QurAlis is making strides in its amyotrophic lateral sclerosis (ALS) therapeutic programs, with QRL-201 advancing to the dose range-finding phase and the first patient dosed in a Phase 1 trial of QRL-101. These developments represent significant milestones in the company's efforts to address critical unmet needs in ALS treatment.
QRL-201: ANQUR Trial Advances to Dose Range-Finding
The ANQUR clinical trial (NCT05633459), evaluating QRL-201, has successfully completed its dose-escalation phase. QRL-201 is an antisense oligonucleotide designed to restore STATHMIN-2 (STMN2) expression, a protein crucial for neural repair and axonal stability. The trial's initial phase demonstrated that cerebrospinal fluid (CSF) exposure levels of QRL-201 met or exceeded the targeted therapeutic range, prompting the advancement to the dose range-finding (DRF) phase.
The DRF phase will assess two doses of QRL-201 and include additional biomarkers to evaluate the drug's impact. Notably, the study design has been amended to include a cohort of participants with C9orf72-related ALS, in addition to those with sporadic ALS. This decision was based on previous expression analysis showing consistent mis-splicing of STMN2 in C9orf72-related ALS patients.
"ALS is a devastating, fatal neurodegenerative disease with a large unmet medical need. Our mission is to make a meaningful difference in patients' lives, and we believe QRL-201 could potentially modify disease progression and improve outcomes in ALS patients who have a loss of STMN2 due to TDP-43 pathology," said Kasper Roet, PhD, CEO and co-founder of QurAlis.
QRL-101: First ALS Patient Dosed in Phase 1 Trial
QurAlis has also dosed the first patient in a Phase 1 clinical trial (NCT06714396) evaluating QRL-101 in adults with ALS. QRL-101 is a first-in-class selective Kv7.2/7.3 ion channel opener designed to reduce nerve cell overactivation, or hyperexcitability, a key mechanism driving disease progression in approximately 50% of ALS patients.
The Phase 1 trial is a proof-of-mechanism study that aims to assess the safety and tolerability of QRL-101, as well as its impact on biomarkers of nerve cell excitability. The study is expected to enroll approximately 12 participants with ALS. Topline data from the trial are anticipated in the first half of 2025.
"The dosing of the first patient with ALS in the clinical development program of QRL-101 is a significant milestone," said Kasper Roet, PhD. "QRL-101 is the only Kv7 ion channel opener being actively studied for the treatment of hyperexcitability-induced disease progression in ALS."
Leonard H. van den Berg, MD, PhD, professor of neurology and chair of TRICALS, added, "Preclinical models of QRL-101 show its strong potential to control motor neuron hyperexcitability-induced neurodegeneration with an attractive side effect profile."
Addressing Unmet Needs in ALS
ALS is a progressive neurodegenerative disease characterized by the loss of motor neurons, leading to muscle weakness, paralysis, and ultimately, death. The average life expectancy after diagnosis is only 2-5 years. Currently, there is no cure for ALS, and available treatments offer limited benefits.
QurAlis's dual approach, targeting both STMN2 restoration with QRL-201 and hyperexcitability with QRL-101, represents a promising strategy to address the complex pathology of ALS and improve outcomes for patients.
