Major Need to Improve Bladder Cancer Treatments
Bladder cancer is the fourth most common cancer in men in North America.  In the U.S. alone, there are more than 500,000 bladder cancer patients with approximately 75,000 new cases per year.

Bladder cancer is typically segmented into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Most bladder cancer patients are diagnosed with NMIBC, before the tumor has invaded into the detrusor muscle deep in the bladder wall. While survival rates for patients with non-muscle-invasive tumors are high, high tumor recurrence rates negatively impact the quality of life of patients and are costly to the healthcare system. As such, there is an opportunity to more effectively treat NMIBC patients, intercepting the repeated cycle of recurrences and reducing the burden on patients and the health care system.

Treatment of NMIBC typically first involves transurethral resection of bladder tumor (TURBT). Unfortunately, microscopic residual tumor remains, leading to recurrence. In attempt to eliminate this residual tumor, chemotherapeutics such as mitomycin-C may be instilled into the bladder of low risk patients. Unfortunately the efficacy of this approach is very poor, largely due to very limited drug exposure (drug concentration and time). Other agents, such as the live vaccine Bacillus Calmette-Guerin (BCG), are administered in higher risk patients, and although the efficacy is greater than chemotherapeutics, significant tolerability limitations and a risk of systemic infection pose considerable challenges with this approach.

STK-01 for Non-Muscle-Invasive Bladder Cancer
Sitka Biopharma is developing a NMIBC treatment (STK-01) that combines our HPG nanoparticle platform technology with the established chemotherapeutic docetaxel. Docetaxel is a well-tolerated and effective chemotherapeutic that currently fails to be utilized in bladder cancer due to drug delivery challenges that prevent sufficient concentrations of the drug from gaining access to the tumors.

Through the unique design of our HPG nanoparticles, STK-01 is able to overcome the challenges of conventional intravesical chemotherapy and adhere to the bladder wall, transiently modulating the barrier function of the urothelium (tight junctions) and thereby facilitating penetration of docetaxel into the bladder wall. With a much higher concentration of docetaxel now gaining access to the interior tumors, STK-01 is poised to substantially enhance treatment benefit for bladder cancer.

With STK-01, we aim to develop the first front-line intravesical chemotherapeutic treatment for intermediate- and high-risk NMIBC patients.

Conventional Intravesical Chemotherapy

  1. Water soluble drugs instilled, held for 2 hrs
  2. Bladder wall prevents uptake of water (urine) soluble materials into tissue
  3. As a result, virtually all of the drug is expelled at end of procedure, no uptake into tissue and no residual drug to effect anti-tumor activity
Sitka Technology (HPG-docetaxel) addresses key issues

  1. Water soluble, mucoadhesive formulation quickly delivers drug to bladder surface
  2. Hydrophobic drug partitions into tissue wall
  3. Creates a long-lasting reservoir of high concentration drug, mm depth to treat any residual superficial tumor

Preclinical Studies Show Significant Improvement with STK-01
In preclinical studies, STK-01 has been demonstrated to significantly improve bladder tissue uptake and penetration when compared to standard formulations of docetaxel.

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Further, in animal models of bladder cancer, STK-01 demonstrated superior efficacy over docetaxel alone. This important demonstration provided preclinical proof-of-concept for the benefit of improved drug delivery (penetration and residence).