This is a Phase 1/2, multicenter study with an open-label dose escalation followed by a randomized placebo controlled and double-blind phase of SLN124 in adult patients with Polycythemia Vera (PV) to assess the safety, tolerability, efficacy, pharmacokinetic (PK), and Pharmacodynamic (PD) response of SLN124.

Phase 1 and Phase 2

Inclusion Criteria:

• Male and female patients aged 18 years or older.
• A confirmed diagnosis of PV according to the revised 2016 World Health Organization criteria:
• Suitable phlebotomy history
• Must agree to adhere to appropriate contraception requirements
• Patients who are not receiving cytoreductive therapy must have been discontinued from any prior cytoreductive therapy for at least 24 weeks before dosing and have recovered from any adverse events due to cytoreductive therapy.
• Patients receiving cytoreductive therapy with hydroxyurea, interferon, busulfan or ruxolitinib must have received a stable dose of cytoreductive therapy for at least 12 weeks before dosing and with no planned change in dose.
• Patients must have had a dermatological examination within 28 weeks prior to dosing.
• Must have an Eastern Cooperative Oncology Group score of 0, 1, or 2.

Exclusion Criteria:

Phase 1 and Phase 2

• Drug intolerance:

  1. History of intolerance to oligonucleotides, or GalNAc, or any component of SLN124.
  2. History of intolerance to s.c. injections.

• Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 12 weeks of screening.

• History of major bleeding events and/or a requirement for blood transfusion therapy owing to bleeding in the last 6 months prior to screening.

• Meets the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment

• Any investigational drug less than 6 weeks prior to the first dose of study drug or not recovered from effects of prior administration of any investigational agent.

• Any investigational or marketed product using GalNAc targeting less than 48 weeks prior to administration of any investigational agent (excludes patients with PV who participated in Phase 1 of this study).

• Clinically significant co-morbidities

• Biochemical and hematological parameters:

  1. Biochemical evidence of significant liver disease during screening
  2. Phase 1: Hematological parameters at screening as follows: platelets > 1,000,000/µL; or white blood cell (WBC) count > 25,000/µL; or peripheral blasts > 1%.

  b. Phase 2: Hematological parameters at screening as follows: platelets > 1,000,000/µL; or WBC count > 30,000/µL; or peripheral blasts > 1%.