Urogen (URGN) has a data read-out of its Phase 3 Olympus study for low-grade UTUC, testing a formulation of Mitomycin C (MMC) in its hydrogel formulation, in January. I believe they have the data, and it will be released during JPM, probably by Thursday 1/10/19, the day of their presentation.

Let’s back up a bit: What is UTUC? It’s Upper Tract Urothelial Carcinoma, a cancer that can occur any way from the inner lining of the kidney, down the ureter, in the bladder, down the urethra. 92% of such occur in the bladder. The incidence rate in the US is about 6,000/year, with 1/3 of that categorized as low-grade. Low grade refers to the aggressiveness of the cancer (as opposed to Stage 0/1/2/3 which refers to invasiveness; kind of a precision vs. accuracy illustration). Non-aggressive cancer, though, doesn’t mean it won’t be invasive. The average age of patients is high, around 73 years old. 

Current standard of care is radical nephroureterectomy (removal of kidney). Some patients may be eligible for nephron-sparing surgery, or endoscopic ablation (usually uteroscopy or a laser), but higher recurrence rates are associated (Lerner 2018). From a systematic review, almost 53% of patients recurred 6-12 months after a procedure (Kapoor 2018). Adjuvant chemo/immunotherapy (Bacillus Calmette-Guerin, BCG, and generic Mitomycin C) is given to attempt to reduce recurrence, and has shown mild success, lowering 1-year recurrence by 17%-27 vs SoC (Leow 2016). BCG has shown to have sepsis issues, though. Another study showed adjuvant MMC with a 3-year recurrence-free rate of 60% vs 41% with BCG (Metcalfe 2017). The issues here arise because the contact time and dwell time of generic MMC is very low, due to constant urine production and flow (Kleinmann 2018).

Treatment-wise, urologic cancers have always been a bit of the child left behind. Not much progress has been made, and no drugs are currently approved for UTUC. Urogen has formulated MMC with its hydrogel technology. It’s actually based on a device called Backstop (marketed by Boston Scientific), which uses a hydrogel to keep kidney stones in place during extraction. The hydrogel formulation is liquid in cold temperatures, but solid at warmer ones. This increases contact time to 4-6 hours. There aren’t any non-invasive strategies to treat UTUC, which is a problem given the health risk of the older patient population. UGN-101 is intended to be a surgery-free option, and has shown about a 44% CR rate in a compassionate use program, with 3 responses lasting 18-30 months. However, 1 recurred at 4 months, 1 at 8 months, and 2 at 9 months (Kleinmann 2018). It’s important to note that compassionate use programs are more like individual case studies, since these patients have differing baselines and have no other treatment option. Positively, all of the CRs were seen in low-grade UTUC. In the interim Phase 3 data, 59% of patients had CR. It’s important to think about the patient population that cannot undergo surgery – Urogen may have a solution.

UGN-101 will likely be good enough, as a 20% CR rate is approvable according to the FDA. The stock has run up quite a bit into the data, since it’s largely expected to be positive.

UGN-102, MMC hydrogel for NMIBC, non-muscle-invasive bladder cancer, also has a Phase 2 data readout in 1H19. It’s a much larger population, as 400,000 patients world-wide (4th most common cancer) have bladder cancer, and 75% are categorized as NMIBC. 50% of these patients, after resection+chemo, recur due to tumor cell reseeding after surgery. Phase 2a data showed 86% CR at 80mg (40mg 45%, 120mg 83%), and 80% show durability 12 months after treatment. Durability will be a large focus in this dataset.