CAMBRIDGE, Mass. — QurAlis Corporation said it has observed evidence of target engagement in patients with amyotrophic lateral sclerosis in a Phase 1 proof-of-mechanism clinical trial of QRL-101, a selective Kv7.2/7.3 ion channel opener being developed for neurodegenerative and neurological diseases.
Topline results from the study showed reduced motor-neuron hyperexcitability compared with placebo, a finding that was generally consistent with signals previously observed in healthy volunteers. The company said the safety and tolerability profile of QRL-101 in ALS patients was also consistent with earlier clinical data.
QRL-101 is designed to selectively open Kv7.2/7.3 voltage-gated potassium channels, which play a key role in regulating neuronal excitability and membrane potential. Hyperexcitability is believed to contribute to disease progression in both sporadic and genetic forms of ALS, including cases linked to mis-splicing of the KCNQ2 gene. The company is also developing QRL-101 for developmental and epileptic encephalopathies.
According to QurAlis, study participants treated with QRL-101 demonstrated reduced motor-neuron hyperexcitability, with more pronounced effects observed in patients with higher drug exposure. The results included consistent directional changes across multiple electrophysiological measures, including strength-duration time constant, rheobase, and the majority of parameters assessed through motor nerve excitability threshold tracking. These findings aligned with patterns previously seen in healthy volunteer studies.
“This is the first time we are seeing target engagement of QRL-101 in ALS patients with a biomarker which predicts survival in ALS,” said Kasper Roet, Ph.D., chief executive officer and co-founder of QurAlis. “These data are extremely encouraging and further support the underlying disease mechanism involving Kv7.2/7.3 dysfunction. We are excited by the potential of QRL-101 to provide a therapeutic benefit for patients with ALS.”
The trial also confirmed that the pharmacokinetic, safety, and tolerability profile of QRL-101 remained consistent with earlier studies. No serious adverse events or treatment discontinuations due to adverse events were reported.
The Phase 1 study enrolled 12 ALS patients and evaluated three dose levels of QRL-101 in a single-dose, placebo-controlled design. Participants were randomized in a 3:1 ratio between active treatment and placebo. The primary objective was to explore the pharmacokinetic and pharmacodynamic relationship of QRL-101, and the study was not designed to demonstrate statistically significant differences between treatment arms.
QurAlis said it plans to advance QRL-101 into Phase 2 proof-of-concept clinical trials as a potential best-in-class therapy for ALS and developmental and epileptic encephalopathies.
