TBC-1002 is a proliposomal intravesical paclitaxel formulation (PLIP), in development for intravesical administration in the treatment of non-muscle invasive bladder cancer (NMIBC). NMIBC is a common and highly recurrent disease that can often be difficult to treat. TBC-1002 would be the first chemotherapeutic therapy to be approved by the U.S. Food and Drug Administration for this indication in almost two decades.

LIPAC Oncology, a subsidiary of TesoRx Pharma, recently announced the successful completion of a Phase 1 clinical study and the initiation of a Phase 2A study to further investigate TBC-1002. Phase 1 study results showed escalating doses of TBC-1002 to be well tolerated with no dose limiting toxicity, and no irritative voiding (cystitis) symptoms. No systemic exposure or toxicity was observed, even with high concentrations of TBC-1002 being delivered topically to the bladder wall. Phase 1 results also indicated preliminary efficacy with no evidence of bladder tumor recurrences observed up to 15 months after dosing in all but one patient. Adverse events were minor and not considered study related.

Common disease

Bladder cancer is a common disease affecting 3.4 million people globally with approximately 430,000 new cases every year. In the U.S., bladder cancer is the sixth most common type of cancer with more than 500,000 bladder cancer patients and approximately 75,000 new cases per year.

Bladder cancer is generally separated between non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). More than 70 percent of bladder cancer patients are diagnosed with NMIBC, prior to the tumor advancing from the urothelium (bladder lining) into the detrusor muscle of the bladder wall. Although NMIBC survival rates are high it has a recurrence rate of 31-78 percent NMIBC is expensive to treat, placing a significant financial burden on the healthcare system and severely impacting patients' quality of life.

Lack of effective treatments

Treatment of NMIBC is based on risk stratification. Most patients are initially treated with a transurethral resection of bladder tumor (TURBT) followed by a single, immediate instillation of intravesical chemotherapy to eliminate any residual tumor cells. Subsequent therapy is typically based on risk and consists of one year of intravesical treatments of the live vaccine Bacillus Calmette-Guerin (BCG).  Another common type of postoperative intravesical chemotherapy used to treat NMIBC is mitomycin C, usually given immediately or soon after TURBT.

Unfortunately, mitomycin C and BCG are inadequate for many patients with NMIBC. BCG is occasionally poorly tolerated and may introduce risk for systemic infections. Mitomycin C is hydrophilic and does not penetrate the urothelium on the bladder wall resulting in limited drug exposure to tumors and overall low efficacy. Additionally, limited supply of BCG has resulted in it only being available for the most serious patient cases.

Formulation benefits

  • Highly active against metastatic bladder cancer with in vitro studies showing it is 200-fold more effective than paclitaxel alone

  • Enhanced tolerability and no systemic toxicity

  • Liposomal formulation fuses to the bladder wall targeting bladder cancer cells and penetrating the lamina propria

  • Optimized off-load-kinetics and intratumoral concentration relative to Abraxane

  • Closed packaging system allows for less complicated storage and ease of handling

  • In vitro studies indicated PLIP penetrates the bladder wall more effectively than paclitaxel alone

  • The PLIP formulation is prepared as a dry powder that mitigates the potential risks of scale up and manufacturing

  • Can be stored in office by physicians and safely transported without the degradation issues common in liposomal formulations

  • At time of treatment, water for injection (WFI) is added into the closed system to hydrate TSD-001, forming a liposomal formulation for intravesical instillation

  • Higher drug load in proliposomal formulation results in increased potency against cancer cells

  • Paclitaxel is an existing molecule with a well-established efficacy and safety profile. Given this and previous regulatory approvals, LIPAC has a 505(b)2 pathway agreed to with the U.S. Food and Drug Administration