Inclusion Criteria:

1. Male or Female, age ≥18 to 65
2. Focal seizures, clinically defined as Temporal Lobe Epilepsy (TLE)
3. Has failed to achieve seizure control despite adequate trials of at least 2 ASDs at appropriate doses.
4. Currently on stable doses (at least 1 month) of approved ASDs
5. Single seizure focus confirmed as within one temporal lobe by all of the following:
   1. Ictal Electroencephalogram (EEG) recording of ≥1 habitual seizures showing antero-temporal onset. NOTE: for subjects who have had intracranial EEG studies, the seizure onset must be within the hippocampus.
   2. Magnetic Resonance Imaging (MRI) scan findings of ipsilateral hippocampal sclerosis
   3. Seizure semiology (for all seizures) consistent with a single focus.
6. For subjects entering Stage 1, seizure focus is in the non-dominant hemisphere, or in the dominant hemisphere with a test of verbal memory (one of: Rey Auditory Verbal Learning Test [RAVLT, delayed recall subscale], California Verbal Learning Test, Logical Memory subscale of the Wechsler Memory Test, or equivalent test as approved by the Sponsor) assessed within one year of screening, or at the screening visit (RAVLT), that is at least 1.0 standard deviation below the population mean. The test item corresponding to delayed free recall shall be used.
7. Seizure frequency averages ≥2 per 28-day period over the 6 months prior to screening. Historical seizure frequency includes all focal seizures with an objective manifestation and also focal aware seizures, which are stereotypic and confirmed as ictal by video-EEG recording.
   1. Stage 1: Baseline seizure frequency by history
   2. Stage 2: Baseline seizure frequency by review of written subject seizure diaries or by review of clinic records containing at least monthly assessments of seizure frequency
8. Considered (by Investigator) to be a candidate for temporal lobectomy (TL) or Laser Interstitial Thermal Therapy (LITT) following evaluation at a qualified epilepsy surgery program (National Association of Epilepsy Centers [NAEC] Level 4)
9. Subjects of childbearing potential will use highly effective contraception (defined as documented failure rate ≤1%) while taking immunosuppressants. For females using enzyme-inducing ASDs (EI-ASD), hormonal contraception will not be considered as effective (EI-ASD determined from US Prescribing Information).
10. No prior history of craniotomy (may have had prior stereotactic procedures, subdural grid, or other EEG procedures), and no prior temporal lobe resection or ablation.
11. Either 10th grade education or equivalent or full-scale intelligence quotient (IQ) ≥70, assessed either within 12 months of screening or during the screening period.
12. Able to converse and read in English or Spanish. Able to participate in required study procedures and provide signed informed consent

Exclusion Criteria: 

1. Epilepsy due to other and/or progressive neurologic disease.
2. Significant other medical conditions which would impair safe participation in study-specified procedures, including imaging (magnetic resonance imaging contrast [MRI-contrast]), surgery, and immunosuppression. These include but are not limited to: moderate hepatic impairment (either alanine transaminase >2x or aspartate transaminase >2x Upper Limit of Normal [ULN]), creatinine clearance <60 mL/min (by Cockraft-Galt), platelets <80% of lower limit of normal [LLN], international normalized ratio [INR] >1.3.
3. Primary or secondary immunodeficiency
4. Suicide attempts in the past year, assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) at screening
5. Severe psychiatric disorders
6. Chronic indwelling intracranial device (shunt, neurostimulator, etc.). Transient use of diagnostic stereotactic EEG electrodes allowed (responsive neurostimulation to be discussed with the Sponsor)
7. MRI indicating potential malignant lesion (low-grade glioma of any type is excluded) in any location or non-malignant potentially epileptogenic lesion outside the hippocampus. Small (<2 cm) non-invasive meningioma, remote from the affected temporal lobe, is not exclusionary.
8. Pregnancy or currently breastfeeding
9. Prior exposure to NRTX-1001 product
10. Prior exposure to gene or cell therapy treatments (of any kind)
11. Participation in another investigational trial within the past 30 days, excepting non-interventional studies
12. Detection of clinically relevant donor-specific allo-Human Leukocyte Antigen (HLA) reactive antibodies
13. Evidence of active cytomegalovirus (CMV) infection (symptomatic or asymptomatic as demonstrated by positive plasma polymerase chain reaction [PCR] or Nucleic Acid Amplification Test [NAAT] and immunoglobulin M [IgM] tests). Subjects may re-screen after infection is resolved.
14. Clinical diagnosis of autoimmune epilepsy, supported by the presence of any serum antibodies detected on a standard test panel (Labcorp Autoimmune Epilepsy Evaluation Profile test 505490, or Mayo Clinic Laboratories Epilepsy, Autoimmune/Paraneoplastic Evaluation test EPS2, or similar with approval from Sponsor), either within 3 years of screening or during the baseline period.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 06/07/2024. Questions regarding updates should be directed to the study team contact.