A Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of APG-5918.

The trial is composed of ttwo parts. Part A is a randomized, double-blind, placebo- controlled, single-dose escalation study in up to 7 cohorts to evaluate the safety, tolerability, and PK characteristics of APG-5918 in healthy volunteers and to explore whether MTDS will be achieved within the range of projected therapeutic doses for anemia.

Part B is an open-label,, multi-dose escalation trial in up to 6 cohorts to evaluate the safety, tolerability, PK and preliminary efficacy of APG-5918 in patients with anemia.

Inclusion criteria

• Healthy Subjects:

• Age: 18 to 55 years. 2. Body Mass Index (BMI): 18-28 kg/m² (inclusive). 3. Hemoglobin value: 120 g/L-160 g/L (inclusive). 4. Normal body iron stores. 2. Anemic Subjects:

• Age: ≥ 18 years.
• Including beta-thalassemia and other related anemias, with screening Hb ≤ 100.0 g/L.
• Body weight ≥ 40 kg.
• Serum folate and vitamin B12 levels above the lower limit of normal (LLN).
• ALT, AST ≤ 2×ULN, and direct (unconjugated) total bilirubin (DBIL) ≤ 2×ULN. Higher levels may be accepted after excluding other diseases based on investigator judgment.
• No active or chronic bleeding.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.

• For female subjects of childbearing potential, a negative blood or urine pregnancy test within 7 days prior to the first dose.

• Subjects and their partners must voluntarily agree to use effective contraceptive measures as required by the protocol during the treatment period and for at least 3 months after the last dose of study drug.

• Ability to understand and voluntarily sign a written informed consent form, which must be signed before any trial-specific procedures are performed.

Exclusion criteria

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• Healthy Subjects:

• History of any disease or clinical condition that, in the investigator's opinion, may confound the study results or pose additional risk to the subject with administration of the study drug.
• ALT or AST > 2×ULN, or TBIL > 1.5×ULN at screening.
• Undergone surgery (excluding minor cosmetic or dental procedures) within 3 months prior to screening.
• Blood donation or blood loss exceeding 400 mL within 3 months prior to screening, or planned donation of blood or blood components during the study period.
• Use of another investigational product within 30 days or 5 half-lives (whichever is longer) prior to dosing, or current participation in a prospective study of an investigational product or medical device.
• History of substance abuse within 6 months prior to screening.
• Positive alcohol breath test.

• Anemic Subjects:

• Presence of clinically significant or uncontrolled ongoing autoimmune disease.
• Severe cardiac disease.
• Severe renal disease, defined as estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m², or dependence on dialysis.
• Active malignancy, history of cancer, or presence of a known or suspected familial cancer syndrome in linealrelatives.
• A history of persistent hemolysis or hemolytic syndrome due to causes other than the study diseases.
• A history of thrombosis or newly developed thrombus within 4 weeks prior to screening.
• Receipt of intravenous iron supplementation within 28 days prior to first dosing.
• Any active infection requiring systemic antibiotic therapy (including oral, intravenous, or intraperitoneal administration) within 14 days prior to first dosing.
• A history of organ transplantation.
• Any condition that may affect drug absorption.
• Participation in another clinical study and still using another investigational products, or without completion of a washout period of at least 5 half-lives within 4 weeks prior to first dosing.
• Receipt of cytotoxic agents, high-dose systemic corticosteroids, immunosuppressive agents, or anticoagulant therapy such as warfarin within 28 days prior to first dosing.

• Positive results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody, or Treponema pallidum antibody at screening.

• A history of regular alcohol consumption within 6 months prior to screening, defined as an average daily intake of ≥30 grams (for males) or ≥20 grams (for females) of ethanol.

• Standard 12-lead ECG with QTcB > 450 ms for males or QTcB > 470 ms for females.

• Female subjects who are pregnant, planning to become pregnant, or breastfeeding; or male subjects whose partners are planning to become pregnant.

• Any subject deemed unsuitable for participation in this study based on the investigator's judgment.