A Study Evaluating the Safety and Tolerability of QRL-201 in ALS

Prior treatment

• Currently enrolled in any other clinical study involving either an investigational product (IP) or off-label use of a drug or device
• Prior exposure to stem cell or gene therapy products
• Any contraindication to intrathecal drug administration
• Currently enrolled in any other clinical study involving either an investigational product (IP) or off label use of a drug or device
• Participated in another clinical study within 30 days, or 5 half-lives of the previous investigational product, whichever is greater, prior to the first dose
• Prior exposure to stem cell or gene therapy products

Other illness

• Significant infection or known inflammatory process
• Any sign and/or history of neurological conditions and other neuromuscular disorders that could affect the electrophysiological recordings.
• An EEG that shows signs of abnormal electrical activity (e.g., epilepsy)
• Off-label use of drugs or devices that are being used as disease-modifying therapies in ALS

Lab values

• Abnormal laboratory values deemed clinically significant by the Investigator

Other

• Pathogenic variant, likely pathogenic variant, or variant of uncertain significance in the superoxide dismutase 1 (SOD1) and/or fused in sarcoma (FUS) genes
• Is not suitable for inclusion in the Open-Label Extended Dosing period of the study, in the opinion of the Investigator
• An EEG that shows signs of abnormal electrical activity (NOTE: Cohort 1 and Cohort 2 participants only)

• Male or female participants aged 18 to 80 years diagnosed with ALS
• ALS symptom onset within 24 months of Screening
• Slow vital capacity \>50%
• Clinical or electrodiagnostic evidence of lower motor neuron involvement
• Not pregnant and not nursing
• Willing and able to practice effective contraception
• Able to tolerate lumbar puncture
• If on approved therapies for the treatment of ALS during the course of the study, must be on a stable dose (at the Sponsor's discretion)
• Male or female participants in the sporadic ALS and C9orf72 ALS Cohorts of QRL-201-01 who have completed through at least Day 253 of safety follow up in the double-blind study period OR have completed Cohort 1 of Cohort 2
• Not pregnant and not nursing
• Willing and able to practice effective contraception
• Can visit study site for required visits
• Able to tolerate lumbar puncture
• If on approved therapies for the treatment of ALS during the course of the study, must be on a stable dose (at the Sponsor's discretion)