QurAlis Doses First ALS Patient in Phase 1 Trial of QRL-101 Kv7 Therapy

QurAlis Corporation, a biotechnology company in the clinical stage, is making strides in developing treatments for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The company has recently initiated a Phase 1 clinical trial to evaluate QRL-101, a drug designed to address hyperexcitability-induced disease progression in ALS patients. QRL-101 targets the Kv7.2/7.3 ion channel, a crucial element in regulating neuronal excitability and membrane potential. Mis-splicing of the KCNQ2 gene pre-mRNA leads to Kv7 hyperexcitability, which is present in about 50 percent of ALS patients.

The trial, identified as QRL-101-04, is set to enroll approximately 12 ALS patients. It aims to assess the safety and tolerability of QRL-101, as well as its impact on excitability biomarkers such as the strength-duration time constant (SDTC), a known predictor of survival in ALS patients. This Phase 1 proof-of-mechanism (PoM) single-dose, placebo-controlled clinical trial is a significant step in determining the potential of QRL-101 to control motor neuron hyperexcitability-induced neurodegeneration.

QRL-101 is unique as it is the only Kv7 ion channel opener currently being investigated for treating hyperexcitability-induced disease progression in ALS. Kasper Roet, Ph.D., the CEO and co-founder of QurAlis, emphasized that this milestone could pave the way for a much-needed therapeutic option for ALS patients. He also highlighted the relevance of Kv7 in both ALS and epilepsy, which is corroborated by QurAlis' ongoing Phase 1 study evaluating biomarkers of these conditions in healthy volunteers.

Professor Leonard H. van den Berg, M.D., Ph.D., a renowned neurologist, expressed optimism about QRL-101's potential based on preclinical models. He noted the urgent need for effective therapies for ALS, a disease that significantly shortens life expectancy and currently lacks curative treatments. The results from this initial Phase 1 study are eagerly anticipated by the scientific community and patients alike.

In addition to the ALS-focused trial, QurAlis is also conducting another Phase 1 PoM biomarker trial, QRL-101-05, to study the biomarkers of ALS and epilepsy in healthy volunteers. These studies will help inform the future development program for QRL-101, including determining appropriate dosage levels for subsequent proof-of-concept studies. Topline data from the QRL-101-04 trial is expected in the first half of 2025.

ALS, commonly known as Lou Gehrig's disease, is a progressive neurodegenerative disorder that affects nerve cells in the brain and spinal cord, leading to loss of muscle function and control. The disease, which can be caused by mutations in over 25 different genes, typically has a rapid progression, with an average life expectancy of three years post-diagnosis. Currently, there is no cure for ALS, making the development of new treatments like QRL-101 crucial.

Kv7.2/7.3 channels play an essential role in the regulation of neuronal excitability. The mis-splicing of Kv7.2 in sporadic ALS results in loss of function and abnormal electrical activity, contributing to motor neuron degeneration. Activating these channels can potentially reduce spinal and cortical/motor neuron excitability, offering hope for ALS patients suffering from hyperexcitability-induced neurodegeneration.

QurAlis Corporation, founded by a team of neurodegenerative biologists from Harvard Medical School and Harvard University, is committed to developing precision medicines that address severe disease pathology in specific patient populations. The company leverages a robust pipeline of therapeutic candidates targeting both genetic mutations and clinical biomarkers associated with neurodegenerative diseases.