The following criteria is provided for health care professionals.

Inclusion Criteria:

* Age \>= 18 years of age
* For Part 1, participants have R/R MDS post-HMA failure, defined as prior receipt of 4 cycles of HMA therapy (including but not limited to decitabine, azacitidine, investigational HMAs such as SGI-110, and oral HMAs such as oral decitabine and cedazuridine \[ASTX727\] and oral azacitidine \[CC-486\]) with failure to attain a response or progression of disease or relapse at any time after prior response to HMA therapy

a. Note: participants with HR-CMML (CMML-1 or 2 by World Health Organization \[WHO\]) are eligible. Hydroxyurea administration will be allowed on the study to lower the white cell count to \<= 10 000/μL prior to the initiation of therapy
* For Part 2, participants will be divided into 2 cohorts:

1. HMA Failure Cohort: participants with R/R MDS post-HMA failure. Participants who have previously received venetoclax are eligible and will be stratified accordingly in the HMA failure cohort;
2. Newly Diagnosed Cohort: Participants with treatment-naïve newly diagnosed HR-MDS (revised International Prognostic Scoring System \[IPSS-R\] score \>3.5) are eligible for enrollment only after all prior cohorts have been completed. Hydroxyurea administration will be allowed on the study to lower the white cell count to \<= 10 000/μL prior to the initiation of therapy. Participants with HR-CMML (CMML-1 or 2 by WHO) are eligible

Exclusion Criteria:

* Participants with newly diagnosed MDS with Revised International Prognostic Scoring System (IPSS-R) lower-risk category (IPSS-R score \< 3.5)
* Participants with CMML-0 by WHO
* History of other malignancy within the past 2 years prior to enrollment (with some exceptions as listed in full list of criteria)
* Excluded prior and/or concomitant therapies as listed in the full list of criteria
* Participants who are fit and deemed eligible by the investigator for intensive salvage therapy