Abstract: Reanalysis of the SIMPLIFY 1 and 2 trials data indicates MMB is effective in JAKi-naïve patients and in second line therapy to RUX, providing benefits of reducing enlarged spleens, improving myelofibrosis-related symptoms, and increasing transfusion independence in patient at risk for thrombocytopenia from the underlying disease and RUX therapy. Accordingly, methods of treating myeloproliferative neoplasms (MPN) such as myelofibrosis are described. The methods can include administering a therapeutically effective amount of momelotinib or a pharmaceutically acceptable salt thereof to a subject identified as having (i) myelofibrosis and (ii) a platelet count of less than 150×109/L.

Abstract: This disclosure provides methods of using a checkpoint kinase 1 (Chk1) inhibitor in the treatment of cancer in a subject having at least an intermediate tumor mutational burden (TMB), or a genetic abnormality in one or more particular genes associated with replicative stress. Accordingly, methods of treating cancer in a subject having at least an intermediate tumor mutational burden (TMB-I) are provided. Also provided are methods of treating cancer in a subject having a genetic abnormality in one or more particular genes selected from cell cycle regulation genes, replication stress genes, oncogenic driver mutations and DNA damage response and repair network genes. Methods of selecting subjects for Chk1 inhibition therapy are provided. The methods can include administering to the subject an effective amount of a SRA737 compound, in some cases in combination with low dose gemcitabine.

Abstract: Reanalysis of the SIMPLIFY 1 and 2 trials data indicates MMB is effective in JAKi-naïve patients and in second line therapy to RUX, providing benefits of reducing enlarged spleens, improving myelofibrosis-related symptoms, and increasing transfusion independence in patient at risk for thrombocytopenia from the underlying disease and RUX therapy. Accordingly, methods of treating myeloproliferative neoplasms (MPN) such as myelofibrosis are described. The methods can include administering a therapeutically effective amount of momelotinib or a pharmaceutically acceptable salt thereof to a subject identified as having (i) myelofibrosis and (ii) a platelet count of less than 150×109/L.