Lifordi Immunotherapeutics has moved its lead antibody-drug conjugate LFD-200 into Phase 1 clinical testing for rheumatoid arthritis while presenting nonclinical data showing the compound delivers sustained glucocorticoid exposure to immune cells without evidence of systemic toxicity. The company announced the initiation of its single ascending dose/multiple ascending dose study in rheumatoid arthritis patients and expects preliminary data from healthy participants by the end of 2025.
The data presented at the American College of Rheumatology Convergence 2025 meeting demonstrated that LFD-200 achieves sustained glucocorticoid exposures in immune cells of non-human primates for at least seven days following a single dose. The compound suppressed proinflammatory cytokine expression without evidence of toxicity after 13 weekly, clinically relevant doses. Immunohistochemistry detected glucocorticoid payload in immune tissues of lymph nodes and spleen seven days after administration, while vehicle controls showed no staining.
Dr. Matthew W. McClure, Chief Medical Officer of Lifordi, presented results showing 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 at 5 mg/kg or 20 mg/kg. Critically, the compound demonstrated no cortisol suppression at clinically relevant doses, unlike dexamethasone controls, and showed no reduction in bone formation markers or bone mineral density after 13 weekly doses at 25 mg/kg.
The development represents a potential breakthrough in autoimmune treatment, addressing what Dr. McClure described as the "holy grail" of the field for 75 years: harnessing glucocorticoids' anti-inflammatory effects while limiting systemic toxicities. Rheumatoid arthritis affects millions worldwide, and while glucocorticoids remain highly effective for most patients, their long-term use has been severely limited by side effects including adrenal suppression, osteoporosis, and metabolic complications.
Lifordi's approach targets the VISTA protein on immune cells to deliver glucocorticoids directly to the cells driving inflammation. The company has advanced LFD-200 from laboratory research to clinical testing in just over two years. The Phase 1 study will first evaluate safety and cytokine suppression in healthy participants before moving to proof-of-mechanism testing in rheumatoid arthritis patients. For additional information about the company's research, visit https://www.lifordi.com.
The successful translation of these findings to human studies could fundamentally change how immune and inflammatory diseases are treated, potentially enabling long-term glucocorticoid therapy without the debilitating side effects that have restricted their use. This development comes at a critical time as autoimmune diseases continue to rise globally, creating substantial unmet medical need for safer, more targeted treatment options.
