FUSION is a clinical study of an investigational antisense medicine for people living with Amyotrophic Lateral Sclerosis caused by a mutation in the Fused in Sarcoma (FUS) gene.

The purpose of the FUSION study is to determine if a potential new treatment, or “investigational antisense medicine,” is safe and effective in halting, reversing, or slowing deterioration of clinical functioning and biomarkers of disease severity in ALS patients with FUS mutations
(FUS-ALS).

• Amyotrophic Lateral Sclerosis is a rare neurological disorder that affects the nerve cells in the brain and spinal cord. People with ALS may have trouble with certain muscle movements like speaking, walking, or gripping. About 1-5% of ALS cases are caused by a mutation in the FUS gene, leading to quicker ALS progression beginning at an earlier age.

• The investigational antisense medicine or placebo will be injected into the spinal fluid in the lower spine region and circulate to the spinal cord and brain. ION363 is designed to target and stop the production of the FUS protein in the body. Targeting this protein may improve symptoms by reducing FUS protein buildup in motor neurons.

To pre-qualify for FUSION, you must:

• Be at least 12 years of age

• Have ALS with a confirmed mutation in the FUS gene

• In addition to the requirements above, other tests and information will be required to determine your eligibility. For additional information or questions, please contact us at [email protected] or 844-421-0104.

• If you qualify for and participate in the FUSION study, you will be randomly assigned to receive either the investigational antisense medicine or placebo, which will be injected into the spinal fluid in the lower spine region and circulate to the spinal cord and brain. (You have a greater chance of receiving the investigational study treatment compared to the placebo.)

• To help keep the study results as accurate as possible, you, the doctor, and the staff conducting the FUSION study will not know if you are being given the investigational antisense medicine or the placebo.

• Your total participation in the FUSION study will be for a little less than 3 years, (65 or 74 visits total over 152 weeks) including screening for eligibility, treatment, and follow-up.

• Over 152 weeks, you will receive 8 doses of the investigational antisense medicine or placebo during Part 1 of the study, and 12 or 20 doses of the investigational antisense medicine during Part 2 of the study.

• During Part 1 of the FUSION study, you will attend 8 study visits. During the first visit, you will be required to stay overnight for monitoring. For the rest of the visits, you will be required to stay for at least 6 hours following injection. During Part 2 of the FUSION study, you will attend either 12 or 20 study visits depending on your group assignment. In between visits you will be monitored and assessed from your home.