Compassionate Use of MitoGel in Upper Tract Urothelial Carcinoma

Upper urinary tract urothelial carcinoma (UTUC) is a rare malignant neoplasm arising from
the urothelial lining of the renal collecting system and ureters. The current treatment
paradigm for UTUC involves endoscopic resection, when technically feasible and oncologically
sound, or complete resection of the kidney and ureter (nephroureterectomy) in cases in which
organ-sparing treatment is not feasible.

Both organ-sparing and complete resection options present significant technical and clinical
challenges. For patients with bilateral disease, an anatomic or functionally solitary
kidney, or significant underlying medicorenal disease, treatment with nephroureterectomy
would result dialysis dependence, a state which carries with it a significant risk of 5-year
mortality in the often elderly and co-morbid patient population affected by UTUC.

MitoGel is a novel investigational product composed of RTGel, a unique hydrogel polymer
which exists as liquid at cold temperatures and a viscous gel at body temperatures, and
Mitomycin C, a clinically proven safe and effective treatment for urothelial carcinoma in
the bladder. MitoGel can be instilled into the upper urinary tract as a cold liquid, where
it solidifies to a gel upon warming to body temperature. The agent remains in the upper
tract for a period of 4-6 hours, resulting in sustained contact between the tissues and
Mitomycin C. Preclinical studies of MitoGel in the Yorkshire swine have demonstrated that
both single and serial instillations into the pelvicalyceal system via both retrograde and
antegrade approaches are safe, with no observable adverse clinical, laboratory, or
histological effects. For these reasons, MitoGel has generated interest as a treatment for
UTUC.

For patients with UTUC in whom nephroureterectomy would result in dialysis dependence, and
in whom the disease is difficult to manage endoscopically, there is no currently available
means to effectively deliver adjuvant chemotherapy to the upper tracts. These patients are
thus either condemned to treatment with complete resection of their kidney and resultant
hemodialysis, or risk progression of disease to an incurable and unmanageable state. MitoGel
represents a promising treatment option for patients who have no other therapeutic options.
For these reasons, MitoGel has been granted Orphan Designation Status by the FDA. While
clinical trials of MitoGel are currently being planned, no trials are open to date.

The aim of this study is to evaluate the feasibility, safety, and efficacy of MitoGel in the
treatment of UTUC in a human subject with low-grade UTUC which is endoscopically
unresectable or rapidly recurring, and in whom nephrectomy would likely result in the need
for permanent hemodialysis. The study drug would be obtained under the single patient access
program approved by the FDA. The patient would then undergo instillation of MitoGel into the
affected kidney. The catheter would be left indwelling in the ureter and would be
externalized through a urethral catheter. The ureteral and urethral catheters would remain
indwelling for the duration of the 6 treatments, which would occur twice weekly for 3 weeks.
Following the final instillation, the catheters would be removed. The patient would then
undergo ureteroscopic evaluation at 3 months following the final instillation of MitoGel.
The total duration of study would be 3 months. The total number of study patients is 1.

Inclusion criteria:

- Therapy to be utilized as part of the FDA Compassionate use IND

- Histologically confirmed low grade upper tract urothelial carcinoma which is
high-volume and difficult to control using standard ablative therapies

- Anatomically solitary kidney or renal insufficiency significant enough such that
nephroureterectomy would result in dialysis dependence

- Willing to consent and participate in a single-patient expanded access use under an
FDA IND agreement

- Willing to maintain an indwelling foley catheter for a period of 3 weeks

Exclusion criteria

- Hypersensitivity to mitomycin C or any of the other drug components

- Is currently participating in or has participated in a study of an investigational
agent or using an investigational device within 4 weeks of the first dose of
treatment

- Has an active urinary tract infection

- Is unable to tolerate the treatments

- Demonstrates progressively worsening renal dysfunction

- Has a known additional malignancy that is progressing or requires active treatment

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial