Resolution Therapeutics Announces New Breakthrough Clinical Data for Macrophage Cell Therapy in End Stage Liver Disease at EASL 2024

MATCH Phase 2 data underscores significant potential of macrophage cell therapy treatment for advanced liver cirrhosis

Resolution Therapeutics presents novel discovery platform for engineered macrophage cell therapy to enhance therapeutic efficacy

EDINBURGH, Scotland and LONDON, June 5, 2024 /PRNewswire/ -- Resolution Therapeutics Limited ("Resolution"), a clinical-stage biopharmaceutical company developing macrophage cell therapies to treat end-stage liver disease today announces key data presentations with the University of Edinburgh at the EASL Congress 2024, held in Milan, Italy which demonstrate the significant potential of macrophage cell therapy as a treatment for advanced liver cirrhosis.

The data are presented in two posters;

• Extended MATCH Phase 2 clinical data by Dr Paul Brennan from the University of Dundee and Professor Stuart Forbes, scientific founder of Resolution Therapeutics and Professor of Transplantation and Regenerative Medicine at the University of Edinburgh; and
• Proprietary discovery platform for engineered macrophage cell therapies for end stage liver disease (ESLD) by Dr Lara Campana, scientific co-founder and Vice President of Research Operations at Resolution Therapeutics.

New data from the MATCH Phase 2 study continue to show excellent safety and efficacy post treatment with autologous non-engineered macrophages in a population of compensated and decompensated patients with liver cirrhosis and baseline MELD score 10 - 16. After thirty months post-randomisation (which includes an 18-month extended follow-up period) the macrophage infusion group had significantly improved outcomes when analysing either patient survival (Chi-square=4.35; p=0.037), or transplant free survival (Chi-square=7.07; p=0.0078). A significant reduction in all-cause mortality and a significant increase in transplant-free survival was observed. Details of the MATCH study can be found on clinicaltrialsregister.eu  EudraCT Number: 2015-000963-15.

The MATCH 2 data provide clear clinical proof of concept for macrophage cell therapy as an effective and durable treatment for advanced liver cirrhosis, and Resolution Therapeutics now owns exclusive rights to the technology and data, licensed from the University of Edinburgh and Edinburgh Innovations, the University's commercialisation service.

Resolution has also developed a platform to engineer and cryopreserve autologous macrophages with a pro-regenerative phenotype for the treatment of patients with ESLD. The data showcase an improved differentiation protocol and a more automated process to maximise manufacturing yields without compromising the phenotype. Furthermore, the data demonstrate robust engineering and a cryopreservation method to allow for multiple dosing from a single leukapheresis collection. These advances have resulted in reduced manufacturing time, improved yield and a more robust manufacturing process.

Professor Forbes, Scientific Co-Founder of Resolution Therapeutics and Professor of Transplantation & Regenerative Medicine at the University of Edinburgh, said: "

"We are greatly encouraged by the data from the MATCH Phase 2 study and this long term follow up study. We will continue monitoring patients with the aim of reporting further data at the American Association for the Study of Liver Disease (AASLD) meeting in November 2024. The macrophage production and engineering platform that has been created at Resolution is the next step in tackling this severely underserved condition. We are looking forward to seeing further platform progress and publications in the coming months."

Resolution's upcoming Phase 1/2 EMERALD study will investigate the safety and efficacy of engineered macrophage cell therapy, RTX001, in patients with decompensated liver cirrhosis following hospitalisation due to a recent decompensation event. The primary analysis will focus on safety and major clinical events including all-cause mortality. The EMERALD study is anticipated to start recruiting patients in Q3 2024.

Dr Lara Campana, Scientific Co-Founder and Vice President of Research Operations of Resolution Therapeutics, added: "The data from Professor Forbes' group has shown that autologous macrophages are a safe and effective treatment for patients with advanced liver cirrhosis. Our advanced macrophage engineering and production platform aims to maximise the transformative potential of macrophages, increasing their pro-regenerative properties, potentially leading to fewer liver transplants being needed and a longer life expectancy for those with ESLD."

Dr Amir Hefni, Chief Executive Officer of Resolution Therapeutics, said: "The data presented at EASL further support the robust scientific and clinical evidence in our approach. Our engineered macrophage cell therapy platform has the potential to transform outcomes in a patient population with a very high unmet need. ESLD is our first indication in our vision to treat patients with inflammatory organ diseases."

About Resolution Therapeutics

Resolution Therapeutics is a clinical-stage biopharmaceutical company pioneering macrophage cell therapy for transformative outcomes in inflammatory organ diseases. The Company leverages its proprietary platform to engineer autologous macrophages with distinct pro-regenerative properties as cell therapy medicines capable of delivering superior patient outcomes across the spectrum of inflammatory organ disease. Resolution's initial focus is on developing RTX001, its lead product candidate with first-in-class potential supported by preclinical data demonstrating anti-fibrotic and anti-inflammatory advantages relative to non-engineered macrophages, for patients diagnosed with end-stage liver disease. The Company is also advancing efforts to expand the potential of its platform beyond the liver into indications where engineered macrophages have therapeutic potential. Resolution Therapeutics is based in Edinburgh and London. Learn more by visiting https://resolution-tx.com/ and engage with us on LinkedIn.

About RTX001

RTX001 is an engineered autologous macrophage cell therapy designed to deliver increased anti-fibrotic and anti-inflammatory effects in patients with end-stage liver disease. The product candidate is engineered using a unique combination of therapeutic genes known to be expressed in macrophages to enhance the inherent regenerative properties of the modality for superior efficacy and durability. The clinical development program for RTX001 currently consists of two clinical studies. The ongoing OPAL study is a multi-center natural history study in patients with liver cirrhosis who have been hospitalized for the first time with hepatic decompensation. The objective of the OPAL study is to generate novel data on disease trajectory to optimize the control arm for the planned EMERALD study. The planned Phase 1/2 EMERALD study is an open-label first-in-human study of RTX001 measuring clinical events as the primary efficacy endpoint. The EMERALD study is expected to initiate as early as the third quarter of 2024.

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.

About EASL

EASL, the European Association for the Study of the Liver, founded in 1966, is a medical association dedicated to pursuing excellence in liver research, to the clinical practice of liver disorders, and to providing education to all those interested in hepatology. As of 2023, EASL serves 5,300 members from 112 countries.