Safety, Tolerability, and Pharmacokinetics of C2N-8E12 in Subjects With Progressive Supranuclear Palsy

This study evaluates the safety, tolerability, pharmacokinetics, and maximum tolerated dose
(within dosing range) of intravenous (IV) infusion of C2N-8E12 in 32 patients with
progressive supranuclear palsy (PSP). Four sequential cohorts will receive increasing single
doses of either C2N-8E12 or placebo. Out of every 4 patients enrolled 3 patients will receive
drug and 1 will receive placebo. Study participants will be followed for a minimum of 2
months post-treatment to monitor for the safety, tolerability, pharmacokinetics, and
immunogenicity of C2N-8E12.

Key Inclusion Criteria:

- Meets NINDS-SPSP possible or probable criteria as modified for NNIPPS and AL-108-231
clinical trials

- Brain MRI at Screening is consistent with PSP;

- Stable medications for Parkinsonism for at least 2 months prior to Screening;

- Agree to use protocol specified methods of contraception.

Key Exclusion Criteria:

- Signs of a progressive neurological disorder that better meets the criteria for types
of neurological disorders other than PSP;

- Currently on any other biologic or immunomodulatory therapy;

- Subjects that reside at a skilled nursing or dementia care facility;

- Diagnosis of any other significant unrelated neurological or psychiatric disorders
that could account for cognitive deficits;

- Untreated major depression at baseline evaluation, based on clinical judgment and
results in geriatric depression scale;

- Unable to tolerate MRI scan at Screening or any other contraindication to MRI;

- Any contraindication to or unable to tolerate lumbar puncture at Screening, including
use of anti-coagulant medications.