A Study of BN104 in the Treatment of Acute Leukemia

Inclusion Criteria:

1. Have been fully informed about the study and have voluntarily signed the ICF;

2. Patients diagnosed with relapsed/refractory acute leukaemia (including AML, ALL, andmixed-phenotype acute leukaemia, excluding acute promyelocytic leukaemia) accordingto the World Health Organization (WHO) criteria in 2022, with bone marrowmorphological changes (blasts/immature cells ≥ 5%), and who have been evaluated bythe investigator to have no better treatment options, must meet at least one of thefollowing conditions:

• Primary refractory disease, newly diagnosed disease that show no response after 2 cycles of standard treatment;

• First relapse, relapsed within 12 months after CR/CRh/CRi followingconsolidation/intensive therapy;

• Relapsed after 12 months and unresponsive to conventional salvage chemotherapy;

• Patients with 2 or more relapses;

• Patients intolerant to intensive chemotherapy who experience diseaseprogression during continuous low-intensity therapy; Note: Patients withsecondary AML or AML transformed from MDS, MPN, can also be enrolled, but theyneed to meet the above criteria after the disease has transformed into AML;

3. For all Phase I patients, the presence of NPM1 mutation, or KMT2A rearrangement, orNUP98 rearrangement must be confirmed,During Phase I, patients with other acuteleukemia subtypes shown to depend on menin-KMT2A interaction (e.g., UBTF-TD) ordriven by HOXA/MEIS1 overexpression may also be eligible after consultation with theSponsor's Medical Monitor;

4. Patients in the Phase II (single-arm pivotal clinical study) must have a confirmedNPM1 mutation or KMT2A rearrangement. Enrollment based on local testing results isacceptable with a copy of the test report provided; however, all patients arerequired to submit screening bone marrow samples to the central laboratory ,EligibleNPM1 mutations include exon12 type A, B, and D mutations ; other NPM1 mutationscausing cytoplasmic localization require sponsor pre-approval for enrollment. KMT2Arearrangements exclude non-fusion rearrangements involving KMT2A partial tandemduplication (KMT2A-PTD).

5. Peripheral blood white blood cell count ≤ 35 × 109/L (use of hydroxyurea to controlperipheral white blood cell count is permitted);

6. Age ≥ 12 years (for adolescent patients aged 12 years or older but not yet 18 yearsold, weight must be ≥ 40 kg);

7. ECOG score 0-2;

8. Adequate hepatic, renal, and cardiac functions

9. Expected survival of more than 12 weeks as judged by the investigator

10. For patients with D-dimer test results > 5 × ULN during screening, relevant tests (such as rechecking coagulation function after a certain interval, lower extremitydeep vein ultrasound, etc.) are required to exclude deep vein thrombosis,hypercoagulation, and disseminated intravascular coagulation before enrollment;

11. Able to undergo treatment, visits, and study-related examinations as required by theprotocol;

12. Female patients of childbearing potential or male patients whose female partners areof childbearing potential must agree to use effective methods of contraceptionduring the study and for 30 days after the last dose of study drug, such as doublebarrier methods, condoms, oral or injectable contraceptives, intrauterine devices,etc. Postmenopausal women (> 45 years old and amenorrheic for more than 1 year) andsurgically sterilized women are not subject to this condition.

Exclusion Criteria:

1. Known active central nervous system (CNS) leukaemia (including imaging abnormalitiesand CSF smear or flow cytometry indicating leukaemia cells; prior CNS leukaemia thathas been treated and controlled is acceptable, but requires screening lumbarpuncture and CSF test for confirmation, or routine standard CNS prophylaxis isacceptable);

2. Known history of clinically significant liver disease, including viral or otherhepatitis or hepatic cirrhosis:

• Hepatitis B surface antigen (HBsAg) seropositive, requires Hepatitis B virus (HBV) DNA negative for enrollment;

• For Hepatitis C virus (HCV) antibody seropositive patients, HCV RNA negativeresult is required for enrollment.

3. Known human immunodeficiency virus (HIV) infection;

4. Pregnancy (positive pregnancy test at screening) or lactating females;

5. Any of the following cardiac-related criteria is met:

• Hereditary long QT syndrome or QTcF > 450 msec;

• Various clinically significant cardiovascular disorders, including acutemyocardial infarction, unstable angina pectoris, coronary artery bypass surgerywithin 6 months prior to enrollment, cardiac failure congestive of New YorkHeart Association (NYHA) Class 2 or higher (including Class 2), etc.;

6. Patient has other concomitant malignant tumours, except for:

• Curatively treated skin basal cell carcinoma, breast cancer in situ, orcervical carcinoma in situ, etc.;

• Patients with low-grade lymphoma who are in CR, asymptomatic, without largemass lesions, and do not require systemic therapy or radiotherapy;

• Other malignant tumours treated with curative intent, with CR achieved for atleast 2 years, and no requirement for systemic maintenance therapy orradiotherapy;

7. Received autologous haematopoietic stem cell transplant (ASCT) or Chimeric AntigenReceptor T-cell (CAR-T) therapy within 60 days prior to screening, or toxicityrelated to ASCT or CAR-T therapy has not yet resolved;

8. Underwent allogeneic HSCT within 100 days prior to screening, or the patient stillhas Grade ≥ 2 acute graft versus host disease or chronic graft versus host diseaserequiring systemic treatment, or the patient still requires immunosuppression (prednisone ≤ 10 mg/day or equivalent dose of other corticosteroids is permissiblefor screening; corticosteroids need to be gradually tapered and discontinued afterenrolment unless there is a specific reason);

9. Received donor lymphocyte infusion (DLI) within 28 days prior to screening;

10. Prior anti-leukaemia therapy, including chemotherapy, radiotherapy, hormone therapy,targeted therapy, or immunotherapy (excluding hydroxyurea), etc., less than 2 weeksor 5 half-lives (whichever is shorter) before the start of study treatment;

11. Previous participation in other drug clinical studies, with less than 2 weeks or 5half-lives since the last use of a small molecule drug, or less than 4 weeks or 5half-lives for large molecule drugs (such as antibody drugs), whichever is shorter;

12. Previous treatment targeting menin;

13. Toxicity from previous anti-leukaemia therapy has not recovered to Grade 0 or 1 (except for alopecia and cytopenias reasonably considered related to the underlyingdisease);

14. Patients who had a chest CT scan within 1 month prior to screening showing pulmonarynodules need to undergo a T-SPOT.TB test (Tuberculosis infection T-cell spot test)during screening; those with a positive result must be excluded (no additional testrequired if no chest CT scan was performed within 1 month prior to screening);

15. Uncontrolled active infection:

• Patients with non-severe infectious complications (such as oral candidainfection or uncomplicated urinary tract infection) currently receivingoral/topical anti-infective therapy may be enrolled;

• Patients with severe infection requiring hospitalisation or intravenousantibiotic therapy within 14 days prior to enrollment, patients with noevidence of infection receiving prophylactic anti-infective, anti-fungal, oranti-viral therapy due to prolonged neutropenia may be enrolled;

• Patients receiving intravenous antibiotic therapy or hospitalized for febrileneutropenia, but with no evidence of infectious etiology found, and whose bodytemperature has been normal for more than 72 hours without antipyretics, may beenrolled;

16. Patient has known dysphagia, short-bowel syndrome, gastroparesis, or otherconditions limiting oral drug intake or gastrointestinal absorption;

17. History of severe allergy to menin inhibitors or allergy to any component of BN104;

18. Investigator-judged insufficient compliance of the patient to participate in thisclinical study;

19. Any other disease, metabolic abnormality, physical examination abnormal, orclinically significant laboratory test abnormal that, in the investigator'sjudgment, gives reason to suspect that the patient has a disease or conditionunsuitable for the use of the study drug, or that will affect the interpretation ofthe study results, or place the patient at high risk.