– Clinical proof-of-concept achieved for macrophage cell therapy in end-stage liver disease, supporting development of a future commercial product –
– Resolution Therapeutics is developing an engineered macrophage cell therapy product for commercialisation, RTX001, with the potential to deliver improved efficacy and durability –
– Resolution’s natural history OPAL study is now underway; Phase 1/2 EMERALD study for RTX001 will begin recruitment in 2024 –
Edinburgh and London, UK, 13 November 2023 – Resolution Therapeutics Limited (“Resolution”), a clinical-stage biopharmaceutical company developing macrophage cell therapies to treat end-stage liver disease, today announced important new data from the MATCH Phase 2 study presented at the American Association for the Study of Liver Diseases (AASLD) annual meeting on the 13th of November 2023 in Boston, USA.
The MATCH Phase 2 study, involving 50 patients with advanced liver cirrhosis, showed that treatment with fresh autologous monocyte-derived macrophages was well-tolerated, and helped to dramatically reduce serious liver-associated complications, including death.
This study provides a clinical proof-of-concept that autologous macrophage cell therapy is well-tolerated and efficacious, supporting Resolution’s mission to develop improved macrophage cell therapy products designed for commercialisation.
Resolution has developed RTX001, a leading first-in-class engineered autologous macrophage cell therapy designed to transform patient outcomes by delivering increased anti-fibrotic and anti-inflammatory effect compared to the macrophages used in the MATCH study. To achieve this, RTX001 is engineered using a unique combination of therapeutic genes known to be expressed in macrophages. This unique combination enhances the inherent regenerative properties of macrophages to provide a more effective and durable treatment for end-stage liver disease.
Resolution’s lead programme, RTX001, is comprised of two clinical studies. OPAL, a natural history study of end-stage liver disease will provide new insights on end-stage liver disease progression, key to informing the development of RTX001. The OPAL study is currently underway in 9 sites across the UK, and the first patient has already been recruited.
EMERALD, a Phase 1/2 study, will begin recruitment in 2024. The EMERALD study will investigate the safety and efficacy of RTX001 in patients with decompensated liver cirrhosis following hospitalisation due to their first decompensation event. The primary analysis will focus on safety, major clinical events including death, and Model for End-Stage Liver Disease (MELD) score which is used to assess disease severity and prioritise patients for a transplant.
To support the clinical development and future commercialisation of macrophage cell therapies, Resolution has developed a consistent manufacturing process and robust IP strategy to deliver autologous macrophage therapies to patients at scale. Technology transfer of the manufacturing process has already been completed to a partner organisation to support EMERALD study delivery, ready to manufacture GMP qualification batches.
“We are very encouraged by the MATCH Phase 2 data which provides a powerful clinical proof-of-concept for our lead product RTX001, which is engineered to enhance the anti-fibrotic and anti-inflammatory effect of macrophages in patients with end-stage liver disease,” said Dr. Amir Hefni, Chief Executive Officer of Resolution. “The OPAL and EMERALD studies led by Resolution represent a significant step forward in bringing these potentially transformative therapies to patients with decompensated liver cirrhosis, a disease which represents a severe unmet need and major growing economic burden on healthcare systems.”
There are currently over 1.3 million patients with decompensated liver cirrhosis across the US and Europe¹. There are no therapeutic options for these patients beyond liver transplant, which is a highly invasive procedure limited by organ availability, patient eligibility and complex aftercare. These patients are at risk of serious and rapid decline in health, with median survival of 2 years after their first decompensation event, dropping to 9 months after the second decompensation event². Decompensated cirrhosis also represents a major economic burden, with hospitalisation of patients with decompensated cirrhosis costing the healthcare system $4.5 Bn annually in the US alone³.
Vanessa Hebditch, Director of Communications and Policy at the British Liver Trust said, “The UK is facing a liver disease crisis with the numbers dying doubling in the last 20 years. There are limited treatment options so from a patient perspective this innovative research is really promising. We’re looking forward to seeing the Phase 1/2 EMERALD study results in due course.”
– Ends –
|+44 (0)7818 430877
Notes for Editors:
Resolution Therapeutics is a biotechnology company developing macrophage cell therapies to treat end-stage liver disease. The company is built upon more than a decade of research by the scientific founders characterising the role of macrophages in organ repair, including the liver, both in the pre-clinical and clinical settings. Resolution will discover, develop, and take to market macrophage cell therapies based on its proprietary platform of macrophage biology, cell engineering and manufacturing processes. www.resolution-tx.com
University of Edinburgh / Edinburgh Innovations Press Release
New cell therapy shows progress in treating advanced liver disease
– New study shows macrophage cell therapy was associated with reduced liver-related serious events, such as hospitalisation and death
– Data from this study, called ‘MATCH Phase 2’, will be presented at the American Association for the Study of Liver Diseases (AASLD) conference
A new type of cell therapy to treat patients with liver scarring, or cirrhosis, shows promise of being the first medical treatment for this common and lethal condition.
Results from a clinical trial of the treatment will be presented at the American Association for the Study of Liver Diseases (AASLD) conference in Boston today (November 13, 2023).
The innovative new approach to treating cirrhosis uses macrophage immune cells – the cells associated with tissue repair – derived from the patient’s own cells. It was tested in a clinical study, called ‘MATCH Phase 2’, involving 50 patients in Scotland with cirrhosis caused by a variety of different factors, such as alcohol, fatty-liver disease and viral hepatitis.
The data shows the treatment – pioneered by Professor Stuart Forbes’ lab at the University of Edinburgh – helped dramatically reduce serious liver-related complications during this one-year study. These complications can lead to hospitalisation and death.
The results indicate the treatment might help delay the need for a liver transplant, which is currently the only treatment option available to patients with advanced liver disease, but is a highly invasive procedure severely limited by organ availability, patient eligibility and complex aftercare.
Chronic liver diseases and associated cirrhosis account for approximately one million deaths per year globally, with 4,000 deaths per year in the UK alone.
In MATCH Phase 2, 26 patients received the macrophage treatment, and 24 patients in the control group received standard medical care only. After one year, there were no liver-related clinical events in any of the 26 patients treated with macrophages. In the control group, four patients out of the 24 developed liver-related severe adverse events, and there were three deaths.
Professor Stuart Forbes, a clinical hepatologist and Director of the University of Edinburgh’s Centre for Regenerative Medicine, has spent over a decade researching macrophages, supported by Edinburgh Innovations, the University’s commercialisation service. He and his team, funded by the Medical Research Council, have been investigating ways to understand and enhance the natural regenerative features of macrophage cells to create more effective medicines for liver disease.
An initial smaller study led by Professor Forbes in 2019, called MATCH Phase 1, showed the treatment was well tolerated, exhibiting none of the side effects commonly observed with immune cell therapy treatments. This was repeated in the MATCH Phase 2 results.
Professor Forbes said: “We are encouraged by the new results. This trial shows the treatment is safe, without side effects in this patient population, and is associated with reducing the clinical complications in patients with end-stage liver disease.”
Co-investigator Professor Jonathan Fallowfield said: “Currently, there is little hope for patients with advanced cirrhosis, apart from a liver transplant and a life on immunosuppressants. Liver-related complications in cirrhosis can be fatal and put huge pressure on health services. We are cautiously optimistic that we can bring hope to patients with this neglected condition.”
In 2020, Professor Forbes co-founded Resolution Therapeutics, a biotech company focused on engineering macrophage cell therapies to deliver a more effective and durable treatment for patients with end-stage liver disease. The company has developed RTX001, a leading first-in-class macrophage cell therapy designed to transform patient outcomes by delivering increased anti-fibrotic and anti-inflammatory effect. To support this therapy as a future commercial product, Resolution has developed a consistent manufacturing process and robust IP strategy to deliver autologous macrophage therapy to patients at scale. A clinical study for RTX001 is expected to begin in the UK in 2024.
Dr Amir Hefni, Chief Executive Officer of Resolution Therapeutics, said: “The data presented by Professor Forbes is exciting as we progress Resolution’s own programme to treat end-stage liver cirrhosis towards the clinic.
“Macrophage cell therapy has the potential to transform patients’ lives and we are very encouraged that in the treatment arm we continue to see a well-tolerated therapy with liver function stabilised and patients staying out of hospital with fewer complications. The MATCH Phase 2 data provide a strong clinical proof-of-concept for macrophages cell therapies which supports the development of RTX001, our lead engineered macrophage cell therapy.”
— Ends —
Notes to editors
Dr Paul Brennan, Clinical Lecturer and Specialty Registrar in Gastroenterology, Hepatology and General (Internal) Medicine at the University of Dundee, former Hepatology Clinician Scientist at the University of Edinburgh, will present the MATCH Phase 2 results at AASLD in a session entitled 160: An open-label parallel-group phase 2 randomised controlled trial of autologous monocyte derived macrophage infusion in compensated cirrhosis. Ballroom A, Hynes Convention Center, on Monday, November 13, 2023, 08:45 am – 09:00 am EST
For press enquiries relating to the University of Edinburgh team, please contact Megan Welford, Communications Manager at Edinburgh Innovations, email@example.com or on 07721 120217
For press enquiries relating to Resolution Therapeutics please contact Julia Wilson, firstname.lastname@example.org, 0781 8430877
About the University of Edinburgh/Edinburgh Innovations
The University of Edinburgh is a global university, rooted in Scotland. We are globally recognised for our research, development and innovation and we have provided world-class teaching to our students for more than 425 years. We are the largest university in Scotland, with more than 41,000 students and 15,000 staff. We are a founding member of the UK’s Russell Group of leading research universities and a member of the League of European Research Universities. Edinburgh Innovations is the University of Edinburgh’s commercialisation service. We bring University of Edinburgh research to industry, working to identify ideas with value, and facilitating the process of bringing them to life in real-world applications. We make ideas work for a better world.
Resolution Therapeutics is a biotechnology company developing macrophage cell therapies to treat end-stage liver disease. The Company is built upon more than a decade of work in the Founders’ laboratories characterising the role of macrophages in organ repair, including the liver, both in the pre-clinical and clinical settings. Resolution will discover, develop, and take to market macrophage cell therapies based on its proprietary platform of macrophage biology, cell engineering and manufacturing processes. www.resolution-tx.com