Novartis gets in on alpha-synuclein

Novartis is hardly known for novel CNS projects. But today the group took a punt on a potentially disease-modifying mechanism for Parkinson’s, via a deal with UCB. The target, alpha-synuclein, has had its fair share of setbacks, with Roche and Prothena last year reporting mixed data with their antibody, prasinezumab, and Biogen this year discontinuing BIIB054. At least Novartis has not paid top dollar: the company is giving UCB $150m up front, although it is on the hook for up to $1.5bn in milestones. In return, the Swiss company gets global co-development and co-commercialisation rights to UCB0599, an oral, brain-penetrant alpha-synuclein misfolding inhibitor, and an option on UCB7853, an anti-alpha-synuclein antibody. The two projects could complement each other, UCB noted. As well as Roche and Prothena, which are pressing on with prasinezumab, other companies looking at this target include include AC Immune, which struck its own deal here in July. Annovis Bio’s ANVS401, meanwhile, inhibits amyloid-beta and tau as well as alpha-synuclein – that group is planning phase 3 trials in both Parkinson’s and Alzheimer’s, but phase 2 data have been far from convincing.

Alpha-synuclein-targeting projects in clinical development
Project Company Description Trial details
Phase 2
ANVS401 Annovis Bio Small molecule amyloid precursor protein, alpha-synuclein & Tau inhibitor Ph2 PD data reported Oct 2021, ph3 planned
Prasinezumab (PRX002/RO7046015) Prothena/Roche Anti-alpha-synuclein Mab PD: Ph2 Pasadena failed, Ph2b Padova began May 2021
ENT-01 Enterin Small molecule alpha-synuclein aggregation inhibitor Ph2 Karmet in PD-related constipation completed Jul 2021; Ph2 planned in PD+psychosis & PD+dementia
Lu AF82422 Lundbeck/Genmab Anti-alpha-synuclein Mab Amulet in multiple system atrophy completes May 2023
UCB0599 Novartis/UCB (licensed from Neuropore Therapies) Small molecule alpha-synuclein misfolding inhibitor Ph2 in PD completes Jul 2024
Phase 1
ACI-7104 (PD01 ) AC Immune (via Affiris) Anti-alpha-synuclein vaccine Ph1 completed, ph2 to start "shortly"
MEDI341 (TAK-341) Astrazeneca/Takeda Anti-alpha-synuclein Mab MAD trial in PD completes Jul 2022
ION464 (BIIB101) Biogen/Ionis Alpha-synuclein antisense Horizon in multiple system atrophy completes Jul 2022
UB-312 Vaxxinity Anti-alpha-synuclein vaccine Ph1 in healthy volunteers & PD pts completes Dec 2022
UCB7853  UCB (Novartis has option) Anti-alpha-synuclein Mab Ph1 in healthy volunteers & PD pts completes Jun 2023
ABBV-0805 Abbvie/Bioarctic Anti-alpha-synuclein Mab Ph1 withdrawn for "strategic reasons", project still listed on pipeline
Source: Evaluate Pharma &

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