Hepatitis C is a silent killer, thus, many companies are working feverishly to be the first to get a treatment on the market. Although none have yet been successful to find an acceptable treatment. It is believed that NASH (Non-Alcoholic Steatohepatitis) will replace hepatitis C by 2020. Indeed, there have already been a number of high-profile disappointments in the US this year. In February, Gilead’s anti-fibrosis drug selonsertib failed at phase III and Ionis delayed releasing results from their antisense gene therapy trial in patients with the condition. Despite a number of high-profile trial failures recently, there are several promising candidates competing to be the first to get a therapy for the liver disease NASH approved.
What is NASH?
NASH is an acronym that stands for Non-Alcoholic SteatoHepatitis. It is the most severe form of non-alcoholic fatty liver disease (NAFLD), and is characterized by the presence of an abnormal accumulation of fat in the liver which in some individuals can progress to liver cell injury (hepatocellular ballooning) and inflammation. Hepatocellular ballooning and inflammation – sometimes called necroinflammation – are commonly considered as the drivers of disease progression, or as the underlying causes of the disease. As NASH evolves, over time it can result in excessive scarring in the liver (fibrosis), a natural response to injury which can lead to liver cirrhosis or liver cancer.
A modern day lifestyle disease, NASH is closely related to the triple epidemic of obesity, pre-diabetes, and diabetes, and can be defined as the liver manifestation of the metabolic syndrome. It is heavily influenced by lifestyle (e.g. chronic excessive calorie intake, sedentary activity) and is distinct from other fatty liver diseases caused by alcohol abuse or medication side effects.
Gilead And Insitro Makes NASH Deal
Less than one year after it was launched, South San Francisco-based Insitro has inked a three-year collaboration with Gilead Sciences to discover and develop therapies for patients with nonalcoholic steatohepatitis (NASH). The move comes not long after the drugmaker released some disappointing late-stage results for its NASH candidate selonsertib, which failed to meet its main goal of improving fibrosis without worsening of NASH. That data came as a setback for Gilead, which, like many other drugmakers, is competing for the first-to-market status in NASH.
However, the chances of Gilead being the first candidate to make the breakthrough is overshadowed by Intercept’s recent FDA filing of its own NASH candidate Ocaliva, although that drug is making investors nervous with its mixed efficacy results. Nevertheless, Gilead is hoping the new deal will help revive its fortunes, with the company offering Iinsitro an upfront payment of $15m to create NASH-based disease models and help discover targets that have an influence on clinical progression and regression of the disease.
To do this, Insitro will utilize it’s Human (ISH) platform, which applies machine learning, human genetics and functional genomics to generate in vitro models and drive therapeutic discovery and development. The deal with Gilead marks Insitro’s first pharmaceutical based partnership, and what’s particularly appealing to Gilead is the tech’s ability to suggest candidate targets and predict patient response to potential therapeutic interventions.
John McHutchison, Chief Scientific Officer and Head of Research and Development, Gilead Sciences says,
“Through this collaboration we will utilise deep learning to explore the scientific underpinnings of the biology and clinical spectrum of NASH, with the goal of accelerating the development of highly effective treatment options for patients with this disease. We are excited about the opportunity to partner with insitro to tackle the scientific challenges associated with this complex disease.”
“Gilead is committed to researching and developing treatments for patients living with NASH, particularly those with advanced fibrosis who have the greatest unmet need.”
As per terms of the deal, Gilead can advance up to five targets identified through this collaboration and will be responsible for chemistry and development against these targets. Insitro could also receive up to $200 million for the achievement of preclinical, development, regulatory and commercial milestones for each of those targets; and up to low double-digit tiered royalties on net sales.
For Gilead, the partnership marks the second deal in NASH it has made this year; the first being with Novo Nordisk to develop a three-drug cocktail. That deal will see the companies combine Novo’s diabetes blockbuster semaglutide with Gilead’s cilofexor and firsocostat in a proof-of-concept study.
Stanford professor and Coursera founder Daphne Koller, who founded and helms Iinsitro said,
“NASH will be the primary cause for liver transplants in the U.S. Koller said she and her team are excited to work with Gilead to identify new therapeutics for NASH and help patients across the globe.”
Why is NASH Necessary?
It is estimated that NASH affects more than 16 million people in the U.S. alone. If untreated, NASH patients face serious consequences, including end-stage liver disease, liver cancer and the need for liver transplantation Also, they are at a significantly higher risk of liver-related mortality. Current treatment standards for NASH are lifestyle changes, including diet, weight loss, and exercise. Due to the lack of approved treatments for NASH, it has become a wildly popular target for companies. There are nearly 200 experimental treatments in the pipeline of drugmakers. With the plethora of companies aiming resources at NASH and the increasing growth of the disease, GlobalData has speculated the NASH market will hit $18.3 billion by 2026.
In addition to its deal with Gilead, Insitro also secured $100 million in a Series A funding round led by Arch Venture Partners, Foresite Capital, GV, and Third Rock Ventures.