QurAlis Confirms Signal of Target Engagement in ALS Patients in Phase 1 Clinical Trial of QRL-101, a Potentially Best-in-Class Selective Kv7.2/7.3 Ion Channel Opener

Results demonstrated reduced motor-neuron hyperexcitability that was generally consistent with the signal previously observed in healthy volunteers

Safety and tolerability profile consistent with previously reported results for QRL-101

QurAlis intends to advance QRL-101 into Phase 2 proof-of-concept clinical trials as a potentially best-in-class treatment for both DEE and ALS

CAMBRIDGE, Mass.–(BUSINESS WIRE)–QurAlis Corporation (“QurAlis”), a clinical-stage biotechnology company driving scientific breakthroughs into powerful precision medicines that have the potential to alter the trajectory of neurodegenerative and neurological diseases, today announced topline data from its Phase 1 proof-of-mechanism (PoM) clinical trial of QRL-101 in people living with amyotrophic lateral sclerosis (ALS). Results from this study demonstrate for the first time, evidence of target engagement with a selective Kv7.2/7.3 ion channel opener in ALS patients.

Kv7.2/7.3 is a voltage-gated potassium channel whose role is crucial for the regulation of both neuronal excitability and membrane potential. QRL-101 is a potentially best-in-class selective Kv7.2/7.3 ion channel opener for the treatment of hyperexcitability-induced disease progression in ALS, which occurs in both sporadic and genetic forms of ALS, with the majority caused by the mis-splicing of the KCNQ2 gene in the pre-mRNA. Kv7 is a clinically validated target to regulate the hyperexcitable state in epilepsy; and QurAlis is also advancing QRL-101 in developmental and epileptic encephalopathies (DEE). Preclinical studies have demonstrated that QRL-101 is more potent and exhibits the potential for fewer clinical adverse events than ezogabine, a less selective, first-generation, Kv7.2/7.3 channel opener.

“This is the first time we are seeing target engagement of QRL-101 in ALS patients with a biomarker which predicts survival in ALS. This is extremely encouraging as new research published in Nature Neuroscience provides additional evidence that loss of TDP-43 function drives mis-splicing of the KCNQ2 potassium channel, producing a dysfunctional isoform that disrupts neuronal excitability in ALS and frontotemporal dementia, further validating this disease mechanism,” said Kasper Roet, Ph.D., CEO and co-founder of QurAlis. “QurAlis’ co-founders and collaborators had previously demonstrated that loss of Kv7.2/7.3 leads to motor neuron death and we are excited by these data which confirm that QRL-101 has the potential to provide a therapeutic effect for ALS patients. We look forward to advancing the clinical program for QRL-101 in ALS, as well as in epilepsy, so that we can rapidly bring a much-needed precision medicine option to multiple patient populations.”

Results showed reduced motor-neuron hyperexcitability compared to placebo, with a more robust response being observed in patients with higher exposure to QRL-101. In addition, there was a consistent, expected directional change across multiple measures including strength-duration time constant (SDTC), rheobase, and eight of the nine additional measures evaluated as part of the motor nerve excitability threshold tracking (mNETT) assessment. These results are generally consistent with the signal previously observed in healthy volunteers (QRL-101-05, NCT06681441) across these measures.

Results also demonstrated that the pharmacokinetic (PK), safety, and tolerability profile of QRL-101 was consistent with previously reported study results evaluating QRL-101. There were no serious adverse events or discontinuations due to adverse events reported observed in the study.

QRL-101-04 (NCT06714396) was a Phase 1 PoM single-dose, placebo-controlled clinical trial designed to evaluate the safety and tolerability of QRL-101 in people living with ALS. QRL-101-04 enrolled 12 participants with ALS and evaluated the impact of QRL-101 on mNETT across three different dose levels, randomized 3:1 between QRL-101 and placebo. The primary endpoint of the study was exploration of the PK and pharmacodynamic relationship of QRL-101 and was not powered to demonstrate a statistically significant difference between QRL-101 and placebo arms.

More information about the QRL-101-04 clinical trial can be found at www.clinicaltrials.gov.

About QurAlis Corporation

At QurAlis, we are neuro pioneers on a quest to cure, boldly seeking to translate scientific breakthroughs into powerful precision medicines. We work collaboratively with a relentless pursuit of knowledge, precise attention to craft, and compassion to discover and develop medicines that have the potential to transform the lives of people living with neurodegenerative and neurological diseases. QurAlis is the leader in development of precision therapies for amyotrophic lateral sclerosis (ALS). In addition to ALS, QurAlis is advancing a robust precision medicine pipeline to bring effective disease-modifying therapeutics to patients suffering from severe diseases defined by genetics and clinical biomarkers. For more information, please visit www.quralis.com or follow us on X @QurAlisCo or LinkedIn.

Contacts

Kathy Vincent

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