US Phase I Study of ECT-001-CB in Patients With Sickle-Cell Disease

Inclusion Criteria:

   1. Be ≥ 5-30 years of age.

   2. Have a diagnosis of SCD, with either βS/βS, βS/β0, βS/β+ or βS/βC genotype and
   followed at a center of excellence for SCD with at least 2 years of detailed past
   medical records available.

   3. Have severe disease i.e. have experienced one or more of the following SCD related
   events, in spite of appropriate supportive care measures (e.g. pain management,
   penicillin prophylaxis):

      1. Recurrent severe vaso-occlusive crisis (VOC) (≥2 episodes/year in the prior 2
      years): an episode of pain lasting >2 hours severe enough to require care at a
      medical facility. Note that priapism that lasts >2 hours and requires care at a
      medical facility is also considered a VOC. To meet this criterion, subjects must
      have either experienced hydroxyurea failure at any point in the past (defined as
      >1 VOC or ≥1 acute chest syndrome (ACS) after taking hydroxyurea for ≥3 months)
      or must have intolerance to hydroxyurea (defined as inability to be maintained on
      an adequate dose of hydroxyurea due to marrow suppression or severe drug-induced
      toxicity [e.g. gastrointestinal distress, fatigue]).

      2. ACS (≥2 total episodes in the prior 2 years, with at least one episode in the
      past year), defined as an acute event with pneumonia-like symptoms, hypoxemia and
      the presence of a new pulmonary infiltrate. To meet this criterion, subjects must
      have either experienced hydroxyurea failure or have intolerance to hydroxyurea,
      as defined above.

      3. History of an overt stroke, defined as a sudden onset neurologic deficit lasting
      more than 24 hours that is accompanied by cerebral MRI changes.

      4. patients on chronic transfusions are eligible, provided medical records
      documenting any of the above severity criteria are available prior to starting
      the transfusion program.

   4. Availability of 1 CB unit ≥ 6/8 HLA match (when A, B, C and DRB1 are performed at the
   allelic level resolution) with of at least CD34+ cell count 1.5 x 105/kg and total
   nucleated cells (TNC) 1.5 x 107/kg (pre-freeze)

   5. Have adequate organ function to undergo a myeloablative (reduced toxicity
   conditioning) HSCT.

   6. Have a Lansky/Karnofsky performance status of ≥ 80.

   7. An appropriate and willing HLA-matched sibling donor is not available.

Exclusion Criteria:

   1. Prior HSCT or gene-therapy.

   2. Positive for presence of HIV-1 or HIV-2, hepatitis B virus (HBV), or hepatitis C virus
   (HCV). (Note that patients who have been vaccinated against hepatitis B [hepatitis B
   surface antibody (HBsAb)-positive] or patients with positive hepatitis B core and/or
   hepatitis B-e antibodies are also eligible provided viral load is negative by
   quantitative polymerase chain reaction (qPCR). Patients who are positive for
   anti-hepatitis C antibody are eligible as long as they have a negative HCV viral load
   by qPCR). Positive serology for human T-lymphotropic virus-1 (HTLV-1), syphilis (rapid
   plasma reagin (RPR)), toxoplasmosis.

   3. Clinically significant and active bacterial, viral, fungal, or parasitic infection as
   determined by PI.

   4. A white blood cell count <2 × 10e9/L, and/or platelet count <50 × 10e9/L.

   5. Any prior or current malignancy or myeloproliferative or a significant coagulation or
   immunodeficiency disorder.

   6. Advanced liver disease, defined as:

      1. Persistent aspartate transaminase, alanine transaminase, or direct bilirubin
      value >5 times the upper limit of normal (ULN); or

      2. Cirrhosis or bridging fibrosis; or

      3. Baseline prothrombin time or partial thromboplastin time > 1.5 x ULN; or

      4. in chronically transfused patients a liver iron concentration (LIC) of ≥ 15 mg/g
      on T2* Magnetic Resonance Imaging [MRI] of liver.

   7. Left ventricular ejection fraction (LVEF) <45% and for patients on chronic
   transfusions a cardiac T2* < 10 ms by MRI.

   8. Baseline estimated glomerular filtration rate < 60 mL/min/1.73 m2.

   9. Baseline oxygen saturation < 85% without supplemental oxygen (excluding periods of SCD
   crisis or infection).

10. Diffusion capacity of carbon monoxide (DLCO) <50% of predicted (corrected for
   hemoglobin and/or alveolar volume).

11. Any contraindication to general anaesthesia.

12. Participation in another clinical study with an investigational drug within 30 days of
   Screening.

13. Diagnosis of a significant psychiatric disorder as deemed as the PI that could
   seriously impede the subject's ability to participate in the study.

14. Pregnancy or breastfeeding in a postpartum female or absence of adequate contraception
   for fertile patients. Females of child bearing potential are required to use effective
   contraception from enrollment through at least 6 months after drug product infusion.
   Male patients are required to use effective contraception from enrollment through at
   least 6 months after drug product infusion.

15. An assessment by the PI that the subject would not comply with the study procedures
   outlined in the protocol.

16. Any abnormal condition or laboratory result that is considered by the PI capable of
   altering patient condition or study outcome.

Note: should a patient be out of range for any numerical exclusion criteria, the PI is
allowed to repeat the dosage once during the screening period to definitely determine
eligibility