Rare Daily Staff

GlaxoSmithKline and Alector announced a strategic global collaboration to develop and commercialize two clinical-stage, potential first-in-class monoclonal antibodies targeting neurodegenerative disorders.

The two experimental drugs, AL001 and AL101, are designed to elevate progranulin (PGRN) levels. PGRN is a key regulator of immune activity in the brain with genetic links to multiple neurodegenerative disorders, including frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease.

Under the terms of the collaboration, Alector will receive $700 million in upfront payments and will be eligible to receive up to an additional $1.5 billion in clinical development, regulatory and commercial launch-related milestone payments.

Alector will lead the global clinical development of AL001 and AL101 through Phase 2 proof-of-concept. Thereafter, Alector and GSK will share development responsibilities for all late-stage clinical studies for AL001 and AL101 and all costs for global development will be divided between the two companies.

The companies will be jointly responsible for commercialization in the United States and will share profits and losses. Alector will lead commercial efforts associated with AL001 in orphan indications and GSK will lead the commercialization of AL101 in Alzheimer’s and Parkinson’s disease. Outside the United States, GSK will be responsible for commercialization of AL001 and AL101 and Alector will be eligible for tiered royalties.

The collaboration brings together Alector’s immuno-neurology expertise with GSK’s R&D focus on the science of the immune system and human genetics, proven late-stage drug development capabilities and global footprint. Enrolment is currently underway for a pivotal phase 3 trial for AL001 in people at risk for or with frontotemporal dementia due to a progranulin gene mutation (FTD-GRN). FTD-GRN is a rapidly progressing and severe form of dementia found most frequently in people less than 65 years old at the time of diagnosis and has no approved treatments. AL001 is also currently in a phase 2 study in symptomatic FTD patients with a mutation in the C9orf72 gene and is planned to enter phase 2 development for amyotrophic lateral sclerosis (ALS) in the second half of 2021. AL101 is in a phase 1a clinical trial and is designed to treat patients suffering from more prevalent neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease.

“Working with Alector’s world class scientists will allow us to investigate the potential of these immuno-neurology therapies to help patients with frontotemporal dementia, a devastating disease without any currently approved treatments, as well as explore the ability to help patients with other neurodegenerative diseases, such as ALS, Parkinson’s and Alzheimer’s,” said Hal Barron, chief scientific officer and president of R&D at GSK.

Decreased levels of PGRN, a key regulator of immune response, lysosomal function, and neuronal survival in the brain, are genetically linked to many neurodegenerative disorders. AL001 and AL101 are novel human monoclonal antibodies that elevate levels of progranulin by blocking the sortilin receptor responsible for progranulin degradation.

“This collaboration is designed to fully support AL001 and AL101’s development and to enable Alector to continue building a fully integrated company as we strive to address the high unmet medical need in patients suffering from neurodegenerative diseases,” said Arnon Rosenthal, CEO of Alector.

Photo: Arnon Rosenthal, CEO of Alector

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