MagicRNA's First-in-Human Clinical Data Demonstrating Feasibility of In Vivo CAR T Therapy in Systemic Lupus Erythematosus Published in The New England Journal of Medicine.

• First-ever clinical data supporting safety and efficacy of in vivo CAR-T Therapy in refractory systemic lupus erythematosus (SLE) patients.
• Data shows low dose of HN2301 reprogrammed up to 60% of CD8⁺ CAR⁺ T-cells in the peripheral blood of patients, resulting in complete depletion of circulating B cells and up to 20-points reduction in patient's SLEDAI scores within three months.
• Favourable safety profile with no neurotoxic effects or other severe adverse events, no clinically significant elevation of liver enzymes was observed during or after treatment in any of the 5 patients.

SHENZHEN, China, Sept. 17, 2025 /PRNewswire/ -- MagicRNA, a clinical-stage biotechnology company pioneering in vivo CAR T-cell therapies, today announced the publication of the world's first clinical data of an mRNA-lipid nanoparticle (mRNA-LNP) based in vivo CAR T candidate, HN2301, in The New England Journal of Medicine. The study, titled "In vivo CD19-CAR T-Cell Therapy for Refractory Systemic Lupus Erythematosus", represents the first-ever demonstration of in vivo CAR T generation and activity in SLE patients.

"This study is an important milestone for the entire field of cell therapy," said Prof. Georg Schett, pioneer in the use of CD19 CAR T cell therapy in SLE and achieved a revolutionary breakthrough. "For the first time, we see functional CAR T cells generated directly in patients' body, achieving rapid B-cell clearance and clinical improvement of autoimmune disease. These findings, together with the favorable safety profile, pave the way for a new era of immunotherapy."

The clinical trial enrolled five patients with long-standing, treatment-refractory SLE, four of whom also had lupus nephritis. Built on MagicRNA's EnC-LNP delivery platform technology, HN2301 was administered intravenously without prior lymphodepletion to deliver CAR-encoding mRNA to CD8+ T cells, reprogramming them into CD19-targeted CAR T cells in vivo.

"This study marks the first clinical proof-of-concept of the cell targeted-LNP based in vivo CAR T-cell in autoimmune disease, validating its therapeutic potential in patients," said Dr. Gavin Zha, CEO of MagicRNA. "By achieving deep B-cell depletion, in vivo CAR T technology offers a new level of disease control that potentially goes beyond what has been achieved with conventional approaches such as monoclonal antibodies and T-cell engagers. At the same time, it overcomes the major limitations of ex vivo CAR T therapies, including complex manufacturing, long preparation times, high costs, and the requirement for lymphodepletion. Our platform has the potential to make transformative cell therapies broadly accessible and scalable for patients."

At a minimal dose (2 mg per infusion), single or repeated administration of HN2301 induced CAR T-cells generation and B-cell reduction. At a bit higher dose (4 mg per infusion) up to 60% of CD8⁺ CAR⁺T-cells were reprogrammed within six hours, leading to complete depletion of circulating B cells, which persisted for 7-10 days. Consistent with B-cell depletion, anti-nucleosome and anti-dsDNA antibodies significantly decreased, and low complement levels in some patients normalized at the last visit. In addition, Disease Activity Index (SLEDAI-2000) scores significantly decreased by as much as 20 points in all 5 patients 3 months after the infusion of HN2301. The treatment was generally well tolerated, no patients experienced grade ≥3 CRS, and no neurotoxic effects or other severe adverse events were observed during or after treatment.

Based on these encouraging clinical results, MagicRNA will continue the dose-escalation studies to further evaluate HN2301's ability to achieve immune reset and long-term drug-free remission, with the goal of accelerating clinical development and ultimately bringing this therapy to patients worldwide.

About HN2301
HN2301 is MagicRNA's lead investigational therapy and the world's first in vivo CAR T candidate to enter clinical testing in SLE patients. HN2301 encapsulates CD19 CAR-encoding mRNA in a proprietary T-cell-targeted lipid nanoparticle (EnC-LNP), enabling direct reprogramming of patient T cells into functional CAR T cells in vivo. In preclinical studies, including nonhuman primates and mouse models, HN2301 achieved rapid and robust CAR T reprogramming and complete depletion of B cells in blood and tissues. Early first-in-human data demonstrated feasibility, clinical efficacy, and favourable safety profile.

About MagicRNA
MagicRNA Biotechnology, founded in 2021, is a clinical-stage biotech company pioneering next-generation mRNA and lipid nanoparticle (LNP) technologies to expand the reach of RNA-based medicines. The company's proprietary Engineered Cell-targeted LNP (EnC-LNP) platform enables precise delivery of mRNA into non-antigen presenting cells (non-APC) outside the liver, overcoming a key limitation of conventional liver-targeted LNPs. MagicRNA is establishing itself as a global leader in the field of engineered cell-targeted LNP based therapeutics. In addition to its lead program, HN2301, MagicRNA is advancing a pipeline of in vivo cell reprogramming therapeutics and cell-targeted LNP based medicines across immune-related diseases.

About SLE
Systemic Lupus Erythematosus (SLE) is a chronic, multisystem autoimmune disease affecting an estimated 3.4 million people globally, with a prevalence of approximately 44 per 100,000 individuals. The disease disproportionately affects women of childbearing age and is characterized by immune-mediated inflammation and tissue damage across multiple organs, with lupus nephritis being one of the most severe and life-threatening manifestations. Traditional standard treatments for SLE, including corticosteroids, immunosuppressants, and biologics, can help control symptoms, but many patients continue to experience recurrent relapses driving progressive multiple-tissue damage and life-threatening complications. B cells play a pivotal role in the pathogenesis of SLE by producing autoantibodies, and the "B cell reset"-induced drug-free remission of SLE has been extensively validated by clinical reports.

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SOURCE Shenzhen MagicRNA Biotech Co., Ltd.