Restoring Liver Function and Regenerating the Liver
The spectrum of liver diseases and causes is broad. From genetic mutations to environmental or dietary challenges to viral infection… over time these hepatic insults impede the liver’s normal physiological function and its ability to repair itself.
Whether inherited, acute or chronic in nature, and regardless of cause, these diseases all impede the liver’s normal physiological function and its ability to repair itself.
Regardless of the underlying cause, we are focused on harnessing the natural regenerative properties of the liver to restore normal liver function.
Broadening the application of cell and gene therapies to patients with severe liver diseases
Ambys was founded upon the premise that cell and gene therapies could be applied to the millions of liver disease patients with unmet needs. To date, cell and gene therapies while revolutionary, have been largely focused on modulating specific activities for certain cancers and rare diseases and to treat relatively small numbers of patients.
Our team continues to elucidate the complexities of liver disease biology and build a comprehensive understanding of the mechanisms through which the liver regenerates itself to maintain homeostasis and healthy function.
Our lead programs harness these natural regenerative properties of the liver to target a spectrum of severe acute and chronic liver diseases, and include ‘off the shelf’ hepatocyte replacement cell therapies and hepatocyte-directed gene therapies to restore normal liver function.
Hepatocytes: The Master Orchestrator
Acute on Chronic Liver Failure
Acute Alcoholic Hepatitis
Cirrhosis
Monogenic diseases
Cell Therapy Platform
The scientific community has considered the potential of cell therapy approaches utilizing hepatocytes for more than 20 years, given the various functional roles they are responsible for in the liver, including regeneration.
However, the progress of cell therapies to replace healthy human hepatocytes has been stymied by various hurdles, including:
- Need for large doses of cells to provide therapeutic benefit
- Inability to grow fully functional, mature hepatocytes in cell culture
- Existing sources of donor hepatocytes result in inconsistent quality and lack ability to scale
- Lack of reliable assays to characterize hepatocyte function and potency
- Need for long-term immuno-suppressive treatment
A single patient benefits greatly from a single liver donor transplant. We are focused on amplifying the benefit of a single donor liver to impact thousands of patients. By addressing the hurdles that have plagued hepatocyte transplantation, we aim to bring the promise and potential of hepatocyte replacement therapies to patients with severe liver disease.
Cell therapies for acute and chronic liver disease
We are advancing allogeneic, or ‘off the shelf’, cell therapies to deliver healthy human hepatocytes to patients in acute and chronic liver disease settings to restore liver function. We are also pursuing next generation cell therapies to address the more intractable long-term progression of severe liver disease, including genetic metabolic diseases that have been challenged by more conventional gene therapies.
Building the infrastructure to advance Ambys cell therapies
Producing mature, fully functional human hepatocytes
Historically, the production and availability of ample quantities of high-quality donor hepatocytes has been one of the biggest hurdles to producing hepatocyte replacement cell therapies.
The average adult human liver is composed of approximately 200 billion hepatocytes. Replacing just 10 percent of these cells would require 20 billion donated cells.
Numerous attempts to grow and differentiate hepatocytes in the laboratory have been pursued, but none has resulted in mature, fully functional hepatocytes capable of being transplanted to restore liver function. In addition, the donor livers discarded as unsuitable for transplant are poorer in quality and insufficient in number to provide a viable source of healthy hepatocytes for cell transplantation at commercial scale.
At Ambys, we are pioneering a novel in vivo expansion process to produce mature, fully functional human hepatocytes.
Coming in 2021
We are building a cGMP manufacturing facility that will enable us to industrialize and scale this process to meet our clinical supply needs.
Ambys Industrialized
Cell Therapy Manufacturing Process
Gene Therapy Platform
Gene therapy directed toward the liver and other selected organs has gained significant momentum in the last several years, thanks in large part to advancements in gene delivery technologies. Encouraging clinical results, including two FDA-approved therapies, have been achieved with adeno-associated virus (AAV) vectors delivering target genes to hepatocytes, typically for the potential treatment of monogenic diseases.
The ultimate frontier of liver-regenerating therapy is the ability to reverse the course of disease, particularly in cirrhotic patients. Cirrhosis is caused by chronic liver damage that leads to the accumulation of fibrotic scar tissue and is characterized by a severe reduction in liver function due to the loss or de-differentiation of hepatocytes over time, resulting in severe complications.
Our First-Of-Its-Kind Gene Therapy Approach
Our gene therapy platform is focused on the delivery of genes to hepatocytes that restore the synthetic and metabolic functions of the liver, and/or reduce fibrosis and inflammatory signals that are hallmarks of advancing disease, in order to ultimately improve health outcomes in patients. By delivering genes that can impact multiple therapeutic pathways, we ultimately aim to stop or reverse disease and restore the normal regenerative properties of the liver.
Applying gene therapy to enable the liver’s natural regenerative capacity represents a radically different approach to address cirrhosis. A central component of our efforts is enhancing AAV-based gene-therapy delivery. We believe our vector enhancements have the potential to address current deficiencies in AAV-based therapies and could be leveraged to generate a pipeline of gene therapies to address cirrhosis and a spectrum of other liver diseases.