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20-F
AC IMMUNE SA filed this Form 20-F on 03/21/2019
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Preclinical safety

 

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Ref: AC Immune unpublished data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:

 

Product Candidate Target Lead Indication Partner Platform
Morphomer Abeta Abeta Glaucoma N/A Morphomer

Morphomer

alpha-synuclein

alpha-synuclein PD N/A Morphomer

Anti-alpha-synuclein antibody

 

alpha-synuclein

 

N/A

 

N/A

 

SupraAntigen

 

Anti-TDP-43 antibody TDP-43 N/A N/A SupraAntigen

 

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.

 

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© AC Immune 2015