau vaccine
Reported Phase 1b/2a interim analysis from highest dose group in Q1; disclose future late-stage development plans in H2
ACI-24 (optimized)
anti-Abeta vaccine
ACI-24 (optimized vaccine formulation) Phase 1b/2a First-Patient-In (AD) in H1
Phase 1b in AD readout and decision to move into DS in H2
Crenezumab
anti-Abeta antibody
Top line Phase 2 results from AD prevention trial in patients with autosomal dominant AD in H1
Semorinemab
anti-Tau antibody
Additional fluid biomarker data from the Phase 2 Lauriet study in mild-to-moderate AD in H2
PI-2620
Tau-PET tracer
Phase 2 and Phase 1 results in AD and progressive supranuclear palsy (PSP) respectively, in H2
ACI-7104
anti-a-syn vaccine
Initiate Phase 2 trial in early PD in H2
Analysis of Financial Statements for the year ended December 31, 2021
▪Cash Position: The Company had a total cash balance of CHF 198.2 million, composed of CHF 82.2 million in cash and cash equivalents and CHF 116.0 million in short-term financial assets. This compares to a total cash balance of CHF 225.9 million as of December 31, 2020. The Company’s cash balance provides enough capital resources to progress through at least Q1 2024 without consideration of potential incoming milestone payments.
▪Contract Revenues: The Company did not record contract revenues for the year ended December 31, 2021, a decrease of CHF 15.4 million from the comparable period in 2020. The overall decrease is predominantly related to a CHF 10 million milestone payment as well as CHF 4.3 million associated with R&D activities in our agreement with Lilly that were recognized in 2020 and did not repeat in the current period.
▪R&D Expenditures: R&D expenses increased by CHF 2.8 million for the year ended December 31, 2021, to CHF 62.3 million.
oDiscovery and preclinical expenses (- CHF 0.4 million): The Company decreased expenditures across a variety of its discovery and preclinical programs. This was predominantly led by a decrease in investment for the research of alpha-synuclein antibodies and other discovery programs.
oClinical expenses (- CHF 2.3 million): The Company decreased expenditures across multiple clinical programs, notably for Phase 1 activities associated with our Morphomer Tau compound and expenses. These decreases were offset predominantly by ACI-35.030, which was driven by R&D cost sharing and increased patient enrollments into the Phase 1b/2a study.
oSalary- and benefit-related costs (+ CHF 2.3 million): The Company’s salary- and benefit-related costs increased primarily due to the internal reallocation of certain employees’ salaries and the annualization of 2020 hires.
▪G&A Expenditures: For the year December 31, 2021, G&A decreased by CHF 0.6 million to CHF 17.9 million. This decrease is predominantly related to a reallocation of CHF 2.8 million of certain IT and facilities costs offset by transaction costs incurred to complete the asset acquisition for Affiris’ alpha-synuclein portfolio.
▪Other Operating Income: The Company recognized CHF 1.2 million in grant income for R&D activities performed under our Michael J. Fox Foundation for Parkinson’s Research (MJFF) and Target ALS grants, a decrease of CHF 0.1 million compared to the prior period.
▪IFRS Loss for the Period: The Company reported a net loss after taxes of CHF 73.0 million for the year ended December 31, 2021, compared with a net loss of CHF 61.9 million for the comparable period in 2020.
2022 Financial Guidance
▪For the full year 2022, the Company expects its total cash burn to be in the range, CHF 75 million to CHF 80 million. The Company defines cash burn as operating expenditures adjusted to include capital expenditures and offset by significant non-cash items (including share-based compensation and depreciation expense).