Inclusion Criteria:

1. Be able to provide informed consent.
2. Be 18 or older at the time of informed consent.
3. Disease criteria:

Histologically confirmed diagnosis of either:
1. R/R AML, defined as relapse after transplantation, second or later relapse, refractory to initial induction or reinduction treatment or to initial treatment with hypomethylating (HMA)-based combinations, relapse after initial treatment, or otherwise considered relapsed or refractory in the opinion of the Investigator.
2. High-risk and very-high-risk (VHR) MDS (higher-risk) per the International Prognostic Scoring System-Revised (IPSS-R) and/or International Prognostic Scoring System-Molecular (IPSS-M).
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Has agreed to undergo serial blood and bone marrow sampling.
6. Participants must have completed systemic non-investigational therapy at least 14 days prior to initiating REM-422. Hydroxyurea is permissible for controlling peripheral leukemic blasts prior to enrollment and for up to 28 days following initiation of REM-422.
7. Toxicities from prior therapy must be either stable or recovered to ≤ Grade 1.
8. Participants must be able to swallow and retain oral medications.
9. Oxygen saturation \> 92% on room air or up to 2 L/min supplemental oxygen by nasal cannula with ≤ Grade 1 dyspnea.
10. People of childbearing potential (POCBP) must have a negative serum beta-human chorionic gonadotropin test result.
11. POCBP must agree to use acceptable, effective methods of contraception and not donate ova from screening until 6 months after discontinuation of REM-422. Women who have undergone surgical or ablative sterilization or who have been postmenopausal for ≥ 2 years are not considered to be of childbearing potential.
12. Men must agree to use acceptable, effective methods of contraception and must agree not to donate sperm from the start of receiving REM-422 until 6 months after discontinuation of REM-422.
13. Adequate organ function and laboratory parameters

Exclusion Criteria:

1. Active central nervous system (CNS) leukemia or a confirmed diagnosis of CNS leukemia.
2. Has undergone hematopoietic stem cell transplantation (HSCT) within 60 days of the first dose of REM-422 or is receiving immunosuppressive therapy post HSCT at the time of screening, or has GVHD requiring systemic treatment (topical steroids for ongoing skin GVHD is permitted).
3. Has immediate, life-threatening, severe complications of leukemia, such as uncontrolled bleeding, pneumonia with hypoxia or sepsis, and/or disseminated intravascular coagulation.
4. Known hypersensitivity or contraindication to any component of REM-422 or to drugs chemically related to REM-422 or its excipients.
5. Clinically significant active infection. Note: Patients with simple urinary tract infection or uncomplicated bacterial pharyngitis responding to active treatment are permitted. Note: Patients receiving intravenous (IV) antibiotics ≤ 7 days prior to enrollment are excluded (prophylactic antibiotics, antivirals, or antifungals are permitted).
6. Evidence of active HIV infection.
7. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
8. Primary immunodeficiency.
9. Current or expected need for daily systemic corticosteroid therapy ≥ 10 mg of prednisone equivalent.

Note: Patients who are receiving topical or inhaled corticosteroids with minimal systemic absorption are eligible for enrollment and may continue with minimal corticosteroid use as long as they are on a stable dose.
10. Live vaccine ≤ 6 weeks prior to the start of REM-422.
11. Use of strong CYP3A inhibitors (except azole antifungals) or CYP3A inducers
12. Drugs that reduce gastric acidity, such as H2-receptor antagonists (eg, ranitidine, famotidine) and proton pump inhibitors (eg, omeprazole, esomeprazole) within 7 days prior to the initiation of REM-422 administration or during the study.
13. Currently pregnant, have intentions to become pregnant during the study duration, or are currently lactating.
14. Has dysphagia, short-gut syndrome, gastroparesis, or any other condition that limits the ingestion or gastrointestinal absorption of orally administered drugs.
15. Current use of prohibited medication ≤ 1 week before starting REM-422.
16. Clinically significant cardiovascular disease:
17. Has undergone major surgery (opening a mesenchymal barrier such as the pleural cavity, peritoneum, or meninges or surgical procedures requiring general anesthesia) \< 4 weeks prior to enrollment.
18. History of organ transplant that requires use of immunosuppressive agents.
19. History or current autoimmune disease requiring systemic treatment (eg, Crohn's disease, ulcerative colitis, rheumatoid arthritis, systemic lupus).
20. Radiation therapy ≤ 7 days prior to the start of REM-422.
21. Concurrent or previous other malignancy ≤ 2 years of enrollment, except curatively treated malignancies including basal or squamous cell skin cancer, breast cancer, prostate intraepithelial neoplasm, and carcinoma in situ of the cervix.
22. Receiving any other investigational treatment for any indication ≤ 3 weeks prior to enrollment.
23. Unwillingness or inability to follow protocol requirements.
24. Any condition that, in the opinion of the Investigator, would interfere with evaluation of REM-422 or interpretation of the participant's safety or study results.