QurAlis Shares Phase 1 Results of QRL-101 for ALS and Epilepsy Biomarkers in Healthy Volunteers

QurAlis Corporation, a biotechnology firm focused on developing precision medicines for neurodegenerative and neurological disorders, has announced promising results from its Phase 1 clinical trial of QRL-101. Conducted with healthy volunteers, the trial evaluated biomarkers linked to amyotrophic lateral sclerosis (ALS) and epilepsy.

The primary findings from the trial revealed a notable dose-dependent reduction in the motor nerve excitability threshold tracking (mNETT) strength-duration time constant (SDTC), which is crucial for understanding ALS progression. SDTC is a recognized biomarker of peripheral motor excitability, where elevated levels have been associated with a quicker disease progression and higher mortality rates in ALS patients. The reduction in SDTC observed with QRL-101 was approximately 50% greater than that reported for ezogabine, a Kv7 potassium channel opener, in previous studies involving ALS patients. Additionally, the trial showed significant impacts on various secondary and exploratory measures related to motor nerve excitability.

The trial also explored the effects of QRL-101 on epilepsy-related biomarkers, demonstrating significant results on secondary and exploratory endpoints. Transcranial magnetic stimulation electromyography (TMS-EMG) revealed intracortical facilitation, indicating cortical excitability inhibition, while electroencephalography (EEG) highlighted increases in beta and gamma spectral power, suggesting effective brain penetration and target engagement. There was little to no effect on the delta and theta EEG bands, pointing to a minimal risk of GABA-A receptor activation and sedation. However, the study did not achieve statistical significance in the TMS-EMG motor evoked potential (MEP) amplitude, another measure of corticospinal excitability.

The safety and tolerability of QRL-101 were consistent with previous studies, showing no serious adverse events or discontinuations. Kasper Roet, Ph.D., CEO and co-founder of QurAlis, expressed enthusiasm about the potential therapeutic effects of QRL-101 for ALS and epilepsy. He noted that the reduction in SDTC was significantly greater than what was previously recorded for ezogabine, underscoring the promise of QRL-101 as a potential therapy, particularly given the encouraging outcomes from prior ezogabine studies in ALS patients.

The company is keen to advance QRL-101 into proof-of-concept studies, aiming for it to become a leading treatment option for both ALS and epilepsy. QRL-101 is designed to be a selective Kv7.2/7.3 ion channel opener, targeting the hyperexcitability-induced disease progression in ALS caused by mis-splicing of the KCNQ2 gene. This gene is vital in regulating neuronal excitability and membrane potential. By targeting the Kv7 ion channel, QRL-101 holds potential not only for ALS but also as a therapeutic option for epilepsy, offering enhanced efficacy with potentially fewer side effects compared to first-generation openers like ezogabine.

The Phase 1 study, conducted at the Centre for Human Drug Research in Leiden, Netherlands, was a randomized, double-blind, placebo-controlled, three-way crossover trial. It assessed two dose levels of QRL-101 against a placebo, focusing on motor nerve excitability and cortical excitability as primary endpoints, alongside additional secondary measures related to cortical excitability, resting-state pharmaco-EEG, and safety.

QurAlis continues to push forward with various clinical trials for QRL-101, including first-in-human and multiple-ascending dose studies. The research aims to explore the safety, tolerability, pharmacokinetics, and overall impact of QRL-101 on ALS and epilepsy, with the ultimate goal of bringing effective, precision therapies to patients suffering from severe neurodegenerative diseases.