Resolution Therapeutics Announces New Clinical and Preclinical Data Showcasing Regenerative Macrophage Therapy at AASLD The Liver Meeting® 2024 to Support the Ongoing Phase 1/2 Study for RTX001 in End-Stage Liver Disease

– Complete 3-year clinical data from the MATCH Phase 2 study demonstrate long-term efficacy and safety with autologous, non-engineered macrophages in patients with advanced liver cirrhosis.

– New preclinical data support superior anti-inflammatory and anti-fibrotic effect of RTX001, an engineered macrophage investigational therapy, compared to non-engineered macrophages.

– RTX001 has recently entered into a Phase 1/2 interventional study in end-stage liver disease.

Edinburgh and London, UK, 11 November 2024 – Resolution Therapeutics Limited (“Resolution” or “Company”), a clinical-stage biopharmaceutical company spun out of the University of Edinburgh pioneering regenerative macrophage therapy in inflammatory and fibrotic diseases, today announces new clinical and preclinical data highlighting the anti-inflammatory and anti-fibrotic effect of regenerative macrophage therapy. The data will be presented in oral and poster presentations at the American Association for the Study of Liver Disease (AASLD) The Liver Meeting® 2024, which is being held in San Diego, California from 15-19 November 2024.

“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. 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.” said Dr Amir Hefni, Chief Executive Officer of Resolution Therapeutics. “With the EMERALD study now open for enrolment and actively recruiting patients, we look forward to generating important clinical data on RTX001 and bringing its therapeutic potential closer to patients in need.”

3-year MATCH Phase 2 study demonstrates long-term safety and efficacy with non-engineered macrophages

Data will be presented in an oral presentation titled, “Autologous macrophage therapy decreases major clinical outcomes in patients with compensated cirrhosis: extended data from a randomized controlled Phase 2 trial,” by Professor Stuart Forbes. Patients with advanced liver cirrhosis were randomised to triple infusion of macrophages (n = 3), single infusion of macrophages (n = 23) and standard of care (n = 24). Key findings from the data include:

• Significant reduction in deaths and liver transplants: 3 years after randomisation, 11 patients in the control group experienced 8 deaths and 3 liver transplants collectively, compared to 2 deaths and 0 liver transplants in the treatment groups (Chi-square=7.96, p=0.005).
• Objective improvement in patient survival: Kaplan Meier analysis demonstrated improved outcomes in overall survival (log-rank test, p=0.018) and transplant-free survival (log-rank test, p=0.002) with macrophage treatment.

Additional clinical insights will be shared during the oral presentation.

Professor Stuart Forbes, Scientific Co-founder of Resolution Therapeutics and Professor of Transplantation & Regenerative Medicine at the University of Edinburgh, said, “We are greatly encouraged by this data which reinforce the longer-term safety and efficacy of macrophage therapy in patients with advanced liver cirrhosis. 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.”

New preclinical data suggest superior anti-inflammatory and anti-fibrotic effect of RTX001 relative to non-engineered macrophages

In a poster presentation titled, “Preclinical proof of concept of safety and efficacy for RTX001, a novel autologous macrophage cell therapy product for end-stage liver disease,” Dr Lara Campana will present preclinical proof-of-concept safety and efficacy data for RTX001. Key findings from the data include:

• Engineering with IL-10 and MMP9 delivers enhanced anti-inflammatory and anti-fibrotic effect: RTX001 showed superior anti-inflammatory and anti-fibrotic effect in vitro versus non-engineered macrophages.
• Well-tolerated safety profile: In vivo testing of RTX001 showed no safety concerns and a reduction in fibrosis score, further supporting its anti-fibrotic effect.
• Preclinical profile supportive of clinical development: Preclinical data generated to date on RTX001 provide a rationale to progress the product candidate into clinical evaluation.

Dr Lara Campana, Scientific Co-Founder and Vice President of Research Operations of Resolution Therapeutics, said, “These preclinical data underscore the strength of RTX001’s engineering to provide superior anti-inflammatory and anti-fibrotic effect relative to non-engineered macrophages without any compromise to safety. We look forward to deepening our understanding of RTX001 as it enters the clinic and to delivering on the opportunity of macrophage therapy to revolutionise the way inflammatory and fibrotic diseases are treated.”

Presentation materials will be made available on the Publications page of the Company's website following the event.

The EMERALD Phase 1/2 interventional study for RTX001 is now recruiting, to investigate the safety and efficacy of RTX001 in patients with ESLD who have recovered from a recent hepatic decompensation.