AT-1501 (anti-CD40L) is an experimental therapy aiming to delay the onset of amyotrophic lateral sclerosis (ALS) and slow its progression.

Eledon Pharmaceuticals, previously known as Novus Therapeutics, is developing the potential therapy, which it acquired when it purchased Anelixis Therapeutics, a subsidiary of the ALS Therapy Development Institute (ALS TDI).

How AT-1501 works

ALS is a progressive neurodegenerative disease for which there currently is no cure. Disease symptoms result from damage to motor neurons (nerve cells that control the movement of muscles) that can kill these cells. While its exact cause is not clear, researchers think the immune system may contribute to its progression by causing inflammation in the nervous system, leading to motor neuron damage. 

AT-1501 is an antibody against a protein called CD40 ligand (CD40L). Antibodies are proteins that bind to and block a particular target. CD40L is present on the surface of some immune cells. It is a protein that plays a role in regulating the immune response and that can trigger inflammation in the spinal cord. Research has shown that the CD40L pathway is overactive in ALS patients.

The exact mechanism of action of AT-1501 in ALS is not clear, but researchers think that by inhibiting CD40L, the potential therapy could block or delay the activation of the damaging inflammatory immune response. This could delay ALS onset or slow its progression, improving patient outcomes. 

AT-1501 in clinical trials

Researchers extensively studied AT-1501 in preclinical trials with positive results.

One such study, using a mouse model of ALS, found that AT-1501 significantly increased the time until disease onset in the animals, and improved their body weight and survival compared with untreated mice. 

A Phase 1 safety and tolerability in healthy volunteers and ALS patients then opened, testing single-ascending doses of AT-1501. Trial results showed that all participants tolerated all dose levels in the trial well. The pharmacokinetics (movement in the body) of the treatment was also as expected. 

An open-label and ascending-dose Phase 2a trial (NCT04322149), which opened in 2020, is now assessing the safety and tolerability of AT-1501, and levels of biomarkers of inflammation and ALS progression, in 54 adult patients across multiple sites in the U.S. and one in Montreal, Canada. This study is still enrolling; contact and location information is available here.

Participants are given one of four ascending doses of AT-1501, administered into a vein (IV infusion). Each patient will receive six infusions, given every other week for 11 weeks, and will be monitored for treatment safety and tolerability for another eight weeks. The study lasts a total of 19 weeks (about five months), and is expected to conclude in March 2022.

Other information

The U.S. Food and Drug Administration granted AT-1501 orphan drug designation. This designation provides companies with benefits, such as tax credits for clinical trials, while they are developing treatments for rare disorders.


Last updated: Aug. 27, 2021


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