A First-in-human Study of S230815 in Pediatric Participants With KCNT1-related Developmental and Epileptic Encephalopathy

Inclusion Criteria:

• Male or female pediatric participants aged 2-12 years old at screening, with agenetically confirmed diagnosis of Developmental Epileptic Encephalopathy (DEE) dueto a pathogenic or likely pathogenic variant in KCNT1 confirmed by central genetictesting.

• Stable dose of other regular medications and/or stable antiseizure interventions (such as ketogenic diet and vagal nerve stimulation).

Exclusion Criteria:

• Other clinical phenotypes associated with pathogenic or likely pathogenic variantsin KCNT1 other than Epilepsy of Infancy with Migrating Focal Seizures or Early-OnsetEpileptic Encephalopathy

• Documented pathogenic or likely pathogenic variants in any other gene known to causeepilepsy identified through prior genetic testing. Variants of uncertainsignificance in other genes known to cause epilepsy may be considered on discussionwith the sponsor.

• Clinically significant medical history or clinical findings on physical examination,other than DEE, that in the judgment of the investigator, make the participantunsuitable for participation in the study and/or completion of the trial procedures,including, but not limited to:

• Clinically significant prior or ongoing medical conditions within 30 days ofthe screening visit, as per investigator judgement.

• Clinically significant abnormality on Electrocardiogram (ECG) at the screeningvisit, as per investigator judgement.

• Clinically significant abnormality on laboratory testing at screening,including, but not limited to:

• Renal insufficiency, which is defined as creatinine clearance < 40 mL/minassessed as estimated glomerular filtration rate (eGFR) using Modification ofDiet in Renal Disease (MDRD) formula

• Hepatic derangement defined as transaminase values more than 3 times the UpperLimit of Normal (ULN) range, or total bilirubin values more than 1.5 times theULN.

• Positive hepatitis B surface antigen test, positive hepatitis C antibody test,positive for human immunodeficiency virus (HIV), as reported by a laboratory testwithin 6 months prior to the screening visit, or on screening bloods.

• Bone, spine, bleeding disorders, or other disorder that exposes the participant torisk of injury or unsuccessful Lumbar puncture (e.g., haemophilia, Von Willebrand'sdisease, liver disease).

• Contraindications to undergoing Magnetic Resonance Imaging (MRI), Lumbar punctureprocedure and Intrathecal administration.

• History of Central Nervous System (CNS) tumors or malignancies, including CNSmetastatic disease.

• Continuous respiratory support, defined as oxygen supplementation or non-invasiveventilation (e.g.: continuous positive airway pressure, bi-level intermittentpositive airway pressure), required during waking hours. This does not includesuctioning; cough assist devices or other devices that may be used regularly toclear airways.

• Invasive ventilation including the presence of a tracheostomy.

• Use of quinidine within 30 days prior to the screening visit.

• Current use or anticipated use of antiplatelet or anticoagulant therapy during thestudy.

• Current or past enrolment in an interventional clinical study in which aninvestigational therapy is/was administered within 30 days (or 5 half-lives of studyagent, whichever is longer) prior to the screening visit.

• Implantable CNS device that may interfere with the ability to administer the studydrug via Lumbar puncture.

• Known hypersensitivity to any oligonucleotide, as demonstrated by a systemicallergic reaction (e.g., changes in pulse, blood pressure, breathing function,etc.), or any other drug that in the opinion of the investigator may preclude studyparticipation.