Resolution Therapeutics to present data showing macrophage therapy reduced mortality and liver transplant rates in patients with end-stage liver disease.
University of Edinburgh spinout Resolution Therapeutics has announced new clinical and preclinical data for its regenerative macrophage therapy approach, highlighting its potential in treating inflammatory and fibrotic diseases. The latest findings will be presented at The Liver Meeting 2024, hosted by the American Association for the Study of Liver Disease (AASLD) in San Diego later this month.
According to Resolution, macrophages, immune system cells known for protecting us against pathogens, also play a crucial role in tissue repair. Their ability to promote healing involves clearing dead cells and transforming into pro-restorative macrophages, which reduce inflammation and repair damaged tissues. However, prolonged injury, such as that seen in liver cirrhosis, impairs this transformation, exacerbating inflammation and scarring.
Based on research led by Professor Stuart Forbes at the University of Edinburgh, Resolution was founded to develop therapies designed to harness and enhance the regenerative capabilities of macrophages. The company’s platform is built around engineering macrophages to exhibit robust pro-regenerative properties, aiming to deliver transformative outcomes for patients suffering from liver and other fibrotic diseases. The company’s ambitions extend beyond liver disease, with plans to develop regenerative macrophage therapies for other conditions such as graft-versus-host disease and lung fibrosis.
Three-year data from the University of Edinburgh’s MATCH Phase 2 study, which explored the long-term efficacy and safety of autologous, non-engineered macrophages in patients with advanced liver cirrhosis, has revealed significant clinical benefits, including reduced mortality and liver transplant rates. In the randomized trial, patients were divided into groups receiving triple or single macrophage infusions or standard care. After three years, the control group showed a higher incidence of deaths and liver transplants compared with the treatment cohorts. Statistically significant improvements in overall and transplant-free survival were also observed.
The data from the MATCH study led to the formation of Resolution, and the development of its lead compound, RTX001, an engineered macrophage investigational therapy currently under investigation for end-stage liver disease.
“We are greatly encouraged by this data which reinforce the longer-term safety and efficacy of macrophage therapy in patients with advanced liver cirrhosis,” said Forbes. “The significant reduction in clinical events and improved survival observed encourage the further clinical development of novel macrophage therapies with first-in-class potential, like RTX001.”
The company will present data from preclinical studies for RTX001 demonstrating anti-inflammatory and anti-fibrotic properties compared with non-engineered macrophages. Engineered to amplify the natural reparative effects of macrophages, RTX001 demonstrated superior efficacy in laboratory settings and maintained a favorable safety profile during in vivo testing, with evidence of reduced fibrosis.
Last month, Resolution secured £63.5 million in Series B financing led by Syncona to advance the development of RTX001, which is now recruiting participants across the UK and Spain for a Phase 1/2 clinical trial. The first-in-human, open-label trial is investigating the therapy’s safety and effectiveness in patients with end-stage liver disease who have recently experienced hepatic decompensation.
“We believe this strong data reinforces the differentiated potential of regenerative macrophage therapy to meet significant unmet patient needs across the spectrum of inflammatory and fibrotic disease,” said Dr Amir Hefni, CEO of Resolution. “Based on the clinical data from the MATCH Phase 2 study, and the preclinical data on RTX001, we are confident engineered macrophages can transform patient outcomes in liver cirrhosis and beyond.”
