UB-312 in Patients With Synucleinopathies

Inclusion Criteria:

1. Written informed consent is signed and dated by the participant.

2. Male or female aged 40 to 75 years old, inclusive, at screening.

3. Participants must have a body mass index (BMI) between 18 and 32 kg/m2, inclusive atscreening, 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 monthsbefore screening or surgically sterile) or, if of childbearing potential, must beusing medically acceptable contraceptive measures throughout the study and for atleast 24 weeks after their last dose of study treatment.

6. Male participants and their partners of childbearing potential must commit to usingmedically acceptable contraception for the study duration and at least 90 days aftertheir last dose of study treatment. Men must refrain from donating sperm during thissame period. The female partners should use a medically acceptable contraceptionmethod, and these contraceptive measures should be used throughout the study and forat least 90 days after their last dose of study treatment.

7. A diagnosis of PD or MSA, confirmed by the PI, as per the current Movement DisordersSociety's criteria (Postuma 2015, Wenning 2022).

8. Stable treatment of permitted antiparkinsonian medications from 30 days before firststudy drug administration or 60 days for MAO-B inhibitors and expected to remainstable throughout the study unless required adjustment or initiation per theinvestigator's judgment; except for short-acting rescue medications, which areallowed (see Section 7.1 for the list of permitted medications).

9. Eligible participants must be fully vaccinated against COVID-19 according to localguidelines. Participants also must have received a COVID-19 booster vaccination, andthe interval between booster vaccination and sample collection for inflammatorymarkers at Screening should be at least seven days.

10. Subjects with a MOCA score > 21 at screening and throughout enrollment.

Exclusion Criteria:

1. Clinically significant abnormalities, as judged by the investigator, in test results (including hepatic and renal panels, complete blood count, chemistry panel, a levelof anti-cyclic citrullinated peptide (anti-CCP) above the upper limit of normal (ULN) at Screening, positive antinuclear antibodies (ANA), except judged to beclinically irrelevant by the investigator, urinalysis, ECG and imaging), or vitalsigns. In the case of uncertain or questionable results, tests performed duringscreening may be repeated before randomization to confirm eligibility or judged tobe clinically irrelevant.

2. History of medical, neurological, or psychiatric conditions, which in the opinion ofthe investigator, may compromise the participant's safety or scientific value of thestudy, posing an unacceptable risk to the participant or interfering with theparticipant's ability to comply with the study procedures or abide by studyrestrictions.

3. History of Substance Use Disorder within the past 2 years before screening (Diagnostic and Statistical Manual of Mental Disorders-5 [DSM-V] criteria).

4. Acute or chronic infection with human immunodeficiency virus (HIV), hepatitis Cvirus (HCV), or hepatitis B virus (HBV) at Screening or any confirmed or suspectedimmunosuppressive or immunodeficient condition, including HIV-1, HIV-2 infection, orcytotoxic therapy in the previous 5 years.

5. History or evidence of an autoimmune disorder (e.g. Sjogren's syndrome, systemiclupus erythematosus, rheumatoid arthritis, multiple sclerosis, etc.), which in theopinion of the investigator may compromise the patient's safety or scientific valueof the study, posing an unacceptable risk to the participant.

6. History of anergy.

7. Any confirmed significant allergic reactions (urticaria or anaphylaxis) against anydrug or vaccine, or multiple drug allergies (non-active hay fever is acceptable).

8. History of cancer (except basal cell and in situ squamous cell carcinomas of theskin that have been excised and resolved) which has not been in remission for atleast 5 years before Screening.

9. Contraindications to MRI, including but not limited to the presence of metal devicesor implants (e.g., pacemaker, vascular- or heart-valves, stents, clips), metaldeposited in the body (e.g. bullets or shells), or metal grains in the eyes.

10. Receipt of an investigational product or device, or participation in a drug researchstudy within 90 days before baseline at V1.

11. Participated/participating in any clinical trial with monoclonal antibodies orvaccines directed at aSyn.

12. Underwent any procedures/studies involving intracranial surgery, implantation of adevice into the brain, or stem cell study.

13. Pregnancy, confirmed by a positive pregnancy test.

14. Participants who are currently breastfeeding or intend to breastfeed during thestudy. Participants should not be willing to get pregnant and breastfeed till 24weeks after the last injection.

15. Use of any prohibited medications within 30 days or 5 half-lives (whichever isgreater) before Screening till the end-of-study; also excluded administration ofchronic (defined as more than 14 days) immunosuppressants or other immune modifyingdrugs within 6 months of Screening (including prednisone or equivalent, greater thanor equal to 0.5 mg/kg/day; except Intranasal, inhalation, and topical steroids areallowed).

16. Immunization or vaccination will be prohibited within 2 weeks before Screening.Regular vaccinations scheduled for preventative illnesses (e.g., flu, COVID-19)required as per local guidelines after Screening until Week 16 need to be discussedwith the Investigator and approved on a case-by-case basis. Vaccinations after Week 16 until the end of the study are allowed if not within 2 weeks of (e.g., 2 weeksbefore and 2 weeks after) each post-baseline IP administration.

17. Any contraindication to undergoing a lumbar puncture (e.g., anatomical variations orlocal skin infection), as judged by the investigator.

18. Loss or donation of blood over 500 mL within three months before Screening orintention to donate blood or blood products for transfusion during the study and 13months after their last dose.

19. Received blood and/or blood derivatives treatment within 3 months before Screening.

20. Positive test result for SARS-CoV-2 infection (if test performed according to localguidelines) in the 2 weeks before the first dose.

21. Other known or suspected causes of Parkinsonism other than idiopathic PD or MSA,including but not limited to, progressive supranuclear gaze palsy, drug- ortoxin-induced parkinsonism, essential tremor, primary dystonia, or vascularparkinsonism.