LY4256984

The drug was invented by QurAlis, a Cambridge, Massachusetts biotech, as QRL-204. In June 2024 Lilly paid $45 million upfront for worldwide rights, with up to $577 million more in milestone payments, and now runs the clinical trials. Lilly has said little publicly about the programme beyond the trial registrations.

In most people with ALS a protein called TDP-43 leaves the cell nucleus, where it normally helps edit genetic instructions. Without it, the instruction for UNC13A, a protein needed at the junctions where nerve cells pass signals, is edited wrongly and less working UNC13A is made. LY4256984 is an antisense oligonucleotide (ASO), a short strand of genetic material designed to correct that editing error. Lab studies showed it restored UNC13A, but it has not yet been shown to help people.

The first trial (Lilly code J6I-MC-OWAA) started in August 2025 and tests four rising doses, each in a group of 8 people (6 on the drug, 2 on placebo), given four times over about 3 months. In May 2026 Lilly started a long-term extension for people who have finished the first trial, so the first participants have already been through dosing. Lilly has not announced how many people have been treated.

No results have been reported. The trial's main goal is to see whether the drug is safe and how the body handles it. It is too small and short to show whether it slows ALS.

This is the most favourable result reported. See all key studies for the full picture.

The trial is for adults aged 18 to 75 with sporadic ALS (no known ALS gene), whose symptoms began less than 24 months ago and whose breathing capacity is at least 50% of normal. The drug is given by lumbar puncture, a needle into the lower back. Faulty UNC13A editing is thought to occur in most ALS, so if it works it could apply widely.

Lilly has not given a date for results. The trial registry estimates the main data will be collected by August 2027 and the study will finish in September 2027.

In the main trial, the registry lists sites recruiting in Leuven, Utrecht, Lübeck, Valencia, Barcelona, Montreal and Toronto, with more in Germany and Canada still to open. Each person has a 1 in 4 chance of getting placebo. The extension study only takes people who were in the first trial. We found no expanded access programme.

• J6I-MC-OWAA (Phase 1) (NCT07100119) recruiting · Belgium, Netherlands, Germany, Spain, Canada
• OL01 long-term extension (for people from the first trial) (NCT07571174) recruiting · Canada; European sites not yet open