Eisai forges CNS alliance with UK’s Wren Therapeutics

Japanese drugmaker Eisai has teamed up with UK biotech Wren Therapeutics on an R&D programme seeking drugs for neurodegenerative disorders.

The two companies will focus their efforts on alpha-synuclein, a pathway that has been implicated in disorders such as dementia with Lewy bodies (DLB) and Parkinson’s disease (PD).

DLB and PD are both so-called synucleinopathies, diseases that are characterised by mutations in the SNCA gene coding for alpha-synuclein, leading to the production of misfolded, toxic forms of the protein that clump together and are thought to damage nerve cells.

Wren – a spinout from the universities of Cambridge in the UK and Lund in Sweden – has developed a drug discovery platform that can be used to screen small-molecule drugs to see if they can bind to misfolded proteins and correct their structure, preventing them from aggregating.

It’s a similar concept to interfering with the aggregation of beta-amyloid to form neurotoxic plaques in diseases like Alzheimer’s disease – another of Wren’s research targets.

Under the terms of the agreement, Cambridge-based Wren’s “network kinetics” platform will be deployed alongside Eisai’s drug discovery expertise in neurodegenerative disorders.

Eisai has a long heritage in this area, having been involved in the development of well-established Alzheimer’s drug Aricept (donepezil) and various other drugs for epilepsy, with a late-stage pipeline that includes Biogen-partnered anti-amyloid drug aducanumab, currently under review by the FDA.

“Synucleinopathies such as dementia with Lewy bodies and Parkinson’s disease represent a significant unmet medical need due to the lack of any effective disease-modifying treatments,” said Dr Teiji Kimura, who heads up drug discovery in Eisai’s neurology division.

“The accumulation of alpha-synuclein oligomers with protein misfolding is an important hallmark of these diseases,” he added.

Last summer, Wren raised 23 million in first-round financing to advance its internal R&D in the area of protein-misfolding diseases.

Other companies are also targeting alpha-synuclein, although Eisai and Wren are unusual in that they are seeking small-molecule candidates. Rivals include Roche and Prothera, which have an antibody in late-stage testing, as well as AstraZeneca/Takeda, Biogen, Lundbeck, AbbVie/BioArctic and Denali.

Roche licensed the antibody – called prasinezumab – from Prothera in a $600 million deal that dates back several years. Earlier this year however, the programme had a setback when a phase 2 trial in PD missed the mark.

The partners said the data showed some signs of efficacy, and prasinezumab is now heading for a phase 2b trial as an add-on therapy to standard levodopa therapy in PD.

Biogen has an antibody candidate called cinpanemab (BIIB054) in the phase 2 SPARK trial, due to generate results next year, while Lundbeck started a phase 1 trial in 2018 of Lu AF82422, another antibody, that could read out before year-end.

AZ and Takeda started a first phase 1 trial of their MEDI 1341 antibody in 2017, adding a second earlier this year that is due to run until 2022, while AbbVie's ABBV-0805 cleared a phase 1 trial but seems to have been sidelined for strategic reasons.

Denali’s project is earlier in development. Its preclinical candidate ATV:aSyn is a bispecific antibody designed to penetrate the central nervous system more effectively, with one end targeting alpha-synuclein and another targeting a transporter in the blood-brain barrier.