BB-101 for the Treatment of Diabetic Lower Leg and Foot Ulcers

Inclusion Criteria:

• Male or female, at least 20 years of age (inclusive) at the date of Screening

• Subject or legally authorized representative who is able to understand the nature ofthis study and accepts to enter the study by signing written informed consent

• Subject agrees to comply with ulcer care regimen for the duration of the study andis willing to return for all mandatory visits as defined in the protocol

• Subject with Type 1 or Type 2 diabetes mellitus (criteria for the diagnosis ofdiabetes mellitus per American Diabetes Association) and is under the care of aphysician for the management of diabetes mellitus

• Subject with glycosylated hemoglobin (HbA1c) ≤ 12%

• Subject with at least one diabetic foot ulcer meets the following criteria atScreening

Visit:

i. Located below knees; ii. Not healing for ≥ 4 weeks prior to Screening Visit despite appropriate care; iii. Ulcer size of ≥ 1 cm2 to ≤ 10 cm2 measured by the electronic measuring device following sharp debridement (if necessary) at Screening Visit and reconfirmed at Randomization Visit; iv. The largest ulcer will be selected as target ulcer. If ≥ 2 ulcers have the largest size, the one with the worst grade by Wagner Classification will be selected. If ≥ 2 ulcers have the largest size and grade, the one with longest duration will be selected; v. The target ulcer is classified as Grade 1 to Grade 2 according to Wagner Classification System for diabetic foot ulcer; vi. The target ulcer should be without clinical signs and symptoms of infection

• Subject with adequate circulation to the affected lower limb, as demonstrated by atleast one of the following criteria: i. Dorsum transcutaneous oximetry (TcPO2) ≥ 30mmHg ii. Ankle brachial pressure index (ABPI) ≥ 0.7 iii. Absolute toe blood pressure > 30 mmHg iv. Doppler ultrasonography showed < 75% stenosis in the lower extremityarteries

• Subject with adequate hepatic and renal function: i. Serum creatinine ≤ 3 mg/dL ii. ALT and AST ≤ 2 × ULN

• Subject with adequate hematology function: i. Absolute neutrophil count (ANC) ≥ 1,500 cells/μL ii. Total white blood cell (WBC) ≥ 3,000 cells/μL iii. Platelets ≥ 100,000 counts/μL iv. Hemoglobin ≥ 10 g/dL formale, ≥ 9 g/dL for female

• Female subjects show negative serum pregnancy test results within 21 days prior tothe first study treatment.

• All male subjects and female subjects with child-bearing potential (between pubertyand 2 years after menopause) should use at least any one of the appropriatecontraception methods during dosing and for at least 4 weeks after stopping studytreatment.

Exclusion Criteria:

• Clinical signs and symptoms of infection of target ulcer assessed by clinicalevaluation.

The presence of infection is defined by ≥ 2 of the items presented as:

• Local swelling or induration

• Erythema > 0.5 cm around wound

• Local tenderness or pain

• Local increased warmth

• Purulent discharge

• Subject with cellulitis or gangrene on the lower leg or foot with the targetulcer

• Subject with active osteomyelitis

• With target ulcer size decreased or increased by at least 30% after receiving 2weeks of standard-of-care for diabetic foot ulcer before Randomization visit

• Subject with another open ulcer < 2 cm away from target ulcer, on the samelower leg or foot

• Subject with target ulcer caused primarily by etiologies not related todiabetes

• Subject with target ulcers related to an incompletely healed amputation wound

• Subject with any structural deformity of the lower leg or foot under study thatwould prevent off-loading of the target ulcer; subject with conditions whichmay interfere the off-loading effect may be excluded by the Investigators'judgment

• Subject is scheduled to (or has received within 4 weeks prior to Screen Visit)receive any of the following medications or treatments:

• Platelet-derived product (e.g., becaplermin) or other growth factors on the targetulcer

• Systemic corticosteroids (other than for inhalation), immunosuppressive agents,radiation therapy, or chemotherapeutic agents

• Participation in a clinical trial of an investigational drug or device

• Previous use of autologous graft or allogeneic graft, or dermal substitute orliving skin equivalent (e.g., Dermagraft® or Apligraf® ) on the target ulcer orhyperbaric oxygen therapy within 2 weeks prior to Screening Visit

• Use of any topical antimicrobials or enzymatic debridement treatment to treatthe target ulcer within 7 days prior to Screening Visit

• Subject with history of cancer or current cancer, with the exception of basalcell carcinoma, squamous cell carcinoma in situ of the skin, or cervicalcarcinoma in situ that has been treated with no evidence of recurrence, orsquamous cell carcinoma of the skin that has been treated with no evidence ofrecurrence within 5 years prior to administration of any study agent

• Vasculitis, connective tissue diseases, or any medical conditions known toimpair ulcer healing, other than diabetes

• Subject diagnosed with sickle cell disease

• Subject with clinically significant electrocardiogram (ECG) abnormality, asdetermined by the Investigator

• Poor nutritional status (serum albumin < 2.5 g/dL)

• C-reactive protein (CRP) > 50 mg/dL

• Subject had a history of drug abuse or alcohol abuse according to theDiagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5)criteria.

• Patient with positive result of Human immunodeficiency virus (HIV)

• Female subject in lactation during the study period

• Subject with underlying medical, mental or psychological conditions that wouldimpair the treatment compliance, or in the opinion of the Investigator wouldnot permit to participate in the study