Phase I Dose Escalation Study of Intravenously Administered S64315 in Combination With Orally Administered Venetoclax in Patients With Acute Myeloid Leukaemia

Inclusion Criteria:

1. Male or female aged ≥ 18 years;

2. Patients with cytologically confirmed and documented de novo, secondary or
therapy-related AML as defined by World Health Organization (WHO) 2016 classification
(Arber, 2016), excluding acute promyelocytic leukaemia (APL, French-American British
M3 classification):

- With relapsed or refractory disease without established alternative therapy or

- Secondary to MDS treated at least by hypomethylating agent and without
established alternative therapy or

- ≥ 65 years not previously treated for AML and who are not candidates for
intensive chemotherapy nor candidates for established alternative therapy

3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

4. Able to comply with study procedures

5. Adequate renal function within 7 days before the inclusion of the patient defined as:

• Serum creatinine ≤ 1.5 x ULN (upper normal limit) or calculated creatinine clearance
(determined by MDRD) > 50 mL/min/1.73m2

6. Adequate hepatic function within 7 days before the inclusion of the patient defined
as:

- AST and ALT ≤ 3 x ULN

- Total serum bilirubin level ≤ 1.5 x ULN, except for patients with known Gilbert's
syndrome, who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin >
1.5 x ULN

Exclusion Criteria:

1. Participant already enrolled and treated in the study

2. Pregnancy, breastfeeding or possibility of becoming pregnant during the study

3. Participation in another interventional study requiring investigational treatment
intake at the same time or within 2 weeks or at least 5 halflives (whichever is
longer) prior to first dose of IMP (participation in non-interventional registries or
epidemiological studies is allowed). In case of biologic agents with a long half life
such as CART cells, immune checkpoint antibodies, bispecific antibodies a flat
wash-out of 28 days will be acceptable

4. Presence of ≥ CTCAE Grade 2 toxicity (except alopecia of any grade) due to prior
cancer therapy, according to the National Cancer Institute Common Terminology Criteria
for Adverse Events (NCICTCAE, version 4.03).

5. Known carriers of HIV antibodies

6. Known history of significant liver disease

7. Uncontrolled hepatitis B or C infection

8. Known active acute or chronic pancreatitis

9. History of myocardial infarction (MI), unstable angina pectoris, coronary artery
bypass graft (CABG) within 6 months prior to starting study treatment