This study will evaluate the safety and tolerability (maximum tolerated dose (MTD) within the specified dosing range) of single intravenous (IV) infusion of C2N-8E12 in patients with progressive supranuclear palsy (PSP).

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.