A phase 2 trial of AT-1501, a potential ALS treatment invented by the ALS Therapy Development Institute (ALS TDI), is now fully enrolled according to its current sponsor, Eledon Pharmaceuticals.

AT-1501 (antiCD40L) is an antibody therapeutic with comprehensive and promising preclinical data. It blocks specific immune cell activation and protects nerves against the progression of ALS and Alzheimer's disease. It is the first potential ALS treatment to be invented by a nonprofit biotech and advanced into human clinical trials.

After being invented at ALS TDI, AT-1501 was advanced through clinical trials by Anelixis Therapeutics, a for-profit clinical-stage development company. In 2019, Anelixis successfully completed phase 1 trials of AT-1501. In 2020, Anelixis was acquired by Novus Therapeutics (now Eledon Pharmaceuticals), a publicly traded company. This acquisition helped AT-1501 advance to the next stage of clinical development, a phase 2 trial, which recently completed the enrollment of the third of four patient cohorts.

AT-1501’s phase 2 trial in ALS is an open-label, multiple dose study to determine the drug’s safety and tolerability, as well as its effect on ALS progression. Participants are given one of four ascending doses through an intravenous infusion every other week over 11 weeks, along with another eight weeks of observation. The study is expected to be completed in March, 2022, with topline results coming later in the year.

AT-1501 is the culmination of years of research and experimentation at ALS TDI. After ALS TDI conducted the world's largest gene expression analysis of the SOD1 mouse model, they discovered a key innate immune system pathway (CD40L) to be over-active and increasing in activity across multiple tissues related to ALS disease progression. Following these findings, ALS TDI began rigorously testing compounds to see if they could regulate the activity of the CD40L pathway.

In 2010, ALS TDI scientists published a paper, From transcriptome analysis to therapeutics anti-CD40L treatment in the SOD1 model of amyotrophic lateral sclerosis, in Nature Genetics. Their work showed that the compound they invented, antiCD40L, was able to slow down disease progression, improve body weight retention over time and increase overall survival in mouse model. In 2011, ALS TDI began to study preclinical mechanism of action and dose ranging for antiCD40L. ALS TDI performed hundreds of additional experiments to understand how blocking CD40L worked, and how best to optimize the drug as a potential treatment for ALS. In 2018, the FDA gave AT-1501 an orphan drug designation, citing its potential to slow ALS onset progression

Bringing a drug from the lab and into clinical trials is extremely risky and expensive. For this reason, when ALS TDI discovers or invents a promising treatment, it then needs to be handed off to an external company that has the funding to take it through trials. In order to access capital needed to advance AT-1501 (antiCD40L) through clinical trials, ALS TDI established Anelixis Therapeutics as a for-profit clinical stage development company. Anelixis completed a phase I trial in healthy volunteers and people with ALS in 2019 which demonstrated that it was well tolerated at all doses. In 2020, Anelixis was acquired by Novus Therapeutics (now Eledon Pharmaceuticals), helping the drug’s path to its current phase 2 trial in ALS.

For more information about ALS TDI’s invention of AT-1501, click here. To learn more about our additional research to end ALS, click here.

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