Lifordi Immunotherapeutics Advances Glucocorticoid Antibody Drug Conjugate LFD-200 into Phase 1 Rheumatoid Arthritis Trial

Lifordi Immunotherapeutics, Inc. presented nonclinical data on its lead antibody-drug conjugate LFD-200 at the American College of Rheumatology Convergence 2025 meeting and announced the initiation of its Phase 1 study in Rheumatoid Arthritis. The company anticipates initial data from healthy participants by year-end 2025. The presented data 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.

Arthur Tzianabos, Ph.D., President & Chief Executive Officer, stated that the company has started its Phase 1 SAD/MAD clinical study of LFD-200 in RA, describing it as a multifactorial disease with a large unmet need. He emphasized the rapid progression from laboratory to clinic within just over two years, highlighting the immune-cell selectivity of their VISTA-targeted delivery approach. The company's progress can be followed through their official communications at https://www.lifordi.com.

In the poster presentation, Dr. Matthew W. McClure, Chief Medical Officer of Lifordi, presented comprehensive results from studies of LFD-200 in non-human primates. The data showed that a single dose of LFD-200 achieves glucocorticoid exposure in immune cells lasting seven days or longer. Immunohistochemistry detected the glucocorticoid payload in immune tissues of lymph nodes and spleen seven days after a single dose, with no staining observed in vehicle controls.

The research demonstrated that LFD-200 dose-dependently reduces proinflammatory cytokines after ex vivo stimulation of whole blood and bone marrow. Specifically, reduced levels of TNFα and IL-1β were observed after a single dose of LFD-200 at 5 mg/kg or 20 mg/kg. Crucially, LFD-200 does not suppress cortisol at clinically relevant doses, with no change seen in cortisol after a single dose at ≤20 mg/kg for up to 14 days, unlike the dexamethasone control. No cortisol reduction was observed after receiving clinically relevant doses of LFD-200 (25 mg/kg) following weekly dosing for 13 weeks.

Additionally, LFD-200 does not suppress bone markers at clinically relevant doses. After 13 weekly doses of LFD-200 at 25 mg/kg, no reduction in bone formation (P1NP) or bone mineral density was observed. Dr. McClure described the ability to harness glucocorticoids' anti-inflammatory effects while limiting systemic toxicities as the 'holy grail' of autoimmune treatment for 75 years. He noted that the data show a steroid can be delivered directly to immune cells with sustained exposures that deliver anti-inflammatory effects without impacting cortisol or bone biomarkers after 13 weekly clinically relevant doses.

Lifordi's current goal is to determine if these promising results translate to human studies, first by demonstrating that LFD-200 is safe and able to suppress inflammatory cytokines in healthy participants, followed by proof of mechanism in patients with Rheumatoid Arthritis. This approach addresses a prevalent disease where glucocorticoids are highly effective in almost all patients, but their use has been historically limited by toxicity concerns. The company's innovative targeting of myeloid and lymphoid cells using the highly internalized cell surface membrane protein VISTA represents a significant advancement in autoimmune disease treatment strategies.