SNS-301 Monotherapy in High Risk MDS and CMML

Inclusion Criteria: 1. Signed informed consent. 2. Be 18 years of age or older. 3. Confirmed diagnosis of MDS or CMML. 4. Assessment of high-risk-MDS/CMML status defined as follows: 1. MDS: IPSS-R criteria for categorization ≥ Intermediate Risk-3 2. CMML: WHO criteria for CMML-2 (peripheral blasts of 5% to 19%, and 10% to 19% bone marrow blasts and/or presence of Auer rods). 5. Be willing to provide a fresh bone marrow aspirate sample at pre-treatment and demonstrate ASPH expression by flow cytometry. 6. Patient who has relapsed or is refractory / intolerant of hypomethylating agents (HMAs) or not responding to 4 treatment cycles of decitabine or 6 treatment cycles of azacytidine or progressing at any point after initiation of an HMA. 7. Patient refuses or is not considered a candidate for intensive induction chemotherapy using consensus criteria for defining such patients. 8. Patients with CMML must have been treated with at least 1 prior therapy (hydroxyurea or an HMA). 9. Eastern Cooperative Oncology Group (ECOG) Performance Scale 0-1. 10. Demonstrate adequate organ function: renal, hepatic, coagulation parameters. 11. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two highly effective contraceptive methods during the treatment period and for at least 180 days after the last dose of study treatment. For male patients: Agree that during the period specified above, men will not father a child. Male patients must remain abstinent, must be surgically sterile during the treatment period and for at least 180 days after the last dose of study treatment. Exclusion Criteria: 1. Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 0. 2. Participated on a clinical trial of an investigational agent and/or investigational device within 28 days prior to Day 0. 3. Malignancies other than indications open for enrollment within 3 years prior to Day 0. 4. Diagnosis of a core binding factor leukemia (t(8;21), t(16;16); or inv(16)) or diagnosis of acute promyelocytic leukemia (t(15;17)). 5. Active or history of autoimmune disease or immune deficiency. 6. History of HIV. HIV antibody testing recommended per investigator's clinical suspicion. 7. Active hepatitis B (hepatitis B surface antigen reactive) or active hepatitis C (HCV qualitative RNA detected); testing recommended per investigator's clinical suspicion. 8. Severe infections within 4 weeks prior to enrollment. 9. Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 0. 10. History or current evidence of any condition, therapy or laboratory abnormality that in the opinion of the treating investigator might confound the results of the trial. 11. Known previous or ongoing, active psychiatric or substance abuse disorders that would interfere with the requirements of the trial. 12. Treatment with systemic immunomodulating agents (including but not limited to IFNs, IL-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to first dose. 13. Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study.