Deep Brain Stimulation Clinical Trials

• Diagnosis of idiopathic PD according to MDS Clinical Diagnostic Criteria for Parkinson's Disease (Postuma et al., 2015) and

• a. Cohort 1: Participated in a prior PD clinical trial with buntanetap. i. A legally authorized representative is required for any participant whose MMSE \<21 at screening.

• b. Cohort 2: Has been receiving DBS treatment in either 1) the subthalamic nucleus or 2) the globus pallidus internus for at least 12 months after a successful DBS surgery that achieved the goal.

• i. Female or male adults aged 40 to 85 years. ii. H\&Y stage 1-3 in ON state. iii. MMSE 21-30 at screening and baseline.

• Have a support person who will accompany the participant on study visits at designated times.

• Female participants of childbearing potential\* must have a negative urine pregnancy test at screening, must be non-lactating, and must agree to use a highly effective method of contraception (i.e., a method resulting in a failure rate of less than 1% per year when used consistently and correctly) during the trial and for one month after the last dose of trial treatment, such as:

‣ Oral, intravaginal, or transdermal combined (estrogen plus progestogen) hormonal contraception associated with inhibition of ovulation,

⁃ Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation,

⁃ Intrauterine device (IUD),

⁃ Intrauterine hormone-releasing system (IUS),

⁃ Bilateral tubal occlusion,

⁃ Vasectomized partner (a vasectomized partner is a highly effective contraception method provided that the partner is the sole male sexual partner of the participant, and the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used),

⁃ Sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant).

∙ Non-childbearing potential includes surgically sterilized or postmenopausal with no menstrual bleeding for at least one year prior to study start.

• Protocol ANVS-25002 Ver. 2.1; 09-23-2025 Confidential Page 30 of 54

• Male participants must be sterile or sexually inactive or agree not to father a child during the study and one month after the last dose of study medication and must agree to use a barrier method for contraception. Female partners of male participants must adopt a highly effective method of contraception with a failure rate of less than 1% per year when used consistently and correctly such as:

‣ Oral, intravaginal, or transdermal combined (estrogen plus progestogen) hormonal contraception associated with inhibition of ovulation,

⁃ Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation,

⁃ IUD,

⁃ IUS,

⁃ Bilateral tubal occlusion.

• No evidence of current suicidal ideation or previous suicide attempt in the past month as evaluated in the C-SSRS.

• Stability of permitted medications for at least 4 weeks prior to screening. Refer to Concomitant Medications section above for details on prohibited and permitted medications.

‣ Standard of care anti-parkinsonian medication,

⁃ Cholinesterase inhibitors and/or memantine medication,

⁃ Anticonvulsant medications used for epilepsy or mood stabilization, or neuropathic pain indications, and have not had a breakthrough seizure 3 years prior to screening,

⁃ Mood-stabilizing psychotropic agents including, but not limited to, lithium,

• Adequate visual and hearing ability (physical ability to perform all the study assessments).

• Good general health with no disease expected to interfere with the study.