This is a Phase 2a study to assess the safety and tolerability of TPN-101 patients with PSP.

This is a Phase 2a multi-center, randomized, double-blind, placebo-controlled parallel-group, 4-arm study with an open-label treatment phase in patients with PSP. This study includes a 6-week Screening Period, a 24-week Double-blind Treatment Period, a 24-week Open label Treatment Period, and a Follow-up Visit 4 weeks post treatment.

Inclusion Criteria:

1. Clinical diagnosis of probable progressive supranuclear palsy (PSP)
2. Presence of PSP symptoms for less than 5 years
3. Has a reliable caregiver/informant to accompany the patient to all study visits.
4. Score ≥ 18 on the Mini Mental State Exam (MMSE) at Screening
5. Patient must reside outside a skilled nursing facility or dementia care facility at the time of Screening, and admission to such a facility must not be planned. Residence in an assisted living facility is allowed

Exclusion Criteria:

Patients must not meet any of the following criteria:

1. Presence of other significant neurological or psychiatric disorders
2. History of clinically significant brain abnormality
3. Presence of cerebellar ataxia, choreoathetosis, early symptomatic autonomic dysfunction, or moderate to severe resting tremor, responsive to levodopa
4. Known history of serum or plasma progranulin level less than one standard deviation below the normal patient mean
5. Known presence of disease-associated mutation in TARDBP, GRN, CHMPB2, or VCP genes; or any other frontotemporal lobar degeneration causative genes not associated with underlying tau pathology
6. History of clinically significant hematological, endocrine, cardiovascular, renal, hepatic, or gastrointestinal disease