Study of NEROFE, a Novel Hormone-Peptide in Adult Patients With Advanced MDS and AML

Inclusion Criteria:

1. Confirmed diagnosis of one of the following:

2. Relapsed/refractory Acute Myelogenous Leukemia (AML) where no alternative lifeprolonging therapy exists. Adverse genetic risk treatment naïve patients mayalso be considered eligible if, in the opinion of the investigator, thesepatients are unlikely to benefit from alternative therapy (e.g., an olderpatient with adverse risk MDS who progresses to AML after failing treatment forMDS (i.e. hypomethylating agent (HMA) or HMA and Venetoclax and is not acandidate for traditional AML induction chemotherapy).

3. Relapsed/refractory Myelodysplastic Syndrome (MDS) those who fail to achieve acomplete remission (CR) with at least 4 cycles of HMA (e.g. decitabine orazacitidine); or those who have progressive disease or have intolerance of HMAtherapy after at least 2 cycles. Intolerance to HMA includes those patientsforced to stop the HMA after at least 2 cycles due to severeinfections/worsening cytopenias and are otherwise considered eligible. Patientswith MDS have to have intermediate, high, or very high risk disease byInternational Prognostic Scoring System - Revised (IPSS-R score).

4. Adult male or female patients 18 years of age or older.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.

6. Patients must satisfy the following laboratory criteria:

7. Pre-treatment bone marrow staining must demonstrate expression of the ST2receptor by IHC (low or high expression is allowed).

8. Total bilirubin < 1.5 x greater upper limit of normal (UNL). Elevated indirectbilirubin associated with post-transfusion hemolysis is allowed.

9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be < 3x UNL

10. Creatinine < 2 x UNL or calculated creatinine clearance > 40 ml/min; orEstimated Glomerular Filtration Rate (eGFR) <50 according to MDRD (Modificationof Diet in Renal Disease) method.

11. White blood cell count (WBC) < 25,000/uL before the administration of NEROFE onCycle 1 Day 1. Use of hydroxyurea to control the level of circulating leukemicblast cell counts is allowed before and during the study.

12. Suitable venous access to allow for all study related blood sampling (safety andresearch).

13. Estimated life expectancy, in the judgment of the investigator, which will permitreceipt of at least 8 weeks of treatment.

14. Voluntary written consent must be given before performance of any study relatedprocedure not part of standard medical care, with the understanding that consent maybe withdrawn by the patient at any time without jeopardy to future medical care.

15. Female patients who are:

16. Postmenopausal for at least one year before the screening visit, OR

17. Surgically sterile, OR

18. If they are of childbearing potential: Agree to practice one highly effective method and one additional effective (barrier)method of contraception, at the same time, form the time of signing the informedconsent through 4 months after the last does of study drug (female and male condomsshould not be used together), OR Agree to practice true abstinence, when this is inline with the preferred and usual lifestyle of the participant. (Periodic abstinencee.g. calendar, ovulation, symptothermal, postovulation methods; withdrawal;spermicides only; and lactational amenorrhea are not acceptable methods ofcontraception).

19. Male patients even if surgically sterilized (e.g. status post vasectomy), who:

20. Agree to practice effective barrier contraception during the entire studytreatment period and through four months after the last dose of study drug (female and male condoms should not be used together), OR

21. Agree to practice true abstinence, when this is in line with the preferred andusual lifestyle of the participant. (Periodic abstinence e.g. calendar,ovulation, symptothermal, postovulation methods; withdrawal; spermicides only;and lactational amenorrhea are not acceptable methods of contraception).

22. Able to undergo bone marrow examination at screening

Exclusion Criteria:

1. Patients with a diagnosis of acute promyelocytic leukemia (APL).

2. Screening bone marrow slide without staining for ST2 receptor. (Low or Highexpression by Immunohistochemistry [IHC] allowed on study).

3. Therapy with any investigational products, anti-neoplastic therapy, or radiotherapywithin 14 days of Cycle 1 Day 1. Patients actively receiving hydroxyurea areeligible and may continue to receive this medication during treatment on thisprotocol.

4. Candidates for standard and/or potentially curative treatments. (A candidate isdefined as a patient that is both eligible and willing to have these treatments.)

5. Major surgery within 30 days of the first dose of any study drug or a scheduledsurgery during study period.

6. Grade 2 or higher diarrhea (as defined by NCI CTCAE Version 5.0) despite optimalanti-diarrheal supportive care within 7 days prior to Cycle 1 Day 1.

7. Known cardiopulmonary disease as defined by one of the following:

8. Clinically significant arrhythmia including: history of polymorphic ventricularfibrillation or torsade de pointes; atrial fibrillation > 7 days and requiringcardioversion in the 4 weeks before screening; incompletely controlled,symptomatic atrial fibrillation. Patients with Afib are permitted to enroll ifit is < Grade 3 for a period of 6 months or greater and the rate is controlledwith a stable regimen.

9. Congestive heart failure (New York Heart Association (NYHA) Class III or IV; orClass II with a recent decompensation requiring hospitalization or referral toa heart failure clinic within four weeks of screening; myocardial infarction (MI) and/or revascularization (e.g.coronary bypass graft/stent) within 6 months of first dose of study drug.;

10. Patients with ischemic heart disease who have had acute coronary syndrome (ACS), MI< and/or revascularization greater than 6 months before screening andwho are without cardiac symptoms may enroll.

11. Moderate to severe aortic and/or mitral valve stenosis or other ongoingvalvulopathy;

12. Pulmonary hypertension (symptomatic)

13. Prolonged rate corrected QT (QTc) interval >480 msec, calculated according toinstitutional guidelines;

14. Known, active left ventricular ejection fraction (LVEF) < 50% as assessed byechocardiogram or radionuclide angiography (not required at screening);

15. Known moderate to severe chronic obstructive pulmonary disease (COPD),interstitial lung disease and/or pulmonary fibrosis (e.g., requiring home O2therapy).

16. Active and uncontrolled infection or severe infectious disease, such as severepneumonia, meningitis, or septicemia (stable or resolving infection on antibioticsis allowed).

17. Known human immunodeficiency virus (HIV) seropositive.

18. Known Hepatitis B surface antigen seropositive (note: patients who have isolatedpositive hepatitis B core antibody [e.g. in the setting of negative hepatitis Bsurface antigen and negative hepatitis B surface antibody] must have an undetectablehepatitis viral load).

19. Known or suspected active hepatitis C infection. Patients with treated Hep C treatedwith a negative viral load are eligible.

20. Females of child bearing potential who refuse to practice two effective methods ofcontraception at the same time or abstain from heterosexual intercourse from thetime of signing consent through four months after the last dose of study drug.

21. Males of child bearing potential who refuse to practice effective barrier methods ofcontraception at the same time or abstain from heterosexual intercourse from thetime of signing consent through four months after the last dose of study drug.

22. Female patients who are both lactating or breastfeeding, or have a positive serumpregnancy test during the screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug.

23. Female patients who intend to donate eggs (ova) during the course of this study orwithin four months after receiving their last dose of study drug.

24. Male patients who intend to donate sperm during the course of this study or withinfour months after receiving their last dose of study drug.

25. Any serious medical or psychiatric illness that could, in the investigator'sopinion, potentially interfere with the completion of study procedures.

26. Symptomatic central nervous system (CNS) involvement.

27. Diagnosed or treated for another malignancy within 2 years with evidence of residualdisease.

28. Known hepatic cirrhosis or severe pre-existing hepatic impairment.

29. Patients with uncontrolled coagulopathy or bleeding disorder.

30. Use of systemic steroids (prednisone) >10mg/day or any equivalent corticosteroidswithin 7 days of Cycle 1 Day 1. Patients on other immunosuppression (such aspost-transplant) and also ineligible. Patients with active, uncontrolled GVHD (GraftVersus Host Disease) are also ineligible. Otherwise patients are eligible post-bonemarrow transplantation.

31. Life-threatening illnesses unrelated to cancer.