Our antibody humanisation work played an important part in the discovery of lecanemab, an experimental drug that has recently shown small but clear benefits for people with early Alzheimer’s disease.

In October, a landmark phase 3 clinical trial showed lecanemab slowed down cognitive decline – confusion or memory loss – in people with early Alzheimer’s. The results were heralded as a ‘historic moment’ – as lecanemab is the first treatment that’s ever been shown to slow the course of dementia.

LifeArc scientists collaborated with biotechnology company BioArctic Neuroscience to humanise the monoclonal antibody targeting a toxic form of a protein called amyloid beta that builds up in the brains of Alzheimer’s patients.

Should lecanemab go on to receive approval, it could offer an effective treatment option for people with early signs of dementia – offering hope to millions of patients and their families around the world.

Targeting amyloid

Alzheimer’s disease is the most common type of dementia, affecting more than half a million people in the UK. It is an irreversible, progressive brain disorder that slowly destroys memory, thinking and language skills. Sadly, there are currently no treatments that can prevent, slow down or reverse the disease.

One of the hallmarks of Alzheimer’s disease is the build-up of abnormal structures called ‘amyloid plaques’ in the brain. For many years, a great deal of research has focused on the amyloid hypothesis, which assumes that these plaques have a role in damaging brain cells and causing cognitive decline. But several other drug candidates that break down these toxic plaques in the brain have failed in late-stage clinical trials, which had led many to question whether this was the right approach.

In 2006, LifeArc partnered with BioArctic to sequence and ‘humanise’ their mouse monoclonal antibody mAb158, which targeted a specific form of the amyloid beta protein called protofibrils. This work generated the clinical candidate BAN2401, or lecanemab.

The results of the latest trial, which involved around 1,800 patients with early-stage Alzheimer’s disease, showed that the cognitive abilities of people who received lecanemab declined by 27% less than those on the placebo after 18 months. While the effects were small, with the potential for some significant side effects, it’s the first time that any treatment has been shown to offer help to people affected by this devastating disease.

Testament to our expertise

Our scientists have extensive experience in antibody humanisation, which involves replacing the mouse regions of the antibody with human sequences until only the most critical parts remain that are of mouse origin. This reduces the chances of the patient’s immune system recognising the antibody as ‘foreign’ and rejecting it.

We have successfully humanised more than 90 therapeutic antibodies, including four that are now approved treatments and four in clinical trials.

Dr Preeti Bakrania, Head of Biologics Discovery and Development at LifeArc said: “We’re really proud to have played a small but important part in discovering this promising new therapeutic antibody for Alzheimer’s disease. It feels like a turning point for the amyloid hypothesis – and it reminds us that the translational work that we perform here may one day go on to deliver valuable benefits for patients.

Preeti explains:

“It’s particularly pleasing to find out that the humanised antibody sequence that left our laboratory all those years ago is exactly the same as the version that’s now being tested in the clinic, which is a true testament to our expertise in this area. We’ve since collaborated with BioArctic on several other projects – demonstrating the confidence they have in our abilities to engineer therapeutic antibodies.”

LifeArc scientists have also worked on another humanised antibody treatment for Alzheimer’s called TAP01_04, which targets different, low molecular weight soluble forms of the amyloid beta protein. As the TAP01_04 antibody does not bind to plaques, it could potentially cause fewer side effects than lecanemab.

Work with us

Find out more about LifeArc’s antibody engineering capabilities – from initial generation to lead candidate – and ways of working with us.