STMN2

AcuraStem Leverages iNeuroRx® Platform to Drive Innovative SYF2 and UNC13A Treatments Forward Toward Clinical Trials PASADENA, Calif., Jan. 30, 2024 /PRNewswire/ -- AcuraStem, a patient-based biotechnology company advancing treatments for amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative diseases, announced today that it has successfully raised nearly $7 million in grant funding for ALS / FTD research from the National Institutes of Health (NIH) and the Department of Defense (DOD). This latest achievement—building upon the recent licensing agreement with Takeda worth $580 million to develop and commercialize AcuraStem's PIKFYVE targeted therapeutics including AS-202—enables the company to advance multiple programs towards clinical trials. "We are thrilled to receive continued support from NIH and the DOD," said Sam Alworth, MS, MBA, AcuraStem co-founder and CEO. "Leaders from the scientific community selected AcuraStem for these awards through a rigorous peer-review process, which demonstrates the excellence of our research." AcuraStem has made a significant advancement in understanding the pathophysiology of ALS, focusing on the crucial role of UNC13A. An overwhelming majority of ALS cases, and roughly half of FTD cases, are characterized by TDP-43 pathology. TDP-43, a RNA-binding protein typically found in the nucleus, is mislocalized to the cytoplasm in affected neurons, leading to RNA processing errors. These errors result in the incorporation of a cryptic exon into the UNC13A messenger RNA, causing a loss of UNC13A protein. This loss is further exacerbated by a risk variant in the UNC13A gene, closely linked to the TDP-43 binding site and associated with reduced survival in ALS and FTD patients. AcuraStem's iNeuroRx® platform has successfully replicated UNC13A pathology in patient neurons, enabling the rapid development and testing of antisense oligonucleotides (ASOs). These ASOs effectively suppress the cryptic exon and restore normal UNC13A function, offering a promising therapeutic approach for TDP-43 proteinopathies and a deeper understanding of UNC13A's role in disease progression. Additionally, AcuraStem has made a pivotal discovery with its focus on SYF2, a novel target in TDP-43 pathology. In collaboration with co-founder Dr. Justin Ichida's lab at USC, AcuraStem's extensive research on patient neurons via the iNeuroRx® platform, coupled with a comprehensive bioinformatic analysis, identified SYF2 as a key therapeutic target. SYF2, a pre-mRNA splicing factor, plays a crucial role in the regulation of splicing affected by the depletion of nuclear TDP-43, a common feature in most ALS cases (Linares GR et al Cell Stem Cell 2023). AcuraStem's findings highlight that SYF2 can address both the toxic aggregation of TDP-43 in cytoplasm and also counter the widespread gene dysregulation, including critical genes like UNC13A and STMN2, caused by TDP-43's absence from the nucleus. Targeting SYF2 could offer a more direct and potentially effective therapeutic strategy compared to addressing each dysregulated gene individually. Funding from NIH and the DOD was awarded through rigorous peer-reviewed processes, suggesting the award matches the health-related missions established by each agency. For additional information, please visit AcuraStem at acurastem.com and follow on LinkedIn, Facebook and X. Disclaimer This project will be supported by an NIH grant (R44AG085411). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs and the Defense Health Agency J9, Research and Development Directorate, or the U.S. Army Medical Research Acquisition Activity at the U.S. Army Medical Research and Development Command, in the amount of $839,898.40 through the ALSRP under Award No. HT9425-23-1-0469. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. About AcuraStem AcuraStem is a patient-based biotechnology company pioneering treatments for neurodegenerative diseases including sporadic ALS and FTD. AcuraStem's best-in-class disease modeling platform, iNeuroRx®, enables the discovery of innovative, effective, and broadly acting treatments. The team's strong expertise in ASO technology provides for the rapid advancement of treatments to the clinic. AcuraStem's research is funded in part by support from the Alzheimer's Drug Discovery Foundation, Harrington Discovery Institute, Alzheimer's Association, Rainwater Charitable Foundation, Muscular Dystrophy Association, Department of Defense and the National Institute of Neurological Disorders and Stroke. Contact: Kissy Black [email protected] 615.310.1894 SOURCE AcuraStem - Patient-Based Therapeutics

New location in Leiden, The Netherlands will serve as hub for European operations and production of QurAlis' products for clinical trials through commercialization CAMBRIDGE, Mass., Jan. 3, 2024 /PRNewswire/ -- QurAlis Corporation, a clinical-stage biotechnology company driving scientific breakthroughs into powerful precision medicines that will alter the trajectory of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative diseases, today announced the opening of its European Union (EU) headquarters in Leiden, The Netherlands. This new location will serve as the hub for the Company's European operations including the production of QurAlis' products for its clinical trials through commercialization. "The expansion of our operations into Europe represents a new chapter for QurAlis, building upon the tremendous momentum of our organization," said Kasper Roet, Ph.D., CEO and co-founder of QurAlis. "In a short period of time, QurAlis has made significant progress with regulatory approvals for our clinical programs in the EU, Canada, and the UK. The successful completion of the quality systems inspection by the Dutch regulatory agency will allow us to directly leverage our world-class ASO manufacturing expertise and control our end-to-end production supply chain. With our new European headquarters, and the skilled talent network in Leiden and the region, we will further strengthen our position as we bring breakthrough precision medicines to patients with ALS, FTD, and other neurodegenerative diseases." 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 mutations and clinical biomarkers. The company is focused on patients who have a loss of Kv7.2/7.3, patients who have loss of STATHMIN-2, as well as patients with loss of UNC13A and impairment in synaptic signaling. The QurAlis team is leveraging insights, platforms, and successes in ALS to collaborate and expand its pipeline to other neurodegenerative diseases, such as FTD. There are currently no cures for ALS or FTD. Limited therapeutic options are available for ALS and FTD patients who are in desperate need for effective therapies. "QurAlis' new location in Leiden is designed to not just meet our current needs, but also to scale with our business as we continue to grow," said Hagen Cramer, Ph.D., chief technology officer of QurAlis. "Our new European headquarters will allow us to release ASOs and other products into the European market for our programs so that we can deliver innovative solutions and make a meaningful difference in patients' lives." In addition to the new Leiden office, QurAlis' global corporate headquarters are in Cambridge, Massachusetts. 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 will alter the trajectory of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative diseases. Founded by an internationally recognized team of neurodegenerative biologists from Harvard Medical School and Harvard University, QurAlis is advancing a pipeline with therapeutic candidates that target specific components of ALS and FTD pathology and defined patient populations based on both disease-causing genetic mutation(s) and clinical biomarkers. For more information, please visit or follow us on Twitter @QurAlisCo. SOURCE QurAlis

EU CTA marks second regulatory clearance for Phase 1 ANQUR clinical trial of QRL-201 in ALS ANQUR is first-ever clinical trial to evaluate a therapy that rescues STATHMIN-2 expression in ALS patients QurAlis recently announced first patient dosed in Canada; enrollment completed in Cohort 1 portion of ANQUR CAMBRIDGE, Mass., June 6, 2023 /PRNewswire/ -- QurAlis Corporation, a clinical-stage biotechnology company developing breakthrough precision medicines for amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases with genetically validated targets, 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. "This EU Clinical Trial Authorisation marks the second regulatory clearance for QRL-201 as we execute our global strategy focused on bringing breakthrough precision medicines to patients with ALS and other neurodegenerative diseases," said Kasper Roet, Ph.D., CEO and co-founder of QurAlis. "We believe QRL-201 has the potential to halt disease progression, which could transform the care and treatment of ALS. We are dedicated to ensuring efficient advancement of our ANQUR clinical trial so that we can fulfill our mission to make a meaningful difference in patients' lives." QRL-201 is a first-in-class precision 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. STMN2 is a well-validated protein important for neural repair and axonal stability and is the most significantly regulated gene by TDP-43 exclusively in humans. Its expression is significantly decreased in nearly all ALS patients and it is the most consistently decreased gene over all sporadic ALS patient data sets. QRL-201 rescues STMN2 loss of function in QurAlis ALS patient-derived motor neuron disease models in the presence of TDP-43 pathology. The Clinical Trial Authorisation (CTA) in Europe is part of a global regulatory strategy established by QurAlis for the clinical development of QRL-201, which also includes a cleared CTA in Canada. 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. About the ANQUR Clinical Trial ANQUR (NCT05633459) is a first-in-human global, multi-center, randomized, double-blind, placebo-controlled multiple-ascending dose Phase 1 clinical trial designed to evaluate the safety, tolerability, and pharmacokinetics of QRL-201 versus placebo in patients with amyotrophic lateral sclerosis (ALS). The primary objective of the study is to determine the safety and tolerability of multiple doses of QRL-201 in people living with ALS. The ANQUR clinical trial is expected to include 64 study participants with ALS across sites in Canada, the European Union, U.S., and United Kingdom. Visit for more information about the ANQUR study. About STATHMIN-2 and TDP-43 STATHMIN-2 (STMN2) is a well-validated protein important for neural repair and axonal stability, the expression of which is significantly decreased in nearly all ALS patients. Also known as SCG-10, STMN2 is a protein essential for the stabilization of microtubules which form an important component of the cytoskeleton of cells and axons. STMN2 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 and loss of muscle innervation, which is the primary functional deficit that leads to paralysis in ALS patients. Using human neuronal stem cell models from ALS patients, QurAlis co-founder and former Harvard professor Kevin Eggan, Ph.D., discovered in 2019 that the expression of STMN2 is regulated by TDP-43. The Eggan Lab showed that loss of normal TDP-43 function leads to a highly significant decrease in expression of STMN2 and an impairment in neuronal repair which could be rescued by restoring STMN2 levels. These results were published in Nature Neuroscience. In addition to nearly all ALS patients, TDP-43 pathology is also associated with approximately 50 percent of patients with frontotemporal degeneration (FTD), the second most common form of dementia; about a third of Alzheimer's Disease patients; and up to seven percent of Parkinson's disease patients. There are currently no cures for ALS or FTD. Limited therapeutic options are available for ALS and FTD patients who are in desperate need for effective therapies. About QurAlis Corporation QurAlis is trailblazing the path to conquering amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases with genetically validated targets with next-generation precision medicines. QurAlis' proprietary platforms and unique biomarkers enable the design and development of drugs that act directly on disease-causing genetic alterations. Founded by an internationally recognized team of neurodegenerative biologists from Harvard Medical School and Harvard University, QurAlis is advancing a deep pipeline of antisense oligonucleotides and small molecule programs including addressing sub-forms of ALS that account for the majority of ALS patients. For more information, please visit or follow us on Twitter @QurAlisCo. SOURCE QurAlis