Lifordi Immunotherapeutics Advances Glucocorticoid ADC for Rheumatoid Arthritis with Promising Nonclinical Data

Lifordi Immunotherapeutics has presented compelling nonclinical data for its lead candidate LFD-200 at the American College of Rheumatology Convergence 2025 meeting while simultaneously launching Phase 1 clinical trials in rheumatoid arthritis patients. The company's antibody-drug conjugate represents a potential breakthrough in autoimmune treatment by targeting glucocorticoids specifically to immune cells, addressing a fundamental limitation that has plagued corticosteroid therapies for decades.

The data presented demonstrated that LFD-200 achieves sustained glucocorticoid exposure in immune cells of non-human primates for at least seven days following a single dose. Importantly, the treatment suppressed proinflammatory cytokine expression without evidence of toxicity after 13 weekly, clinically relevant doses. This sustained effect could translate to less frequent dosing regimens for patients while maintaining therapeutic benefits.

Dr. Matthew W. McClure, Chief Medical Officer of Lifordi, presented findings showing 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, the treatment showed no suppression of cortisol at clinically relevant doses, unlike traditional glucocorticoid therapies that commonly cause adrenal suppression. After 13 weekly doses of LFD-200 at 25 mg/kg, researchers observed no reduction in bone formation markers or bone mineral density, addressing another major concern with chronic steroid use.

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 CEO, emphasized the significance of progressing from laboratory to clinical studies in just over two years, highlighting the immune-cell selectivity of their VISTA-targeted delivery approach.

Dr. McClure characterized the ability to harness glucocorticoids' anti-inflammatory effects while limiting systemic toxicities as the "holy grail" of autoimmune treatment for 75 years. The non-human primate data suggest that steroids can be delivered directly to immune cells with sustained exposures that deliver anti-inflammatory effects without impacting cortisol or bone biomarkers. The company's immediate goal is to determine if these promising results translate to human studies, first by demonstrating safety and cytokine suppression in healthy participants, followed by proof of mechanism in rheumatoid arthritis patients.

Rheumatoid arthritis represents a significant unmet medical need where glucocorticoids have demonstrated high effectiveness in almost all patients, but their clinical use has been severely limited by toxicity concerns. The VISTA-targeted approach could potentially revolutionize treatment paradigms for this and other autoimmune conditions by enabling the therapeutic benefits of steroids without the debilitating side effects that have restricted their long-term use. Additional information about the company's research can be found at https://www.lifordi.com.