Inclusion Criteria:
1. Male and female subjects aged 18-75 years (inclusive);
2. Subjects diagnosed with polycythemia vera (PV) according to the 2016 world health organization (WHO) criteria;
3. Hydroxyurea-resistant/intolerant and/or interferon α-resistant/intolerant:
1)Hydroxyurea-resistant or -intolerant Must meet the definition of hydroxyurea (HU) resistance or intolerance in the 2024 chinese society of clinical oncology (CSCO) Guidelines for the diagnosis and treatment of malignant hematological diseases and satisfy at least one of the following criteria:a) Resistance: Despite ≥3 months of HU treatment at a dose of ≥2 g/d, phlebotomy is still required to maintain HCT \<45%; after ≥3 months of HU treatment at a dose of ≥2 g/d, bone marrow proliferation remains uncontrolled (e.g., platelets \>400×10⁹/L and WBC \>10×10⁹/L); after ≥3 months of HU treatment at a dose of ≥2 g/d, a palpable massive splenomegaly fails to reduce by \>50% or splenomegaly-related clinical symptoms do not fully resolve;b) Intolerance: At the minimum hydroxyurea (HU) dose required to achieve a complete or partial clinical hematologic response for the disease, absolute neutrophil count (ANC) \<1.0×10⁹/L or PLT count \<100×10⁹/L or Hemoglobin (HGB) \<100 g/L occurs; during HU treatment at any dose, lower extremity ulcers or other intolerable non-hematological toxicities emerge, such as skin and mucous membrane manifestations (skin, teeth, or nail darkening; oral ulcers, mucositis; skin ulcers, rash, etc.), gastrointestinal symptoms (nausea, anorexia, indigestion, vomiting, abdominal pain, constipation, etc.), pneumonia, fever, etc.; 2)Interferon α-resistant or -intolerant Must satisfy at least one of the following criteria:a) Resistance: After achieving at least 12 weeks of interferon α therapy and a dose of at least 25×10⁶ U/week (or the subject's maximum tolerated dose if it is less than 25×10⁶ U/week), phlebotomy is still required to maintain HCT \<45%, or PLT \>400×10⁹/L and WBC \>10×10⁹/L, or palpable splenomegaly (starting \>10 cm from the left costal margin) fails to reduce by \>50%;b) Intolerance: At the minimum interferon α dose required for complete or partial clinical hematologic remission, ANC \<1.0×10⁹ or PLT \<100×10⁹ or hemoglobin \<100 g/L (\<10 g/dL) occurs, or depression, influenza-like symptoms, neuropsychiatric symptoms, autoimmune issues, or other unacceptable non-hematological toxicities related to interferon-alpha (IFN-α) emerge, defined as common terminology criteria for adverse events (CTCAE) V5.0 grade 3-4 events, or CTCAE V5.0 grade 2 events lasting over 1 week, or permanent discontinuation of interferon α, or interruption of interferon α until toxicity resolves, or hospitalization due to interferon α toxicity.
4.The subject has intact skin at the injection site, and the investigator deems it is suitable for subcutaneous injection; 5.Eastern cooperative oncology group (ECOG) performance status score is 0, 1, or 2; 6.The subject has undergone bone marrow biopsy within 12 months prior to enrollment; 7.The subject or the subject's legal guardian has signed a written informed consent, and the subject is able to comply with the study requirements.
Exclusion Criteria:
1. A history of intolerance to oligonucleotides, N-Acetylgalactosamine (GalNAc), or excipient components, or a history of intolerance to subcutaneous injections.
2. Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 12 weeks before screening.
3. Major bleeding event or blood transfusion for bleeding within 6 months before screening.
4. Meets the international working group for myeloproliferative neoplasms research and treatment criteria for post-PV myelofibrosis.
5. Received any investigational drug within 6 weeks before the first study drug administration, or not recovered from the effects of prior investigational drugs.
6. Received any clinical studies or marketed products of GalNAc-targeted drugs within 48 weeks before the first study drug administration.
7. Laboratory abnormalities:a) Liver function tests: alanine aminotransferase (ALT) or aspartate aminotransferase (AST)\>2.0×Upper Limit of Normal (ULN), total bilirubin（TBIL）\>1.5×ULN;b) Renal function tests: estimated glomerular filtration rate (eGFR)\<60 mL/min/1.73㎡ (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation);c) Blood routine tests: platelet count\>1000×10⁹/L, WBC count\>25×10⁹/L;d) Coagulation tests: international normalized ratio (INR)\>1.5×ULN;e) Others: presence of peripheral blood blasts.
8. Subjects with symptomatic splenomegaly (e.g., splenic infarction, left upper quadrant fullness or pain, early satiety, portal hypertension).
9. Due to potential genotoxicity, mutagenicity, and teratogenicity of the study drug, exclude:a) Men and women planning to conceive within 5 years without prior in vitro sperm/ovum preservation;b) Pregnant or breastfeeding women;c) Women within 2 years of menopause unwilling to use acceptable contraception until 6 months after the last study drug dose.
10. Presence of other active malignancies requiring treatment that may interfere with the study.
11. Comorbid conditions:a) Poorly controlled diabetes (random glucose≥11.1mmol/L or HbA1c≥8.5% despite antidiabetic treatment) assessed by the investigator;b) Severe pulmonary disease (CTCAE V5.0 grade III-IV);c) Severe cardiac disease (defined as any of the following:Left ventricular ejection fraction (LVEF) \<50% as determined by multigated acquisition scan (MUGA) or Echocardiogram (ECHO);QT interval corrected using the Fridericia method (QTcF) interval \>450 ms for males or \>470 ms for females;Unstable angina;Symptomatic pericarditis;Myocardial infarction within the past 6 months with persistent elevation of cardiac enzymes or evidence of persistent regional wall abnormalities on LVEF assessment;History of congestive heart failure (new york heart association functional class III-IV) or cardiomyopathy;d) Significant renal or hepatic impairment;e) Poorly controlled active hepatitis B or C, or other diseases with clinically significant active infections, including hepatitis B (HBV), hepatitis C (HCV), or syphilis. Active HBV is defined as Hepatitis B Surface Antigen (HBsAg) or Hepatitis B e Antigen (HBeAg) positivity with HBV DNA≥2000 IU/ml (10⁴ copies/ml). If HBV DNA is below this level, antiviral therapy is required until one year post - study. Active HCV is defined as HCV RNA above the assay's upper limit. For syphilis, a positive non-treponemal test requires confirmation with a treponemal antibody test. If the latter is negative and the investigator confirms past infection with syphilitic cure, the subject can be included;f) Known human immunodeficiency virus （HIV） positivity or primary immunodeficiency;g) Deemed unsuitable for study participation due to a history of psychosis, family history of psychiatric illness, or mood disorders, as determined by the investigator or psychiatrist;h) Uncontrolled hypertension (systolic BP≥180mmHg and/or diastolic BP≥110mmHg);i) Severe medical conditions with a risk of major bleeding or history of major bleeding.
12. Concomitant use of drugs that may prolong the QT interval or cause torsades de pointes.
13. History of alcohol or drug abuse within the past year.
14. Subjects deemed unsuitable for this treatment regimen by the investigator.
