A Study Evaluating Temferon in Patients with Glioblastoma & Unmethylated MGMT

Inclusion Criteria:

• Histologically confirmed, newly diagnosed supratentorial glioblastoma withunmethylated MGMT gene promoter.

• Patients have undergone complete or partial tumor resection.

• Able and willing to provide written informed consent and comply with the studyprotocol and procedures.

• Eligible for radiotherapy.

• Life expectancy of 6 months or more at Screening.

• Women of child-bearing potential enrolled in the study must have a negativepregnancy test at screening and agree to use acceptable methods of contraceptionduring the trial.

• Men enrolled in the study with partners who are women of child-bearing potential,must be willing to use an acceptable barrier contraceptive method during the trialor have undergone successful vasectomy at least 6 months prior to entry into thestudy. Successful vasectomy needs to have been confirmed by semen analysis.

≥70.

Additional inclusion criteria to be assessed within 20 days of Temferon administration:

• Adequate cardiac, renal, hepatic and pulmonary function as evidenced by:

• Left ventricular ejection fraction (LVEF) ≥ 45% by echo and normal electrocardiogram (ECG) or presence of abnormalities not significant for cardiac disease.

• Absence of severe pulmonary hypertension;

• Diffusing capacity of the lung for carbon monoxide (DLCO) >50% and forced expiratoryvolume in 1 sec (FEV1) and forced expiratory vital capacity (FVC) > 60% predicted (if non cooperative: pulse oximetry > 95% in room air);

• Serum creatinine < 2x upper limit normal and estimated glomerular filtration rate (eGFR) ≥ 30ml/min/1.73m^2;

• Alkaline phosphatase (ALP), alanine aminotransferase (ALT) and/or aspartateaminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 2.0 mg/dl.

• Hemoglobin ≥10 g/dL, platelet count ≥100000/mm^3, absolute neutrophil count >1500/mm^3.

Exclusion Criteria:

• Use of other investigational agents or procedures within 4 weeks prior to studyenrolment (within 6 weeks if use of long-acting agents) or participation in aprevious gene therapy study.

• Known hypersensitivity to carmustine (or any other nitrosurea), busulfan, thiotepa,lenograstim, plerixafor, or any excipients used in these products.

• Receipt of any oral or parenteral chemotherapy or immunotherapy within 2 years ofScreening.

• Previous allogeneic bone marrow transplantation, kidney or liver transplant.

• Clinical evidence of persistent raised intracranial pressure following surgicalresection.

• Clinically relevant active viral, bacterial, or fungal infection at eligibilityevaluation.

• Active autoimmune disease or a relevant history of important autoimmunemanifestations, in particular psoriasis, systemic lupus erythematosus (SLE),rheumatoid arthritis, vasculitis, immunemediated peripheral neuropathies.

• History of sarcoidosis.

• History or current evidence of neuropsychiatric illness including depression,schizophrenia, bipolar disorders, impaired cognitive function, dementia or suicidaltendency.

• History of severe cardiovascular disease such as prior stroke, coronary arterydisease requiring intervention or unresolved arrhythmias in the past 6 months.

• Evidence of any hematological neoplasm.

• Positivity for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2) (serology orRNA), and/or Hepatitis B Virus Surface Antigen (HbsAg) and/or Hepatitis B Virus (HBV) DNA and/or Hepatitis C virus (HCV) RNA (or negative HCV RNA but on antiviraltreatment) and/or Treponema Pallidum or Mycoplasma active infection.

• Active alcohol or substance abuse within 6 months of the study.

• Current pregnancy or lactation.

• Known bleeding diathesis or history of abnormal bleeding, or any other knowncoagulation abnormalities that would contraindicate lumbar puncture for CSF orfuture surgery.

• Use of immunosuppressants with the exception of steroids. The maximum permitteddexamethasone (or equivalent) dose is 4 mg per day.