STMN2

PK data analysis in dose-escalation phase indicated exposures of QRL-201 met or exceeded the targeted therapeutic range prompting advancement to the DRF phase ANQUR protocol amended to include additional biomarkers and cohort of participants with C9orf72-related ALS; Company to present update at 35th International Symposium on ALS/MND CAMBRIDGE, Mass., Nov. 19, 2024 /PRNewswire/ -- QurAlis Corporation, a clinical-stage biotechnology company driving scientific breakthroughs into powerful precision medicines that have the potential to alter the trajectory of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative and neurological diseases, today 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. QRL-201 is a first-in-class precision therapeutic product candidate that has the potential to restore STATHMIN-2 (STMN2) expression in ALS patients with the aim to modify disease progression and improve outcomes. 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. Based on previous expression analysis, patients with C9orf72-related ALS show consistent mis-splicing of STMN2. The ANQUR clinical trial is currently active in Canada, the United Kingdom (UK), and the European Union (EU). Cohorts 1 and 2 have successfully completed dosing and an amendment to the DRF study design has been approved in Canada and the UK, with anticipated approval from the EU in the near future. The first participant in the DRF phase has been dosed in Canada. "ALS is a devastating, fatal neurodegenerative disease with a large unmet medical need. Our mission is to make a meaningful difference in patients' lives, and we believe QRL-201 could potentially modify disease progression and improve outcomes in ALS patients who have a loss of STMN2 due to TDP-43 pathology," said Kasper Roet, Ph.D., CEO and co-founder of QurAlis. "The PK data analysis from the first two completed cohorts of ANQUR indicated CSF exposures of QRL-201 met or exceeded the targeted therapeutic range. These findings further support our confidence in the potential therapeutic effect of QRL-201 in the treatment of sporadic ALS." 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 is the most consistently decreased gene 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 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 FTD, the second most common form of dementia, and with about a third of Alzheimer's Disease 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. "We are pleased that the first participant in Canada has been dosed in the dose range-finding stage of the ANQUR clinical trial," said Doug Williamson, M.D., QurAlis' chief medical officer. "This represents a significant milestone in the QRL-201 program to evaluate a potential transformative breakthrough precision medicine for patients 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, in Montreal, Canada and virtually. Details of the presentation are as follows: Title: QRL-201-01 (ANQUR): A multicenter, randomized, double-blind, placebo-controlled multiple ascending dose study to evaluate the safety and tolerability of QRL-201 in amyotrophic lateral sclerosis Date/Time: Saturday, December 7, 2024 5:00-7:00PM ET Theme: Clinical Trials and Trial Design Abstract Number: CLT-11 Session: Poster Session B Presenter: Emma Bowden, Ph.D., senior vice president, head of clinical development, QurAlis About the ANQUR Clinical Trial ANQUR (QRL-201-01; NCT05633459) is the first-ever clinical trial to evaluate a potential therapy to rescue STATHMIN-2 (STMN2) expression in people with amyotrophic lateral sclerosis (ALS). ANQUR is a global, multi-center, randomized, double-blind, placebo-controlled multiple-ascending dose Phase 1 clinical trial designed to evaluate the safety and tolerability of QRL-201 versus placebo in participants with ALS. The primary objective and endpoint of the study is to determine the safety and tolerability of multiple doses of QRL-201. The secondary objective and endpoint is the plasma pharmacokinetic (PK) profile of QRL-201 after multiple doses. ANQUR also intends to evaluate multiple exploratory endpoints including biomarkers of neuronal loss and STMN2 biology (neurofilament levels, STMN2 levels, Chitinase-3-like protein 1, and miRNA profiles), clinical outcome measures (ALSFRS-R, ALSAQ-5, ROADS, King's Staging, SVC, muscle strength, electrophysiology markers of denervation [maximum compound muscle action potential/CMAP and repetitive nerve stimulation/RNS]), and cerebrospinal fluid (CSF) PK profile. The ANQUR clinical trial is expected to include 64 study participants with ALS across sites in Canada, the European Union (EU), and United Kingdom (UK). Sites participating in the ANQUR clinical trial: Canada – University of Alberta (Edmonton, Alberta) University of Calgary (Calgary, Alberta), Montréal Neurological Institute-Hospital (Montreal, Quebec), and CHUM-Hopital Notre-Dame (Montréal, Quebec); EU – Universitaire Ziekenhuizen Leuven (Leuven, Belgium), Charité Research Organisation (Berlin, Germany), University Hospital Schleswig-Holstein Campus Lübeck (Lübeck, Germany), Universitätsklinikum Ulm (Ulm, Germany), Universitair Medisch Centrum Utrecht (Utrecht, The Netherlands); and UK – St. James Hospital (Dublin, Ireland), Kings College Hospital NHS Foundation Trust (London, England), and The University of Sheffield, Royal Hallamshire Hospital (Sheffield, England). The ANQUR clinical trial successfully completed the dose-escalation phase, based on PK data analysis from Cohorts 1 and 2, indicating CSF exposure levels of QRL-201 met or exceeded the targeted therapeutic range. The dose range-finding phase will evaluate two doses of QRL-201 and will enroll an additional 48 participants: 32 participants with sporadic ALS and 16 participants with C9orf72-related ALS. Visit for more information about the ANQUR study. About QurAlis Corporation At QurAlis, we are neuro pioneers on a quest to cure. We work with a relentless pursuit of knowledge, a precise attention to craft, and an optimistic mindset to discover and develop effective precision medicines that have the potential to alter the trajectory of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative and neurological diseases. Founded by an internationally recognized team of neurodegenerative biologists from Harvard Medical School and Harvard University, QurAlis is advancing a robust precision medicine pipeline with therapeutic candidates aimed at modifying severe disease pathology in defined patient populations based on both disease-causing genetic mutation(s) and clinical biomarkers. For more information, please visit or follow us on X @QurAlisCo or LinkedIn. SOURCE QurAlis WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Oral presentation at ASN on lead program, ABO-101 for primary hyperoxaluria type 1 (PH1), supporting in vivo proof of pharmacology. On-track for year-end IND/CTA filing.Oral presentation at ALS One and a poster presentation at ESGCT on lead ALS program ABO-202, highlighting in vivo reversal of ALS-associated STMN2 aberrant splicing and phenotypic outcomes in human motor neurons.Poster presentation at ESGCT demonstrating targeted gene knock-in and broader applicability of type V nuclease platform for monogenic diseases. CAMBRIDGE, Mass., Oct. 22, 2024 (GLOBE NEWSWIRE) -- Arbor Biotechnologies, Inc., a biotechnology company discovering and developing the next generation of genetic medicines, today announced oral and poster presentations on pipeline and early discovery programs at upcoming medical and scientific meetings: American Society of Nephrology (ASN) 2024 Kidney Week Meeting, October 23-27 in San Diego, California31st Annual European Society of Gene and Cell Therapy (ESGCT), October 22-25 in Rome, ItalyALS One 7th Annual ALS Research Symposium, November 13-15, Virtual At ASN Kidney Week, Arbor will present in vivo non-human primate (NHP) proof-of-pharmacology data supporting continued development of ABO-101, its most advanced gene editing therapeutic candidate designed to address primary hyperoxaluria type 1 (PH1) through inactivation of the HAO1 gene in the liver. Arbor is on track to file the IND/CTA for ABO-101 in PH1 by year-end. At the ALS One 7th Annual ALS Research Symposium and at ESGCT, Arbor will detail data on its lead ALS program ABO-202, supporting genetic disruption of STMN2, preventing errors in the processing of its mRNA, and elucidating a path towards proof of concept for a therapeutic CRISPR gene editing approach for the treatment of amyotrophic lateral sclerosis (ALS). The company will also showcase novel data at ESGCT demonstrating targeted gene knock-in at an endogenous promoter achieving equivalent or improved knock-in efficiency when compared to type II nucleases. This data supports the efficiency and breadth of applicability of Arbor’s type V nucleases to monogenic diseases. Details for the presentations are as follows: ASN 2024 Kidney Week:Oral Presentation Title: Development of ABO-101, A Novel Gene Editing Therapy for Primary Hyperoxaluria Type 1 Session Date and Time: Thursday, October 24, 2024, 4:30-6:00pm PDT Location: Room 23, Convention Center Presenter: Winston Yan, MD, PhD Abstract Number: TH-OR88 ESGCT 2024:Poster Title: Gene Editing with a Type V CRISPR-Cas Enzyme Disrupting the Aberrant Splicing of STMN2 as a Potential Treatment for ALS Session Date and Time: Poster Session 1, October 22, 7:30-9:00pm CEST Location: Forum, La Nuvola Presenter: Chee Yeun Chung, PhD Abstract Number: P0327 Poster Title: Targeted Knock-In at the Human TTR Locus Using Type V Nucleases Session Date and Time: Poster Session 3, October 24, 2:00-3:30pm CEST Location: Concourse Level 1 and Mezzanine Concourse, La Nuvola Presenter: Whitney J. French, PhD Abstract Number: P0603 ALS One 7th Annual ALS Research Symposium:Oral Presentation Title: Gene Editing with a Type V CRISPR-Cas Enzyme Disrupting the Aberrant Splicing of STMN2 as a Potential Treatment for ALS Session Date and Time: November 14, 3:40-4:00pm EDT Presenter: Priscilla D. Negraes, PhD About Arbor Biotechnologies, Inc.Arbor BiotechnologiesTM, a next-generation gene editing company based in Cambridge, MA, is advancing a pipeline of novel gene editing therapeutics to address a wide range of genetic conditions - from the ultra-rare to the most common genetic diseases. Our unique suite of optimized gene editors goes beyond the limitations of early editing technologies to unlock access to new gene targets and has fueled a robust pipeline of first-in-class assets focused on diseases of high unmet need. We are rapidly advancing our lead program in primary hyperoxaluria type 1 to the clinic and focusing our research and development efforts on genomic diseases of the liver and CNS for which there are no existing functional cures. For more information, please visit: arbor.bio Media Contact:Peg RusconiDeerfield Groupprusconi@deerfieldgroup.com

Presented data which, along with ongoing IND-enabling studies, demonstrate efficacy and pharmacology of ABO-101 in non-human primates (NHPs), supporting continued development as a potential novel gene editing therapy for patients with primary hyperoxaluria type 1 (PH1) Other presentations include preclinical evidence of editing in the central nervous system (CNS) using novel CRISPR-Cas systems, signaling potential for an effective STMN2-targeting gene editing approach for amyotrophic lateral sclerosis (ALS) Data demonstrate applicability of Arbor’s platform to identify and optimize new nucleases, including a novel type V nuclease ABR-004, and fuel a robust portfolio of gene editing programs spanning indications in the liver and CNS CAMBRIDGE, Mass., May 09, 2024 (GLOBE NEWSWIRE) -- Arbor Biotechnologies®, a biotechnology company discovering and developing the next generation of genetic medicines, today presents preclinical data demonstrating the potential of ABO-101, its novel gene editing therapeutic designed to address primary hyperoxaluria type 1 (PH1), as well as its broader discovery capabilities and their application to enable novel gene editing therapeutics in a suite of presentations at the 2024 American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting in Baltimore, Maryland. “At Arbor, we are building upon the potential of CRISPR-Cas approaches by leveraging our proprietary nuclease discovery and development platform to enable efficient identification and optimization of novel gene editing tools for a focus on translation of these tools into therapeutics,” said Devyn Smith, Ph.D., Chief Executive Officer of Arbor. “This approach has fueled our robust pipeline of genetic medicines which address a range of liver and CNS indications, including PH1 and ALS. The data presented at ASGCT reinforce the vast potential of our approach and demonstrate the tremendous progress we have made advancing our platform and programs toward the clinic.” In an oral presentation, Arbor shares in vivo data that highlights the therapeutic potential of its lead program, ABO-101, to address PH1. The data show highly specific targeting of the HAO1 gene in the liver and preservation of genomic integrity upon editing. The results further demonstrate efficient in vivo editing of HAO1 in a preclinical model of PH1, which resulted in a corresponding, therapeutically relevant reduction in urinary oxalate. ABO-101 was well tolerated in nonhuman primates (NHPs) at multiple doses. NHP data confirmed the efficacy and pharmacology of ABO-101, with efficient editing of HAO1 yielding reduced glycolate oxidase activity and increased serum glycolate. Together, this strong preclinical data package and the ongoing IND-enabling studies support continued advancement of ABO-101 toward clinical evaluation. Preclinical data shared in a poster presentation confirm that novel type V nucleases, discovered and optimized using Arbor’s discovery platform, can prevent aberrant splicing of STMN2, providing preclinical evidence of editing in CNS cells. In vitro studies in cellular models and human motor neurons and in vivo studies in STMN2 transgenic mice showed that STMN2 motif disruption increased full-length STMN2 mRNA and decreased mRNA levels for the aberrantly spliced novel exon of STMN2 (Exon 2A). These results show that leveraging a novel nuclease capable of achieving targeted deletions can reverse aberrant splicing of STMN2 and demonstrate the therapeutic potential for an effective gene editing approach for sporadic ALS in patients with TDP43 proteinopathy. The company also highlights the potential of its end-to-end nuclease discovery and optimization platform in a third presentation outlining the identification of a unique, compact type V nuclease. Arbor used structure-guided design to enhance activity and specificity of a compact CRISPR-Cas type V-L system identified via metagenomic search. The resulting nuclease, ABR-004, demonstrated the ability to achieve potent, therapeutically relevant silencing of PCSK9 in mice and non-human primates, signaling opportunities for future development for broader therapeutic applications. The data demonstrate the feasibility of applying Arbor’s discovery and targeted nuclease optimization capabilities to develop new gene editing tools with the potential to power the next generation of genomic medicines. David Cheng, Chief Technology Officer at Arbor, also participated in the scientific symposium, delivering a presentation on the significance and future of AI in the discovery and development of new genomic medicines as part of a session titled The Impact of Artificial Intelligence (AI) on CGT. Details for the presentations are as follows: Scientific Symposium: The Impact of Generative Artificial Intelligence (AI) on CGT Presentation Title:Generative AI Progress and Applications for Cell and Gene Therapies Session Date and Time: Wednesday, May 8, 2024, 8:00-8:25 am ET Location: Room 318-323 Presenter: David R. Cheng Oral Presentation Title: Development Of ABO-101, A Novel Gene Editing Therapy For Primary Hyperoxaluria Type 1 Abstract Number: 165 Session Date and Time: Thursday, May 9, 2024, 2:00-2:15 pm ET Location: Room 307-308 Presenter: Tia DiTommaso, PhD Oral Presentation Title: Identification and Engineering of ABR-004, a Compact, High-fidelity Nuclease for Therapeutic Gene Editing Abstract Number: 150 Session Date and Time: Thursday, May 9, 2024, 1:30-1:47 pm ET Location: Ballroom 3 Presenter: Jeffrey Haswell, PhD Poster Title: Disruption of Aberrant Splicing of STMN2 by Gene Editing with a Type V CRISPR-Cas Enzyme as a Potential Treatment for ALS Abstract Number: 1598 Session Date and Time: Friday, May 10, 2024, 12:00-7:00 pm ET Location: Exhibit Hall Presenter: Jace Jones-Tabah, PhD About Arbor Biotechnologies® Arbor Biotechnologies is a next-generation gene editing company based in Cambridge, MA. Combining the promise of CRISPR with advanced computational AI-driven discovery, high throughput screening, and robust protein engineering approaches, our co-founders Feng Zhang and David Walt laid the groundwork for our proprietary discovery engine, which has yielded an extensive toolbox of gene editors, far exceeding the number of editors published in the literature to date. We envision a future of gene editing that extends beyond simple knockdowns to include precision writing, precise excisions and large insertions. This affords us the potential to treat a broad spectrum of patients, from ultra-rare to the most common genetic diseases. Guided by a deep understanding of the molecular basis of disease and our access to a unique suite of optimized editors, we are rapidly advancing our discovery-stage programs with an initial focus on genomic diseases of the liver and CNS for which there are no existing functional cures. As we advance toward the clinic with our lead program in primary hyperoxaluria type I, we look to expand our strategic partnerships around in vivo gene editing across multiple therapeutic areas and ex vivo cell therapy programs to broaden the reach of our novel nuclease technology. For more information, please visit: arbor.bio Media Contact: Peg Rusconi Verge Scientific Communications prusconi@vergescientific.com