QurAlis Corporation, a clinical-stage biotechnology company driving scientific breakthroughs into powerful precision medicines with the potential to alter the trajectory of neurodegenerative and neurological diseases, has officially published positive topline data from QurAlis’ Phase 1 proof-of-mechanism (PoM) clinical trial of QRL-101.
According to certain reports, the trial evaluated biomarkers related to amyotrophic lateral sclerosis (ALS) and epilepsy, with the results showcasing a dose-dependent, statistically significant decrease in motor nerve excitability threshold tracking (mNETT) strength-duration time constant (SDTC), co-primary endpoint of the trial related to ALS.
For better understanding, SDTC would be a well-established electrophysiological biomarker of peripheral motor excitability related to ALS, where elevation of SDTC has been clinically shown to predict faster disease progression and mortality. The decrease in SDTC observed with QRL-101 in this study, however, was approximately 50% greater than previously reported for the Kv7 potassium channel opener ezogabine during a single-dose study in people with ALS.
More on QurAlis’ trial would reveal how it went on to demonstrate a statistically significant impact on multiple secondary and exploratory endpoints related to epilepsy. These endpoints included transcranial magnetic stimulation electromyography (TMS-EMG) intracortical facilitation, thus indicating effective inhibition of cortical excitability.
Not just that, significant increases in electroencephalography (EEG) spectral power, across beta and gamma spectral bands, further relay cortical target engagement and brain penetration.
Complementing that would be how there was minimal to no impact on the slower delta and theta EEG bands, something which treads up a long distance to suggest a low potential for GABA-A receptor activation and sedation. The study also did not reach statistical significance on the co-primary endpoint of TMS-EMG motor evoked potential (MEP) amplitude, another measure of corticospinal excitability.
“We are excited by these topline data from our biomarker study in healthy participants which suggest that QRL-101 has the potential to provide a therapeutic effect for both ALS and epilepsy,” said Kasper Roet, Ph.D., CEO and co-founder of QurAlis. “Loss of Kv7.2/7.3 function from the mis-splicing of the KCNQ2 gene leading to hyperexcitability-induced neurodegeneration was one of the first genetic breakthroughs from human ALS motor neuron stem cell models made by our founders at Harvard. QurAlis was started to develop a best-in-class Kv7 ion channel opener for the treatment of hyperexcitability-induced disease progression in ALS.”
Among other things, we ought to mention the fact that this Phase 1 PoM study was a randomized, double-blind, placebo-controlled, three-way crossover trial. The study was conducted at the Centre for Human Drug Research, an early-phase Contract Research Organization.
Apart from the one under focus here, QurAlis has also conducted several other trials within the established discipline. For instance, it has successfully completed QRL-101-01, which was the first-in-human, single-ascending dose clinical trial that enrolled 88 healthy participants.
During the course of this clinical trial, QRL-101 was gauged as well tolerated. The study completed, in essence, supported a tolerable dose range for subsequent studies.
Next up, the company initiated a QRL-101-03, a randomized, double-blind, placebo-controlled, multiple-ascending dose clinical trial which evaluated the safety, tolerability, and PK of QRL-101 in up to 60 healthy participants.
To follow that up, QurAlis would conduct a still-ongoing QRL-101-04 trial. The stated trial translates to a Phase 1 PoM single-dose, placebo-controlled clinical trial focused on assessing the safety and tolerability of QRL-101 in people living with ALS. In total, QRL-101-04 is likely to enroll 12 participants with ALS, while simultaneously assessing the impact of QRL-101 on mNETT.
The company is also working on a QRL-101-06, a Phase 1 randomized, open-label, single dose, cross-over study, to evaluate the PK of three formulations of QRL-101 in a fasted condition or in the presence of a high fat meal in healthy participants.
“The decrease in SDTC observed with QRL-101 in this study was approximately 50% greater than previously reported for the Kv7 opener ezogabine in a single-dose study in people with ALS. QRL-101 has the potential to be a promising therapeutic, especially considering the encouraging results from a previous study with ezogabine in ALS patients showing positive effects on both SDTC and the disease progression biomarker compound muscle action potential (CMAP). We are encouraged by these results,” said Dr. Roet.
