Tsinghua University

BEIJING, China I March 24, 2025 I SineuGene Therapeutics Co., Ltd. (“SineuGene”), a clinical-stage biotech company pioneering innovative therapies for neurological disorders, today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for SNUG01 — a first-in-class TRIM72 (Tripartite Motif Protein 72)-targeted gene therapy candidate for amyotrophic lateral sclerosis (ALS). The clearance authorizes a global Phase I/IIa clinical trial designed to evaluate SNUG01’s safety, tolerability, and preliminary efficacy in adults with ALS through a dose-escalation and expansion study. ALS is a rapidly progressive neurodegenerative disorder marked by motor neuron degeneration in the brain and spinal cord, leading to muscle weakness, atrophy, and eventually respiratory failure. Median survival time post-diagnosis is 3–5 years. Despite being the most prevalent adult-onset motor neuron disease, existing therapies offer limited clinical benefits, slowing progression only marginally and leaving no curative options for patients. SNUG01 leverages groundbreaking research carried out by Dr. Yichang Jia’s laboratory at Tsinghua University, whose team identified TRIM72 as a multifunctional neuroprotectant. The therapy utilizes a recombinant adeno-associated virus serotype 9 (rAAV9) capsid to deliver the human TRIM72 gene via intrathecal administration. Preclinical studies demonstrate TRIM72’s ability to counteract ALS pathogenesis through several synergistic mechanisms such as reducing oxidative stress by scavenging reactive oxygen species (ROS), restoring mitochondrial homeostasis, suppressing stress granule dysregulation, inhibiting neuroinflammatory cascades, and enhancing neuronal membrane repair capacity In an investigator-initiated trial (IIT) at Peking University Third Hospital, SNUG01 demonstrated a favorable safety and tolerability profile, along with early efficacy signals in both functional clinical assessments and key biomarkers of neurodegeneration. These results enhance the translational validation of TRIM72, bridging target discovery, preclinical models, and human proof-of-concept. Unlike mutation-targeting gene therapies, SNUG01 leverages multiple neuroprotective mechanisms, offering a critical advantage for over 90% of ALS patients with sporadic (non-familial) disease. This unique multi-target approach positions SNUG01 as a first-in-class candidate for the majority of ALS cases, addressing an urgent unmet need in this underserved population. SineuGene will partner with a leading global consortium of academic and clinical institutions to conduct a multi-regional clinical trial, expediting validation of SNUG01’s safety and therapeutic efficacy profile across a diverse ALS patient populations. About SineuGene SineuGene Therapeutics Co., Ltd., often referred to as “SineuGene,” is a biotechnology company focused on developing innovative therapies for neurological diseases. Established in late 2021, the company builds on over a decade of scientific research conducted by Dr. Yichang Jia’s team from School of Medicine, Tsinghua University. SineuGene uses advanced technologies such as adeno-associated virus (AAV) vector-mediated gene delivery and editing and antisense oligonucleotide (ASO)- based gene expression regulation. The company has created a diverse pipeline that targets major neurological diseases, including Amyotrophic Lateral Sclerosis (ALS), stroke, Parkinson’s disease, Alzheimer’s disease, Spinocerebellar Ataxia type 3, and Huntington’s disease. SineuGene is dedicated to transforming groundbreaking research into effective treatments, aiming to meet the unmet medical needs in the field of neurology. Website: www.sineugene.com SOURCE: SineuGene Therapeutics

A project in China that is developing an autonomous and self-evolving virtual healthcare setting is targeted to go public next year. This is confirmed to Healthcare IT News by Yang Liu, a professor at Tsinghua University's Department of Computer Science and Technology and co-research head of the Agent Hospital project. The virtual hospital concept, developed by researchers at the university's Institute for AI Industry Research (AIR), simulates the real-world cycle of the hospital treatment process, from disease onset to follow-up. The institute claims the concept as the first of its kind globally. Findings from this research were first published in May in arXiv, Cornell University's open-access online research paper repository. WHY IT MATTERS All virtual actors in Agent Hospital, including patients, nurses, and doctors, are generated via a large language model (LLM). These AI characters will represent real people once the system goes live in public by the first half of 2025. A public pilot, to be conducted by AIR's spinoff startup Tairex, will begin sometime in the first quarter, said Prof Yang. For the virtual hospital concept, researchers proposed a design method called MedAgent-Zero, which enables AI doctors to continuously learn and improve and become accurate in performing clinical tasks by interacting with patients, reviewing medical literature, and accumulating experience from handling both successful and unsuccessful cases. Their research findings showed that through this novel method, AI doctors achieved 88%, 95.6%, and 77.6% accuracy in examining, diagnosing, and treating patients, respectively. "The doctor agent is able to complete the diagnosis and treatment of tens of thousands of patients within a few days, which would typically take at least two years for a human doctor," the researchers also noted. Meanwhile, an AI doctor also showed up to 93% accuracy in answering a subset of the MedQA dataset – mostly based on the competitive United States Medical Licensing Examination, covering questions on major respiratory diseases. As part of the concept's development, researchers plan to expand its range of disease coverage and extension in more medical departments. The virtual platform currently features 42 AI doctors in 21 medical departments, including emergency, respiratory, and cardiology. They also plan to incorporate more features, including medical position promotions, changes in disease distribution with time, and historical patient medical records. There is also a plan to optimise the selection and implementation of the base LLM. OpenAI's ChatGPT model versions 3.5 and 4 are currently utilised in their research. "We will use the latest and most advanced LLM," Prof Yang said. THE LARGER TREND Other research initiatives in China have also developed medical LLMs for clinical decision support. A project at the Tongji University School of Medicine built a model called MedGo , which was trained using 6,000 medical textbooks and has since been integrated and utilised at the affiliated Shanghai East Hospital. An AI-focused institute under the Chinese Academy of Sciences – one of China's national research centres – introduced early this year the CARES Copilot chatbot based on Meta's Llama 2 LLM, which assists doctors in making medical diagnoses and treatments.

While these results remain to be scaled to broader patient populations, the study authors wrote that they point to the promise of a donor-derived, off-the-shelf allogeneic CD19-targeted CAR-T therapy for autoimmune diseases. Three people with autoimmune diseases have responded positively to allogeneic CAR-T therapy, marking a first for the "off-the-shelf" cell therapy tech. The study, conducted in China and published in Cell on July 15, is the first sign of the potential of allogeneic CAR-T therapies in treating autoimmune diseases, according to William Blair analysts. A large team of researchers, led by clinical immunologist Huji Xu, Ph.D., of Tsinghua University in Beijing, engineered CAR-T cells from donors to target CD19, a protein found on the surface of B cells. They also knocked out human leukocyte antigen in the cells and then amplified the cells negative for CD3, in order to prevent conflicts between donor cells and host cells. CD19 targeting is an emerging therapy for treating B cell malignancies, but it hasn’t successfully been used to treat B cells that have gone rogue, as is the case in autoimmune diseases. Xu and colleagues intravenously infused the therapeutic cells into one patient with immune-mediated necrotizing myopathy (IMNM) and two patients with diffuse cutaneous systemic sclerosis (dcSSc). The patient trio first stopped taking immunosuppressants and underwent a standard preconditioning treatment of fludarabine and cyclophosphamide. The researchers then monitored the patients' blood to track the CAR-T cells. In one to two weeks, the engineered CAR-T cells proliferated within the patients and B cells began to disappear until they were undetectable. In the IMNM patient, B cells rebounded by six months after treatment, while the two dcSSC patients saw their B cells bounce back by month three. The B cell reset worked. The IMNM patient went into remission at month two, which lasted through to month six and was accompanied by an increase in muscle mass and improved quality of life. The dcSSC patients improved their American College of Rheumatology Composite Response Index in Systemic Sclerosis scores to 0.99 in the first month and sustained that score through month six. Scores greater than 0.6 are considered an improvement. They also saw improved skin elasticity, lung function, cardiac function, and fibrosis. None of the three patients showed any signs that their bodies were rejecting the transplanted cells. The study, sponsored by Shanghai-based Bioray Laboratories, represents “the first clinical proof-of-concept supporting the therapeutic potential of an allogeneic CAR-T therapy for the treatment of autoimmune diseases, to our knowledge,” according to a note from William Blair analysts. The analysts also pointed out that it’s unclear how much tinkering with the cell’s genomes influenced treatment efficacy. The data should be a boon to biotechs currently developing allogeneic CAR-T cell autoimmune therapies of their own, according to the analysts, including CRISPR Therapeutics, Allogene, and Poseida, as well as for firms developing other CAR-T therapies for autoimmune diseases, like Cabaletta. “We view the additional data in IMNM (i.e., myositis) and SSc as supportive of the continued evaluation of CAR-Ts in additional indications outside lupus,” the analysts wrote in the report. While these results remain to be scaled to broader patient populations, the study authors wrote that they point to the promise of a donor-derived, off-the-shelf allogeneic CD19-targeted CAR-T therapy for autoimmune diseases.