Abstract Details

Title QRL-201-01—A Multi-center, Randomized, Double-blind, Placebo-controlled Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of QRL-201 in Amyotrophic Lateral Sclerosis

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P6 - Poster Session 6 (8:00 AM-9:00 AM)

Poster/Presentation
Number 11-010

Objective Evaluate the safety and tolerability of QRL-201 in people living with amyotrophic lateral sclerosis.

Background A hallmark of amyotrophic lateral sclerosis (ALS) in >90% of patients, is the presence of cytoplasmic TAR DNA Binding Protein 43 (TDP-43) aggregates and loss of nuclear expression. Loss of nuclear TDP-43 leads to Stathmin-2 (STMN2) mis-splicing, resulting in decreased expression in the majority of people living with ALS. STMN2 is important for neural repair, axonal stability, and neuromuscular junction innervation. Our therapeutic approach is to correct STMN2 mis-splicing, thereby restoring protein function. QurAlis has shown that this can be accomplished using a splice switching antisense oligonucleotide (ASO) in non-clinical studies. QRL-201 is an investigational ASO that rescues STMN2 expression and protein function in QurAlis’ patient-derived neuronal disease models, even in the continued presence of TDP-43 pathology.

Design/Methods QRL-201-01 is a double-blind, multiple-ascending dose study in which approximately 64 people living with ALS will receive QRL-201, or matching placebo, in a 6:2 ratio. The study design includes six dose escalation cohorts and two exploratory cohorts. This study includes the collection of data on numerous biomarkers, employs sentinel participant dosing, and includes multiple safety reviews.

Results The primary endpoint will be incidence of adverse events. The secondary endpoints will be measurements of multiple dose pharmacokinetics (PK). This study will include multiple exploratory endpoints – 1) biomarkers of neuronal loss and STMN2 biology; 2) clinical outcome measures (ALSFRS-R, ROADS, SVC, HHD, electrophysiology testing); and 3) CSF PK profile.

Conclusions QurAlis’ mission is to bring breakthrough precision medicine technology to people living with ALS. QRL-201-01 is designed to evaluate the safety and tolerability of multiple doses of QRL-201 in people living with ALS, and explore the hypothesis that restoration of STMN2 is a suitable disease-modifying approach in ALS.

Authors/Disclosures
Angela L. Genge, MD (Mcgill University) PRESENTER	Dr. Genge has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AL-S Pharma. Dr. Genge has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amylyx. Dr. Genge has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Quralis. Dr. Genge has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MTPA. Dr. Genge has received personal compensation in the range of $0-$499 for serving as a Consultant for WAVE. Dr. Genge has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for eikonizo. Dr. Genge has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for rapa.
Kristiana Salmon, Other (QurAlis Corporation)	Miss Salmon has received personal compensation for serving as an employee of QurAlis Corporation. Miss Salmon has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for ProJenX. Miss Salmon has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant with ALS Canada.
John Polzer (QurAlis)	No disclosure on file
Clarida Martinez (QurAlis Corporation)	No disclosure on file
Bryan Boggs (Quralis Corp)	No disclosure on file
Victoria C. Eon, CRC (University of California Irvine)	Ms. Eon has received personal compensation for serving as an employee of QurAlis Corporation.
Rakhee Ganti (QurAlis Corporation)	No disclosure on file
Sandy Hinckley (QurAlis)	No disclosure on file
Kristina Johnson (QurAlis Corporation)	Ms. Johnson has received personal compensation for serving as an employee of QurAlis. Ms. Johnson has stock in QurAlis.
Dan Elbaum (QurAlis)	No disclosure on file

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