NeuLiv for NASH

NASH is nonalcoholic steatohepatitis – a chronic, progressive but silent liver disease that has reached epidemic proportions in the US.  NASH can be classified as a social disease unique to our culture.  The disease occurs most commonly in patients, adult and pediatric, with obesity, many whom also suffer from Type 2 diabetes.  The histologic hallmarks of the disease include steatosis (a fatty infiltrate of the liver), hepatitis (inflammation of the liver), hepatocyte ballooning (sick hepatocytes that may die) and fibrosis (formation of scar tissue called cirrhosis).  These characteristics can progress to end-stage liver disease requiring transplant and patients are a risk for the development of hepatocellular carcinoma (HCC).  It is estimated that 20 million people in the US have NASH!  NASH is a big problem that needs a solution.

NASH is a “silent disease”.  Most people with NASH do have not symptoms.  It doesn’t hurt, cause bloating, ruin appetite, keep you up at night or cause any other symptoms.  To find the disease, your physician must look for it with some combination of blood tests and medical imaging studies (ultrasound and/or MRI).  If left untreated, NASH can kill.  NASH can be quite advanced when it starts to “make noise”.  One way the disease gets noticed is with the development of HCC – one of the worst cancers to get.  Another way it is noticed is by abnormalities of blood tests of liver function.  Sometimes it goes unnoticed until there are symptoms of advanced liver disease.  NASH patients with end-stage liver disease have few treatment options.  Today, there are no drugs approved for the treatment of NASH – although that may change soon.  For advanced disease, liver transplant may be the only solution.  In fact, transplant for NASH is expected to be the most common cause for liver transplant by 2030.

Clearly a solution is needed to slow this epidemic.  At INmune Bio, we believe NASH is a treatable disease caused by 3 inflammatory cycles (see figure below). 

3cycles

The easily understood peripheral inflammatory cycle is caused by obesity and insulin resistance.  The less obvious regional inflammatory cycle is caused by intestinal inflammation and mesenteric fat.  Mesenteric fat of “pot belly” fame, also know as central obesity, is more toxic than peripheral fat (‘love handles”), is a risk factor for metabolic syndrome, cardiovascular disease and NASH.  Intestinal inflammation is caused by a leaky gut syndrome where the “tight junctions” between intestinal cells become loose and leak inflammatory intestinal contents in the blood.  The inflammatory pathology of the regional cycle drains directly into the liver via the portal vein.  The local inflammatory cycle occurs in the liver and leads directly to the diagnosis of NASH.  Lipotoxicity due to steatosis results in innate immune cell inflammation of hepatic stellate cells and Kuepfer cells that cause hepatocyte ballooning and death resulting in fibrosis and cirrhosis. 

INmune Bio believes that targeting the innate immune inflammation that causes the three inflammatory cycles with NeuLiv, the name of our DN-TNF drug for treating liver disease, may be an effective therapy for NASH.  Based in animal data in models of NAFLD (nonalcoholic fatty liver disease) and NASH, treatment with NeuLiv decreases at least 6 important elements in the pathophysiology of NASH (please refer to NASH slides in corporate presentation):

  1. decreases insulin resistance
  2. decreases inflammation caused by inflamed adipocytes in peripheral fat and mesenteric adipocytes
  3. decreases intestinal leak by promoting translation of the proteins responsible for the integrity of intestinal tight junctions
  4. decreases steatosis or fatty infiltrate of the liver that promotes lipotoxicity
  5. decreases liver inflammation that causes hepatocyte ballooning the sign of “sick” hepatocytes
  6. decreases liver fibrosis, the cause of cirrhosis

We believe these pre-clinical data support the study of NeuLiv in a Phase IIa clinical trial.  INMB is in the process of working closely with its clinical advisors to design the trial.  We will announce trial design and enrollment of the first patient at the appropriate time.  NeuLiv is identical in composition to INB03 for cancer and XPro1595 for the treatment of Alzheimer’s disease.

FORWARD LOOKING STATEMENT

This content contains “forward-looking statements” Forward-looking statements reflect our current view about future events. When used in this presentation, the words “anticipate,” “believe,” “estimate,” “expect,” “future,” “intend,” “plan,” or the negative of these terms and similar expressions, as they relate to us or our management, identify forward-looking statements. Such statements include, but are not limited to, statements contained in this presentation relating to our business strategy, our future operating results and liquidity and capital resources outlook. Forward-looking statements are based on our current expectations and assumptions regarding our business, the economy and other future conditions. Because forward–looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. Our actual results may differ materially from those contemplated by the forward-looking statements. They are neither statements of historical fact nor guarantees of assurance of future performance. We caution you therefore against relying on any of these forward-looking statements. Important factors that could cause actual results to differ materially from those in the forward-looking statements include, without limitation, our ability to raise capital to fund continuing operations; our ability to protect our intellectual property rights; the impact of any infringement actions or other litigation brought against us; competition from other providers and products; our ability to develop and commercialize products and services; changes in government regulation; our ability to complete capital raising transactions; and other factors relating to our industry, our operations and results of operations. Actual results may differ significantly from those anticipated, believed, estimated, expected, intended or planned. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We cannot guarantee future results, levels of activity, performance or achievements. Except as required by applicable law, including the securities laws of the United States, we do not intend to update any of the forward-looking statements to conform these statements to actual results.

Have a Question?
858 964 3720
Email Us
dmoss@inmunebio.com
Opening Hours
M - F 8am to 5pm PST