VONJO is the first and only MF treatment that targets multiple pathways—ACVR1, IRAK1, and JAK2—while sparing the JAK1 pathway.1

ACVR1 inhibition

  • VONJO is a potent inhibitor of ACVR1, which regulates hepcidin production2,3
  • Hepcidin acts as an iron regulatory hormone, which may lower serum iron levels4

IRAK1 inhibition

  • VONJO is an inhibitor of IRAK11,5
  • Innate immune signaling (facilitated by the IRAK1-NFKB signaling pathway) plays an essential role in inflammation5-8
    • IRAK1 inhibition suppresses downstream NFKB activation, which can decrease cytokine expression and chronic inflammation. In MF, inflammation can lead to bone marrow fibrosis, splenomegaly, constitutional symptoms, and cytopenias
    • This signaling is increasingly being recognized as an important mediator in myeloid malignancies

JAK2 inhibition

  • VONJO inhibits wild type JAK2, the JAK2V617F mutation, and FLT3, which helps mediate cytokine signaling and key growth factors for hematopoiesis and immune function1


  • VONJO does not inhibit JAK1 at clinically relevant concentrations1
    • JAK1 inhibition has been shown to exacerbate thrombocytopenia and immunosuppression in MF9,10

Evolving Pathways in Myelofibrosis

Infographic of 3 myelofibrosis pathways (JAK-STAT, IRAK1-NFκB, and ACVR1) and possible impact of inhibition.
  • ACVR1=activin A receptor, type 1; FLT3=FMS-like tyrosine kinase 3; IRAK=interleukin-1 receptor-associated kinase; JAK=janus kinase; NFKB=nuclear factor kappa-light-chain-enhancer of activated B cells; SMAD=suppressor of mothers against decapentaplegic; STAT=signal transducer and activator of transcription.
  • References: 1. VONJO. Prescribing information. CTI BioPharma Corp.; 2023. 2. Yacoub A, et al. JCO Precis Oncol. 2023;7:e2200523. 3. Oh S, et al. Clin Lymphoma Myeloma Leuk. 2022;22:S327. 4. Falzacappa MVV, Muckenthaler MU. Gene. 2005;364:37-44. 5. Singer JW, et al. Oncotarget. 2018;9(70):33416-33439. 6. Vainchenker W, Kralovics R. Blood. 2017;129(6):667-679. 7. Rhyasen GW, Starczynowski DT. Br J Cancer. 2015;112(2):232-237. 8. Fisher DAC, et al. Leukemia. 2019;33(8):1978-1995. 9. Marcellino BK, et al. Clin Lymphoma Myeloma Leuk. 2020;20(7):415-421. 10. Mascarenhas J, et al. Haematologica. 2017;102(2):327-335.