Liver Disease Market Heating Up Small Biotechs

Non­Alcoholic Steatohepatitis (NASH), often called a “silent epidemic” that is slowly destroying the livers tens of millions of Americans, has attracted the attention of over a dozen pharmaceutical companies, including Gilead, Merck and Pfizer. The NASH treatment race started a couple of years ago and has recently heated back up on news that Allergan Plc is buying three companies focused on liver disease, including Tobira Therapeutics (TBRA) for a combined $2.4 billion. But, investors may also want to consider a few other companies that have a chance to be the best solution for treating NASH.

Endonovo Therapeutics, Inc. (ENDV) is a leading challenger to the Allergen acquisitions, and gives investors much more profit potential if it wins the race.

Endonovo is a developer of non­invasive electroceuticals targeting inflammatory conditions in vital organs. The company is initially concentrating on inflammatory conditions in the liver, such as acute liver injury and NASH. It brings a completely different approach to NASH than the rest of the competition that is developing drugs, in that it is developing a non­invasive approach that uses electrical stimulation to reduce inflammation in vital organs to treat the disease in its early stages. Endonovo’s device, which it has called Immunotronics, harnesses magnetically induced electrical field pathways in cells and organs to illicit an anti-inflammatory response. The company’s technology has already been shown to be a very potent anti-inflammatory device in a pharmaceutical “gold standard” model of inflammation. The company represents the most differentiated approach to the treatment of NASH and other inflammatory conditions in vital organs, and its biggest advantage is that it is a non­invasive device, so its regulatory pathway is much simpler than drugs.

Why NASH is So Hot Right Now

Non­Alcoholic Steatohepatitis (NASH) is liver inflammation and damage that is caused by a buildup of fat in the liver that is not caused by excessive alcohol consumption. It is a “silent” liver disease because most people with NASH feel well and are not aware that they have a liver problem. However, if left untreated, NASH can be severe and lead to cirrhosis, a condition where the liver is permanently damaged and can no longer function correctly.

This “silent epidemic” is being driven by the increasing number of Americans with obesity. NASH is estimated to affect 2 to 5 percent of Americans, and as much as a quarter of the American population has fat in their livers, a precursor condition to NASH called Non­Alcoholic Fatty Liver Disease (NAFLD).

There are currently no approved treatments for NASH. Therefore, it represents one of the last untapped multi­billion dollar therapeutic areas. The market could be worth $5 billion to $10 billion a year, according to a May estimate by RBC Capital Markets analyst Michael Yee.

Pharmaceutical companies are still studying how different components of the disease ­ inflammation, scarring and metabolic changes ­ interact and how different treatment mechanisms can be developed.

With so many companies entering the race for a NASH treatment, they’ll have to work very hard to distinguish themselves from the field.

Other Challengers

Besides the Gileads and Pfizers, there are a few other small biotechs aiming to treat NASH and other similar liver diseases.

Galectin Therapeutics, Inc. (GALT) is a microcap biotechnology company focused on targeting galectin proteins. Galectin’s NASH candidate, GR­MD­02, has quietly come toward that pivotal data readout in the first of its two major NASH clinical trials. GR­MD­02 has a Fast Track designation from the US Food and Drug Administration (FDA). The recent Allergan spending spree on NASH has resulted in a massive rally of Galectin’s shares on the potential of GR­MD­02 to treat fibrosis caused by NASH and the lead up to the report of topline results from its NASH­FX trial by the end of September. However, GALT reported topline results from its Phase 2a study, called NASH-FX, which failed both its primary and secondary endpoints.

Conatus Pharmaceuticals, Inc. (CNAT) is a biotech focused on the development of medicines to treat liver disease. Its lead candidate Emricasan (an orally­active pan­caspase protease inhibitor) is in a Phase 2b trial in patients with NASH fibrosis. Conatus has Fast Track designation from the US Food and Drug Administration (FDA) for the treatment of NASH cirrhosis. CNAT has multiple studies planned for different NASH populations.

Galmed Pharmaceuticals Ltd. (GLMD) is an Israel-­based clinical stage company that is developing a once­daily, oral therapy for the treatment of liver diseases and cholesterol gallstones utilizing its synthetic fatty­acid/bile­acid conjugate (FABAC), called Aramchol. Aramchol affects liver fat metabolism and has been shown in a Phase IIa clinical study to reduce liver fat content, as well as improve metabolic parameters associated with Nonalcoholic Steatohepatitis (NASH). The company is currently evaluating Aramchol in a Phase 2b study in patients with NASH, who are overweight or obese, and who are pre­diabetic or type­II diabetic. Aramchol also has FDA Fast Track designation status in the US.