NRTX-1001 / Neurona Therap - LARVOL DELTA

Clinical Update: NRTX-1001 GABAergic Interneuron Cell Therapy for Drug-Resistant Focal Epilepsy (AES 2025) - P1/2 | "The data from two ongoing Phase I/II studies of NRTX-1001 GABAergic interneuron cell therapy have been encouraging. One-time NRTX-1001 administration offers potential for durable seizure control in drug-resistant MTLE without brain tissue removal or ablation. Phase III EPIC, a randomized, sham-controlled, double-blind study evaluating NRTX-1001 in adults with drug-resistant MTLE is expected to begin enrollment in 2H 2025."

Clinical • CNS Disorders • Epilepsy

MTLE: Study of NRTX-1001 Neural Cell Therapy in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy (EPIC (EPIlepsy Cell Therapy)) (clinicaltrials.gov) - P3 | N=88 | Recruiting | Sponsor: Neurona Therapeutics | Phase classification: P1/2 ➔ P3 | N=58 ➔ 88 | Trial completion date: Feb 2042 ➔ Sep 2043 | Trial primary completion date: Feb 2028 ➔ Feb 2029

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Phase 3 EPIC (EPIlepsy Cell Therapy) Clinical Trial Design: NRTX-1001 GABAergic Interneuron Cell Therapy for the Treatment of Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy (MTLE) (AES 2025) - P1/2 | "The Phase 3 EPIC study will evaluate the safety and efficacy of NRTX-1001 GABAergic interneuron cell therapy for the treatment of drug-resistant unilateral MTLE with hippocampal sclerosis. Enrollment is expected to begin in the second half of 2025. One-time administration of NRTX-1001 regenerative cell therapy may offer the potential for substantial seizure control while preserving neurocognitive function by avoiding removal or ablation of brain tissue."

Clinical • P3 data • CNS Disorders • Epilepsy

Progression of hippocampal pathology in a mouse model of chronic focal epilepsy and its alteration by inhibitory interneuron cell therapy (NRTX-1001) (Neuroscience 2025) - P1/2 | "These data suggest that NRTX-1001 transplantation into epileptic mice limits the progression of sclerosis and additional dispersion of the GCL, demonstrating prevention and potential partial repair of epileptic histopathology. In future studies, the mechanism of action for reduction of the GCL area will be investigated.The results of these preclinical studies support ongoing clinical trials (NCT05135091, NCT06422923) to evaluate NRTX-1001 in people with drug-resistant temporal lobe epilepsy."

Preclinical • CNS Disorders • Epilepsy

Dissecting in vitro mechanisms of GABAergic inhibition in a co-culture system using human pluripotent stem cell-derived pallial interneurons (Neuroscience 2025) - P1/2 | "We have developed a cell therapy product, NRTX-1001, composed of human pluripotent stem cell (hPSC)-derived post-mitotic MGE pallial-type GABAergic interneurons (hpINs), designed to restore balanced neural activity in drug-resistant focal epilepsy, which is being investigated in ongoing clinical trials (NCT05135091, NCT06422923)...Additionally, perturbation of GABA signaling using toxins and receptor antagonists enabled specific disruption of GABA release and/or its binding to receptors, which further helped to delineate the role of synaptic inhibition in seizure-like dynamics. Our results provide mechanistic insight into how GABAergic interneurons regulate excitatory network activity in vitro and lay the foundation for evaluating therapeutic strategies that target inhibitory circuitry in epilepsy and related disorders."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy

Preclinical characterization of a human inhibitory interneuron cell therapy candidate for drug-resistant epilepsy in the intrahippocampal kainate mouse model (Neuroscience 2025) - P1/2 | "No ectopic tissues, tumors, or teratomas were observed following transplantation of NRTX-1001, and no deleterious effects were observed in behavioral testing. NRTX-1001 is being evaluated for safety and efficacy in two ongoing phase I/II clinical trials (NCT05135091, NCT06422923) for drug-resistant MTLE."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy

Neurona Therapeutics Announces Priority Medicines (PRIME) Designation Granted by the European Medicines Agency (EMA) to NRTX-1001 in the Treatment of Drug-Resistant Focal Epilepsy (GlobeNewswire) - 'The EMA awarded the PRIME designation to NRTX-1001 based on robust preclinical evidence, emerging clinical data, and the unmet need in patients with drug-resistant focal epilepsy....Neurona plans to present updated data from across the clinical development program for NRTX-1001 in MTLE at the Annual Meeting of the American Epilepsy Society (AES) in December 2025, including early data from recently added cohorts of bilateral and non-MTS MTLE subjects."

P1/2 data • PRIME • Epilepsy

Neurona Expands Investigation of NRTX-1001 Cell Therapy into Mesial Temporal Lobe Epilepsy (MTLE) without Mesial Temporal Sclerosis (MTS) (The Manila Times) - "First subject received unilateral administration of NRTX-1001 in a new non-MTS cohort; no significant surgical complications or adverse events reported to date; Data from this non-MTS cohort, together with results from Neurona’s ongoing Phase 1/2 trials in unilateral and bilateral MTLE and planned Phase 3 EPIC study, are intended to support a future BLA submission for NRTX-1001 in drug-resistant MTLE; Neurona to provide an update on its unilateral and bilateral MTLE programs at the American Epilepsy Society’s Annual Meeting in December 2025...the Phase 3 EPIC (EPIlepsy Cell Therapy) trial is planned to start in 2H 2025."

New P3 trial • Trial status • Epilepsy

Neurona Doses First Patient in Phase 1/2 Trial of NRTX-1001 Cell Therapy in Adults with Drug-Resistant, Bilateral Mesial Temporal Lobe Epilepsy (MTLE) (GlobeNewswire) - "Neurona...announced dosing of the first patient in its Phase 1/2 clinical trial of NRTX-1001 cell therapy in adults with drug-resistant bilateral mesial temporal lobe epilepsy (MTLE). MTLE is the most common type of epilepsy in adults and is characterized by seizures originating primarily in the hippocampus from either one hemisphere of the brain (unilateral) or both hemispheres (bilateral)....Neurona plans to present extended durability data from the first ten unilateral MTLE patients treated with low (Cohort 1) and high (Cohort 2) doses of NRTX-1001, along with new results from the eight additional patients who were enrolled in the unilateral MTLE expansion cohorts, as well as early data from the first bilateral MTLE patients at the American Epilepsy Society’s Annual Meeting in December 2025."

P1/2 data • Trial status • Epilepsy

A Phase 1/2 Study of NRTX-1001 Neuronal Cell Therapy in Drug-Resistant Bilateral Mesial Temporal Lobe Epilepsy (MTLE) (clinicaltrials.gov) - P1/2 | N=10 | Recruiting | Sponsor: Neurona Therapeutics | Trial completion date: Jul 2040 ➔ Jun 2042 | Trial primary completion date: Jul 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

Neurona Therapeutics Presents Positive Clinical Data Update from NRTX-1001 Cell Therapy Trial in Drug-resistant Epilepsy at American Academy of Neurology Annual Meeting (GlobeNewswire) - P1/2 | N=58 | NCT05135091 | Sponsor: Neurona Therapeutics | "EFFICACY: 92% median reduction in disabling seizures during 7-12-month efficacy endpoint period, and 80% (4/5) of patients responding with >75% seizure reduction in Cohort 1; DURABILITY: All responders (4/4) in Cohort 1 continue to have durable seizure control for 18-24 months after a single-dose of NRTX-1001; COGNITION AND QUALITY OF LIFE: All patients (5/5) in Cohort 1 had significantly improved quality-of-life test scores, with no patient experiencing persistent decline in cognition; SAFETY: NRTX-1001 continues to be well-tolerated at both high and low doses with no adverse events attributed to the cell therapy; NEXT STEPS: Phase 3 EPIC trial planned to start enrolling in 2H 2025, as aligned with FDA under RMAT designation, to support submission of a Biologics License Application (BLA)."

New P3 trial • P1/2 data • Epilepsy

MTLE: FIH Study of NRTX-1001 Neural Cell Therapy in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy (clinicaltrials.gov) - P1/2 | N=58 | Recruiting | Sponsor: Neurona Therapeutics | N=40 ➔ 58 | Trial completion date: May 2026 ➔ Feb 2042 | Trial primary completion date: May 2025 ➔ Feb 2028

Enrollment change • Trial completion date • Trial primary completion date • CNS Disorders • Epilepsy

First-in-Human Trial of NRTX-1001 GABAergic Interneuron Cell Therapy for Focal Epilepsy - Updated Clinical Trial Results (AAN 2025) - P1/2 | "NRTX-1001 administration has been well-tolerated in ten patients with drug-resistant TLE, with preliminary data suggesting significant reductions in seizure frequency and potential cognitive improvements. Unlike current surgical treatment options, NRTX-1001 may provide a non-destructive, cell-based therapeutic approach, potentially providing a restorative option for focal epilepsy."

Clinical • P1 data • CNS Disorders • Epilepsy

Neurona Unveils Phase 3 EPIC Study for NRTX-1001 Cell Therapy in Epilepsy (GlobeNewswire) - "Neurona Therapeutics...announced plans to initiate the Phase 3 EPIC clinical trial for its lead product candidate, NRTX-1001. NRTX-1001 is the first investigational human cell therapy for drug-resistant epilepsy. The EPIC trial is anticipated to begin in the second half of 2025 and is designed as a randomized, sham-controlled, double-blind study of NRTX-1001 in people living with drug-resistant mesial temporal lobe epilepsy (MTLE), which is the most common type of epilepsy in adults."

New P3 trial • Epilepsy

A Phase 1/2 Study of NRTX-1001 Neuronal Cell Therapy in Drug-Resistant Bilateral Mesial Temporal Lobe Epilepsy (MTLE) (clinicaltrials.gov) - P1/2 | N=10 | Recruiting | Sponsor: Neurona Therapeutics | Not yet recruiting ➔ Recruiting | Phase classification: P1 ➔ P1/2

Enrollment open • Phase classification • CNS Disorders • Epilepsy

First-in-human Trial of NRTX-1001 Gabaergic Interneuron Cell Therapy for Drug-resistant Focal Epilepsy – Updated Results (AES 2024) - P1/2 | "A first-in-human study of NRTX-1001 GABAergic interneurons for focal epilepsy is underway, and the preliminary safety and efficacy results are encouraging. One-time administration of NRTX-1001 cell therapy offers the potential for seizure control in patients with drug-resistant MTLE without removal or ablation of brain tissue."

P1 data • CNS Disorders • Epilepsy

Effect of NRTX-1001, a Cellular Therapy Product, for the Treatment of Refractory Bilateral TLE (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Neurona Therapeutics | Initiation date: Jul 2024 ➔ Nov 2024

Trial initiation date • CNS Disorders • Epilepsy

Speaker (Neuroscience 2024) - "This session will consider interneuron (IN) transplantation as a novel, cell-based therapy for human epilepsy. A panel with expertise in development, regenerative medicine, and surgical epilepsy management will discuss 1) cortical IN development and function, 2) preclinical studies of IN transplantation in animal models, 3) the generation of a clinical-grade human IN cell product (NRTX-1001), and 4) preliminary insights from a first-in-human study of IN transplantation for focal epilepsy."

CNS Disorders • Epilepsy

Speaker (Neuroscience 2024) - "This session will consider interneuron (IN) transplantation as a novel, cell-based therapy for human epilepsy. A panel with expertise in development, regenerative medicine, and surgical epilepsy management will discuss 1) cortical IN development and function, 2) preclinical studies of IN transplantation in animal models, 3) the generation of a clinical-grade human IN cell product (NRTX-1001), and 4) preliminary insights from a first-in-human study of IN transplantation for focal epilepsy."

CNS Disorders • Epilepsy

Speaker (Neuroscience 2024) - "This session will consider interneuron (IN) transplantation as a novel, cell-based therapy for human epilepsy. A panel with expertise in development, regenerative medicine, and surgical epilepsy management will discuss 1) cortical IN development and function, 2) preclinical studies of IN transplantation in animal models, 3) the generation of a clinical-grade human IN cell product (NRTX-1001), and 4) preliminary insights from a first-in-human study of IN transplantation for focal epilepsy."

CNS Disorders • Epilepsy

Chair (Neuroscience 2024) - "This session will consider interneuron (IN) transplantation as a novel, cell-based therapy for human epilepsy. A panel with expertise in development, regenerative medicine, and surgical epilepsy management will discuss 1) cortical IN development and function, 2) preclinical studies of IN transplantation in animal models, 3) the generation of a clinical-grade human IN cell product (NRTX-1001), and 4) preliminary insights from a first-in-human study of IN transplantation for focal epilepsy."

CNS Disorders • Epilepsy

BTCR03. Cortical Interneurons: From the Developing Brain to the Operating Room — Derek G. Southwell (Neuroscience 2024) - "A panel with expertise in development, regenerative medicine, and surgical epilepsy management will discuss 1) cortical IN development and function, 2) preclinical studies of IN transplantation in animal models, 3) the generation of a clinical-grade human IN cell product (NRTX-1001), and 4) preliminary insights from a first-in-human study of IN transplantation for focal epilepsy...Learning Objective 2 Understand the key principles of in vitro MGE-type cortical interneuron derivation from pluripotent stem cells, and assess the validation and pre-clinical testing of an investigational human MGE-type interneuron cell product. . Learning Objective 3 Understand the clinical context, study design, and preliminary results of an ongoing first-in-human trial of MGE-type interneuron transplantation."

CNS Disorders • Epilepsy

Establishing assays to support the development of inhibitory cell therapy, NRTX-1001, for drug-resistant mesial temporal lobe epilepsy (MTLE) (Neuroscience 2024) - P1/2 | "Preliminary results suggest that MGE-pINs modulate burst frequency, network activity, and synchrony of glutamatergic cultures. These data support the ongoing clinical investigation of NRTX-1001 and will help to elucidate interneuron cell therapy mechanism of action."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Epilepsy

Neurona Therapeutics Receives FDA’s Regenerative Medicine Advanced Therapy (RMAT) Designation for NRTX-1001 in Focal Epilepsy (GlobeNewswire) - "Neurona Therapeutics...announced that the U.S Food and Drug Administration (FDA) has granted the company’s lead product candidate, NRTX-1001, the RMAT expedited program designation for drug-resistant mesial temporal lobe epilepsy (MTLE)....'In the near-term, we are focused on completing the ongoing Phase 1/2 study and engaging with the FDA to discuss our product development plan'....The ongoing multicenter Phase 1/2 clinical trial is designed to evaluate the safety and efficacy of a single administration of NRTX-1001 for drug-resistant unilateral MTLE. The first stage of the trial is an open-label dose-escalation study in 10 subjects, recently expanded to up to 16 subjects..."

FDA event • Trial status • CNS Disorders • Epilepsy

Effect of NRTX-1001, a Cellular Therapy Product, for the Treatment of Refractory Bilateral TLE (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Neurona Therapeutics

New P1 trial • CNS Disorders • Epilepsy