Alector, Inc.

Combating Neurodegeneration by Empowering the Immune System

Studies have shown that multiple neurodegenerative diseases like Parkinson’s disease, ALS, and Alzheimer's disease are linked to a dysfunctional brain immune system. The immune system of the brain performs various critical functions to protect against disease and age-related neurodegeneration, including the clearing of neurodegenerative proteins, regulating synaptic connections, stimulating the regeneration of myelin sheaths around nerve fibers to protect nerve cells, and controlling the neurotoxic activities of rogue microglia. Traditional approaches have focused on just a single degenerative pathology, resulting in therapies with limited efficacy, while Alector is focused on restoring the brain’s immune system as a whole to address all related disease pathologies.

Alector’s product candidates are designed to affect the brain’s immune system by influencing microglia, the primary immune cells of the brain. Microglia are the brain’s first line of immune defense and are responsible for essential activities like responding to infection and damage, nurturing neurons and other brain support cells, clearing cell debris, and modulating the blood-brain-barrier to allow additional immune cells to enter and assist against infection or injury. Major risk genes for neurodegenerative diseases like Alzheimer’s have been shown to express predominantly in the microglia, and even to control the function of these immune cells. Fortunately, microglia analysis has shown that microglia subtypes exist, and they may be capable of addressing specific disease pathologies in the brain. In response, Alector’s product candidates recruit these subtypes and control microglia activity to counteract specific degenerative brain disorders. 

Alector’s product platform currently has produced four product therapies in clinical testing and over a dozen in the research/preclinical phase. 

AL001 for FTD

AL001, also known as latozinemab, is part of Alector’s progranulin (PGRN) franchise. PGRN is a key regulator of microglia function and is strongly associated with frontotemporal dementia (FTD) and other neurodegenerative disorders. The lack of sufficient PGRN leads to rapid neurodegeneration, as it disrupts the function of both neurons and microglia. Studies have indicated that the cellular receptor Sortilin (SORT1) controls the levels of PGRN in the body. SORT1 binds to PGRN in the plasma and brain and transports it to cells to be degraded, which leads to decreasing levels of PGRN. 

Developed in partnership with GSK and currently undergoing phase 3 clinical trials, AL001 is a humanized recombinant monoclonal antibody for the treatment of FTD. FTD is a severe form of brain disease characterized by the early onset of symptoms and rapid progression. Patients experience symptoms like lack of restraint, compulsivity, anxiety, and other behavioral problems. AL001 inhibits the SORT1 degradation mechanism for PGRN, allowing an increase of functional PGRN in the brain. 

AL101 for Alzheimer’s disease and Parkinson’s disease

Similar to AL001, AL101 is a humanized recombinant monoclonal antibody designed to raise levels of PRGN by inhibiting SORT1. AL101 is being developed to treat Alzheimer's and Parkinson’s disease and has already completed a phase 1 clinical trial, with dosed patients showing increased PGRN levels in the brain persisting for one month. Alzheimer's, which affects 6.2 million Americans alone, and Parkinson’s, which affects over 10 million people worldwide, are both devastating neurodegenerative diseases. Alzheimer's has one disease-modifying treatment commercially available, while Parkinson’s disease has none. 

AL002 for Alzheimer’s disease

AL002 is a humanized monoclonal antibody designed to regulate microglia by modulating the TREM2 receptor. TREM2 is a receptor protein that is expressed on some immune cells and on microglia in the brain. A key function of TREM2 in microglia cells is to improve cell survival by promoting cell migration to the site of injury. TREM2 mutations are closely linked to neurodegeneration and increase the risk of Alzheimer’s disease significantly. Developed in coordination with AbbVie, AL002 is currently undergoing phase 2 clinical trials. 

AL044 for Alzheimer’s disease

AL044 is a humanized monoclonal antibody designed to treat Alzheimer's disease by targeting the MS4A gene family, as MS4A is strongly associated with late-onset Alzheimer's disease. The MS4A gene family is responsible for encoding a receptor protein found selectively on microglia, controlling microglia functionality and viability. AL044 is designed to mimic the protective activity of MS4A to potentially decrease the progression of Alzheimer’s. Alector owns worldwide rights to AL044, which is currently undergoing phase 1 clinical trials. 

Operational overview 

Alector has yet to bring any commercially approved products to market since its inception in 2013 and therefore has generated no revenue from product sales. The company has primarily financed its operations through the sale of equity securities, a government grant, and payments received from collaboration agreements. Alector’s collaboration agreement with GSK could be especially lucrative, with over $2 billion of potential payments depending on milestone achievements. The company also has smaller-scale agreements in place with AbbVie and Innovent. 

Alector does not have the infrastructure for internal manufacturing and so relies on third-party manufacturers and its collaboration partners to support both current clinical and future potential commercial manufacturing activities. The company has a patent portfolio that covers 50 patent families, including 20 issued patents and 380 pending. 

Conclusion 

Although biotechnology and the neurodegeneration segment of the industry specifically are immensely competitive, Alector Inc.’s immono-neurology approach sets it apart. Furthermore, Alector leverages the benefits of a diversified business model as the company spreads its development across various product programs like PGRN and TREM2. Beyond neurodegeneration, Alector’s immuno-neurology approach also has potential applications in oncology, including plans on the near horizon to commence clinical testing of cancer patients with multiple compounds. Boasting nods of approval from industry giants like GSK and AbbVie, and a product platform with potential applications across a broad range of diseases, Alector Inc. is a company to be excited about with immense potential to alleviate suffering and improve human longevity.