The OLYMPUS Study - Optimized DeLivery of Mitomycin for Primary UTUC Study

Trial TC-UT-03 is a prospective, open label, single-arm trial, designed to assess the
efficacy, safety, and tolerability of treatment with MitoGel™ instilled in the upper urinary
system of patients with non-invasive low-grade (LG), UTUC.

Upon signing of informed consent, the patients will undergo a screening visit for eligibility
evaluation. Eligible patients will be treated with MitoGel™ once weekly for a total of 6
times; in a retrograde fashion. Patients who will demonstrate CR will be treated with
MitoGel™ once monthly as a maintenance therapy for a total of 11 instillations or up to the
first recurrence whichever comes first.

Five (5) weeks (± 1 w) following the last instillation, the PDE Visit, during which safety
and efficacy will be assessed, will take place. During this visit, the ablative effect of the
MitoGel™ will be assessed visually, by upper tract washed urine cytology, and if there are
remaining tumors, by biopsy or brush biopsy if technically feasible.

Patient demonstrating CR at PDE will undergo monthly maintenance instillations of MitoGel™ up
to 11 months post PDE. Safety follow-up for these patients will be done until one month post
last instillation or at the end of the follow-up period in FU visit 12, which is the earlier.

For patients who did not demonstrate Complete Response, to the extent that it is possible,
all remaining tumors lesions will be biopsied. The patients shall undergo any additional
surgical or other treatment the PI decides deem necessary to remove remaining tumor.

An independent Data Monitoring Committee (DMC) was assigned to this trial. Accumulating
safety, tolerability and efficacy data will be monitored periodically by the DMC according to
a pre-specified process and frequency detailed in the DMC charter.

Main Inclusion Criteria:

1. Patient is at least 18 years of age.

2. Naive or recurrent patients with LG, non-invasive UTUC in the pyelocalyceal system.

3. Patient has at least one (1) measurable papillary LG tumor, evaluated visually, ≤ 15
mm. The largest lesion should not exceed 15mm.

4. Biopsy taken from one or more tumors located above the ureteropelvic junction (UPJ)
showing LG urothelial carcinoma. Diagnosed not more than 2 months prior to the
screening.

5. Patient should have at least one remaining papillary LG tumor evaluated visually with
a diameter of at least 5 mm.

6. Wash urine cytology sampled from the pyelocalyceal system documenting the absence of
HG urothelial cancer, diagnosed not more than 2 months prior to the screening.

7. Patient with bilateral LG UTUC may be enrolled if at least one side meets the
inclusion criteria for the trial and if the other kidney does not require further
treatments (The other kidney can be treated prior to the beginning of the study).

Main Exclusion Criteria:

1. Patient received BCG treatment for UC during the 6 months prior to Visit 1.

2. The patient has untreated concurrent urothelial cancer in other locations other than
the target area (unless treated during screening)

3. Carcinoma in situ (CIS) in the past in the urinary tract.

4. Patient has a history of invasive urothelial carcinoma in the urinary tract during the
past 5 (Five) years.

5. Patient has a history of high grade papillary urothelial carcinoma in the urinary
tract during the past 2 (Two) years.

6. Patient is actively being treated or intends to be treated with systemic chemotherapy
during the duration of the trial.