GSK and Alector Collaborate on Neurodegenerative Disease mAb Candidates

GlaxoSmithKline (GSK) and Alector, a clinical-stage biotechnology company specializing in immuno-neurology, have entered into a strategic global collaboration to develop and commercialize two clinical-stage, potential first-in-class monoclonal antibodies (mAbs), AL001 and AL101, for the potential treatment of a range of neurodegenerative diseases, including frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease. The two mAbs 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, which makes it an attractive genetically validated target for the development of new immuno-neurology treatments, the companies announced in a July 2, 2021 press release.

Under the agreement, 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 II proof-of-concept studies. Following those studies, Alector and GSK will share development responsibilities for all late-stage clinical studies for the two mAbs. All costs for global development will be divided between the two companies.

Both GSK and Alector 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, while GSK will lead the commercialization of AL101 in Alzheimer’s and Parkinson’s disease. Outside the US, GSK will be responsible for commercialization of the two mAbs, and Alector will be eligible for tiered royalties.

With this collaboration Alector’s immuno-neurology expertise will be combined with GSK’s R&D focus on the science of the immune system and human genetics as well as GSK’s late-stage drug development capabilities and global footprint.

A pivotal Phase II trial for AL001 has begun enrollment to study the mAb in people at risk for or with frontotemporal dementia due to a progranulin gene mutation (FTD-GRN). According to the press release, 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 II study in symptomatic FTD patients with a mutation in the C9orf72 gene. A Phase II study for AL001 in the treatment of amyotrophic lateral sclerosis (ALS) is planned for the second half of 2021. Meanwhile, AL101 is in a Phase Ia clinical trial. This mAb is designed to treat patients suffering from more prevalent neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease.

“Our focus on human genetics and the science of the immune system gives us unique insights into the potential of targets such as progranulin to help patients with a number of neurodegenerative diseases. Working with Alector’s [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, CEO and president R&D, GSK, in the press release.

“[T]his 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. We are confident that GSK’s extensive experience launching ground-breaking medicines at the intersection of immunology and human genetics will ensure that AL001 and AL101 are developed to their full potential,” said Arnon Rosenthal, PhD, CEO, Alector, in the press release.

Source: GlaxoSmithKline