Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy

Inclusion Criteria:

• Diagnosed with STXBP1-E or SLC6A1-NDD; confirmed by laboratory report (i.e., agenetic test with a pathogenic or likely pathogenic mutation of STXBP1 or SLC6A1-NDDand a clinical picture consistent with the disorder, as determined by theInvestigator). Patients with the appropriate clinical picture, a de novo variant ofuncertain significance in STXBP1 or SLC6A1-NDD will also be eligible for enrollment,at the discretion of the Investigator.

• Is between 2 months and 17 years of age, inclusive.

• For children with STXBP1-E, the child must have had at least one seizure in the past 30 days prior to enrollment. If there is high demand for the study and we haveseveral subjects to choose, we will prefer to enroll children with a high number ofseizures in the past month.

• For SLC6A1-NDD, seizures occur later in the course (typically middle of 1st decade)and so seizures will not be an entry criteria.

• Is in general good health, aside from neurological consequences of STXBP1-E orSLC6A1-NDD, as determined by having no concurrent medical illness, in the opinion ofthe site investigator, that places the subject at increased risk of adverse drugreactions or that will interfere with study follow-up.

• Has normal laboratory test results (≤ 1.5 × upper limit of normal [ULN]) for serumaminotransferase (aspartate aminotransferas [AST] and alanine aminotransferase [ALT]) concentrations and ammonia at Screening.

• Has normal renal function, with estimated glomerular filtration rate > 90mL/minute/1.73 m2 at Screening (using the Chronic Kidney Disease EpidemiologyCollaboration equation).

• Has a platelet count > 150 × 103/μL at Screening.

• Has a QT interval corrected with Fridericia's formula (QTcF) < 450 msec on theScreening EKG.

• Parent or guardian is able to comprehend and willing to sign an informed consentform (ICF).

Exclusion Criteria:

• Has participated in another investigational study within 30 days or 5 half-lives ofthe test drug's biologic activity (whichever is longer) before the first study drugdose.

• Has a QT interval corrected with Fridericia's formula (QTcF) ≥ 450 msec on theScreening EKG.

• Has an active medical illness that would preclude participation in the study (asdetermined by the Investigator).

• Has a clinical laboratory evaluation outside of the test laboratory reference range,unless deemed not clinically significant by the Investigator and the Sponsor.

• Is unable to comply with the study protocol.

• Has poor venous access and/or cannot tolerate venipuncture.

• Is pregnant

• Is a female of child-bearing age (12 years old or older) and known to be sexuallyactive (for example, as determined through a confidential HEADDSSS history), and nottaking medication for contraception. This will be assessed confidentially as pergood general pediatrics practice

• Known hypersensitivity to phenylbutyrate. Signs of hypersensitivity includewheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash.

• Taking alfentanil, quinidine, cyclosporine, or probenecid (known interactions withphenylbutyrate). For subjects who had taken any of these medications in the past,the last dose must have been taken at least 1 week prior to enrollment into thestudy.

• Inborn errors of beta oxidation.

• Pancreatic insufficiency or intestinal malabsorption

• Diagnosed with a monogenic developmental and epileptic encephalopathy; confirmed bylaboratory report (i.e., a genetic test with a pathogenic or likely pathogenicmutation of a monogenic developmental and epileptic encephalopathy and a clinicalpicture consistent with the disorder, as determined by the Investigator). Childrenwith the appropriate clinical picture, a de novo variant of uncertain significancein a monogenic developmental and epileptic encephalopathy will also be eligible forenrollment, at the discretion of the Investigator. If the mutant is classified asdefinitively non-pathogenic, we would not enroll the child. "Appropriate clinicalpicture" is at the discretion of the Investigator.

• Is between 0 months and 15 years of age, inclusive.

• The child must have had at least one seizure in the past 30 days prior toenrollment. (If there is high demand for the study and we have several subjects tochoose, we will prefer to enroll children with a high number of seizures in the pastmonth.)

• Is in general good health, aside from neurological consequences of their monogenicdevelopmental and epileptic encephalopathy, as determined by having no concurrentmedical illness, in the opinion of the site investigator, that places the subject atincreased risk of adverse drug reactions or that will interfere with studyfollow-up.

• Has normal laboratory test results (≤ 1.5 × upper limit of normal [ULN]) for serumaminotransferase (aspartate aminotransferas [AST] and alanine aminotransferase [ALT]) concentrations and ammonia.

• Has normal renal function, with estimated glomerular filtration rate > 90mL/minute/1.73 m2 at Screening (using the Chronic Kidney Disease EpidemiologyCollaboration equation).

• Has a platelet count > 150 × 103/μL at Screening.

• Has a QT interval corrected with Fridericia's formula (QTcF) < 450 msec on theScreening EKG.

• Parent or guardian is able to comprehend and willing to sign an informed consentform (ICF).

Exclusion Criteria:

• Has participated in another investigational study within 30 days or 5 half-lives ofthe test drug's biologic activity (whichever is longer) before the first study drugdose.

• Has a QT interval corrected with Fridericia's formula (QTcF) ≥ 450 msec on theScreening EKG.

• Has an active medical illness that would preclude participation in the study (asdetermined by the Investigator).

• Has a clinical laboratory evaluation outside of the test laboratory reference range,unless deemed not clinically significant by the Investigator and the Sponsor.

• Is unable to comply with the study protocol.

• Has poor venous access and/or cannot tolerate venipuncture.

• Is pregnant

• Is a female of child-bearing age (12 years old or older) and known to be sexuallyactive (for example, as determined through a confidential HEADDSSS history), and nottaking medication for contraception. This will be assessed confidentially as pergood general pediatrics practice

• Known hypersensitivity to phenylbutyrate. Signs of hypersensitivity includewheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash.

• Taking alfentanil, quinidine, cyclosporine, or probenecid (known interactions withphenylbutyrate). For subjects who had taken any of these medications in the past,the last dose must have been taken at least 1 week prior to enrollment into thestudy.

• Inborn errors of beta oxidation.

• Pancreatic insufficiency or intestinal malabsorption