NEW YORK, NY / ACCESSWIRE / December 10, 2015 / The term 'platform technology' gets a lot of play, some of it hype, but when an emerging and scientifically sound biotech company shows promise of multiple uses for its core drug, investors should take notice. This is the case with Can-Fite BioPharma Ltd. (NYSE MKT: CANF), who last month released convincing preclinical data that its CF102, currently in trials for a common form of liver cancer, has a beneficial effect on non-alcoholic steatohepatitis (NASH), an insidious disease not readily manifested, making it all the more dangerous. No treatment exists, as a fat-infused liver becomes scarred and, finally, non-functional. A patent for CF102 in NASH has been filed and human studies could commence next year.
Using animals rendered diabetic, Can-Fite showed a statistically significant drop in non-alcoholic fatty liver disease (NAFLD) versus placebo that included declines in triglycerides, a major contributor to liver fat and most important, steep decreases in liver inflammation - something at which Can-Fite's drug platform excels (other indications are psoriasis and arthritis, both in mid-stage studies). Can-Fite's compounds in study, all in pill form, are based on the A3 adenosine receptor (A3AR), expressed in abundance in cancer cells and where inflammation occurs. Because A3AR is not found in healthy tissue lends to it a specific therapeutic response, and a high level of safety unlike chemotherapy that takes a shotgun approach to healing.
Adenosine receptors, generally exerting an inhibitory function in tissue, appear throughout the body to serve several functions: in the heart, they regulate blood flow; in the brain, slow metabolic activity with a depressant effect on the central nervous system; and, more recently, stimulation of adenosine receptors in the liver are linked to preventing NASH in rats. Can-Fite previously found that CF102 binding with A3AR found in high abundance in tumor cells exerts a strong anti-tumor effect. Killing liver cancer cells resulted. In early trials, CF102 was used in a patient that has now survived five years.
NASH is known medically as a 'silent' disease because symptoms don't appear as the condition progresses. Up until the time cirrhosis develops, years or even decades later as liver fat accumulates, patients begin to feel fatigue and weakness accompanied by weight loss. Sometimes reversing itself without therapy, more often the effects of NASH manifest in scar tissue, hardening the liver and compromising its function. Severe scarring and cirrhosis leads to fluid retention, intestinal bleeding, muscle wasting (from the absence of vital proteins needed to feed muscle tissue that the liver can no longer supply), and, finally liver failure.
A liver must be 25% functional to regenerate but cirrhosis, as scar tissue, cannot be made into healthy liver tissue again. Few treatments can halt progression and once the muscle atrophy stage is reached, candidates for liver transplant fall significantly. Behind Hepatitis C and liver damage caused by alcohol, NASH is a major source of cirrhosis in the US. Origins are largely unknown but NASH has been linked to obesity, high cholesterol, insulin resistance, or simply liver cell deterioration through an overabundance of free radicals that damage DNA. Antioxidants like vitamin E have been tried to bring down the number of free radicals; nothing by the way of conclusive clinical trial results have been published. Antidiabetic orals like metformin are studied but the nature of NASH and its cloudy roots in biology make trials suspect in the eyes of hepatologists.
As a silent disease, current estimates of treating NASH and its consequences fall short of potential dollar amounts. Approximately 81 million Americans are afflicted with NAFLD (some 10% are children), with up to 30% developing NASH - 24 million people, nearly 8% of our population, of them, another 30% progress to cirrhosis with a high risk of liver cancer. The resulting burden to our already top-heavy healthcare system is shocking: within the next 10 years, NASH treatment and ancillary costs are expected to reach $35 billion, called by many the "Next Big Global Epidemic". Numbers for territories outside of the US mirror those here.
Last October, Can-Fite was granted the European Medicines Agency's coveted Orphan Drug status for CF102, for treating liver cancer that includes a 10-year market restriction to competition in 31 countries of the European Economic Area. The drug also has FDA Fast Track designation and Compassionate Use in Israel. Phase II studies for the indication are currently conducted in all three territories.
Progression of Liver Disease
Competition for NASH treatment is sparse, peppered with failure. Galmed Pharmaceuticals Ltd. (GLMD:NASDAQ), while studying a remedy for gallstones with its lead drug Aramchol, found a reduction in liver fat in mice, then pursued NASH as a potential indication. After a 3-month trial, no significant changes were found in elevated liver enzymes, forcing the company to switch tactics to focus on HIV- associated body fat wasting, with positive effects for NAFLD as a hopeful result. Company officials have made public their desire of a "de-risking" strategy for Aramchol to bring the product eventually to market. Good luck.
Shares of French firm Genfit SA (GNFTF:Other OTC) took a beating in March when Phase II for GFT505, a type of gene therapy, failed to surpass placebo in NASH - showing no liver fat reduction or stabilization of liver fibrosis. Undaunted, Genfit claimed the trial a success when certain data was removed (a clear and audacious example of data-mining), and prepared a Phase III launch by year-end, under FDA accelerated approval. Meanwhile, Genfit contemplates a sale of the company and its assets.
Considered the lead in possible treatments for NASH, Intercept Pharmaceuticals (ICPT:NASDAQ) also disappointed investors when a Phase II Japanese trial of its drug obeticholic acid (OCA), based on intestinal bile, did not pan out as expected. As many as 200 patients endured varying doses of OCA for over one year; only the highest dosage met the primary endpoint - a two-point improvement in scoring for NASH symptoms with stability in liver fibrosis. However, there was no significant difference in fibrosis across the cohorts, and patients left the study due to "intolerable itching"; raised cholesterol levels gave researchers pause when evaluating the drug's safety. Intercept has FDA Breakthrough Designation for NASH with liver fibrosis and plans an extensive Phase III trial, hoping that more patients might mean better outcomes.
Biotech powerhouse Gilead Sciences (GILD:NASDAQ) has a project devoted to NASH; this entails a monoclonal antibody, simtuzumab, supposed to work in battling liver fibrosis. Known more for immunotherapy, Gilead stumbled with its drug last September in a Phase II study for pancreatic cancer where no significant results were proven. Turning to NASH, Gilead uses the same monoclonal antibody in trials but in its third-quarter conference call, frustrated investors with the news the FDA requested a doubling of data - from the submitted 48 weeks to 96 weeks.
A breakdown of competitors appears below:
Besides standard risks accompanying every small biotech, an investment in Can-Fite should include the chance for less-than positive outcomes in late-stage clinical trials. So far, news has been good although larger studies ultimately make or break any new drug. Adenosine receptors are notoriously complex by virtue of their interactions with many other receptors in the body; this could lead to confusing results or none at all. Competitors, recognizing the upcoming NASH epidemic, have more resources to fund clinical trials and although their results have been mixed, efforts remain persistent.
Can-Fite has a unique approach to NASH, one that does not use unsuitable antibodies like Gilead, or bile-based medicine like Intercept Pharmaceuticals. Can-Fite's results in liver cancer have been verified, and can now be applied to NASH. With the NASH market large and growing, Can-Fite looks to be a strong contender in this multi-billion dollar market.
About Small Cap Forecasting, Inc.
Sharon di Stefano has spent 20 years as an analyst, beginning her career at Smith Barney, Harris Upham & Co. specializing in medical devices, pharmaceuticals, healthcare information technology, and bio-pharmacology. Ms. di Stefano had also served as Senior Venture Officer for the Edison Innovation Fund, implemented through the New Jersey Economic Development Authority that provided funding for early-stage life sciences companies. Industry experience includes laboratory research for Johns Hopkins Hospital and the Department of Defense. Ms. di Stefano received a Master's of Science degree, in Business, from Johns Hopkins University in 1986, and a Bachelor of Arts from the University of Delaware in 1984 with a minor in biology.
SOURCE: Small Cap Forecasting, Inc.