Alector, GSK Team Up to Develop 2 Antibody Treatments for ALS

Alector and GlaxoSmithKline (GSK) have established a partnership to develop two investigational antibodies — called AL001 and AL101 — to boost the production of the progranulin protein as a potential treatment for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS).

Low levels of progranulin, known as PGRN, which is a key regulator of immune responses and nerve cell survival in the brain, have been associated with ALS and other disorders.

A Phase 2 study of AL001 in patients with ALS is expected to begin in the second half of this year, the companies said in a press release.

Under the collaboration agreement, Alector will receive up to $2.2 billion in payments and remains responsible for the clinical development of AL001 and AL101 during Phase 2 proof-of-concept studies. Further clinical development and future marketing efforts in the U.S. will be shared by both companies.

“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, PhD, CEO of Alector.

“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,” added Rosenthal.

Progranulin is a secreted protein that plays key roles in the central nervous system (CNS), which is comprised of the brain and spinal cord. The protein helps to regulate anti-inflammatory responses and nerve cell survival.

ALS and an uncommon form of dementia — called frontotemporal dementia or FTD — are two distinct neurodegenerative disorders that share a common key feature: the abnormal accumulation of toxic aggregates, or clumps, of the TDP-43 protein, which causes damage to nerve cells.

In some cases, these abnormal clumps derive from direct mutations in the gene coding for TDP-43. But patients also can be found to have clumps of this protein without a known genetic cause.

Researchers recently found that mutations in the progranulin (GRN) gene can cause the buildup of TDP-43 toxic clumps, likely due to an impaired cellular recycling system. Thus, increasing the levels of progranulin may be a promising approach to clear up those clumps and prevent further disease progression.

AL001 and AL101 are two human monoclonal antibodies designed to elevate the levels of progranulin in people with neurogenerative diseases. The antibodies target and block the activity of sortilin, a receptor protein involved in the degradation of progranulin.

AL101 is being developed exclusively for the treatment of Parkinson’s and Alzheimer’s disease and is currently being investigated in healthy people. AL001, on the other hand, is already in clinical trials for FTD patients and is expected to enter a Phase 2 clinical trial for ALS later this year.

“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,” said Hal Barron, MD, chief scientific officer and president of research and development for GSK.

“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,” Barron added.