Ambys Medicines Presents New Data Further Validating its Novel Liver Cell Replacement Therapy Platform at the ASGCT Annual Meeting

Ambys Medicines, a company pioneering cell-replacement therapies for patients with liver disease, today announced new data on its universal hepatocyte program in an oral presentation at the American Society of Gene and Cell Therapy 25^th Annual Meeting at 3:45 p.m. ET. This presentation accompanies two scientific posters presented earlier in the week on the company's platform technology and cutting-edge hyperfunctional hepatocyte program. Combined, these data demonstrate Ambys's potential to generate high-quality, functional human hepatocytes and further engineer hepatocytes to treat a broad range of diseases.

Ambys's proprietary platform enables the first and only development and manufacture of functional human hepatocytes, unlocking the full potential of hepatocyte replacement therapy. Liver disease is a massively underserved problem in healthcare, leading to irreversible outcomes for most patients and more than two million deaths globally each year.

"Our new data show that Ambys is capable at efficient genetic modification of primary human hepatocytes, unleashing a powerful combination of cell and gene therapy in hepatocytes," said Ron Park, M.D., Chief Executive Officer of Ambys Medicines. "The universal hepatocyte data presented today coupled with the data on our hyperfunctional human hepatocyte program and in vivo bioreactor platform presented earlier this week further validate our breakthrough replacement cell therapy approach for severe liver diseases. We continue to make great progress building our pipeline of enhanced hepatocytes with the goal of bringing hepatocyte cell replacement to patients with liver failure and genetic liver diseases."

Data Highlights

In an oral session, "Primary Human Hepatocytes, Genetically Engineered ex vivo to be Hypoimmunogenic, Can Rescue a Model of Metabolic Liver Disease," Ambys will highlight new data demonstrating the efficient ex vivo genetic engineering of primary human hepatocytes.

Ambys scientists employed multiple different gene editing and delivery technologies, including base editing, CRISPR/Cas9 nucleases and lentiviral vectors, to protect hepatocytes from mismatched donor human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. Immune protection was positively demonstrated in vitro. The engineered cells retained normal human hepatocyte function and robustly engrafted, proliferated, and repopulated in a mouse model of hereditary tyrosinemia type 1 (HT1) (the "FRG mouse"). These cells expanded more than 100-fold in the FRG mouse, showing comparable kinetics and function to non-engineered hepatocytes.

"The development of hepatocyte cell therapies for chronic liver failure and genetic diseases has been limited by a shortage of high-quality hepatocytes and the longitudinal loss of transplanted cells due to immune recognition and clearance," said Markus Grompe, M.D., Founder and Chief Scientific Officer of Ambys Medicines. "Ambys aims to develop a universal human hepatocyte therapy that overcomes the need for immune suppression and addresses the significant unmet need afflicting over half a million people in the U.S. These data provide the first proof-of-concept that our universal hepatocytes are hypoimmune, functional, and can be expanded in our cell production platform, demonstrating our ability to produce high-quality hypoimmunogenic human hepatocytes suitable for a broad spectrum of therapeutic applications in severe liver disease."

Additionally, on May 16, 2022, at ASGCT in two separate poster presentations, Ambys presented new preclinical data on its proprietary in vivo bioreactor production platform and hyperfunctional human hepatocyte program. In the poster presentation, "Human Hepatocytes Expanded in a Novel Rat Bioreactor Maintain Full Functionality in vitro and in vivo," Ambys presented new in vitro and in vivo data fully characterizing the functionality of its expanded primary human hepatocytes, showing superiority compared to other sources, such as hepatocyte-like cells (HLCs).

The study findings showed that the company's expanded human hepatocytes maintained the functional activities of primary human hepatocytes, and robustly expanded in two substantially different mouse models of acquired and genetic disease. Importantly, in the HT1 model, the expanded cells functioned for more than four months, normalizing critical metabolite levels to prevent liver failure. In comparison, other cell types, including HLCs, did not demonstrate comparable functionality and failed to engraft, expand, and repopulate in HT1 mice.

In the poster presentation, "Ex-vivo Genetically Engineered Hyperfunctional Primary Human Hepatocytes Can Produce Clinically-Relevant Levels of Therapeutic Factor IX in vivo," Ambys demonstrated that expanded human hepatocytes can be made hyperfunctional by human Factor IX (hFIX)-lentiviral (LV) transduction. Despite transplantation of a relatively small number of cells into recipient mice, the hypofunctional cells produced hFIX levels at four weeks post-transplantation that were comparable to physiological FIX levels in peripheral blood. These levels persisted until the end of the study (14 weeks).

About Ambys Medicines

Ambys Medicines is focused on pioneering cell replacement therapies for patients with liver failure. Ambys's proprietary platform enables the company to be the first and only company able to develop and manufacture functional human hepatocytes at scale. Our scientific approach has the potential to fundamentally transform the treatment paradigm for patients with acute and chronic liver failure and genetic diseases of the liver. Our lead program, AMI-918, is a hepatocyte replacement cell therapy in development to restore lost hepatic function. Beyond AMI-918, we are building a pipeline of next-generation modified hepatocytes that will rapidly expand the range of treatable patient populations. Learn more at ambys.com and follow us on Twitter, LinkedIn, and Instagram.