NovaTarg’s approach a tissue selective AMPK activators has clear potential in the treatment of hyperproliferative diseases:
Ovarian cancer (OC) has the highest mortality rate of all female cancers; more than 50% of the 21,650 women diagnosed with OC die annually of this disease.
OC is often associated with metabolic disease and increased BMI. However, Type 2 diabetic patients who have taken metformin for the long-term (≥ 30 prescriptions) have a reduced risk of ovarian cancer (OR 0.61, 95% CI 0.30-1.25 for metformin ).
Whereas sulfonylureas (OR = 1.26) and insulin (OR = 2.29) increased the risk of OC, which suggests that insulin itself is a growth factor in the development of OC.
NovaTarg drug candidates inhibit OC growth in 2 ways:
- Activation of AMPK in tumor cells inhibits cell growth via inhibition of the mTOR pathway, and direct effects on cancer stem cells
- Metabolic activity in OC patients is expected to improve insulin sensitivity and reduce insulin levels in patients, reducing levels of a growth factor that drives ovarian cancer
Liver cancer, primarily hepatocellular carcinoma (HCC), accounts for ~662,000 deaths each year and is the third leading cause of death from cancer worldwide. The age-adjusted incidence of HCC tripled between 1975 and 2005 in the U.S., and primary liver cancer mortality rates have increased faster than mortality for any other tumor type.
Only one drug (Nexavar/sorafenib) is approved for HCC, and this extends life by a modest 4 months. Treatment for patients with disseminated disease is dismal, and introduction of new and efficacious therapeutic options is critical for effective management of this disease.
NovaTarg drug candidates not only display liver tumor selective growth inhibition, they also treat the underlying causes of HCC (HCV, liver damage, and T2D). This innovative approach to HCC provides an opportunity for us to develop novel therapies where none exist at present.
GlobalData estimates that the liver cancer market in 2017 will be $1.2B. A novel drug that is complementary to, synergistic with, and equivalent or superior to Nexavar will have significant potential value.
Cancer has tremendous impact on the US healthcare system, with 1.5 million new cancer cases in 2010. This includes 58,240 new cases of renal cancer (92% of those are renal cell carcinoma, or RCC) and 13,040 deaths from renal cancer. With nearly $3.8 billion in direct medical cost attributed to renal cancer alone, it is clear that innovative cancer treatments with less adverse effects are urgently needed.
While surgical removal remains standard of care for localized kidney tumors, recent clinical trials have established the role of targeted therapy as the first line of therapy in patients with metastatic disease. While the number of drugs available for treatment of kidney cancer has increased dramatically since 2005, it is noteworthy that 4 of these (as well as several in late stage development) target angiogenesis while the other 2 are modified rapamycin analogues that target mTOR. Drugs with fewer side effects and a different mode of action would be valuable additions to current treatment regimen.
The NovaTarg approach to tissue selective AMPK activators has enabled us to identify compounds with potent growth inhibitory activity that selectively target kidney epithelial cells and offer an innovative approach to the treatment of RCC.
Polycystic Kidney Disease (PKD), while not a cancerous condition, is characterized by hyperproliferation of kidney epithelial cells and excess fluid secretion into oversized cysts. A number of therapeutic approaches are under consideration, but none has demonstrated convincing efficacy.
The NovaTarg approach to kidney-selective AMPK activators has the potential to both regulate kidney cell growth and fluid secretion – a disease modifying treatment for patients with no therapeutic options.