Phase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)

Inclusion Criteria:

• Men or women aged 30 to 85 years (inclusive), at the time of informed consent.

• Body weight range of ≥40 kg (88 lbs) to ≤110 kg (242 lb) and a BMI of 18 to 34kg/m2.

• Has symptomatic frontotemporal dementia (FTD), including mild behavioral, cognitive,motor or language impairment per Investigator's assessment (behavioral-variant FTD,primary progressive aphasia-FTD, FTD with corticobasal syndrome, or a combination ofsyndromes are allowed for enrollment).

• Score ≥0.5 and ≤15 on CDR plus NACC FTLD sum of boxes.

• Stable use of background medications at least 8 weeks prior to LY3884963 dosing.

• Carrier of a pathogenic progranulin gene (GRN) mutation.

• Negative screening test for Mycobacterium tuberculosis (MTB) or documented negativeMTB test within 1year prior to screening.

• Age- and gender-appropriate cancer screenings are up-to-date and completed.

• Patient and/or patient's legally authorized representative has the ability tounderstand the purpose and risks of the study, and provide written informed consentand authorization to use protected health information.

• Patient has a reliable study partner/informant (e.g. family member, friend) willingand able to participate in the study as a source of information on the patient'shealth status and cognitive and functional abilities.

• Patient is not dependent on a walker or wheelchair.

• Patient is living in the community (i.e. not in nursing home); some levels ofassisted living may be permitted at the discretion of the investigator.

• Pneumococcal pneumonia and shingles vaccines are required within 10 years ofScreening (allowed to be performed during Screening but must be given at least 4weeks prior to initiation of immunosuppressant regimen).

Exclusion Criteria:

• Diagnosis of a significant CNS (central nervous system) disease other thanfrontotemporal dementia (FTD) that may cause FTD symptoms or confound studyobjectives.

• Brain or cervical spine magnetic resonance image (MRI)/MRA imaging showingclinically significant abnormality considered to prevent intracisternal magna (ICM)injection.

• Hypersensitivity or contraindications to corticosteroid, and/or sirolimus use.

• Clinical evidence of peripheral symmetric sensory polyneuropathy (stable sensorymononeuropathies and radiculopathies are not exclusionary).

• Concomitant disease or condition within 6 months of screening that could interferewith, or treatment of which might interfere with, the conduct of the study or thatwould, in the opinion of the investigator, pose an unacceptable safety risk to thepatient or interfere with the patient's ability to comply with study procedures

• Clinically significant laboratory test result abnormalities assessed at screening.

• Participation within 3 months prior to screening in another therapeuticinvestigational drug or device study with purported disease-modifying effects onFTD, unless it can be documented that the patient received placebo only.

• Any type of prior gene or cell therapy.

• Live vaccines in the 4 weeks prior to Screening. NOTE: Pneumococcal vaccine and/orshingles vaccine administration is allowed at least 4 weeks prior to initiation ofimmunosuppressant regimen.

• Use of blood thinners in the 2 weeks prior to screening, or anticipated use of bloodthinners during the study. Antiplatelet therapies are acceptable if the patient ismedically able to temporarily stop 48 hours to 7 days (depending on the antiplateletmedication used) prior to and at least 48 hours after ICM injection and LP. Note:the use of blood thinners as part of prophylaxis or treatment of an emergent VTE oranother AE during the study does not exclude the patient, unless there is a baselinehigh risk of thromboembolic events, and use of blood thinners is highly anticipatedin the opinion of the Investigator.

• Contraindications or intolerance to imaging methods (MRA, MRI, and/or computedtomography [CT]), including claustrophobia and intolerance to contrast agents usedfor MRI, MRA, or CT (including, but not limited to, gadolinium contrast agents andiohexol).

• Contraindications to general anesthesia or deep sedation.

• Positive urine test for drugs of abuse (including opiates, amphetamines, cocaine,barbiturates, and phencyclidine) without prescription at Screening and on Day 1.

Other protocol-defined inclusion/exclusion criteria may apply