• Thursday, April 5, 2018 @ 12:00 am

  • Tau small molecules (Tau Morphomers) demonstrate target-specific reduction of pathological Tau as well as cognitive and functional improvement
  • Significant reduction of microglia activation enhances the benefits on Tau pathology
  • Tau Morphomers are capable of crossing the blood brain barrier and show a promising safety profile
  • Selected Tau Morphomers have entered Investigational New Drug / Clinical Trial Application enabling studies; Phase 1 to commence by the end of 2018

Lausanne, Switzerland, April 5, 2018 - AC Immune SA (NASDAQ: ACIU), a Swiss-based, clinical stage biopharmaceutical company with a broad pipeline focused on neurodegenerative diseases, today announced that several Tau Morphomer candidates have demonstrated target-specific reduction of pathological Tau and cognitive and functional improvement in proof-of-concept studies in Alzheimer's disease. In addition to the Tau inhibition, a significant parallel reduction of microglia activation and neuroinflammation has been observed; another key factor in Alzheimer's and other neurodegenerative diseases. Tau Morphomers are the first candidates derived from AC°Immune's proprietary MorphomerTM platform generating therapeutic CNS small molecules with high selectivity for misfolded proteins in multiple proteinopathies.

Prof. Andrea Pfeifer, CEO of AC Immune, said: "AC Immune has one of the largest Tau pipelines in the industry and our various therapies intervene at key points in the pathway of Alzheimer's disease. The specifically designed Tau Morphomers have a unique mode of action, inhibit intracellular Tau pathology the source of Tau spreading and reduce neuroinflammation. Hence, they are well-positioned to be used in mono- and combination therapies of neurodegenerative diseases."

About the Company's Tau pipeline
The Company's broad Tau pipeline covers the full range of approaches: small molecules (Morphomers), antibodies, vaccines and diagnostics.
 

Product candidate

Target

Target Indication

Partner

Status

ACI-35

(Anti-pTau vaccine)

Tau

AD1 treatment

Janssen Pharmaceuticals

Phase 1b

Anti-Tau antibody

Tau

AD treatment

Genentech*

Phase 2

Morphomer Tau

(Tau inhibitor, small molecule)

Tau

AD treatment

 

Pre-clinical

Tau-PET2 imaging agent

Tau

Diagnostics; AD and PSP3

Piramal Healthcare

Advancing to longitudinal study

1 Alzheimer's disease
2 Positron emission tomography
3 Progressive supranuclear palsy
* Genentech, a member of the Roche group
 

About Tau Morphomers
Several chemical series of small molecules (MorphomersTM) have been identified which selectively and potently reduce toxic intracellular misfolded and aggregated Tau.
Targeting intracellular misfolded and aggregated Tau is widely recognized as an important and attractive approach for interfering with the spread of Tau pathology throughout the brain. The activity of Tau may act as a seed that induces native endogenous Tau forms to misfold and aggregate into toxic species.
In proof-of-concept Tauopathy models, reduction of Tau pathology was also accompanied by a reduction of associated neuroinflammatory markers - another key pathologic feature of Alzheimer's disease (AD).
Lead compounds have been identified which display excellent ADME (absorption, distribution, metabolism and elimination or excretion) and pharmacokinetics properties suitable for targeting the central nervous system. Two candidates in clinical studies are currently undergoing further preclinical safety assessment, with the goal to initiate a clinical Phase°1 study by end 2018.

About the MorphomerTM technology platform
The rational chemical design enables AC Immune to generate small molecules, also known as MorphomersTM, which bind highly specifically to misfolded proteins, break up neurotoxic aggregates and inhibit their aggregation and seeding. Other key assets of the robust library of Morphomers include promising CNS drug features such as excellent brain penetration, bioavailability and metabolic stability which are important for the development of both therapeutic and diagnostic agents for multiple neurodegenerative diseases.
Three therapeutic (Morphomer Tau, Morphomer Abeta and Morphomer a-syn) and two diagnostic development candidates (Tau-PET imaging agent and a-syn-PET imaging agent) originate from the MorphomerTM technology platform.

About Tau in Alzheimer's disease and neurodegenerative diseases
It is becoming increasingly clear that Alzheimer's disease develops because of a complex series of events that take place in the brain over a long period of time. Two proteins - Tau and amyloid-beta (Abeta) - are recognized as major hallmarks of AD. Pathological forms of Tau aggregate inside neurons to form neurofibrillary tangles, and appear to propagate by cell-to-cell spread between neurons. By contrast, Abeta-containing plaques and oligomers form outside the brain cells of people with AD. Tau protein is mostly present in neurons and functions as a component of the cytoskeleton inside the cells. Misfolded Tau protein aggregates in AD and other Tau-related neurodegenerative diseases (e.g. progressive supranuclear palsy, frontotemporal dementia and others). In AD, accumulation of Tau pathology occurs later than the accumulation of Abeta pathology. The progression of Tau pathology throughout the brain is closely associated with the onset and progression of cognitive decline, underscoring the importance of Tau-targeted therapies.