Our Science

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

The liver is capable of a profound degree of regeneration, of which hepatocytes are the primary cellular orchestrator. Hepatocytes and their capabilities in liver function and proliferation are central to our cell and gene therapy platforms.
Restores complete liver function in both patients
Regeneration of partial hepatocyte transplant
Healthy Donor
Regenerates to single lobe
3 - 4 Weeks
Diseased Recipient
Transplanted Lobe
Regenerates to single lobe
8 Weeks
Gene Therapy
Cell Therapy
Acute Liver Failure
Acute on Chronic Liver Failure
Acute Alcoholic Hepatitis
Hepatic encephalopathy
Monogenic diseases
In healthy humans, the liver is continually regenerating itself in order to carry out critical functions that keep us alive and well.
Hepatocytes are the main cell type in the liver responsible for key liver functions.
The loss of hepatocytes or hepatocyte functions is the primary cause of liver failure.
We know from liver transplants – the only therapeutic option for end-stage liver disease – that introducing healthy hepatocytes restores liver function and saves lives.
Current gene therapies primarily focus on correcting a single mutated gene to address a disease. Our gene therapies are focused on reprogramming hepatocytes at the cellular level through various pathways. We aim to rejuvenate hepatocytes so that liver function can be restored and the liver can repair itself.
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
Turning untapped promise into reality

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

Repair and Reverse Course of Disease

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.

Biology that Sets the Stage

The liver is ideally suited for gene therapy-based approaches.
The liver is ideally suited for gene therapy-based approaches for organ repair and reversing the course of disease. Several lines of evidence suggest that various genetic factors can mediate repair of the liver at the cellular and tissue level to reverse the course of disease.