Inclusion Criteria:

1. Patients aged ≥ 18 years of age with newly diagnosed, previously untreated AML (including MDS/AML)

2. Patients are not candidates for intensive induction chemotherapy because they are either unfit or otherwise clinically unsuitable for anthracycline/ cytarabine-based induction therapy

3. White blood cell (WBC) count at the time of C1D1 ≤ 20,000/μL

4. Patients must have previously untreated AML; hydroxyurea for cytoreduction is permitted up to C1D1. Prior therapy for MDS is allowed except for hypomethylating agents and venetoclax.

5. Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 2

6. The patient's laboratory values meet the following criteria:

   1. Creatinine clearance (CrCl) ≥ 45 mL/min;
   2. Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
   3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN

Exclusion Criteria:

1. Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML to enter the study).
2. Diagnosis of acute promyelocytic leukemia or PML:RARA-positive AML.
3. Chronic myeloid leukemia in blast phase or AML with BCR:ABL1.
4. Mixed phenotype acute leukemia or acute leukemia of ambiguous lineage.
5. Active CNS involvement by AML.
6. Signs of leukostasis requiring urgent therapy.
7. Prior organ allograft, or prior allogeneic hematopoietic stem cell transplant within the last 12 months, or with active graph-versus-host disease.
8. Treatment with systemic glucocorticoid therapy or other immune-suppressive drugs ≤ 14 days prior to the first dose of CLN-049.
9. Patients with concomitant second malignancies requiring active treatment in the past 12 months, or if additional therapy is required or anticipated during study participation.
10. Patients with any active autoimmune disease or a history of known or suspected autoimmune disease, or history of a syndrome that requires systemic corticosteroids or immunosuppressive medications
11. Active uncontrolled infection until infection is treated and brought under control.
12. Has a history of, or a positive test for human immunodeficiency virus (HIV) 1/2 or primary immunodeficiency disease such as HIV.
13. Known history of hepatitis B, hepatitis C (HCV) infection, or acute hepatitis A.
14. Active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
15. Patients who have received an investigational agent (for any indication) within 5 half-lives of the agent and until toxicity from this has resolved to Grade 1 or less
16. History of the following events in conjunction with prior treatment with immunotherapy: Grade 3 or greater neurotoxicity, ocular toxicity, pneumonitis, myocarditis, or colitis; liver dysfunction meeting the laboratory criteria for Hy's Law.
17. Live virus vaccines within 28 days of the first dose of CLN-049, during treatment, and until the end of last dose of CLN-049.
18. QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≥ 480 milliseconds.
19. Patient has a history of drug-related anaphylactic reactions to any components of CLN-049, or a history of Grade 4 anaphylactic reaction to any bispecific molecule or monoclonal antibody therapy.
20. Known history of prior human anti-human antibody response.