QRL-201 / QurAlis - LARVOL DELTA

Therapeutic frontiers in ALS: iPSC-based drug discovery, cell therapy, and gene therapy-Advances through 2026. (PubMed, Regen Ther) - "The FDA's accelerated approval of tofersen (Qalsody) in April 2023 marked the first treatment targeting a genetic cause of ALS. iPSC-derived drug candidates, including ropinirole and bosutinib, have completed early-phase clinical trials led by Japanese institutions...The identification of STMN2 as a downstream target of TDP-43 dysfunction has opened a potential TDP-43-downstream nucleic acid therapeutic avenue for sporadic ALS, which constitutes approximately 90% of all cases, with company-reported interim data suggesting target engagement in the ongoing Phase 1/2 ANQUR trial (QRL-201). This review synthesizes the latest evidence across all three therapeutic domains, with attention to the hierarchy of evidence, regulatory milestones, and the pioneering contributions of Japanese research groups."

First-in-human • Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Gene Therapies • Inflammation • Transplantation • STMN2 • TARDBP

Interim Results From ANQUR: A Phase 1 MAD And Dose Range Finding Study To Assess Safety, Tolerability, Pharmacokinetics And Efficacy Of QRL-201, A STMN2 Targeting Splice Switching ASO For The Treatment Of Sporadic And C9orf72 ALS (ENCALS 2026) - "Conclusion ANQUR is the first human trial exploring the hypothesis that restoration of STMN2 may be a suitable disease-modifying approach in ALS. Interim data showed target engagement, biomarker changes suggestive of an effect on disease progression, trend toward slowing of ALSRFS-R decline, and an acceptable safety profile in ALS patients."

Clinical • First-in-human • P1 data • PK/PD data • Amyotrophic Lateral Sclerosis • CNS Disorders • STMN2

CONQUR: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study To Assess QRL-201, A STMN2 Targeting Splice Switching ASO, For The Treatment Of Sporadic ALS (ENCALS 2026) - "Results In CONQUR, QurAlis will evaluate the effect of QRL-201 on the primary endpoint of Change from Baseline in Total ALSFRS-R Score at Week 52. Key secondary endpoints will include survival, a joint rank test (function and survival), NfL and pNfH.Conclusion CONQUR is the first trial to evaluate the efficacy of QRL-201 in people living with ALS with restoration of STMN2 as a disease-modifying approach."

Clinical • P3 data • STMN2 • TARDBP

ANQUR: A Study Evaluating the Safety and Tolerability of QRL-201 in ALS (clinicaltrials.gov) - P1 | N=69 | Active, not recruiting | Sponsor: QurAlis Corporation | Trial completion date: Oct 2026 ➔ Nov 2027 | Trial primary completion date: Oct 2026 ➔ May 2026

First-in-human • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

ANQUR: A Study Evaluating the Safety and Tolerability of QRL-201 in ALS (clinicaltrials.gov) - P1 | N=64 | Active, not recruiting | Sponsor: QurAlis Corporation | N=35 ➔ 64

Enrollment change • First-in-human • Amyotrophic Lateral Sclerosis • CNS Disorders

These data support an open-label extended dosing period to the ANQUR clinical trial protocol under which all eligible trial participants will be given the opportunity to receive QRL-201 at the low dose of the DRF portion of the study. (Businesswire) - "The open-label extended dosing period to the ANQUR clinical trial has been approved in Canada and is currently under regulatory review in the European Union and the United Kingdom. In parallel, QurAlis is preparing to advance QRL-201 into a pivotal Phase 3 clinical trial in 2027."

New P3 trial • Amyotrophic Lateral Sclerosis

QurAlis Demonstrates Effects on Disease Progression and Target Engagement in ANQUR Clinical Trial of QRL-201, a First-in-Class Precision Medicine in Development for Sporadic ALS (Businesswire) - "Target engagement, confirmed through tissue analysis, with broad distribution across the spinal cord and motor cortex, statistically significant increased levels of STMN2, above the estimated therapeutic target, and correction of STMN2 mis-splicing, as compared to a cohort of natural history samples; A statistically significant and clinically meaningful reduction in phosphorylated neurofilament heavy (pNfH) in the low dose group; An encouraging trend of slowing decline in ALSFRS-R in sporadic patients, including a strong trend on the gross motor sub-score, which is critical for patient independence."

P1/2 data • Amyotrophic Lateral Sclerosis

ANQUR, the first-in-human phase 1 study of QRL-201 in ALS advances to dose-range finding using a novel population pharmacokinetic analysis (ALS-MND 2025) - "QRL-201-01 is designed to evaluate the safety and tolerability, explore multiple doses of QRL-201 in ALS, and is the first clinical trial exploring the hypothesis that restoration of STMN2 may be a suitable disease-modifying approach in ALS. The PK model simulations were used to modify the trial design and expand ANQUR from a dose-ranging study to a dose-range finding study. The study is ongoing in Canada, the United Kingdom, Ireland, Belgium, the Netherlands and Germany."

Clinical • First-in-human • P1 data • PK/PD data • STMN2 • TARDBP

QurAlls Pipeline And Development Updates For QRl-101 And QRL-201 In ALS (PACTALS 2025) - "Sponsored by QurAlis Corporation"

ANQUR: A Study Evaluating the Safety and Tolerability of QRL-201 in ALS (clinicaltrials.gov) - P1 | N=64 | Active, not recruiting | Sponsor: QurAlis Corporation | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyotrophic Lateral Sclerosis • CNS Disorders

ANQUR – a study evaluating safety and tolerability of QRL-201 in amyotrophic lateral sclerosis (ALS-MND 2024) - "QurAlis' mission is to bring breakthrough precision medicines to people living with ALS. QRL-201-01 is designed to evaluate the safety and tolerability of multiple doses of QRL-201 in people living with ALS and is the first clinical trial exploring the hypothesis that restoration of STMN2 may be a suitable disease-modifying approach in ALS."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • STMN2 • TARDBP

QurAlis' ANQUR Clinical Trial of QRL-201 in ALS Advances to Dose Range-Finding (DRF) Phase With First Participant Dosed (PRNewswire) - "QurAlis Corporation...announced that the Phase 1 ANQUR clinical trial evaluating QRL-201 for the treatment of ALS has successfully completed the dose-escalation phase, based on pharmacokinetic (PK) data analysis from Cohorts 1 and 2, indicating cerebrospinal fluid (CSF) exposure levels of QRL-201 met or exceeded the targeted therapeutic range....The ANQUR clinical trial (QRL-201-01; NCT05633459) has advanced to the dose range-finding (DRF) phase which will evaluate two doses of QRL-201 and include additional biomarkers. The study design will now also include a cohort of participants with C9orf72-related ALS in addition to participants with sporadic ALS....QurAlis will present an update on the ANQUR clinical trial in a poster presentation at the 35th International Symposium on ALS/MND being held December 6-8, 2024..."

P1 data • Trial status • Amyotrophic Lateral Sclerosis

A Study Evaluating the Safety and Tolerability of QRL-201 in ALS (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: QurAlis Corporation | Trial completion date: May 2025 ➔ Aug 2026 | Trial primary completion date: May 2025 ➔ Aug 2026

Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

QRL-201-01—A Multi-center, Randomized, Double-blind, Placebo-controlled Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of QRL-201 in Amyotrophic Lateral Sclerosis (AAN 2024) - "QurAlis' mission is to bring breakthrough precision medicine technology to people living with ALS. QRL-201-01 is designed to evaluate the safety and tolerability of multiple doses of QRL-201 in people living with ALS, and explore the hypothesis that restoration of STMN2 is a suitable disease-modifying approach in ALS."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • STMN2 • TARDBP

QurAlis and Unlearn Announce Collaboration to Accelerate and Optimize ALS Clinical Trials With Generative Artificial Intelligence Technologies (PRNewswire) - "QurAlis Corporation...today announced they have entered into a collaboration to accelerate and optimize QurAlis' clinical program in ALS with Unlearn's advanced generative artificial intelligence (AI) technology....The collaboration aims to reduce variability and increase the study power in QurAlis' clinical trials for QRL-201 and QRL-101, the Company's lead product candidates in ALS."

Licensing / partnership • Amyotrophic Lateral Sclerosis • CNS Disorders

QurAlis' FlexASOs Show High Potency and Improved Safety Over Standard ASOs (PRNewswire) - "QurAlis Corporation...today announced it will present new preclinical data showing the potential of the company's antisense oligonucleotides (ASOs) generated from its proprietary FlexASO™ Splice Modulator Platform. Data from two of QurAlis' FlexASO programs targeting rescue of STATHMIN-2 (STMN2) and UNC13A showed up to three-fold improvement over standard ASOs in both potency and biodistribution, and significantly reduced off-target effects, often from approximately 50 to 0, in human motor neurons. In addition, QurAlis' FlexASOs were not associated with cytokine or chemokine production. Observations from both programs therefore indicate that FlexASO™ technology results in a higher therapeutic index than observed with traditional ASO."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders

QurAlis Receives Clinical Trial Authorisation (CTA) in European Union (EU) for QRL-201, a First-in-Class STATHMIN-2 Precision Therapy for ALS (PRNewswire) - "QurAlis Corporation...today announced that the European review has been completed for the Clinical Trial Regulation (CTR) and each participating country has issued a notice of acceptance for QRL-201 for the potential treatment of ALS. QurAlis expects to initiate the Phase 1 ANQUR clinical trial of QRL-201 in participating European Union (EU) countries by the fourth quarter of 2023....QurAlis has completed enrolling patients in the Cohort 1 portion of the ANQUR clinical trial in Canada and recently announced the first patient has been dosed. Participating countries in the EU CTA include Germany, Belgium, the Netherlands, and Ireland."

New P1 trial • Trial status • Amyotrophic Lateral Sclerosis • CNS Disorders • Proteinopathy

QurAlis Announces First Patient Dosed With QRL-201, a First-in-Class STATHMIN-2 Precision Therapy for ALS (PRNewswire) - "QurAlis Corporation...today announced that the first patient has been dosed in its Phase 1 clinical trial of QRL-201 for the treatment of ALS (ANQUR). QRL-201 is a first-in-class therapeutic product candidate aiming to restore STATHMIN-2 (STMN2) expression in ALS patients. ANQUR is the first-ever study to evaluate a therapy that rescues STMN2 expression in ALS patients."

Trial status • Amyotrophic Lateral Sclerosis • CNS Disorders

QurAlis secures $88M to advance ALS therapies (ALS News Today) - “QurAlis has secured $88 million to advance the clinical development of QRL-101 and QRL-201, its lead candidates for amyotrophic lateral sclerosis (ALS). The new series B financing, a second round of funding after the company met certain research milestones, brings the total investment to $143.5 million. The proceeds will also support research for candidates in QurAlis’ pipeline targeting components of ALS and the related condition of frontotemporal dementia (FTD).”

Financing • Amyotrophic Lateral Sclerosis • CNS Disorders • Frontotemporal Lobar Degeneration

A Study Evaluating the Safety and Tolerability of QRL-201 in ALS (clinicaltrials.gov) - P1 | N=64 | Recruiting | Sponsor: QurAlis Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders

QurAlis Receives Health Canada Clinical Trial Application Authorization for QRL-201, a First-in-Class STATHMIN-2 Precision Therapy for ALS (PRNewswire) - “QurAlis Corporation…announced the authorization of its clinical trial application (CTA) by Health Canada for QRL-201, a first-in-class STATHMIN-2 (STMN2) precision medicine for ALS. The ANQUR clinical trial is a global, multi-center, randomized, double-blind, placebo-controlled multiple-ascending dose Phase 1 study designed to evaluate the safety and tolerability of QRL-201 in patients with ALS….This clearance from Health Canada is the first part of the global regulatory strategy and plan established by QurAlis for the clinical development of QRL-201; additional clearances across multiple jurisdictions are anticipated in the coming months.”

New P1 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

A Study Evaluating the Safety and Tolerability of QRL-201 in ALS (clinicaltrials.gov) - P1 | N=64 | Not yet recruiting | Sponsor: QurAlis Corporation

New P1 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

THE IMPACTS OF TDP-43 LOSS ON STATHMIN-2 EXPRESSION, GOLGI APPARATUS MORPHOLOGY, AND NEURITE OUTGROWTH IN HUMAN CORTICAL AND MOTOR NEURONS: THE DISCOVERY OF QRL-201 (ADPD 2022) - "TDP-43 pathology is associated with depletion of STMN2 from neurites and leads to golgi structural deficits. Therapeutic ASO treatment restores STMN2 to neurites and Golgi to growth cones suggesting a significant role of STMN2 in the health of human cortical and motor neurons."

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Frontotemporal Lobar Degeneration • Immunology • Proteinopathy • STMN2 • TARDBP