QurAlis' ANQUR Trial of QRL-201 in ALS Moves to Dose Range-Finding Phase with First Participant Dosed

QurAlis Corporation, a biotechnology firm specializing in precision medicines for neurodegenerative and neurological diseases, recently announced significant progress in their Phase 1 ANQUR clinical trial. The trial is evaluating QRL-201 for treating amyotrophic lateral sclerosis (ALS). Pharmacokinetic (PK) data from the dose-escalation phase showed that cerebrospinal fluid (CSF) exposure levels of QRL-201 met or exceeded the targeted therapeutic range, prompting advancement to the dose range-finding (DRF) phase.

QRL-201 is a groundbreaking therapeutic product designed to restore STATHMIN-2 (STMN2) expression in ALS patients, potentially altering disease progression and improving patient outcomes. The ANQUR clinical trial (QRL-201-01; NCT05633459) now includes an additional cohort of participants with C9orf72-related ALS, alongside those with sporadic ALS. This change is due to consistent mis-splicing of STMN2 in C9orf72-related ALS patients.

The trial is active across multiple sites in Canada, the United Kingdom (UK), and the European Union (EU). Cohorts 1 and 2 have completed dosing, and the DRF phase design amendment has been approved in Canada and the UK, with EU approval anticipated soon. The first participant in the DRF phase has already been dosed in Canada.

Kasper Roet, Ph.D., CEO and co-founder of QurAlis, emphasized the potential of QRL-201 to modify disease progression in ALS patients who experience STMN2 loss due to TDP-43 pathology. The PK data from the initial cohorts reinforced confidence in QRL-201's therapeutic potential.

STMN2 is a crucial protein for neural repair, axonal stability, and muscle innervation. It is significantly regulated by TDP-43, a protein exclusively in humans. Loss of nuclear TDP-43 leads to mis-splicing of the pre-mRNA of STMN2, resulting in the loss of the full-length transcript and protein. QRL-201 addresses STMN2 loss of function in ALS patient-derived motor neuron disease models containing TDP-43 pathology. This pathology is linked to nearly all ALS cases, about half of frontotemporal dementia (FTD) cases, and one-third of Alzheimer's Disease cases. Unfortunately, there are no cures for ALS or FTD, and current therapeutic options are limited.

Doug Williamson, M.D., chief medical officer at QurAlis, expressed satisfaction with the progress made in dosing the first participant in the DRF stage. He highlighted this as a significant milestone in evaluating QRL-201's potential as a transformative precision medicine for sporadic ALS patients.

QurAlis is set to present an update on the ANQUR clinical trial at the 35th International Symposium on ALS/MND, scheduled for December 6-8, 2024, in Montreal, Canada, and virtually. The presentation will provide further details on the trial's progress and design.

The ANQUR clinical trial is the first to explore a therapy aimed at rescuing STMN2 expression in ALS patients. It is a global, multi-center, randomized, double-blind, placebo-controlled, multiple-ascending dose Phase 1 trial. The primary objective is to assess the safety and tolerability of multiple QRL-201 doses, with a secondary objective focused on the plasma PK profile of QRL-201. Additionally, the trial will evaluate exploratory endpoints, including biomarkers of neuronal loss and STMN2 biology, clinical outcome measures, and CSF PK profile.

The trial aims to include 64 ALS participants across Canada, the EU, and the UK. Participating sites include the University of Alberta, University of Calgary, Montreal Neurological Institute-Hospital, and CHUM-Hopital Notre-Dame in Canada; Universitaire Ziekenhuizen Leuven in Belgium; Charité Research Organisation, University Hospital Schleswig-Holstein, and Universitätsklinikum Ulm in Germany; Universitair Medisch Centrum Utrecht in the Netherlands; and St. James Hospital, Kings College Hospital NHS Foundation Trust, and The University of Sheffield in the UK.

The dose-escalation phase's success, based on PK data analysis from Cohorts 1 and 2, showing that QRL-201 met or exceeded the targeted therapeutic range, marks a pivotal point for the trial. The DRF phase will further assess two QRL-201 doses and enroll an additional 48 participants, including 32 with sporadic ALS and 16 with C9orf72-related ALS.