A Phase 1 Study to Evaluate the Safety, Tolerability, and Immunogenicity of UBITh® PD Immunotherapeutic Vaccine (UB-312) in Healthy Participants and Participants with Parkinson*s Disease

Participants may be included in the clinical trial only if they meet all of the
following criteria:
1. Written informed consent is signed and dated by the participant
2. Male or female aged 40 to 85 years old, inclusive at screening
3. Participants must have a body mass index (BMI) between 18 and 32 kg/m2,
inclusive at screening, and with a minimum weight of 50 kg
4. Expected to be able to undergo all study procedures
5. Women must be of non-childbearing potential (postmenopausal for at least 12
months prior to screening or surgically sterile documented) or if of
child-bearing potential, must be using medically acceptable contraceptive
measures throughout the duration of the study and for at least 56 weeks after
their last dose of study treatment.
6. Male participants and their partners of childbearing potential must commit
to the use of medically acceptable contraception for the study duration and for
at least 90 days after their last dose of study treatment. Men must refrain
from donating sperm during this same period. The female partners should be
asked to use a contraception method that is medically acceptable, and these
contraceptive measures should be used throughout the duration of the study and
for at least 90 days after their last dose of study treatment.

For Part B only:
7. A diagnosis of PD, confirmed by a neurologist
8. Hoehn & Yahr Stage <= III at Screening
9. Stable treatment of permitted antiparkinsonian medications from 30 days
prior to first study drug administration or 60 days for MAO-B inhibitors, and
expected to remain stable throughout the study unless required adjustment or
initiation per the investigator*s judgement, except for short-acting rescue
medications, which are allowed (see Section 7.1.1 for the list of permitted
medications).
10. For participants that will need a DaTscan: must be willing and able from a
medical standpoint to withhold medication that might interfere with dopamine
transporter SPECT imaging (Neuroleptics, metoclopramide, alpha methyldopa,
methylphenidate, reserpine, or amphetamine derivative) for at least 5
half-lives prior to screening DaTscan imaging

Participants will be excluded from the clinical trial for any of the following
reasons:
1. Clinically significant abnormalities, as judged by the investigator, in test
results (including hepatic and renal panels, complete blood count, chemistry
panel, urinalysis and imaging). In the case of uncertain or questionable
results, tests performed during screening may be repeated before randomization
to confirm eligibility or judged to be clinically irrelevant.
2. History of medical, neurological or psychiatric conditions, which in the
opinion of the investigator may compromise participant*s safety or scientific
value of the study, posing an unacceptable risk to the participant or interfere
with the participant's ability to comply with study procedures or abide by
study restrictions.
3. History of Substance Use Disorder within the past 2 years before screening
(Diagnostic and Statistical Manual of Mental Disorders-5 [DSM-V] criteria) or
confirmed drugs of abuse or alcohol at Screening. Positive urine drug screen
for prescribed medication is allowed at the discretion of the PI.
4. Acute or chronic infection with human immunodeficiency virus (HIV),
hepatitis C virus (HCV) or hepatitis B virus (HBV) at Screening, or any
confirmed or suspected immunosuppressive or immunodeficient condition,
including HIV-1, HIV-2 infection, cytotoxic therapy in the previous 5 years.
5. History or evidence of an autoimmune disorder (e.g. Sjogren*s syndrome,
systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis etc.),
which in the opinion of the investigator may compromise patient*s safety or
scientific value of the study, posing an unacceptable risk to the participant.
6. Level of anti-cyclic citrullinated peptide (anti-CCP) above upper limit of
normal at Screening.
7. Positive antinuclear antibodies (ANA) except judged to be clinically
irrelevant by the investigator.
8. History of anergy.
9. Any confirmed significant allergic reactions (urticaria or anaphylaxis)
against any drug or vaccine, or multiple drug allergies (non-active hay fever
is acceptable).
10. History of cancer (except basal cell and in situ squamous cell carcinomas
of the skin that have been excised and resolved) which has not been in
remission for at least 5 years prior to Screening.
11. Clinically significant abnormal ECG or blood pressure measurement at
screening or before the first dosing, as judged by the Investigator.
12. Contraindication to MRI, including but not limited to the presence of metal
devices or implants (e.g. pacemaker, vascular- or heart-valves, stents, clips),
metal deposited in the body (e.g. bullets or shells), or metal grains in the
eyes.
13. Receipt of an investigational product or device, or participation in a drug
research study within a period of 90 days before baseline at V1.
14. Participated/participating in any clinical trial with monoclonal antibodies
or vaccines directed against aSyn.
15. Underwent any procedures/studies involving intracranial surgery,
implantation of a device into the brain or stem cell study.
16. Pregnancy confirmed by a positive pregnancy test.
17. Participants who are currently breastfeeding, intend to breastfeed during
the study or are planning to get pregnant and breastfeed within 56 weeks after
last injection.
18. Use of any prohibited medications within 30 days or 5 half-lives (whichever
is greater) prior to Screening till end of treatment period; administration of
chronic (defined as more than 14 days) immunosuppressants or other
immune-modifying drugs within 6 months of Screening (including prednisone or
equivalent, greater than or equal to 0.5 mg/kg/day; except intranasal,
inhalation, and topical steroids which are allowed).
19. Vaccination within 30 days prior to Screening till end of treatment period
unless approved by the Sponsor or its designees.
20. Any contraindication to undergoing a lumbar puncture (e.g., anatomical
variations or local skin infection), as judged by the investigator.
21. Loss or donation of blood over 500 mL within three months prior to
Screening or intention to donate blood or blood products for transfusion during
the study and for 13 months after their last dose.
22. Received blood and/or blood derivatives treatment within 3 months prior to
Screening.


For Part B only:
23. Positive test result for SARS-CoV-2 infection (if test performed according
to local guidelines) in the 2 weeks prior to first dose.
24. Other known or suspected cause of Parkinsonism other than idiopathic PD,
including but not limited to, progressive supranuclear gaze palsy, drug- or
toxin-induced parkinsonism, essential tremor, primary dystonia, vascular
parkinsonism.
25. Clinically significant neurological disease other than PD, such as
multi-infarct dementia, Huntington's disease, normal-pressure hydrocephalus,
brain tumor, progressive supranuclear palsy, multiple sclerosis, or history of
significant head trauma followed by persistent neurologic defaults.
26. History or evidence at Screening of PD-related freezing episodes, falls, or
clinically significant orthostatic hypotension, that could interfere with, or
for which the treatment might interfere with, the conduct of the study, or that
would pose an unacceptable risk to the participant in the opinion of the
investigator.
27. Dopamine transporter single-photon emission computerized tomography scan
(DaTscan) inconsistent with dopamine transporter deficit.
28. For participants that will need a DaTscan: current or recent (< 12 months)
participation in studies or procedures involving exposure to ionizing radiation
or radioactively labelled drugs/substances.