TPN-101 in Aicardi-Goutières Syndrome (AGS)

Patients must meet all of the following criteria:

Inclusion

1. Male or female participants of the following ages:

2. Cohort 1: Adults (≥ 18 years of age)

3. Cohort 2: Adolescents (12 to 17 years of age)

4. Cohort 3: Children 5 to 11 years of age

5. Cohort 4: Children 1 to < 5 years of age and >= 10 kg in weight

6. Molecular diagnosis of AGS due to biallelic mutations in 1 of the following 5 genes:TREX1, RNASEH2A, RNASEH2B, RNASEH2C, or SAMHD1, or due to a recognized dominantmutation in TREX1

7. IFN score in peripheral blood > 2 standard deviations above the mean score ofhealthy controls measured on 3 occasions, approximately 2 weeks apart, during the 6-week Screening Period.

8. Clinical syndrome consistent with AGS diagnosis based on clinical, CSF, andradiological findings. The following are examples of such findings (none of theseare required for inclusion):

9. Early onset encephalopathy with psychomotor delay, spasticity, extrapyramidalsigns, and microcephaly, the latter appearing in the first year of life

10. Calcifications particularly visible at basal ganglia level (putamen, pallidus,and thalamus), but also extending to the periventricular white matter

11. Cerebral white matter abnormalities

12. Cerebral atrophy

13. Important systemic symptoms in the early stages of the disease includingirritability, feeding and sleeping difficulties, unexplained fevers, and theappearance of chilblain-like skin lesions on the fingers, toes, and ears

14. Has a reliable caregiver to accompany the patient to all study visits. Caregivermust have frequent contact with patient and be willing to monitor the patient'shealth and concomitant medications throughout the study

Exclusion Criteria:

1. Mutation in IFIH1, ADAR1, LSM11, or RNU7-1.

2. Pre-/perinatal infections, in particular the TORCH complex (toxoplasmosis, rubella,cytomegalovirus, herpes simplex virus)

3. Presence of other significant neurological disorders; brain tumor or otherspace-occupying lesion; history of severe head injury

4. Clinically significant intercurrent illness, medical condition, physical orlaboratory abnormality

5. Autoimmune disease requiring treatment or management (quiescent rheumatoidarthritis, psoriasis, treated autoimmune thyroiditis, or controlled Type 1 diabetesare acceptable)

6. History of human immunodeficiency virus (HIV), hepatitis B, or any active infectionduring Screening

7. History of cancer within 5 years of Screening, with the exception of fully treatednon-melanoma skin cancers

8. Receipt of an experimental agent within 30 days or 5 half-lives prior to Screening,whichever is longer

9. Prior treatment with an immunomodulator other than a JAK inhibitor within 6 monthsof Screening; patients taking JAK inhibitors for AGS must have been on a stable dosefor one month prior to Screening

10. Current treatment with a nucleoside reverse transcriptase inhibitor (NRTI) or otherantiviral drug

11. Receipt of systemic corticosteroids within 30 days prior to Screening

12. Any vaccination within 30 days prior to Screening