Workstream 1
Investigational Medicinal Product (IMP) Identification
Lead Sites for Workstream 1
Aims and Objectives of Workstream 1
Aim: To deliver a continuous pipeline of drugs for workstream 2 using the best available evidence from pre-clinical models and a wide range of data resources, including genomics, AI drug discovery programs and evidence from other neurodegenerative diseases.
Primary objective: To select the most appropriate compounds for prioritisation in EXPERTS-ALS, based on disease relevance, safety profile and central nervous system penetration.
Secondary Objectives: Data from workstream 3 in response to drugs can be fed back to preclinical modelling in workstream 1 to identify new, or refine existing, pathways of disease relevance, and ultimately those which best predict a positive outcome in Phase III trials.
Drugs that show a reduction in NfL will be prioritised for inclusion in Phase III trials, such as MND-SMART and TRICALS. Those which result in no change, or an increase, in NfL will be classed as low priority for these trials. This will not exclude these drugs from future clinical trails, but simply be used as way of prioritising which drugs to test first.
How will IMPs be selected?
This workstream will identify and prioritise compounds to be tested with the EXPERTS-ALS platform. The IMP selection committee will review, rank and select drugs based on explicit evidenced-based criteria. The best drugs will:
engage a well characterised target in a clear disease relevant pathway, demonstrated in pre-clinical models
penetrate the blood brain barrier to access the central nervous system, where ALS pathology is widely distributed
be safe, as previously demonstrated by other trials
have been shown to improve the phenotype across multiple models (multiple types of cell models, different model organisms etc.)
be likely to be effective in all types of ALS, regardless of the cause
Deliverables of Workstream 1
A list of drugs which can be scheduled for entry into the EXPERTS-ALS platform
A standardised document for each drug describing in detail the basis for its priority
Development of an expanding network of experts in clinical translation, drug discovery and pipeline development
IMP Selection Committee Members
Coming soon!
