A Study of PBFT02 in Participants With FTD and Mutations in the Granulin Precursor (GRN) or C9ORF72 Genes

Inclusion Criteria:

1. Documented to be a pathogenic carrier of GRN or C9orf72 mutation

2. Clinical diagnosis of frontotemporal dementia

3. Have a reliable informant / caregiver (and back-up informant / caregiver) whopersonally speaks with or sees the subject at least weekly

4. Living in the community (i.e., not in a nursing home); assisted living may bepermitted at the discretion of the investigator

Exclusion Criteria:

1. Classification of the GRN mutation as "not pathogenic," "likely benign variant," "benign variant," or "pathogenic nature unclear" (FTD- GRN Cohorts 1-3) or C9orf72HRE length ≤ 30 (FTD-C9orf72 Cohorts 4-5).

2. Previous treatment with any gene therapy. Any other therapies with the potential toalter PGRN levels must be washed out for at least 5 half-lives prior to entry intothis study

3. Homozygous GRN mutation carrier (FTD-GRN Cohorts 1-3) or homozygous C9orf72 mutationcarrier (FTD-C9orf72 Cohorts 4-5).

4. Rosen-modified Hachinski Ischemic Scale score > 7

5. Known presence of a structural brain lesion (eg, tumor, cortical infarct) that couldreasonably explain symptoms in a symptomatic subject

6. Known presence of an AD-causing mutation in PSEN1, PSEN2 or APP based on genetictesting history (if performed)

7. Previous history of Korsakoff encephalopathy, severe alcohol or substance dependence (within 5 years of onset of dementia), except where onset of increased alcoholconsumption occurs at the time of FTD disease onset

8. History of untreated vitamin B12 deficiency

9. Presence of untreated hypothyroidism (thyroid stimulating hormone [TSH] > ULN andfree T4 < LLN)

10. eGFR ≤ 30 ml/min (as calculated using the CKD-EPI equation)

11. Alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 2 × ULN, ortotal bilirubin > ULN)

12. Respiratory failure that requires supplemental oxygen, tracheostomy, or reliance onnon-invasive ventilation for >2 hours during waking hours

13. Inability to provide full consent or the lack of a legally authorized caregiver withadequate contact who can provide consent

14. Any contraindication to MRI or lumbar puncture (LP) (eg, local infection, history ofthrombocytopenia, coagulopathy)

15. Any contraindication to the ICM administration procedure

16. Medical conditions or laboratory or vital sign abnormalities that would increaserisk of complications from ICM injection, anesthesia, LP, and/or MRI (e.g., fever,hypoxia, tachycardia, or evidence of active infection)

17. Immunocompromised status

18. Peripheral axonal sensory neuropathy

19. Receipt of a vaccine within 14 days of dosing

20. A positive test result for human immunodeficiency virus (HIV), human T cell leukemiavirus (HTLV) type 1 or type 2, or Hepatitis B or C; a Mycobacterium tuberculosispositive test within 1 year of or determined at screening

21. Malignant neoplasia (except localized skin cancer) or a documented history ofhereditary cancer syndrome

22. Any concurrent disease that, in the opinion of the investigator, may cause cognitiveimpairment unrelated to GRN or C9orf72 mutations, including other causes ofdementia, neurosyphilis, hydrocephalus, stroke, small vessel ischemic disease,uncontrolled hypothyroidism, or vitamin deficiency

23. Current or recent history of clinically significant suicidal ideation within thepast 6 months

24. For women of childbearing potential, a positive serum pregnancy test at thescreening visit, a positive serum result on Day 1 prior to administration of theinvestigational product, or unwillingness to have additional pregnancy tests duringthe study. Women of childbearing potential must use a highly effective method ofbirth control or engage in abstinence until 90 days postdose

25. Women who are breastfeeding

26. For sexually active men, unwillingness to use a medically accepted method ofdouble-barrier contraception (such as a condom/diaphragm used with spermicide) orengage in abstinence from the date of screening until 90 days postdose

27. Any condition (eg, history of any disease, evidence of any current disease, anyfinding upon physical examination, or any laboratory abnormality) that, in theopinion of the investigator, would put the subject at undue risk or would interferewith evaluation of the investigational product or interpretation of subject safetyor study results

28. Any acute illness requiring hospitalization within 30 days of enrollment

29. Failure to meet the protocol-specified coagulation test criteria:

• Platelet count > 100,000 per uL

• INR < 1.5

• aPTT < 40 seconds

30. Use of anticoagulants in the 2 weeks prior to screening, or anticipated use ofanticoagulants during the study. Antiplatelet therapies may be acceptable

31. Hypersensitivity or contraindications to corticosteroid use

32. Known or suspected intolerance or hypersensitivity to PBFT02 or any of itsingredients or to closely related compounds Additional Criteria for FTD-C9orf72 (Cohorts 4-5) ONLY: Presence of concurrent ALSis permitted as long as the following criteria are NOT met:

33. ALSFRS-R < 35 at screening.

34. ALSFRS-R score declining at a rate > 0.4 unit/month from diagnosis to the screeningassessment.

35. SVC < 75% of predicted normal adjusted for sex, age, and height (from the sittingposition).

36. Bulbar-onset ALS.

37. Current or anticipated need, in the opinion of the Investigator, of a diaphragmpacing system (DPS) during the study period.

38. If taking riluzole or edaravone, participant's dose has not been stable for ≥ 30days prior to Day 1 and/or dose adjustments are anticipated before the Day 60 studyvisit.