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

The primary objective of this study is to determine the safety and tolerability of multiple doses of QRL-201 in people living with ALS

Start Date16 Dec 2022

Sponsor / Collaborator

QurAlis Corp.

100 Clinical Results associated with QRL-201

100 Translational Medicine associated with QRL-201

100 Patents (Medical) associated with QRL-201

News (Medical) associated with QRL-201

23 Feb 2026

·endpoints.news

A new ALS drug showed positive signs in early study, but questions remain for pivotal trial

The first clinical results in ALS from the private biotech QurAlis arrived Monday with a handful of questions. The startup believes the biomarker data from the Phase 1/2 study are strong enough to move the drug, QRL-201, to a pivotal trial. But the experiment failed to reach a statistically significant improvement over placebo on a clinical measurement that has been the standard for ALS trials. Any path to approval — which the company thinks it can pursue with a pivotal trial it’s planning — will need to answer more definitively whether QRL-201’s impact on patient biology can translate to helping patients on real-world measures. In the data released Monday, the experimental drug increased by two-fold the levels of a target protein called STMN2 that’s thought to be involved in the vast majority of ALS cases. But in a rating scale of ALS symptoms typically used as a primary endpoint in pivotal studies, the difference between QRL-201 and placebo wasn’t significant. Due to the nuances of how ALS progresses in different individuals, and the disease’s universally fatal nature, those data may be enough to widen testing and make another try at the clinical endpoints. ALS can start with swallowing problems in some patients, and with muscle weakness in others. It can progress quickly, or take months for patients to decline. These factors make clinical assessments more difficult. QurAlis hopes to start that study next year and enroll somewhere between 150 and 300 patients, CEO Kasper Roet told Endpoints News in an interview. “It’s pretty exciting,” Merit Cudkowicz, director of the Healey Center for ALS at Massachusetts General Hospital and an advisor to the company, told Endpoints. “I don’t think it’s enough for approval right now, and that’s for the FDA. But you certainly want to go to the next trial as fast as you can.” Finding a cure for ALS has long been seen as a holy grail of drug development. The disease was discovered in the 1860s, then thrust into the American public’s awareness in 1939, when baseball star Lou Gehrig — who was famous for his durability, earning the nickname “The Iron Horse” — discussed his diagnosis in his retirement speech. Since then, only a handful of drugs have been approved for the disease, and they only modestly help patients. Most recently, in 2023, Biogen and Ionis got approval for Qalsody, a drug for patients with a specific genetic version of ALS representing about 1% to 2% of patients. Roet said QurAlis used Biogen’s development plan as a starting point, since both drugs are antisense oligonucleotides that target the underlying disease biology. But QRL-201 is designed for “sporadic” ALS, which doesn’t have a known genetic cause. About 90% of all ALS patients have sporadic disease. The drug goes after STMN2, which is involved in the buildup of another protein, TDP-43. In ALS, about 97% of patients have toxic buildups of TDP-43, and QurAlis hopes that by targeting STMN2, patients won’t progress as quickly. “Measuring STMN2 levels is measuring something that we think is really able to counteract the disease itself,” Roet said. The clinical measurement for ALS trials is called the revised ALS functional rating scale, or ALSFRS-R. It is considered a gold standard for such studies, though some — including the scale’s creator — have called for an upgrade . Patients are evaluated on 12 different functional measurements, each on a five-point scale from 0 to 4. A healthy individual would receive a 4, for a maximum total of 48 points. As ALS patients lose the ability to walk, breathe and eat independently, their scores fall. In QurAlis’ study, QRL-201 showed an “encouraging trend” in slowing patients’ declines on the scale. After 28 weeks, patients on QRL-201 saw their ALSFRS-R scores decline by 3.5 points, compared with 6.3 points in the placebo group. But the difference between groups wasn’t statistically significant. But when patients were sorted into three groups by how quickly their ALS progressed — slow, medium and fast progressors — QurAlis found a silver lining. QRL-201 induced a statistically significant difference when the fastest progressors were excluded. Now, the company will have to design its trial for success. In Biogen and Ionis’ Qalsody trials, fast progressors also performed worse, and the trial failed on a six-month timeline. But after collecting more data, they won approval from the FDA based on a biomarker. Many patients, though, don’t want to be on a placebo for long, given the disease’s 100% fatality rate, Cudkowicz said. “I like to have hope that drugs will work in everybody,” Cudkowicz said. “You only have one shot, really, in a good trial.” For QurAlis’ pivotal study, Cudkowicz said researchers could maintain the same inclusion criteria and use the ALSFRS-R as the primary endpoint, while also providing an early readout of the drug’s impact on biomarkers. A bigger trial could also split patients into different groups based on how quickly they are worsening. All of that will still have to come after discussions with the FDA, Roet said. “You want to set yourself up for success,” Roet said. “This strategy actually fits perfectly within what people think is the future of ALS clinical trials.” Editor’s note: This article has been updated to correct that QRL-201 increased levels of STMN2 by two-fold, not halved levels of STMN2.

Clinical ResultOligonucleotideDrug Approval

23 Feb 2026

·www.biospace.com

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

First clinical development program in sporadic ALS patients to show potential to restore STATHMIN-2 expression, a statistically significant effect on a neurofilament biomarker, and an overall trend of slowing disease progression as measured by the ALSFRS-R Subgroup analysis showed statistically significant effect on ALSFRS-R Interim data support including an open-label extended dosing period to ANQUR protocol; approval received in Canada and under regulatory review in other regions; preparations underway to advance QRL-201 into pivotal Phase 3 clinical trial in 2027 CAMBRIDGE, Mass.--(BUSINESS WIRE)-- QurAlis Corporation (“QurAlis”), a clinical-stage biotechnology company driving scientific breakthroughs into powerful precision medicines that have the potential to alter the trajectory of neurodegenerative and neurological diseases, today announced interim data from its Proof-of-Concept Phase 1/2 ANQUR clinical trial of QRL-201 in people living with amyotrophic lateral sclerosis (ALS). Results from this study demonstrated QRL-201 had an effect on disease progression in ALS patients; this effect was confirmed by markers of clinical efficacy and changes in a clinically relevant biomarker, along with target engagement. QRL-201 is a first-in-class, potent antisense oligonucleotide (ASO) precision therapeutic in development to restore STATHMIN-2 (STMN2) expression in ALS patients with the aim to modify disease progression and improve outcomes. STMN2 is a protein important for muscle innervation that is regulated by TDP-43 and downregulated in the majority of ALS patients. ANQUR (QRL-201-01; NCT05633459) is the first-ever clinical trial to evaluate a potential therapy to rescue STMN2 expression in people with ALS. The ANQUR study is a double-blind, placebo-controlled study which dosed a total of 69 patients across the dose escalation (n=17) and dose-range finding (DRF) (n=52) phases of the study. “I am encouraged by these data from the ANQUR clinical trial of QRL-201. The combination of effects on target engagement biomarkers, disease biomarkers such as neurofilament, and clinical measures is very promising and remarkable to see from an early stage clinical trial,” said Merit E. Cudkowicz, M.D., M.Sc., director, Sean M. Healey & AMG Center for ALS and executive director of the Mass General Brigham Neuroscience Institute, and the Julieanne Dorn Professor of Neurology at Harvard Medical School. “ALS is a devastating, fatal neurodegenerative disease with a significant unmet medical need. Our mission is to make a meaningful difference for people living with ALS. We believe QRL-201 has the potential to modify disease progression and improve outcomes for sporadic ALS patients,” said Kasper Roet, Ph.D., CEO and co-founder of QurAlis. “These results from the ANQUR clinical trial are well aligned with our understanding of STMN2 biology and the potential of STMN2 restoration to have a positive impact on ALS disease progression. We are grateful to the ANQUR clinical trial team, participants and their families, and look forward to advancing the QRL-201 clinical program to deliver a much-needed precision medicine option for people living with ALS.” Results from the interim analysis of the ANQUR clinical trial show: 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. In a post-hoc analysis excluding patients with the highest levels of baseline neurofilament light, which is associated with faster disease progression, there was a statistically significant and clinically meaningful slowing of decline in ALSFRS-R at the six-month (24 week) timepoint in treated sporadic ALS patients compared to placebo. QRL-201 was generally safe and well tolerated with most adverse events (AEs) reported as mild or moderate. During all phases of the study, and most recently in December 2025, the unblinded Data Safety Monitoring Board has recommended the study continue without modification. 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. 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. About STATHMIN-2 STATHMIN-2 (STMN2) is a well-validated protein important for neural repair, axonal stability, and muscle innervation and is the most significantly regulated gene by TDP-43 exclusively in humans. STMN2 has the most consistently decreased expression across multiple ALS RNA expression studies. Loss of nuclear TDP-43 leads to mis-splicing of the pre-mRNA of STMN2, resulting in loss of full-length transcript and protein. QRL-201 rescues STMN2 loss of function and neurodegenerative phenotypes in QurAlis’ ALS patient-derived motor neuron disease models in the presence of TDP-43 pathology. TDP-43 pathology is associated with nearly all ALS patients, approximately 50 percent of patients with frontotemporal dementia (FTD), the second most common form of dementia, and with about a third of Alzheimer’s Disease (AD) patients. There are currently no cures for ALS or FTD, and there are limited therapeutic options available for ALS and FTD patients who are in desperate need of effective therapies. About ANQUR Clinical Trial QRL-201 is being evaluated in the Phase 1/2 ANQUR clinical trial (QRL-201-01; NCT05633459), the first-ever clinical study designed to assess a potential therapy aimed at rescuing STATHMIN-2 (STMN2) expression in people with amyotrophic lateral sclerosis (ALS). The ANQUR trial completed the dose-escalation phase, based on pharmacokinetic analyses from Cohorts 1 and 2 that demonstrated cerebrospinal fluid exposure levels of QRL-201 met or exceeded the targeted therapeutic range. The study then advanced to the dose range-finding phase, which is evaluating two dose levels of QRL-201 and incorporates additional biomarker assessments. The study is currently active in Canada, the United Kingdom, and the European Union, and includes participants with both sporadic ALS and C9orf72-related ALS. More information about the ANQUR clinical trial can be found at . About QurAlis Corporation At QurAlis, we are neuro pioneers on a quest to cure, boldly seeking to translate scientific breakthroughs into powerful precision medicines. We work collaboratively with a relentless pursuit of knowledge, precise attention to craft, and compassion to discover and develop medicines that have the potential to transform the lives of people living with neurodegenerative and neurological diseases. QurAlis is the leader in development of precision therapies for amyotrophic lateral sclerosis (ALS). In addition to ALS, QurAlis is advancing a robust precision medicine pipeline to bring effective disease-modifying therapeutics to patients suffering from severe diseases defined by genetics and clinical biomarkers. For more information, please visit or follow us on X @QurAlisCo or LinkedIn . Contacts Kathy Vincent kathy.vincent@quralis.com

Clinical ResultPhase 3

23 Feb 2026

·www.quralis.com

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

First clinical development program in sporadic ALS patients to show potential to restore STATHMIN-2 expression, a statistically significant effect on a neurofilament biomarker, and an overall trend of slowing disease progression as measured by the ALSFRS-R Subgroup analysis showed statistically significant effect on ALSFRS-R Interim data support including an open-label extended dosing period to ANQUR protocol; approval received in Canada and under regulatory review in other regions; preparations underway to advance QRL-201 into pivotal Phase 3 clinical trial in 2027 CAMBRIDGE, Mass., February 23, 2026 – QurAlis Corporation (“QurAlis”), a clinical-stage biotechnology company driving scientific breakthroughs into powerful precision medicines that have the potential to alter the trajectory of neurodegenerative and neurological diseases, today announced interim data from its Proof-of-Concept Phase 1/2 ANQUR clinical trial of QRL-201 in people living with amyotrophic lateral sclerosis (ALS). Results from this study demonstrated QRL-201 had an effect on disease progression in ALS patients; this effect was confirmed by markers of clinical efficacy and changes in a clinically relevant biomarker, along with target engagement. QRL-201 is a first-in-class, potent antisense oligonucleotide (ASO) precision therapeutic in development to restore STATHMIN-2 (STMN2) expression in ALS patients with the aim to modify disease progression and improve outcomes. STMN2 is a protein important for muscle innervation that is regulated by TDP-43 and downregulated in the majority of ALS patients. ANQUR (QRL-201-01; NCT05633459) is the first-ever clinical trial to evaluate a potential therapy to rescue STMN2 expression in people with ALS. The ANQUR study is a double-blind, placebo-controlled study which dosed a total of 69 patients across the dose escalation (n=17) and dose-range finding (DRF) (n=52) phases of the study. “I am encouraged by these data from the ANQUR clinical trial of QRL-201. The combination of effects on target engagement biomarkers, disease biomarkers such as neurofilament, and clinical measures is very promising and remarkable to see from an early stage clinical trial,” said Merit E. Cudkowicz, M.D., M.Sc., director, Sean M. Healey & AMG Center for ALS and executive director of the Mass General Brigham Neuroscience Institute, and the Julieanne Dorn Professor of Neurology at Harvard Medical School. “ALS is a devastating, fatal neurodegenerative disease with a significant unmet medical need. Our mission is to make a meaningful difference for people living with ALS. We believe QRL-201 has the potential to modify disease progression and improve outcomes for sporadic ALS patients,” said Kasper Roet, Ph.D., CEO and co-founder of QurAlis. “These results from the ANQUR clinical trial are well aligned with our understanding of STMN2 biology and the potential of STMN2 restoration to have a positive impact on ALS disease progression. We are grateful to the ANQUR clinical trial team, participants and their families, and look forward to advancing the QRL-201 clinical program to deliver a much-needed precision medicine option for people living with ALS.” Results from the interim analysis of the ANQUR clinical trial show: 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. 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. About STATHMIN-2 STATHMIN-2 (STMN2) is a well-validated protein important for neural repair, axonal stability, and muscle innervation and is the most significantly regulated gene by TDP-43 exclusively in humans. STMN2 has the most consistently decreased expression across multiple ALS RNA expression studies. Loss of nuclear TDP-43 leads to mis-splicing of the pre-mRNA of STMN2, resulting in loss of full-length transcript and protein. QRL-201 rescues STMN2 loss of function and neurodegenerative phenotypes in QurAlis’ ALS patient-derived motor neuron disease models in the presence of TDP-43 pathology. TDP-43 pathology is associated with nearly all ALS patients, approximately 50 percent of patients with frontotemporal dementia (FTD), the second most common form of dementia, and with about a third of Alzheimer’s Disease (AD) patients. There are currently no cures for ALS or FTD, and there are limited therapeutic options available for ALS and FTD patients who are in desperate need of effective therapies. About ANQUR Clinical Trial QRL-201 is being evaluated in the Phase 1/2 ANQUR clinical trial (QRL-201-01; NCT05633459), the first-ever clinical study designed to assess a potential therapy aimed at rescuing STATHMIN-2 (STMN2) expression in people with amyotrophic lateral sclerosis (ALS). The ANQUR trial completed the dose-escalation phase, based on pharmacokinetic analyses from Cohorts 1 and 2 that demonstrated cerebrospinal fluid exposure levels of QRL-201 met or exceeded the targeted therapeutic range. The study then advanced to the dose range-finding phase, which is evaluating two dose levels of QRL-201 and incorporates additional biomarker assessments. The study is currently active in Canada, the United Kingdom, and the European Union, and includes participants with both sporadic ALS and C9orf72-related ALS. More information about the ANQUR clinical trial can be found at www.clinicaltrials.gov. About QurAlis Corporation At QurAlis, we are neuro pioneers on a quest to cure, boldly seeking to translate scientific breakthroughs into powerful precision medicines. We work collaboratively with a relentless pursuit of knowledge, precise attention to craft, and compassion to discover and develop medicines that have the potential to transform the lives of people living with neurodegenerative and neurological diseases. QurAlis is the leader in development of precision therapies for amyotrophic lateral sclerosis (ALS). In addition to ALS, QurAlis is advancing a robust precision medicine pipeline to bring effective disease-modifying therapeutics to patients suffering from severe diseases defined by genetics and clinical biomarkers. For more information, please visit www.quralis.com or follow us on X @QurAlisCo or LinkedIn.

Clinical ResultPhase 3OligonucleotidePhase 2

100 Deals associated with QRL-201

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Indication	Highest Phase	Country/Location	Organization	Date
Amyotrophic Lateral Sclerosis	Phase 1	Belgium	QurAlis Corp.	16 Dec 2022
Amyotrophic Lateral Sclerosis	Phase 1	Canada	QurAlis Corp.	16 Dec 2022
Amyotrophic Lateral Sclerosis	Phase 1	Germany	QurAlis Corp.	16 Dec 2022
Amyotrophic Lateral Sclerosis	Phase 1	Ireland	QurAlis Corp.	16 Dec 2022
Amyotrophic Lateral Sclerosis	Phase 1	Netherlands	QurAlis Corp.	16 Dec 2022
Amyotrophic Lateral Sclerosis	Phase 1	United Kingdom	QurAlis Corp.	16 Dec 2022
Frontotemporal Dementia	Preclinical	United States	QurAlis Corp.	27 Jun 2024

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