The Efficacy and Safety of UGN-102 as a Primary Chemoablative Therapy in Patients With LG NMIBC at Intermediate Risk of Recurrence

This study is a prospective, open-label, single-arm, multicenter Phase 2b trial designed to
assess the efficacy and safety of UGN-102 treatment instilled in patients diagnosed with LG
NMIBC, including newly diagnosed patients, and determined to have intermediate risk of
progression, defined as 1 or 2 of the following: multiple tumors, tumors >3 cm, early
recurrence (within 1 year of diagnosis), or frequent recurrence (>1 recurrence within 1 year
of current diagnosis). Eligible patients will be treated with 6 weekly instillations of
UGN-102.

UGN-102 is a reverse thermal hydrogel formulated with MMC. The product is specifically
formulated to achieve a liquid state at 4°C and to transition to a water-soluble gel at body
temperature. The advantage of delivering Mitomycin to the urinary bladder using UGN-102
relies on preclinical and clinical literature documenting that concentration and dwell time
correlate directly with the therapeutic efficacy of MMC when used to treat Urothelial
Carcinoma (UC)

The ablative effect of UGN-102 will be evaluated at the Primary Disease Evaluation (3 MONTH)
assessment, which will take place 5 weeks ±1 week after the last weekly instillation (3
months after initiation of study medication). Response will be determined based on visual
evaluation by cystoscopy (appearance, number, size, and location of the lesions) and, if
there are remaining lesions, by histopathology of the remaining lesions. CR is defined as
having no detectable disease (NDD) and will be assessed visually during cystoscopy and also
upon urine cytology. In the event that the investigator is not sure, and there is suspect
tissue, a small biopsy will be taken from the suspect tissue to confirm CR in addition to
cystoscopy and urine cytology. Patients who achieve a CR will receive monthly maintenance
treatments with UGN-102 and will be assessed at 6, 9, and 12 months after the first
instillation of UGN-102 for evidence of disease recurrence. The group of patients considered
nonresponders (non-CR) will discontinue the study and continue with standard of care
according to their treating physician.

Safety will be determined based on physical examination, laboratory assessments, and a review
of AEs. All safety data will be reviewed on an ongoing basis, including close review and
follow up of any unexpected AE related to UGN-102 and qualified per National Cancer Institute
(NCI) Common Terminology Criteria for Adverse Events (CTCAE) as Grade 3 or 4.

Inclusion Criteria:

1. ≥ 18 years of age.

2. Willing and able to sign an informed consent and comply with the protocol.

3. Has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed by cold cup
biopsy at screening or within 6 weeks of screening

4. Is at intermediate risk for progression, defined as having 1 or 2 of the following:

1. presence of multiple tumors,

2. solitary tumor >3 cm

3. recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis).

5. Has negative voiding cytology for HG disease at or within 6 weeks of enrollment.

6. Willing to use 2 acceptable forms of effective contraception from enrollment through 6
months post treatment if the female partner is of childbearing potential (defined as
premenopausal women who have not been sterilized).

7. Has adequate organ and bone marrow function as determined by routine laboratory tests
as below:

Leukocytes ≥3,000/μL (≥3×109/L), Absolute neutrophil count ≥1,500/μL (≥1.5×109/L),
Platelets ≥100,000/μL (≥100×109/L), Hemoglobin ≥9.0 mg/dL, Total bilirubin ≤1.5 upper
limit of normal (ULN), AST (SGOT)/ALT (SGPT) ≤2.5 × upper limit of normal (ULN), ALP
≤2.5 × ULN, and Estimated glomerular filtration rate (eGFR) ≥30 mL/min.

8. Has no evidence of active urinary tract infection (UTI) at Screening and Baseline
visits.

In the case of symptomatic UTI, the patient will be treated with a full course of
antibiotics, and study medication will be postponed until resolution. In the case of
asymptomatic bacteriuria, the use of prophylactic antibiotics and postponement of study
medication is left to the discretion of the Principal Investigator (PI).

Exclusion Criteria:

1. History of Carcinoma in Situ (CIS) on preliminary cystoscopy within 5 years of
enrollment.

2. Received Bacillus Calmette-Guérin (BCG) treatment for UC within previous 2 years.

3. History of HG papillary UC in the past [2] years

4. Known allergy or sensitivity to mitomycin.

5. Clinically significant urethral stricture that would preclude passage of a urethral
catheter.

6. History of pelvic radiotherapy.

7. History of:

1. neurogenic bladder

2. active urinary retention

3. any other condition that would prohibit normal voiding

8. Past or current muscle invasive (i.e., T2, T3, T4) or metastatic UC or concurrent
upper tract urothelial carcinoma (UTUC).

9. Has participated in a study with an investigational agent or device within 30 days of
enrollment.

10. History of prior treatment with an intravesical chemotherapeutic agent with the
exception of a single dose of chemotherapy immediately post-TURBT.

11. Has an underlying substance abuse or psychiatric disorder such that, in the opinion of
the investigator, the patient would be unable to comply with the protocol.