LIVNateTM 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).
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 LIVNate, 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 LIVNate decreases at least 6 important elements in the pathophysiology of NASH (please refer to NASH slides in corporate presentation):
- decreases insulin resistance
- decreases inflammation caused by inflamed adipocytes in peripheral fat and mesenteric adipocytes
- decreases intestinal leak by promoting translation of the proteins responsible for the integrity of intestinal tight junctions
- decreases steatosis or fatty infiltrate of the liver that promotes lipotoxicity
- decreases liver inflammation that causes hepatocyte ballooning the sign of “sick” hepatocytes
- decreases liver fibrosis, the cause of cirrhosis
We believe these pre-clinical data support the study of LIVNate 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. LIVNate is identical in composition to INB03 for cancer and XPro1595 for the treatment of Alzheimer’s disease.
FORWARD LOOKING STATEMENT
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