Nitto BioPharma, Inc. | San Diego, CA

Novel Treatment for Fibrosis

Using molecular targeting Drug Delivery Systems (DDS) in the development of therapeutic agents for organ fibrosis, NBPI has advanced a candidate into the clinic for treatment of liver fibrosis and cirrhosis.

Back: Technology

NBPI completed Phase 1b/2 clinical trials in June 2016 with a siRNA lipid nanoparticle therapeutic (ND-L02-s0201 Injection). The carrier (vessel) delivers the siRNA drug (cargo) to hepatic stellate cells by means of a vitamin A targeting agent (navigator) using Nitto's patented drug delivery system.

Leadership in Fibrosis

NBPI is developing a first-in-class drug for the treatment of fibrotic diseases of the liver and of other organs. The first clinical indication being tested is liver cirrhosis, or scarring of the liver, an incurable disease which afflicts 6 million people worldwide. Phase 1b/2 clinical trials using ND L02-s0201, an siRNA lipid nanoparticle which targets hepatic stellate cells, have been completed in June 2016. This was an open label, repeat dose, dose escalation study in subjects with moderate to extensive fibrosis (Metavir F3-4).

Liver cirrhosis, as well as fibrosis in other organs, involves the formation of excess connective tissue, usually as the result of injury and/or and chronic inflammation. This process can obliterate the architecture and function of a healthy tissue and result in permanently scarred organs. Collagen is a key constituent of this excess connective tissue and in the liver the collagen is synthesized by hepatic stellate cells.

ND L02-s0201 targets hepatic stellate cells through the use of liposomes that are conjugated to Vitamin A. Hepatic stellate cells will specifically take up Vitamin A, so the drug is delivered to the stellate cells preferentially, and not to other liver cells.

To suppress collagen production, the Vitamin A-coupled liposomes contain an siRNA drug that downregulates procollagen synthesis. siRNAs, or small inhibitory RNAs, are short pieces of double-stranded RNA molecules, 20-25 base pairs in length, which interfere with the expression of genes that have a complementary nucleotide sequence. In the case of NDL02-s0201, the gene being targeted is heat shock protein 47 (HSP47), a collagen-specific chaperone. HSP47 has been implicated in the regulation of procollagen synthesis. HSP47's association with a diverse range of collagen types makes it an ideal candidate for targeting hepatic stellate cell-mediated collagen secretion.

The specific targeting of stellate cells together with delivery of an siRNA that can downregulate collagen production has resulted in the reversal of cirrhosis and liver regeneration in several animal models of the disease.

Basic patents were acquired for this revolutionary treatment for fibrosis first in Japan, China, and Australia, followed in May of 2012 in the United States. In March of 2013, an Investigational New Drug (IND) application was filed with the U.S. Food and Drug Administration to use this therapeutic agent as a treatment for liver cirrhosis. Phase 1 clinical trials were launched in April of 2013.

Currently there is no drug that can cure or prevent liver cirrhosis, and if this therapeutic agent is approved, it will be the first of its kind in the world. Nitto Denko is carrying out further research to apply this technology not only to liver disease but to other forms of organ fibrosis which are responsible for millions of deaths annually.

©NITTO DENKO CORPORATION. 2016 All rights reserved.