QurAlis Begins Phase 1 MAD Trial for QRL-101 in ALS

QurAlis Corporation, a biotechnology firm focused on developing precision medicines for neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), has recently completed dosing the first participant cohort in their Phase 1 multiple-ascending dose (MAD) clinical trial of QRL-101. This compound is designed to reduce disease progression in ALS by targeting hyperexcitability-induced neurodegeneration, a condition present in about 50% of ALS patients.

QRL-101 operates as a selective Kv7.2/7.3 ion channel opener. The Kv7.2 ion channel is a protein that is mis-spliced in sporadic ALS cases, leading to its dysfunction and contributing to abnormal electrical activities in the brain and spinal cord. The opening of these channels aims to address motor neuron hyperexcitability, which is considered a significant factor in ALS progression.

The Phase 1 MAD trial (QRL-101-03) is a randomized, double-blind, placebo-controlled study being conducted at a single site. It evaluates the safety, tolerability, and pharmacokinetics of escalating doses of QRL-101 in approximately 60 healthy adult volunteers. Participants are randomized in a 9:3 ratio to either QRL-101 or a placebo across five cohorts. The dose range for this study was determined based on data and outcomes from a previous Phase 1 single-ascending dose (SAD) trial, which included 88 healthy participants. No significant safety issues or serious adverse events were reported in that trial.

Doug Williamson, M.D., QurAlis' Chief Medical Officer, highlighted the potential of QRL-101 to become a pioneering therapy for ALS, particularly for patients suffering from hyperexcitability-induced motor neuron degeneration. He emphasized the urgency of advancing this clinical program to provide much-needed treatments for ALS patients, who currently have very limited therapeutic options.

Leonard H. van den Berg, M.D., Ph.D., a neurology professor and chair of TRICALS, corroborated Williamson’s optimism. He noted that motor system hyperexcitability affects roughly half of all ALS patients due to potassium channel dysfunctions. Preclinical models have shown that QRL-101 has a strong potential to manage this hyperexcitability with a favorable side-effect profile. The positive findings from the SAD study have generated excitement for the upcoming results from the MAD study, which are anticipated in the first half of 2025.

ALS, often known as Lou Gehrig's disease, is a severe neurodegenerative condition that deteriorates nerve cells in the brain and spinal cord, leading to reduced muscle function and control. It is associated with mutations in over 25 genes and can manifest in various sub-forms, often unpredictably. The disease significantly impacts patients and their families, with an average life expectancy of just three years following diagnosis. Currently, there is no cure for ALS.

The Kv7.2/7.3 ion channels are crucial for regulating neuronal excitability and membrane potential. In sporadic ALS cases, Kv7.2 is often mis-spliced, causing a loss of function and leading to abnormal electrical activity in the spinal cord and brain. Activating these channels has shown potential to reduce spinal and cortical motor neuron excitability, potentially offering an effective therapeutic approach for ALS patients experiencing hyperexcitability-induced motor neuron degeneration.

QurAlis, founded by neurodegenerative biologists from Harvard Medical School and Harvard University, is committed to advancing precision medicine to treat severe neurodegenerative diseases. Their pipeline includes therapeutic candidates targeting disease pathology in specific patient populations, guided by genetic mutations and clinical biomarkers.

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