Inclusion Criteria:

1. Diagnosis of unilateral refractory MTLE
2. History of seizures with on average ≥ 2 focal onset impaired awareness seizures in the 3 months prior to screening.
3. On a stable type and dose regimen of up to a maximum of 4 approved Anti Seizure Drugs for at least 6 months prior to screening.
4. Confirmed unilateral hippocampal pathology and concordant unilateral seizure focus
5. No evidence of focal neurocognitive dysfunction, inconsistent with disease pathology- related MRI and (18F)FDG-PET findings.
6. Women of childbearing potential (WOCBP) and fertile male subjects must be willing and able to use highly effective methods of birth control consistently and correctly throughout the study and for at least 1 year following AMT-260 administration.
7. For WOCBP only: Negative pregnancy test.

Exclusion Criteria:

1. Implanted devices that would contraindicate MRI; MRI-compatible devices must be implanted ≥3 months prior to Screening (vagus nerve stimulation devices will be up to discretion of the Investigator).
2. Any other contraindications for generalized anesthesia or surgery.
3. Medications that could confound clinical (e.g., antipsychotic medication and anti-viral therapy) and laboratory evaluations or could affect a patient's safety or their ability to undergo the neurosurgical procedure or comply with the procedures and study visit schedule.
4. Any psychogenic nonepileptic seizures within the last year.
5. Any seizures with contralateral or extra-temporal ictal onset on EEG.
6. Previous major disease-unrelated neurosurgical intervention due to intracranial tumor, trauma, or bleeding and/or history of previous intracranial surgery for treatment of epileptic seizures.
7. Magnetic resonance imaging evidence of epileptogenic, extra-temporal lesions, or dual temporal lobe pathology.

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

Eligibility last updated 03/11/2025. Questions regarding updates should be directed to the study team contact.