Single and Multiple-Ascending Dose Study of ACE-2223-1 in Healthy Adult Participants (Part A and Part B)

INTERVENTION: This is a Phase 1 first‐in‐human study of orally administered ACE‐2223‐1 consisting of single and multiple ascending dose parts in healthy adult participants. Part A – Single Ascending Dose (SAD): Participants will receive a single oral dose of ACE‐2223‐1 starting at 5 mg. Up to 6 ascending dose cohorts will be evaluated. Dose escalation will be determined by the Safety Review Committee (SRC) based on safety and pharmacokinetic data, with escalation steps not exceeding 3‐fold. The maximum dose is capped at a pre‐specified exposure and the specific dose will be determined from pharmacokinetic data Part B – Multiple Ascending Dose (MAD): Participants will receive ACE‐2223‐1 for 7 consecutive days at a dose shown to be safe and well tolerated in Part A. Up to 6 ascending dose cohorts will be evaluated. Dosing will be once or twice daily as determined by the SRC based on safety and pharmacokinetic data. The maximum dose will not exceed the maximum dose tested in Part A. ACE‐2223‐1 will be administered orally as a liquid formulation in the fasted state. For twice‐daily dosing, fasting requirements may be relaxed. All doses will be administered in a controlled clinical research unit (CRU) under direct supervision of study staff. Participants remain resident in the CRU during the dosing period and scheduled assessments, supporting adherence. CONDITION: Amyotrophic Lateral Sclerosis (ALS); ; Amyotrophic Lateral Sclerosis (ALS) Neurological ‐ Neurodegenerative diseases PRIMARY OUTCOME: Part A (SAD) Safety and tolerability of single ascending doses of orally administered ACE‐2223‐1 in healthy adults will be assessed as a composite outcome based on treatment‐emergent adverse events (TEAEs), vital signs, physical examinations, clinical laboratory tests, and safety EEG and ECG assessments.[TEAEs will be monitored throughout the study. Examples of possible adverse events may include headache, dizziness, gastrointestinal symptoms (e.g., nausea), fatigue, changes in vital signs, or abnormal laboratory findings. Adverse events will be identified through participant self‐report, investigator questioning, continuous clinical observation, physical examinations, vital sign measurements, electrocardiograms, and review of clinical laboratory results. The Investigator will assess severity and relationship to study medication. The number and percentage of participants reporting TEAEs will be tabulated by MedDRA® (current version) system organ class and preferred term, severity, and relationship to study medication.; ; Vital signs (blood pressure, heart rate, respiratory rate, temperature) will be measured at scheduled timepoints. Blood pressure and heart rate will be measured using a sphygmomanometer, respiratory rate by manual breath count, and temperature by tympanic or oral thermometer.; ; Physical examinations will be performed by qualified study clinicians at protocol‐specified timepoints.; ; Clinical laboratory assessments (hematology, clinical chemistry, urinalysis) will be performed using standard accredited laboratory methods and reviewed by the Investigator for clinically significant abnormalities. Safety and tolerability will be assessed from admission on Day ‐1 through discharge on Day 3. TEAEs will be monitored continuously from Day ‐1 through Day 3. Vital signs will be measured at scheduled timepoints on Day ‐1 (pre‐dose baseline), Day 1 (post‐dose), Day 2, and Day 3. Physical examinations and clinical laboratory assessments will be performed on Day ‐1 and Day 3, with additional assessments on Day 1 and Day 2; ] Part B (MAD) Safety and tolerability of multiple ascending doses of orally administered ACE‐2223‐1 in healthy adults will be assessed as a composite outcome based on TEAEs, vital signs, physical examinations, clinical laboratory tests, and safety EEG and ECG assessments.[TEAEs will be monitored throughout the study. Examples of possible adverse events may include headache, dizziness, gastrointestinal symptoms (e.g., nausea), fatigue, changes in vital signs, or abnormal laboratory findings. Adverse events will be identified through participant self‐report, investigator questioning, continuous clinical observation, physical examinations, vital sign measurements, electrocardiograms, electroencephalograms, and review of clinical laboratory results. The Investigator will assess severity and relationship to study medication. The number and percentage of participants reporting TEAEs will be tabulated by MedDRA® (current version) system organ class and preferred term, severity, and relationship to study medication.; ; Vital signs (blood pressure, heart rate, respiratory rate, temperature) will be measured at scheduled timepoints. Blood pressure and heart rate will be measured using a sphygmomanometer, respiratory rate by manual breath count, and temperature by tympanic or oral thermometer.; ; Physical examinations will be performed by qualified study clinicians at protocol‐specified timepoints.; ; Clinical laboratory assessments (hematology, clinical chemistry, urinalysis) will be performed using standard accredited laboratory methods and reviewed by the Investigator for clinically significant abnormalities. TEAEs: Assessed from Day 1 (first dose) through Day 9 (1 day after the final dose) post first administration. Vital signs (blood pressure, heart rate, respiratory rate, temperature): Monitored daily from Day 1 through Day 9. Physical examinations and clinical laboratory tests (hematology, clinical chemistry, urinalysis): Performed at protocol‐specified timepoints between Day ‐1 (baseline) and Day 9 (1 day post final dose).] SECONDARY OUTCOME: Part A (SAD) Evaluate the plasma PK of a single oral dose of ACE‐2223‐1 in healthy adults ; ; [Cmax, Tmax, t½, AUCinf, AUC0‐last, CL/F, Vz/F ; ; ; Blood samples for PK assessment will be collected pre‐dose (Day 1) and at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hours post‐dose.] Part B (MAD) Evaluate the plasma PK following multiple doses of ACE‐2223‐1 in healthy adults ; [Cmax, Ctrough, Tmax, t½, AUC (0‐t), AUCinf (last dose only), AUC0 last (last dose only), AR (Cmax,ss), AR (AUC(0‐t, ss) CL/F, Vz/F ; ; Blood samples for PK assessment will be collected pre‐dose on each dosing day, and on the final dosing day at 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hours post‐final dose.] INCLUSION CRITERIA: Subjects will be eligible for inclusion in the study if they meet all of the following criteria: 1. Adult male or female who is between 18 to 65 years old, inclusive. 2. Weight greater than 50 kg and less than or equal to 110 kg at Screening and at Day –1. 3. Body mass inde X(BMI) greater than or equal to 18 kg/m² and less than or equal to 30 kg/m², inclusive, at Screening and at Day –1. 4. Judged to be in good health. 5. Female participants of child‐bearing or non‐childbearing potential are eligible for inclusion: a. Non‐childbearing potential is defined by either: • Surgically sterile (e.g., removal of both ovaries and/or uterus, or bilateral salpingectomy at least 6 months prior to first dosing), or • Naturally postmenopausal (spontaneous cessation of menses) for at least 12 consecutive months prior to first dosing, with a FSH level >40 mIU/mL at screening consistent with menopausal status. b. Female participants of child‐bear