A Study of Weekly Subcutaneous Injections of SER-214 in Subjects With Parkinson's Disease (PD), to Determine the Safety, Tolerability and Pharmacokinetic (PK) Profile of SER-214

Clinical evidence suggests that dopamine agonists should be considered as an initial or early
symptomatic therapy for PD. Current information indicates that the early use of long-acting
dopaminergic agonists may protect against the development of motor complications by
stimulating dopamine receptors in a non-pulsatile manner and by delaying the introduction of
levodopa. In pre-clinical primate studies, L-dopa (short-acting, pulsatile) and dopaminergic
agonists (long-acting; non pulsatile) provide comparable clinical benefit but with agonists
inducing significantly less dyskinesia.

Chronic L-dopa treated animals develop gene changes that are associated with abnormal
neuronal firing patterns and dyskinesias which are not seen with long-acting dopamine
agonists. Based on pre-clinical and clinical study results, treatment of Parkinson's patients
with long-acting levodopa or dopamine agonists should provide symptomatic benefit, and
significantly delay the onset of motor complications. This can be accomplished with duodopa
or continuous sc apomorphine but these treatments are associated with significant side
effects. To date, no practical method of providing continuous drug delivery using a
dopaminergic agent for therapy of patients with early PD to prevent the development of motor
complications has been advanced through clinical trials.

SER-214 is being developed as a weekly sc injection that provides prompt onset of
dopaminergic stimulation. Continuous levels of released rotigotine within the therapeutic
window for relief of motor fluctuations have been observed in MPTP-treated cynomolgus
macaques. PK determinations in normal monkeys for up to 13 weeks of treatment show that
weekly injections of SER-214 provide continuous drug delivery of released plasma rotigotine
within a predictable therapeutic range.

Inclusion Criteria:

1. Female or male subjects 40-80 years of age inclusive

2. A diagnosis of idiopathic Parkinson's disease (PD) consistent with UK brain bank
criteria

3. De novo PD patients and those on a stable regimen of anti-Parkinson's drugs for at
least 4weeks prior to screening including anticholingerics, amantadine, MAO-B
inhibitors, COMT inhibitors or levodopa, but not dopamine agonists

4. Free of clinically significant motor complications as determined by the investigator

5. Ability to complete up to four weeks of dosing once per week with two weeks of
terminal "wash-out" PK

6. Ability to return to the clinic for blood sampling, clinical and laboratory assessment
on scheduled days, based upon cohort

7. Mini Mental State Exam (MMSE) > 26

8. Women of child-bearing potential (WOCBP) must use a reliable method of contraception
(e.g., oral contraceptive or long-term injectable or implantable hormonal
contraceptive, double-barrier methods [such as condom plus diaphragm, condom plus
spermicidal foam, condom plus sponge], or intra-uterine devices), and must have a
negative serum pregnancy test at Screening and negative urine pregnancy test at
baseline

9. Willing and able to comply with the study requirements including follow-up

10. Provide written informed consent

11. Cognitively intact sufficient to understand and provide informed consent

12. Approved by a central Eligibility Monitoring Committee (EMC) confirmed by EMC
signature on the Enrollment Authorization Form (EAF)

Exclusion Criteria:

1. Subject has previously participated in this study.

2. Myocardial infarction within the past six months from screening

3. Ischemic stroke or transient ischemic event within the past two years from screening

4. Known sensitivity to dopamine agonists including nausea/vomiting, orthostatic
hypotension, excessive sleep or impulse control disorder

5. Any major organ disease that substantially impairs life expectancy

6. History of cancer, other than basal cell carcinoma, within the past 10 years or
subjects with any laboratory or physical exam or diagnostic procedure finding
suggestive of current malignancy

7. Subjects who are known to be immunosuppressed or are receiving chronic treatment with
immunosuppressive drugs

8. Subject with an atypical or secondary Parkinsonian (e.g., due to drugs, metabolic
neurogenetic disorders, encephalitis, cerebrovascular disease or degenerative disease)

9. Any clinically significant medical, surgical, or psychiatric condition, laboratory
value, or concomitant medication which, in the opinion of the Investigator, makes the
subject unsuitable for study entry or potentially unable to complete all aspects of
the study.

10. Subject has moderate renal impairment (creatine > 2.5)

11. Subject has moderate (Child-Pugh categorization B, score 7-9) or severe (Child-Pugh
categorization C, score 10-15) hepatic impairment.

12. Subject has a lifetime history of suicide attempt (including an active attempt,
interrupted attempt or aborted attempt), or has suicidal ideation in the past 6 months
as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the
Columbia-Suicide Severity Rating Scale (CSSRS) at Screening

13. Subject has known hypersensitivity to rotigotine or to any components or excipients of
the study drug

14. Subject has a history of psychosis or hallucinations within the previous 12 months

15. Subject has received an investigational drug within 30 days of screening or is
currently participating in an investigational drug or investigational device trial

16. Subject, who, for any reason, is judged by the Investigator to be inappropriate for
this study, including a subject who is unable to communicate or cooperate with the
Investigator or who has/had a clinically significant illness or abnormal physical
examination that may compromise safety of the subject during the trial or affect
ability of the subject to adhere to study procedures