Safety and Tolerability Study of KNS-760704 in Amyotrophic Lateral Sclerosis (ALS)

This is a double-blind, randomized, placebo-controlled study evaluating the safety and
efficacy of KNS-760704 compared to placebo. The study will be conducted in 2 parts.

In Part 1, approximately 80 eligible patients will be randomized to 1 of 4 treatment groups
for 12 weeks of treatment: placebo; low-dose; mid-dose; or high-dose KNS-760704. Participants
meeting eligibility requirements will be enrolled at approximately 20 centers in the U.S. In
addition to the visit to determine eligibility and the first visit to take study drug,
participants will be required to make 5 additional research clinic visits in Part 1.

Participants who complete all 12 weeks of Part 1 will be eligible for randomization to Part
2. The duration of Part 2 of the study is 76 weeks. Subjects will receive 1 of 2 active
treatment groups for 72 weeks (low-dose or high-dose KNS-760704) and placebo for the
remaining 4-week period in Part 2. Participants will not be told when the 4 weeks of placebo
treatment will be given. During Part 2, participants will be required to make 12 research
clinic visits, including the baseline visit.

Inclusion Criteria:

- Patients with diagnosis of familial or sporadic ALS, defined as meeting the possible,
laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS
according to the World Federation of Neurology El Escorial criteria

- Patients with ALS symptom onset < 24 months from randomization

- Patients with upright VC > 65% of predicted for age, height, and gender

Exclusion Criteria:

- Patients in whom causes of neuromuscular weakness other than ALS have not been
excluded

- Patients without clinical evidence of upper motor neuron dysfunction

- Patients with clinically suspected ALS according to the World Federation of Neurology
El Escorial criteria

- Patients with prior exposure to KNS-760704 or the R(+) enantiomer of pramipexole
(i.e., R(+)-pramipexole)

- Patients taking other investigational agents (including lithium) within 30 days of
randomization or during the study