A Phase 1 Study to Evaluate H3B-8800 in Participants With Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia

Inclusion Criteria:

1. Confirmed diagnosis of MDS, CMML, or AML.

2. The participant must meet the following criteria relevant to their specific diagnosis:

A. Participants with higher-risk MDS/CMML must be intolerant of hypomethylating agents
(HMAs) or not have responded to 4 treatment cycles of decitabine or 6 treatment cycles
of azacitidine, or must have progressed at any point after initiation of an HMA.

B. Participants with lower-risk MDS/CMML must be transfusion-dependent for red blood
cells or platelets (as determined by instructional practices or local standard of
care). Participants who are red blood cell transfusion-dependent must also have failed
erythropoiesis stimulating agents (ESA) (primary resistance or relapse after a
response) or have serum EPO levels > 500 U/L. These lower-risk participants must have
platelet counts above 50,000 mm^3 in the absence of transfusion for 8 weeks.

C. Participants with AML must either refuse or not be considered candidates for
intensive induction chemotherapy using consensus criteria for defining such
participants. Previously treated participants should have evidence of persistent or
recurrent AML in the peripheral blood and/or bone marrow that is refractory to, or has
relapsed from, their most recent prior line of treatment. For AML, participants must
have WBC < 15 × 10^9/L.

D. Participants with CMML must have been treated with at least one prior therapy
(hydroxyurea or a hypomethylating agent [HMA]).

3. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.

4. Adequate baseline organ function

Exclusion Criteria:

1. Diagnosis of a core binding factor leukemia (t(8;21), t(16;16) or inv(16)).

2. Participant is candidate for hematopoietic stem cell transplants at the time of
enrollment.

3. Family history of Leber Hereditary Optic Neuropathy, Autosomal Dominant Optic Atrophy,
Late-Onset Retinal Degeneration, Familial Dysautonomia or other hereditary
mitochondrial disease, unless the causative mutation(s) in the family have been
determined and the participant has tested negative for the mutation(s).

4. Known prior or current retinal or optic nerve disease (example, Retinitis Pigmentosa,
diabetic retinopathy, optic neuritis) based on screening ophthalmology assessment for
eligibility.

5. Corrected vision is worse than 20/40 unless due to cataracts.

6. Vitamin B12, folate or vitamin A deficiency. Rescreening following repletion therapy
is acceptable.