Lifordi Immunotherapeutics, Inc., a clinical-stage biotech company developing antibody-drug conjugates (ADCs) for autoimmune and inflammatory disorders, presented nonclinical data on its lead candidate LFD-200 at the American College of Rheumatology (ACR) Convergence 2025 meeting. The company also announced that its Phase 1 study of LFD-200 in rheumatoid arthritis (RA) is underway, with initial data from healthy participants expected by year-end 2025.
LFD-200 is an ADC that delivers a potent glucocorticoid (GC) directly to immune cells by targeting VISTA, a cell surface protein. The nonclinical data, presented in a poster titled “LFD-200, an Antibody Drug Conjugate that Selectively Delivers a Glucocorticoid Payload to Immune Cells, Provides Sustained Anti-inflammatory Effects Without Systemic Toxicity in Non-human Primates,” demonstrated that a single dose of LFD-200 achieves at least seven days of GC exposure in immune cells of non-human primates (NHPs). Immunohistochemistry detected the GC payload in immune tissues of lymph nodes and spleen seven days after a single dose, with no staining in vehicle controls.
LFD-200 dose-dependently reduced proinflammatory cytokines such as TNFα and IL-1β after ex vivo stimulation of whole blood and bone marrow. Importantly, LFD-200 did not suppress cortisol levels at clinically relevant doses, unlike dexamethasone controls. No change in cortisol was observed after a single dose of ≤20 mg/kg for up to 14 days, and no reduction occurred after 13 weekly doses at 25 mg/kg. Additionally, LFD-200 did not suppress bone formation markers or reduce bone mineral density after 13 weekly doses, addressing a key limitation of systemic glucocorticoid therapy.
“The ability to harness the anti-inflammatory effects of glucocorticoids while limiting systemic toxicities has been the ‘holy grail’ of autoimmune treatment for 75 years,” said Dr. Matthew W. McClure, Chief Medical Officer of Lifordi. “These data in NHPs show that a steroid can be delivered directly to immune cells with sustained exposures that deliver anti-inflammatory effects and have no impact on cortisol or bone biomarkers.”
Arthur Tzianabos, Ph.D., President & CEO, highlighted the rapid progress: “In just over two years we have taken LFD-200 from the lab to the clinic, which is a major accomplishment reflecting the execution by our team and support from our Board of Directors, Clinical Advisors, and industry partners.” The Phase 1 study will first assess safety and the ability to suppress inflammatory cytokines in healthy participants, followed by proof-of-mechanism studies in RA patients. RA is a prevalent disease where glucocorticoids are highly effective but their use is limited by toxicity.
Lifordi’s platform applies ADC technology to autoimmune diseases, with LFD-200 targeting myeloid and lymphoid cells via VISTA. The company is also exploring other payloads, including small molecules, antisense oligonucleotides, and siRNA. Backed by ARCH Venture Partners, 5AM Ventures, and Atlas Venture, Lifordi aims to transform treatment of immune and inflammatory diseases. For more information, visit www.lifordi.com.
