Lifordi Immunotherapeutics has presented nonclinical data for its lead antibody-drug conjugate LFD-200 at the American College of Rheumatology Convergence 2025 meeting and announced the initiation of Phase 1 clinical studies in rheumatoid arthritis. The company's novel approach targets the delivery of glucocorticoids directly to immune cells, potentially overcoming the systemic toxicity that has limited steroid use in autoimmune diseases for 75 years.
The data presented demonstrated that LFD-200 achieves sustained glucocorticoid exposures in immune cells of non-human primates for at least seven days and suppresses proinflammatory cytokine expression without evidence of toxicity after 13 weekly, clinically relevant doses. According to Dr. Matthew W. McClure, Chief Medical Officer of Lifordi, single doses of LFD-200 achieved seven-day glucocorticoid exposure in immune cells, with immunohistochemistry detecting the glucocorticoid payload in immune tissues of lymph nodes and spleen seven days after administration.
Notably, the studies showed that LFD-200 dose-dependently reduces proinflammatory cytokines after ex vivo stimulation of whole blood and bone marrow, with reduced levels of TNFα and IL-1β observed after single doses. Crucially, unlike traditional steroid treatments, LFD-200 did not suppress cortisol at clinically relevant doses, with no change seen in cortisol after single doses up to 20 mg/kg for up to 14 days. After 13 weekly doses of LFD-200 at 25 mg/kg, researchers observed no reduction in bone formation markers or bone mineral density.
The company has now initiated its Phase 1 single ascending dose/multiple ascending dose clinical study of LFD-200 in rheumatoid arthritis, with initial data from healthy participants anticipated by year-end 2025. Arthur Tzianabos, Ph.D., President and Chief Executive Officer, emphasized that the program has advanced from laboratory to clinic in just over two years, reflecting what he described as exceptional execution by the Lifordi team.
Dr. McClure characterized the ability to harness glucocorticoids' anti-inflammatory effects while limiting systemic toxicities as the holy grail of autoimmune treatment. The current Phase 1 study aims to determine if the promising non-human primate data translates to human patients, first by demonstrating safety and cytokine suppression in healthy participants, followed by proof of mechanism in rheumatoid arthritis patients. The company's approach utilizes VISTA-targeted delivery to achieve immune-cell selectivity, potentially revolutionizing how immune and inflammatory diseases are treated. Additional information about the company's research can be found at https://www.lifordi.com.
