Resolution Therapeutics, a U.K.-based biotech company, has secured $85 million in Series B financing to advance its lead product candidate, RTX001, a macrophage therapy for the treatment of end-stage liver disease. The financing, led by Syncona, will support the company in initiating the Phase 1/2 EMERALD clinical trial, scheduled to begin patient recruitment in Q4 2024. RTX001 represents a potential first-in-class solution for patients with end-stage liver disease, where liver transplantation is currently the only effective treatment option.
Engineering Pro-Regenerative Macrophages for Liver Repair
Macrophage therapy is emerging as a promising approach in regenerative medicine, leveraging the critical role of macrophages in tissue repair and inflammation resolution. In healthy individuals, macrophages remove damaged cells and initiate tissue repair processes. Resolution Therapeutics is focusing on engineering pro-regenerative macrophages to counteract the chronic inflammation and fibrosis characteristic of end-stage liver disease.
According to Amir Hefni, CEO of Resolution Therapeutics, the concept originated from studies highlighting the necessity of pro-regenerative macrophages for fibrosis remodeling and liver regeneration. These macrophages inhibit scar formation in models of chronic liver injury. RTX001 is an autologous, engineered macrophage therapy that modifies macrophages to express therapeutic genes, amplifying their anti-inflammatory and anti-fibrotic effects.
Addressing Unmet Needs in End-Stage Liver Disease
End-stage liver disease results in significant inflammation and fibrosis, impairing organ function and leading to multi-organ complications and reduced life expectancy. Liver cirrhosis, a common precursor to end-stage liver disease, has limited treatment options, with liver transplantation being the only definitive solution. The shortage of available organs and the complexity of the surgery underscore the urgent need for new therapies.
RTX001 aims to address this unmet need by leveraging the dual anti-inflammatory and anti-fibrotic activities of pro-regenerative macrophages. These macrophages break down scars and prevent the formation of new scars, enabling the liver to recover sufficient function and avoid further complications. The therapy has been engineered to enhance these properties by delivering payloads that transiently increase the expression of genes already present in macrophages. The company has also improved its manufacturing process to produce and freeze multiple doses from a single leukapheresis.
Expanding Macrophage Therapy Beyond Liver Disease
Resolution Therapeutics is also exploring the potential of macrophage therapy in other therapeutic areas, including graft-vs-host-disease and lung fibrosis. The company believes that the anti-inflammatory and anti-fibrotic properties of macrophages make them well-suited for addressing these conditions.
While other companies, such as Carisma Therapeutics, are developing macrophage therapies primarily for oncology, Resolution Therapeutics' focus on fibrotic conditions distinguishes it in the field. Carisma Therapeutics recently presented preclinical data demonstrating a reduction in liver fibrosis using its macrophage therapy, indicating a potential expansion into non-oncology indications.
Hefni believes that RTX001's pro-regenerative phenotype and engineering to enhance anti-inflammatory and anti-fibrotic properties give it an edge over potential competitors. He also noted that RTX001 has the potential to be outpatient-compatible, with a short infusion time and no requirement for patient pre-conditioning or bridging therapy.
Future Directions for Resolution Therapeutics
The Series B funding will enable Resolution Therapeutics to advance the EMERALD Phase 1/2 study, improve its manufacturing process, and expand its pipeline. The company is also focused on addressing manufacturing challenges associated with autologous cell therapies by investing in process and analytical development to reduce both the cost of manufacturing and the vein-to-vein time of RTX001.
Data from the MATCH study, where non-engineered macrophages were administered to patients with compensated cirrhosis, showed that macrophages were well-tolerated and associated with significant improvements in survival and transplant-free survival. Resolution Therapeutics hopes that the EMERALD study will demonstrate similar safety and efficacy in patients who have recovered from a recent hepatic decompensation.
