GSK and Alector Enter $2.3 Billion Global Collaboration to Develop First-in-Class Monoclonal Antibodies AL001 and AL101 for Neurodegenerative Diseases

On July 2, 2021, GlaxoSmithKline (GSK) and Alector jointly announced a global strategic collaboration aimed at developing and commercializing two clinical-stage potential "first-in-class" monoclonal antibodies, AL001 and AL101, to increase progranulin (PGRN) levels in patients. PGRN is a key regulator of immune activity in the brain and is genetically linked to multiple neurodegenerative diseases. Consequently, it represents one of the most compelling genetically validated targets for the development of novel immunoneurology therapeutics.

The GRN gene encodes the PGRN protein, a key regulator of the human immune response, lysosomal function, and neuronal survival in the brain, and is genetically associated with numerous neurodegenerative diseases. Lysosomes are cellular compartments containing digestive enzymes that process waste and maintain neuronal health; they rely on PGRN to function properly. GRN gene mutations impair the production of PGRN protein within neuronal lysosomes, thereby triggering progressive neuronal degeneration and eventual cell death.

Both AL001 and AL101 are novel monoclonal antibody therapeutics that target the receptor protein sortilin. Genetic studies in humans and mice have identified sortilin as a major negative regulator of PGRN. It mediates the degradation of the PGRN protein. By inhibiting sortilin function, AL001 and AL101 can increase PGRN levels, thereby enabling the treatment of neurodegenerative diseases.

▲ Mechanism of Action of AL001 (Image source: Alector official website)

AL001 is currently being evaluated in a pivotal Phase 3 clinical trial for the treatment of patients at risk of frontotemporal dementia (FTD) due to GRN gene mutations or patients with FTD. Additionally, AL001 is being evaluated in a Phase 2 clinical trial for the treatment of FTD patients carrying C9orf72 gene mutations (FTD-C9orf72).

AL101 is currently in Phase 1a clinical trials, aimed at treating patients with more common neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease.

Under the collaboration agreement, Alector will receive a $700 million upfront payment. Additionally, it will be eligible for up to $1.5 billion in clinical development, regulatory, and commercial milestone payments.

References:

[1] GSK and Alector announce global collaboration in immuno-neurology for two clinical stage first-in-class monoclonal antibodies for neurodegenerative diseases. Retrieved July 2, 2021, from https://www.gsk.com/en-gb/media/press-releases/gsk-and-alector-collaboration-in-immuno-neurology/

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