Abstract Details

Title Evaluating the Safety, Tolerability, and Pharmacokinetics of QRL-101 in Two Phase 1 Studies: QRL-101-01 in Healthy Adults and QRL-101-02 in Adults with ALS

Topic Neuromuscular and Clinical Neurophysiology (EMG)

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

Poster/Presentation
Number 11-019

Objective Evaluate the safety, tolerability, and pharmacokinetics of QRL-101 in healthy volunteers and people living with ALS.

Background Amyotrophic lateral sclerosis (ALS) is a progressively fatal, neurodegenerative disease resulting in the loss of motor neurons in the motor cortex, brainstem, and spinal cord. In ALS, evidence of increased cellular excitability in peripheral nerves and central motor neurons has been observed through advanced neurophysiological, imaging, pathological and biochemical techniques. Clinically, hyperexcitability has been correlated with decreased longevity in people living with ALS. QRL-101 is an investigational product targeting motor neuron hyperexcitability. Preclinical studies in models of ALS have indicated QRL-101, a potent, selective KCNQ2/3 channel positive allosteric modulator, may be effective in reducing motor system hyperexcitability in people living with ALS.

Design/Methods QRL-101 will be evaluated in two, consecutive, randomized, placebo-controlled, double-blind, phase 1 studies. QRL-101-01, is an ongoing first-in-human, single-ascending dose (SAD) study in approximately 40 healthy participants. The study design includes five dose escalation cohorts of 8 participants each, randomized in a 6:2 ratio of study drug to placebo. Information from QRL-101-01 will be used to determine a safe and tolerable dose range for the subsequent multicenter multiple-ascending dose (MAD) study, QRL-101-02, which will evaluate QRL-101 in approximately 24 adults living with ALS. Both studies will utilize a sentinel dosing strategy, as well as multiple safety reviews.

Results In both studies, the primary and secondary endpoints will be incidence of adverse events and measurements of the PK of QRL-101. In QRL-101-02, additional exploratory endpoints will be evaluated to assess the impact of QRL-101 on clinical outcomes, and electrophysiological markers of motor nerve excitability in people living with ALS.

Conclusions The findings from these studies will be used to advance the development of QRL-101, and other next-generation precision medicines for people living with ALS and other neurodegenerative diseases.

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.
Bryan Boggs (Quralis Corp)	No disclosure on file
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.
John Polzer (QurAlis)	No disclosure on file
Samantha Rubino (QurAlis)	No disclosure on file
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.
Dan Elbaum (QurAlis)	No disclosure on file

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