UroGen Pharma candidate products are based on two proprietary platform technologies:
RTGel – a novel proprietary polymeric biocompatible, reverse thermal gelation hydrogel
Unlike the general characteristics of most forms of matter, RTGel is liquid at lower temperatures and converts into gel form when heated. We believe that these characteristics promote ease of delivery into and retention of drugs in body cavities, including the bladder and the upper urothelial tract, by conforming to the anatomy of the target organ while preventing rapid excretion of the drug. . RTGel’s components are polymer-based and are inactive ingredients that have been approved by the FDA for use in other products such as Oraqix, a periodontal gel, Namenda, an oral solution for Alzheimer’s disease, and Xeloda, an oral chemotherapy. We formulate RTGel with an active drug: MMC in the case of MitoGel and VesiGel, and botulinum toxin in the case of BotuGel. The resulting formulations are instilled intravesically in liquid form directly into the bladder or upper urothelial tract using standard instillation methodologies via catheters and thereafter convert into gel form at body temperature. Subsequently, upon contact with urine, RTGel gradually dissolves and releases the active drug over a period of several hours, and is less affected by urine creation and voiding cycles as compared to water formulations.
RTGel, when formulated with an active drug, may allow for the improved efficacy of treatment of various types of urothelial cancer without compromising the safety of the patient or interfering with the natural flow of fluids from the urinary tract to the bladder. RTGel achieves this by:
- Increasing the exposure of active drugs in the bladder and upper urothelial tract by significantly extending the dwell time of the active drug while conforming to the anatomy of the bladder and the upper urothelial tract, which allows for enhanced drug tissue coverage. For example, the average dwell time of the standard MMC water formulation, currently used as adjuvant treatment, in the upper urothelial tract is approximately five minutes, compared to approximately six hours when MMC is formulated with RTGel;
- Administering higher doses of an active drug than would otherwise be possible using standard water-based formulations. For instance, it is only possible to dissolve 0.5 mg of MMC in 1 ml of water while it is possible to formulate up to 8 mg of MMC with 1 ml of RTGel; and
- Maintaining the active drug’s molecular structure and mode of action.
These characteristics of RTGel enable sustained release of MMC in the urinary tract for both MitoGel and VesiGel, and of botulinum toxin in the case of BotuGel. Further, RTGel may be particularly effective in the bladder and upper urothelial tract where tumor visibility and access are challenging, and where there exists a significant amount of urine flow and voiding. We believe that these characteristics of RTGel may prove useful for the local delivery of active drugs to other bodily cavities in addition to the bladder and upper urothelial tract.
Immunotherapy – locally triggering the innate immune system via unique formulation of immune modulating drugs for intravesical use. Based on this technology, UroGen Pharma is developing a unique immune-modulation drug candidate, Vesimune™, based on Toll like receptors 7 (TLR7) stimulators, for the treatment of Carcinoma in Situ (CIS) of the bladder.