U.K.-based antibody discovery company Alchemab Therapeutics has unveiled positive findings for its potential first-in-class treatment for Alzheimer’s disease.
Preclinical studies revealed that the novel human antibody ATLX-1088 was able to restore the function of microglia, which are immune cells in the brain that maintain neural networks and repair damage.
Microglial dysfunction is one of the hallmarks of Alzheimer’s disease, with slow migration to areas of damage, sustained inflammation, and defective phagocytosis.
The antibody discovery company specializes in adaptive immunity, identifying naturally occurring antibodies among individuals resilient to disease then working backwards to develop therapeutics.
“Our approach starts with the body’s response to disease, as opposed to the target itself, and means that the immune system is effectively used as a search engine to identify the most important disease modifying targets,” explained Alchemab CEO Young Kwon to Inside Precision Medicine.
“This has allowed us to identify unique antibodies in individuals that are resilient to Alzheimer’s disease and then identify our target as CD33. The ATLX-1088 antibody has great potential and we hope to use this data to provide a treatment for this devastating disease.”
Initially, the company identifies resilient individuals such as long-term survivors of cancer, people who are susceptible to neurodegenerative disorders but do not progress, or those who are very long lived and healthy without chronic disease.
It mines the antibodies receptors of these resilient individuals to identify naturally occurring antibodies. Deeply sequencing the B cells from these individuals results in billions of antibody sequences that are fed into a drug discovery engine to identify antibodies with similar properties.
Alchemab then identifies the binding targets of these antibodies to reveal their protective properties.
It develops these into therapeutic candidates that can replicate the protective effect and be used in others who lack this protection and have difficult-to-treat disease.
ATLX-1088 targets the cell surface protein CD33, which is thought to play a key role in Alzheimer’s disease, the company reported today at the Antibody Industrial Symposium in Tours, France.
The anti-CD33 antibody was discovered from individuals with Alzheimer’s risk factors, with researchers studying two people who were positive for amyloid, but negative for tau and cognitively normal.
ATLX-1088 causes a significant increase in amyloid beta phagocytosis in human induced pluripotent stem cell microglia.
It also performed well in stability studies and remained unchanged at high and low temperatures, through freezing and thawing and low pH.
“This is the first time we have revealed data from this exciting drug candidate targeting CD33,” said chief scientific officer Jane Osbourn in a press statement.
“There’s strong evidence to show that knocking out CD33 results in lower amyloid-beta levels and reduction in amyloid plaque burden in the brain.
“We believe that ATLX-1088 could be an important step forward in treatment, potentially bringing a much needed new therapy to patients with this debilitating disease.”
