PRD Therapeutics has achieved a significant milestone in lipid metabolism research by initiating dosing in the first-in-human clinical trial of PRD001, a first-in-class SOAT2-selective inhibitor. The Tokyo-based clinical stage company announced that this Phase 1 study marks the first clinical trial of an SOAT2-selective inhibitor, targeting homozygous familial hypercholesterolemia (HoFH) and metabolic dysfunction-associated fatty liver disease (MASH/MASLD).
Novel Mechanism of Action
PRD001 represents a breakthrough in cholesterol management through its unique SOAT2 selectivity. According to Kanji Hosoda, Ph.D., CEO and co-founder of PRD Therapeutics, "Many clinical trials have been conducted on SOAT1/2 dual or SOAT1 selective inhibitors, but this is the first clinical trial of an SOAT2 selective inhibitor." The drug uniquely controls three key pathways of lipid metabolism: cholesterol synthesis in the liver, cholesterol absorption in the small intestine, and uptake of blood LDL-C with a single drug, leading to potent LDL-C reduction independent of the LDL receptor.
Promising Preclinical Results
The development of PRD001 is supported by compelling preclinical evidence from multiple animal models. Studies in LDL-R knockout mice (HoFH model) and high-fat diet-induced MASH model mice demonstrated that PRD001 effectively lowers blood and liver lipids while suppressing the progression of fatty liver and atherosclerosis with no adverse events. These results align with published research on SOAT1 or SOAT2 knockout mice, which suggests that inhibiting only SOAT2 is crucial for demonstrating both safety and efficacy.
Clinical Trial Design and Objectives
The Phase 1 study (NCT07034183) is designed to evaluate the safety, tolerability, pharmacokinetics, and early signs of efficacy of PRD001 in adult healthy volunteers. The trial will specifically assess LDL-C lowering effects and liver fat quantitative values using MRI-PDFF (magnetic resonance imaging-proton density fat fraction). This comprehensive approach allows researchers to evaluate both cardiovascular and hepatic benefits of the therapy.
Addressing Unmet Medical Need
PRD001 has particular significance for patients with homozygous familial hypercholesterolemia, a rare genetic condition characterized by absent or extremely low LDL receptor activity. Hosoda emphasized the potential impact: "PRD001 has the potential to be the first-in-class effective and safe oral therapy for HoFH patients suffering from no or extremely low LDL receptor activity." The drug's mechanism of action, which works independently of the LDL receptor, offers hope for patients who have limited treatment options with current therapies.
Development Support and Future Outlook
The research and development of PRD001 is supported by the Japan Agency for Medical Research and Development (AMED) under the Strengthening Program for Pharmaceutical Startup Ecosystem. The project, titled "Development of First-in-class oral lipid metabolism regulator PRD001 and POC obtained for lipid metabolism disorder," underscores the innovative nature of this therapeutic approach.
As the world's first and only SOAT2-selective inhibitor, PRD001 represents a new frontier in lipid metabolism regulation. The successful initiation of human trials marks a critical step toward potentially providing effective treatment options for patients with rare cholesterol disorders and metabolic liver disease.
