Safety Study of BMX-001 (Radio-protector) in Patients With Newly Diagnosed Anal Cancer

In this Phase 1 study, the investigators will conduct a dose-escalation study of the
combination of BMX-001 with standard radiation therapy (RT) and concurrent 5-fluorouracil
(5FU)/mitomycin in newly diagnosed Anal Squamous Cell Carcinoma (ASCC) patients. The dose
escalation will be a Rolling-6 design, which is an efficient phase I trial design, to
determine the maximum tolerated dose (MTD) of BMX-001 in combination with concurrent
5FU/mitomycin and RT. Subjects will be administered BMX-001 subcutaneously first as a loading
dose at least 2 hours before the initiation of chemoradiation and then at a maintenance dose
(50% of the loading dose) twice a week for up to seven weeks.

Based on Rolling-6 design (1), cohorts of 2-6 patients are concurrently enrolled onto a dose
level, beginning with 0.1 mg/kg, until the maximum tolerated dose (MTD) is defined. The
average number of subjects required for this Phase 1 is estimated to be 20, and the maximum
estimated to be 24. The maximum tolerated dose (MTD) is the highest dose level at which ≤ 1
out of 6 subjects experienced DLT. If no DLT has been identified at the highest dose proposed
(loading dose of 0.6 mg/kg followed by 0.3 mg/kg twice per week) this will be accepted as the
MTD.

In order to evaluate the pharmacokinetics (PK) of BMX-001 in combination with current
chemoradiation, blood samples will be drawn for analysis. Blood will be drawn for PK on the
following days: Day 1 (before and after loading dose), Day 8, Day 22 and Day 36. Measures
will be obtained at approximately the following times: -1 to 0 hour (before loading dose), 30
minutes after the drug is given, 4 hours post-dose, and 24 hours post-dose.

Rectal, GI, and GU symptoms will be measured on the day of screening, weekly during RT, 1
months, 4 months and 10 months after the completion of RT. Perianal skin will be assessed
weekly during RT, 1 month, 4 months, and 10 months after completion of RT. Further follow up
will be per standard of care.

Inclusion Criteria:

- Patients with pathologically confirmed locally advanced anal squamous cell carcinoma
(including oligometastatic disease) who will be receiving concurrent chemoradiation
with standard 5FU/Mitomycin regimen with curative intent.

- Any cancer stage that will require a dose of 59.4 cGy.

- Age ≥ 19 years

- Karnofsky Performance Status (KPS) ≥ 60%

- Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 /dl, platelets ≥ 100,000 /dl (The use of
transfusion or other intervention to achieve Hgb > 9.0 g/dl is acceptable)

- Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times upper limit of
normal

- Signed, written informed consent

- Negative pregnancy test for women of child-bearing potential within 48 hours prior to
first dose of BMX-001

- Women of childbearing potential and male participants must agree to use a medically
effective means of birth control throughout their participation in the treatment phase
of the study and until 12 months following the last study treatment

- PET/CT/ pelvic MRI done within 8 weeks of trial initiation

Exclusion Criteria:

- Breast-feeding

- Active infection requiring IV antibiotics 7 days before enrollment

- Prior, unrelated malignancy requiring current active treatment with the exception of
cervical carcinoma in situ, basal cell or carcinoma of the skin, invasive cancers with
a 5-year disease-free interval, resected cancer of the bladder or low-grade (Gleason 6
or less) prostate cancer

- Prior history of ASCC

- Prior history of pelvic radiotherapy for any other type of malignancy

- Known hypersensitivity to 5FU and/or mitomycin

- Because corticosteroids are anti-inflammatory and could interrupt oxidative stress,
patients will be required to be on stable or decreasing corticosteroids dose at the
time of the study.

- Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg
and/or diastolic blood pressure > 100 mmHg)

- Active or history of postural hypotension and autonomic dysfunction within the past
year

- Known hypersensitivity to BMX-001

- Clinically significant (i.e. active) cardiovascular disease or cerebrovascular
disease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment,
myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York
Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or
serious cardiac arrhythmia uncontrolled by medication or potentially interfering with
protocol treatment

- History or evidence upon physical/neurological examination of central nervous system
disease (e.g. seizures) unrelated to cancer unless adequately controlled by medication
or potentially interfering with protocol treatment

- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
recent arterial thrombosis) within 6 months prior to start of study treatment