The Efficacy and Safety of REX-001 to Treat Ischemic Rest Pain in Subjects With CLI Rutherford Category 4 and DM

Inclusion Criteria:

1. Aged ≥ 18 to ≤ 85 years.
2. Diagnosis of Type I or II DM, established more than one year ago.
3. Glycosylated hemoglobin (HbA1c) < 9%.
4. Subjects with poor or no (surgical or endovascular) revascularization optionclassified as CLI Rutherford Category 4. The blood circulation in these subjects mustbe compromised at screening, defined as:

• Ankle systolic pressure < 50 mm Hg, or
• Toe systolic pressure < 30 mm Hg, or
• TcpO2 < 30 mm Hg, and
• Flat or barely pulsatile ankle or metatarsal PVR

5. In the opinion of the Investigator, the subject is controlled on medical therapyindicated for CLI (unless there is a documented contraindication or intolerance) andpain management is optimized.
6. Women of childbearing potential (i.e., fertile, following menarche and until becomingpost-menopausal unless permanently sterile) must have a negative pregnancy test atscreening. Men and women who are sexually active shall use effective contraceptivemethods for the duration of their participation in this study if the partner of themale participant, or if the female participant is of childbearing potential.

Exclusion Criteria:

1. Advanced CLI defined as presence of major tissue loss as significantulceration/gangrene proximal to the metatarsal heads (CLI Rutherford Category 6).Significant ulceration/gangrene means any ulceration that extends beyond thesubcutaneous tissue layer, or any gangrene or tissue necrosis proximal to themetatarsal heads.
2. CLI Rutherford Category 5.
3. Uncontrolled or untreated proliferative retinopathy.
4. Failed surgical or endovascular revascularization on the index leg within 10 daysafter the procedure.
5. Subjects in whom arterial insufficiency in the lower extremity is the result of acutelimb ischemia or an immunological or inflammatory or non-atherosclerotic disorder (e.g., thromboangiitis obliterans (Buerger's Disease), systemic sclerosis (bothlimited and diffuse forms).
6. Clinical evidence of invasive infection on index leg defined as major tissue loss atthe mid-foot or heel involving tendon and/or bone, and/or when intravenous antibioticsare required to treat the infection according to the Investigator.
7. At screening, the presence of only neuropathic ulcers on the index leg.
8. Amputation at or above the talus on the index leg.
9. Planned major amputation within the first month after randomization.
10. On the index leg, use of concomitant wound treatments not currently approved forischemic wound-healing within 30 days prior to screening or plans to initiate new,nonstandard-of-care treatments to the index leg during the trial.
11. Blood clotting disorder not caused by medication (e.g., thrombophilia).
12. Severe hypertension according to the Joint National Committee on Prevention,Detection, Evaluation, and Treatment of High Blood Pressure.
13. A platelet count < 50,000/ μL.
14. International normalised ratio (INR) > 1.5. For patients on anticoagulant medicationan INR > 1.5 is allowed, provided that the Investigator and the haematologist considerthe patient eligible to collect BM.
15. Evidence of moderate to severe hepatocellular dysfunction according to the treatingphysician.
16. Positive test for human immunodeficiency virus 1 (HIV 1), HIV 2, hepatitis B virus (HBV), hepatitis C virus (HCV) or Treponema pallidum.
17. Subjects who may not be healthy enough to successfully complete all protocolrequirements including BM collection, or who are not expected to survive more than 12months, or in whom results may be particularly difficult to assess, as assessed by theInvestigator.
18. Subjects who participate in another clinical interventional trial.
19. Subjects who have been treated with experimental medication within 30 days ofscreening.
20. Subjects who were treated with other cell therapies for CLI within the last 12 monthspreceding the screening visit.