QurAlis Drug QRL-101 Shows Early Promise in Targeting Nerve Damage in ALS Patients

CAMBRIDGE, MA – December 29, 2025 – In a development offering a new glimmer of hope for patients with amyotrophic lateral sclerosis (ALS), clinical-stage biotechnology company QurAlis Corporation has announced positive topline data from its Phase 1 trial of QRL-101. The results provide the first clinical evidence that the experimental drug can successfully engage its intended biological target in people living with the devastating neurodegenerative disease.

The study demonstrated that QRL-101, a selective Kv7.2/7.3 ion channel opener, successfully reduced motor neuron hyperexcitability, a toxic state of overactivity in nerve cells that is believed to be a primary driver of cell death and disease progression in ALS.

“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., CEO and co-founder of QurAlis. “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.”

Targeting the Electrical Storm in Neurons

ALS is a relentless and fatal disease characterized by the progressive death of motor neurons in the brain and spinal cord, leading to muscle weakness, paralysis, and ultimately, respiratory failure. For decades, the underlying mechanisms have been a complex puzzle for scientists. One of the key pathological features identified in both sporadic and genetic forms of ALS is neuronal hyperexcitability—a state where motor neurons fire electrical signals excessively, leading to cellular stress, damage, and eventual death.

At the heart of this electrical instability is the Kv7.2/7.3 potassium channel. This channel acts as a crucial regulator, or brake, for neuronal activity. Its job is to open and allow potassium ions to flow out of the neuron, which helps the cell return to a resting state after firing. In many ALS patients, a genetic mis-splicing event, often linked to the dysfunction of the TDP-43 protein, leads to faulty Kv7.2/7.3 channels. When these channels fail to function properly, the neuron loses its ability to regulate itself, becoming trapped in a cycle of hyperexcitability.

QRL-101 is a precision medicine designed to address this specific problem. As a selective Kv7.2/7.3 channel opener, it works by forcing these dysfunctional channels open, restoring the outward flow of potassium ions and calming the overactive neuron. This mechanism is already a clinically validated target in epilepsy, another condition driven by neuronal hyperexcitability. QurAlis aims to leverage this established biology to provide a therapeutic effect for ALS.

Decoding the Phase 1 Results

The QRL-101-04 study (NCT06714396) was a Phase 1, single-dose, placebo-controlled clinical trial designed as a “proof-of-mechanism” study. Its primary goal was not to measure a reversal of ALS symptoms, but to confirm that the drug was interacting with its target as intended within the human body. The trial enrolled 12 participants with ALS, who were randomized on a 3:1 basis to receive either a single dose of QRL-101 at one of three levels or a placebo.

To measure the drug's effect, researchers used a sophisticated technique called motor nerve excitability threshold tracking (mNETT). This assessment involves a series of non-invasive electrical measurements that provide a detailed picture of a nerve's health and excitability. The results showed a clear and consistent signal of reduced motor-neuron hyperexcitability in patients who received QRL-101 compared to those on placebo. Furthermore, the data suggested a dose-dependent relationship, with patients who had higher exposure to the drug showing a more robust response.

Key measures within the mNETT assessment, including the strength-duration time constant (SDTC) and rheobase, showed the expected directional changes, reinforcing the evidence of target engagement. These findings in ALS patients were also consistent with the effects previously observed in a study involving healthy volunteers, adding another layer of confidence in the data.

A Safer, More Selective Approach

Importantly, the Phase 1 trial also confirmed a favorable safety and tolerability profile for QRL-101. The company reported no serious adverse events, and no participants had to discontinue the study due to side effects. This safety profile is a critical differentiator for the drug.

The concept of using a Kv7 channel opener is not entirely new. A first-generation, less selective drug, ezogabine, had previously shown that targeting this pathway could have a beneficial effect. However, its use was limited by significant side effects. QurAlis developed QRL-101 to be a potentially best-in-class therapeutic by designing it to be more potent and highly selective for the Kv7.2/7.3 channel subtype, with the goal of maximizing efficacy while minimizing off-target effects and improving the safety profile.

“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,” Dr. Roet added. “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.”

While the journey to an approved therapy is long and fraught with challenges, these early results represent a significant and scientifically-driven step forward. By successfully demonstrating target engagement in ALS patients, QurAlis has validated its therapeutic hypothesis and laid the groundwork for future studies to determine if calming the electrical storm in motor neurons can truly alter the devastating trajectory of this disease.