ACI-3024 has a good in vitro and
in vivo 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, MNT and MLY) and has undergone an extensive
toxicology and safety pharmacology assessment. The NOAEL has been established at 300 mg/kg in rodent and at 450 mg/kg in non-rodent
after 4-week treatment (S. Poli - CTAD 2018).
Effect on neuroinflammation
ACI-3024 efficacy on pathological Tau-induced
neuro-inflammation was assessed in vitro and in vivo. In vitro, ACI-3024 induced a potent reduction of Tau
induced neuroinflammation markers (Figure 25 below). In vivo, in the rTg4510 mice, treatment with ACI-3024 overall reduced
microgliosis, most likely as a downstream consequence of reducing Tau pathology, by reducing the derived pathological Tau induced-microglial
activation (Figure 25 below).
Figure 25: ACI -3024’s
effect on neuroinflammation
Ref: AC Immune unpublished data
Discovery Therapeutic Programs
Using our SupraAntigen and Morphomer platforms,
we have generated additional discovery and pre-clinical stage molecules targeting neurodegenerative diseases, and diagnostics targeting
Tau, alpha-synuclein and TDP-43. We currently have five therapeutic product candidates and two diagnostic product candidates in
various stages of pre-clinical development. A number of our therapeutic product candidates in pre-clinical development are focused
on indications outside of AD and evidence of our expansion strategy. Based on the data to date, our technology platforms can be
applied to misfolded proteins across a broad range of indications. The table below lists four pre-clinical product candidates and
the lead indication being pursued:
Morphomer Abeta: Our Morphomer
Abeta product candidate is a small molecule that inhibits and disrupts Abeta propagation and aggregation, and is currently being
evaluated for the treatment of glaucoma, where its anti-Abeta properties represent a novel mechanism of action for that disease.
In pre-clinical testing, Morphomer Abeta demonstrated a strong ability to protect the eyes of rats exposed to increased ocular
pressure and chronic ocular hypertension which are clinical features of glaucoma.