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 infections or cancer… 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 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 therapies to patients with severe liver diseases

Ambys was founded upon the premise that cell therapies could be applied to the millions of liver disease patients who lack treatment options. To date, cell therapies while revolutionary, have been largely focused on modulating specific activities for certain cancers to treat relatively small numbers of patients. The next frontier is applying cell therapy to non-oncology indications to reach a broader patient population.

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 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 therapy platform.
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
Cell Therapy
Acute
Acute Liver Failure
Acute on Chronic Liver Failure
Acute Alcoholic Hepatitis
Chronic
Hepatic encephalopathy
Cirrhosis
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.
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

Our Cell Therapy Platform

Cell therapy approaches utilizing hepatocytes hold great potential for treating severe liver diseases, given the various functional roles they are responsible for in the liver, including regeneration.

However, the development 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

By addressing the challenges that have plagued hepatocyte transplantation, we aim to finally realize the promise of hepatocyte replacement therapies for patients with severe liver disease.

 

Cell therapies for acute and chronic disease

  • We are advancing allogeneic (or “off the shelf”) cell therapies to deliver healthy human hepatocytes to patients with acute and chronic liver disease 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.
  • Our first program, AMI-918, is an allogenic liver-cell therapy to manage acute liver disease. This therapy would provide a potential life-extending solution to the 100,000 patients in the U.S. alone who, each year, experience liver function crises by improving outcomes, reducing re-hospitalization rates, and extending the time to liver transplantation. We intend to advance AMI-918 into IND-enabling studies in 2022 with the goal of beginning first-in-human clinical trials 2023.
  • Our second program is designed to bring the promise of our liver-cell platform to many more patients by providing extended durability of replacement cells and easier dosing and administration, without the need for immunosuppression. This program aims to slow disease progression and ultimately reverse disease in patients with decompensated or monogenic liver disease.

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 obstacles 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. We have built a cGMP facility that will enable us to industrialize and scale this process to meet our clinical supply needs.

Ambys Industrialized
Cell Therapy Manufacturing Process

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