LM-011 for NASH
Currently in Phase IIa, LM-011 is a repositioned molecule for the treatment of nonalcoholic steatohepatitis (NASH) via targeted delivery.
LM-011 has demonstrated superior efficacy in multiple animal models:
Active against steatosis, liver damage and inflammation in high fat diet (HFD) mouse model either as a preventative treatment or therapeutic intervention.
Protection against acute liver injury in both thioacetamide (TAA) induced and LPS induced mouse models.
Active against fibrosis in TAA induced liver fibrosis model.
Active via either i.p. or oral administration.
NASH is a chronic liver disease characterized by steatosis, hepatocyte injury, inflammation and fibrosis and increasingly recognized as a significant contributor to liver disease mortality.
The prevalence of NASH varies across studies with an average estimate likely around 5% in the US(1, 2, 3) and growing, making it the most common liver disease especially in industrialized countries. According to a recent study that models the epidemiology and disease burden of nonalcoholic fatty liver diseases between 2015 and 2030(3), the prevalence of NASH is projected to grow by more than 60% to reach 27 million cases by 2030, driven by obesity and diabetes rates and an aging population in the US. It is a growing cause of liver cirrhosis and hepatocellular carcinoma (HCC). The incidence of decompensated cirrhosis is expected to increase by 168% and that of HCC by 137%, making it more the pressing to find an effective and safe pharmacological treatment for this serious condition.
NASH is presenting and will continue to present an increasingly huge health and economic burden, and yet there is no FDA-approved treatment for NASH.
Cause and Pathogenesis
Though the pathogenesis of NASH is complex and poorly understood, the activation of sterile inflammation is known to be a key mechanism in the development of NASH(4, 5, 6). Sterile inflammation is a ubiquitous response to cell death in all organs. However, liver is the most notable due to its exceptionally strong response. Sustained activation of sterile inflammation could be a potential therapeutic target for NASH.
1. Vernon G et al, Ailment Pharmacol Ther 2011; 34: 274-285
2. Sayiner M et al, Clin Liver Disease 2016; 20: 205-214
3. Estes C et al, Hepatology 2018; 67 (1): 123-133
4. Kubes P and Mehal WZ, Gastroenterology 2012; 143: 1158-1172
5. Marchesini G et al, Diabetes 2001; 50: 1844-1850
6. Mehal WZ, Sci Am 2015; 312: 4