Neurona Therapeutics Announces Publication in Cell Stem Cell Reporting the Development of Investigational Novel Regenerative Cell Therapy Strategy for Drug-resistant Focal Epilepsy
– Publication demonstrates robust and reproducible generation of pure pallial, medial ganglionic eminence (MGE)-type GABAergic inhibitory interneuron cell therapy candidate derived from a clinical-grade human stem cell line
– Preclinical data demonstrate significant suppression of focal seizures, decreased neuropathology, and increased survival following cell transplantation into a chronic model of mesial temporal lobe epilepsy (MTLE)
– Study supports an ongoing open-label first-in-human Phase I/II trial of NRTX-1001 in adults with drug-resistant MTLE, which has shown promising early clinical data
San Francisco, CA, October 5, 2023 – Neurona Therapeutics, a clinical-stage biotherapeutics company advancing regenerative cell therapy candidates for the treatment of neurological disorders, today announced the publication of the development and characterization of a highly purified population of human stem cell-derived, pallial-specific MGE inhibitory interneurons for the potential treatment of focal epilepsy. In a preclinical study, administration of a single dose of the cells in a chronic model of drug-resistant MTLE resulted in durable and consistent suppression of focal seizures, as well as improvements in neuropathology and an increase in survival of the model. The study also demonstrated a potentially broad, safe and effective dosing range in the preclinical model. The data support the development of Neurona Therapeutics’ regenerative cell therapy candidate, NRTX-1001, which is being evaluated in an ongoing Phase I/II clinical trial of a one-time dose in subjects with drug-resistant MTLE (NCT05135091). The preclinical data were published today in Cell Stem Cell as a Clinical and Translational Report titled “Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy” by first authors Bershteyn, Bröer, Parekh, Maury, and colleagues and is available online.
“We are thrilled to announce this landmark publication, which builds the foundation for NRTX-1001 and exemplifies the phenomenal science being conducted by Neurona employees. This report demonstrates the directed derivation of human pallial-specific MGE GABAergic interneurons that can migrate, functionally integrate, and exhibit disease-modifying activity in a preclinical model of epilepsy,” said Cory R. Nicholas, Ph.D., Neurona’s chief executive officer “Pallial MGE-type GABAergic interneurons represent the most physiologically relevant population for cell replacement therapy in epilepsy, however until now a clinically suitable, reproducible, scalable source of these cells has not been described. I would like to congratulate the entire Neurona team and our collaborators for their dedicated work to advance this novel cellular therapeutic strategy that has the potential to provide a tissue-restorative option for people with drug-resistant focal epilepsy.”
The human stem cell-derived pallial MGE-type, GABAergic interneurons were generated using a proprietary GMP-compliant manufacturing protocol, and, as described in the article, the cells underwent extensive molecular and functional characterization including single-cell RNA sequencing, in vitro migration, and GABA secretion analyses. Following transplantation into the chronic intrahippocampal kainate model of MTLE, the human interneurons were analyzed for cellular migration and persistence, graft composition, synaptic connectivity, and dose-dependent reduction of seizure activity. Single-dose intrahippocampal delivery of the human pallial MGE-type interneurons resulted in consistent and stable suppression of mesiotemporal seizures in the preclinical model, with most of the cell-treated group becoming seizure-free. The grafted human interneurons dispersed locally, functionally integrated, and persisted in the sclerotic hippocampus throughout the 8.5-month study. A pathological hallmark of MTLE, hippocampal dentate granule cell dispersion, was significantly reduced, and survival rates in the epileptic model increased. Suppression of preclinical seizure activity and the reduced neuropathology in the model were cell dose-dependent and indicated a potentially broad therapeutic dosing range. No abnormal tissues or behavioral abnormalities were detected at any dose after cell transplantation.
The data support the development of Neurona’s cell therapy candidate NRTX-1001, which is being evaluated in an ongoing clinical trial (NCT05135091) in adults with drug-resistant MTLE. The first two subjects to receive NRTX-1001 entered the study with a history of significant monthly seizure activity that was not controlled by anti-seizure medications. The first subject had a seven-year history of seizures and, in the six months prior to the administration of NRTX-1001, experienced an average of 32 seizures per month. The second subject treated in the trial had a nine-year history of seizures and averaged 14 seizures per month in the six months prior to treatment. Both patients continue to report >95% reduction in overall seizure counts at one-year post-administration of NRTX-1001. Per protocol, both patients began neurocognitive testing six months post-treatment, and specific neurocognitive scores have increased from baseline levels, highlighting the restorative potential of NRTX-1001. No serious or severe adverse effects of NRTX-1001 have been detected thus far.
About Neurona’s Clinical Trial of NRTX-1001 for Mesial Temporal Lobe Epilepsy (MTLE)
The NTE001 clinical study is designed to evaluate the safety and efficacy of a single administration of NRTX-1001 for drug-resistant MTLE. The first stage of the trial is an open-label dose-escalation study in up to 10 people with MTLE, with five patients to be treated at a starting dose and five at a higher dose. Patients treated with a single infusion of NRTX-1001 cells will be monitored for safety, tolerability, and effects on their epilepsy disease symptoms. Patient recruitment is underway at epilepsy centers across the United States. For more information, please visit www.clinicaltrials.gov (NCT05135091). The first part of the clinical trial is supported by an $8.0 million grant from the California Institute for Regenerative Medicine (CIRM; CLIN2-13355). With $5.5 billion in funding and more than 150 active stem cell programs in its portfolio, CIRM is one of the world’s largest institutions dedicated to helping people by bringing the future of cellular medicine closer to reality.
NRTX-1001 is a regenerative neural cell therapy candidate derived from human pluripotent stem cells. The fully-differentiated neural cells, called interneurons, secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Delivered as a one-time dose, the human interneurons are intended to integrate and innervate on-target, and designed to durably silence seizure activity in the epileptic region of the brain. NRTX-1001 is manufactured in Neurona’s in-house GMP facility using proprietary methods. NRTX-1001 interneurons are cryopreserved and shipped to clinical sites for investigational use as an allogeneic therapy candidate in our ongoing clinical trial.
About Mesial Temporal Lobe Epilepsy
According to the Centers for Disease Control and Prevention, an estimated 3.4 million Americans have epilepsy, and 25 to 35 percent live with ongoing seizures despite treatment with approved drugs, illustrating a huge unmet medical need in this community. MTLE is a common type of focal epilepsy in adults and primarily affects the internal structures of the temporal lobe, where seizures often begin in a structure called the hippocampus. For people with seizures resistant to anti-seizure drugs, epilepsy surgery - where the damaged temporal lobe is surgically removed or ablated by laser - can be an option. However, the current surgical options are not available or effective for all patients, are tissue-destructive, and can have significant adverse effects.
Neurona is focused on developing regenerative cell therapy candidates that have single-dose curative potential. Neurona is developing off-the-shelf, allogeneic neural cell therapy candidates that are designed to provide long-term repair of dysfunctional neural networks for multiple neurological disorders. For more information about Neurona, visit www.neuronatherapeutics.com
Forward Looking Statements
This press release includes forward-looking statements that are subject to risks and uncertainties, including risks and uncertainties inherent in clinical development of therapeutic candidates and obtaining data to support regulatory approval. NRTX-1001 is an investigational candidate and is being evaluated in ongoing clinical trials. NRTX-1001 has not been approved by any regulatory authority for commercial use or deemed to be safe or effective for any indication.
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