Daoyuan Portfolio Company Huaxia Yingtai Achieves Breakthrough with Off-the-Shelf STAR-T Therapy YTS109 in Refractory Lupus Nephritis

August 27, 2025, Daoyuan's Outstanding Invested ProjectsHuaxia YingtaiIn collaboration with Professor Xu Huji's team from the Second Affiliated Hospital of Naval Medical University and Professor Lin Xin from Tsinghua University,A groundbreaking study was published in the prestigious international journal *Nature Medicine* (Impact Factor 58.7). This study reports for the first time globally on the efficacy and safety of allogeneic universal CD19-specific STAR-T cells — YTS109 in treating refractory systemic lupus erythematosus (SLE) complicated with lupus nephritis (LN).Notably, among the currently published clinical studies of this kind, the lupus nephritis patients included in this study are not only...Baseline Condition Most Severe`, and`The largest number of patientsThe representativeness and reference value of the research data are particularly prominent. The publication of this study in an international top journal not only signifies the high recognition from the international academic community of the clinical value of YTS109, but also strongly validates the development potential of the universal STAR-T technology in the field of autoimmune diseases, offering new treatment options for patients with autoimmune diseases.

The study focuses on addressing the unmet clinical needs of patients with refractory systemic lupus erythematosus (SLE), particularly those with severe lupus nephritis (LN).These patients have long faced the clinical dilemma of limited efficacy and high recurrence rates associated with traditional immunosuppressants. While existing autologous CD19 CAR-T therapies have shown treatment potential, they are limited by challenges such as lengthy personalized manufacturing cycles, high costs, risks of random genomic insertion, and the risk of disease progression due to the need to discontinue immunosuppressive treatments prior to manufacturing. In response to this, Huaxia Yingtai (Beijing) Biotechnology Co., Ltd. has developed an innovative universal CD19 STAR-T product, YTS109, aiming to overcome these bottlenecks and provide a safe and effective new treatment option for patients with refractory lupus.

YTS109 is based on the STAR technology platform and incorporates advanced gene editing strategies.Huaxia Yingtai's novel STAR (Synthetic T cell Receptor and Antigen Receptor)-T technology, which combines the direct antigen recognition of CAR and the natural signal transduction of TCR, demonstrates technical advantages such as high sensitivity, strong infiltration, resistance to exhaustion, natural dual targeting, and good safety.The universal STAR-T further developed by the team utilizes the CRISPR-Cas9 gene editing tool and an adeno-associated virus (AAV) targeted integration strategy for enhancement. STAR compensates for some functions lost due to the knockout of the endogenous T-cell receptor, reducing the graft-versus-host disease (GVHD) and host-versus-graft reaction (HVGR) of the universal STAR-T cells, while enhancing their resistance to immunosuppression and tumor-killing capabilities.。Non-clinical studies have confirmed that YTS109 possesses characteristics such as highly efficient targeted killing (especially for cells with low CD19 expression), low immunogenicity, effective reduction of NK cell killing, alleviation of host T-cell responses, controllable off-target effects, and no safety risks such as chromosomal structural abnormalities.

In this investigator-initiated clinical study (IIT) (NCT06379646)Between April and July 2024, five patients (four women and one man, aged 23-41 years, disease duration 3-30 years) with severe, refractory SLE combined with LN (ISN/RPS III+V or IV+V type) were enrolled. All patients had high baseline disease activity (SLEDAI-2K: 16-32; SLE-DAS: 15.06-42.02) and had failed multiple treatments, including steroids, immunosuppressants, and biologics.Clinical results showed that, after the infusion of YTS109, the outcomes were surprisingly positive, with all patients demonstrating rapid and sustained clinical benefits:

•Achieve 100% SLE Responder Index 4 (SRI-4).All patients rapidly reached the primary endpoint SRI-4 sustained response criterion at M1 after infusion.

•The SLE activity index (SELENA-SLEDAI) scores of 4 patients dropped to 0, with complete resolution of clinical symptoms such as proteinuria, arthritis, alopecia, vasculitis, and rash., the level of dsDNA antibodies in patients showed a significant decrease, and the complement levels recovered rapidly;

• Four patients achieved Lupus Low Disease Activity State (LLDAS) remission; two patients achieved Systemic Lupus Erythematosus (SLE) Definition of Remission in SLE (DORIS) remission.

• According to the evaluation criteria for Lupus Nephritis (LN), 2 patients achieved Complete Response (CR) with urine protein levels <500mg/24h; 2 patients achieved Partial Response (PR).Urinary protein levels decreased by more than 50%, all patients are currently in continuous remission.

• Two patients experienced Grade 1 cytokine release syndrome (CRS);No serious adverse events such as graft-versus-host disease (GVHD) or immune effector cell-associated neurotoxicity syndrome (ICANS) were observed.Grade 3-4 major adverse events were leukopenia, neutropenia, and lymphopenia, with no severe infections occurring.

•Deep B-cell Depletion: After the infusion of YTS109, B cells in the patient's peripheral blood were rapidly depleted, lasting for 1-2 months. Subsequently, B cells began to reconstitute, primarily consisting of immature/naive B cells.

•Systemic Immune ResetSingle-cell RNA/BCR sequencing showed that YTS109 could reshape the composition and function of immune cells. After YTS19 infusion, the pathogenic IGHG and IGHA populations were effectively eliminated, and newly emerged B cell receptor (BCR) clones, distinct from baseline, appeared, predominantly featuring IGHM and IGHD.

•Significant Repair of Kidney TissueRenal Pathological Biopsy and Related Tests Were Performed on Two Patients Before and After the Infusion: Results Show Significant Improvement in Renal Tissue Pathology Compared to Baseline After YTS109 Infusion

• In addition, plasma proteomics analysis showed that the body presented a systemic immune quiescent state transition after YTS109 infusion, with pro-inflammatory pathways such as neutrophil chemotaxis and cytokine signaling being downregulated, while pathways related to tissue repair, integrin signaling, and immune regulation were upregulated. These synergistic mechanisms suggest that...YTS109 can not only reshape the renal immune microenvironment but also induce broad immunomodulatory effects at the systemic level.

As an "off-the-shelf" universal product, YTS109 has broad clinical application prospects.Based on the positive results of this study, Huaxia Yingtai (Beijing) Biotechnology Co., Ltd. will further expand the sample size and conduct multi-center, long-term follow-up registered clinical research to verify its efficacy and safety in a larger scale of patients, providing solid data for subsequent product registration applications. Meanwhile, given the broad-spectrum potential of YTS109 in immune resetting, the team plans to and has begun expanding its application in other autoimmune diseases.Including indications such as autoimmune hemolytic anemia and scleroderma; Relevant exploratory research has currently been initiated, offering hope to provide new treatment options for more patients with autoimmune diseases.

The principal investigator of this project and the corresponding author of this article, Professor Xu Huji from the Second Affiliated Hospital of Naval Medical University, stated:"Patients with refractory systemic lupus erythematosus, especially those with severe lupus nephritis, have long faced treatment challenges. YTS109, as a new generation of universal cell therapy product, has demonstrated exciting efficacy and good safety in this exploratory clinical study. The 'immune reset' phenomenon it induces provides a new perspective for understanding the mechanisms of disease remission. We look forward to its subsequent research results ultimately changing clinical practice and advancing the treatment of refractory autoimmune diseases into a new chapter of precision cell therapy."

Lin Xin, Professor at Tsinghua University and Scientific Founder of Huaxia Yingtai (Beijing) Biotechnology Co., Ltd., stated"This research achievement published in *Nature Medicine* marks a significant breakthrough in the application of our STAR-T technology platform to autoimmune diseases. The breakthrough of YTS109 not only validates the ability of universal STAR-T technology to address the bottlenecks of autologous cell therapy (long cycle, high cost, and significant manufacturing risks) but also offers the potential to transition autoimmune disease treatment from 'lifetime medication' to 'functional cure.' We will fully advance the subsequent clinical development of YTS109 in lupus and other severe autoimmune diseases, accelerating the delivery of this innovative therapy to patients worldwide who urgently need it."