Pipeline Targeting Major Disease Drivers in Patients
QurAlis is currently advancing a pipeline with therapeutic candidates that target specific components of ALS pathology and defined ALS patient populations based on both disease-causing genetic mutation(s) and clinical biomarkers. We are targeting patients that have loss of STATHMIN-2 (STMN2), patients who have a loss of Kv7, and patients with TDP-43 gain-of-function toxicity and autophagy impairment.
Our lead therapeutic product candidates are QRL-201 and QRL-101. QRL-201 is a first-in-class molecule for the treatment of ALS that aims to restore STMN2 expression in ALS patients and QRL-101 is a first-in-class Kv7 opener for the treatment of ALS that aims to reduce hyperexcitability-induced neurodegeneration.
QRL-201 and QRL-101 are currently undergoing IND-enabling studies. QurAlis plans to initiate clinical development for QRL-201 and QRL-101, respectively, in the second half of 2022.
STATHMIN-2 is a well-known protein important for neural repair and axonal stability, the expression of which is significantly decreased in the majority of ALS patients. Also known as SCG-10, STMN2 is a protein important for stabilization of microtubules which form an important component of the cytoskeleton of cells and axons. STATHMIN-2 is highly expressed in human motor neurons, the cells that primarily degenerate in patients suffering from ALS. In animal models, STMN2 deletion was found to cause axonal degeneration, which is the primary functional deficit that leads to paralysis in ALS patients.
Kv7.2/7.3 is a hetero-tetrameric voltage-gated potassium channel in cell membranes which is encoded by KCNQ2 and KCNQ3. Kv7.2/7.3 is the dominant component of the neuronal M-current in human motor neurons, which stabilizes the membrane potential and controls neuronal excitability. Therapies that reduce abnormal electrical activity in the brain by activating or opening the Kv7.2/7.3 ion channel show the potential to decrease spinal and cortical motor neuron excitability in patients with ALS and the potential to positively effect CMAP (compound muscle action potential) amplitude, suggesting that this may be an effective therapeutic approach for patients suffering from hyperexcitability-induced motor neuron degeneration.