Changyun Hu

TregShield Bio is pioneering tissue-restricted activation of biologics to treat autoimmune and inflammatory diseases with unmatched precision. Our platform ensures activation occurs only within diseased organs — unlocking powerful immune modulation safely. Our lead program, TRS-001, is a first-in-class pancreas-activable biologic for type 1 diabetes, with a dual mechanism of action: neutralizing pathogenic T cells and boosting regulatory T cells (Tregs). Beyond T1D, the platform is designed to expand into multiple high-value immune indications.

• Develop scientific vision and research strategy for immuno-oncology. • Build and mentor the research team. • Establish internal research capability and external scientific collaborations. • Lead antibody drug discovery, in vitro MOA, and in vivo efficacy studies. • Identify and manage CROs.

1. Co-led the project team and discovered GS-1811 (afucosylated anti-CCR8) that specifically depletes tumor-infiltrating regulatory T cell from target identification to development candidate selection. Supported IND enabling studies of GS-1811 for IND application. Contributed to its license-out to Gilead Bioscience. 2. led antibody drug projects targeting tumor-associated stroma and myeloid cells to enhance anti-tumor immunity by overcoming immune checkpoint blockade resistance.

co-led programs and matrix managed cross-functional team members. Responsible for reagent design and generation, assay development, and antibody drug discovery etc. Spearheaded the establishment of internal antibody generation and engineering capabilities.

Acted as leading Senior Scientific Researcher to design and execute antibody discovery projects. Has successfully developed immunization strategies against difficult targets including sodium ion channel, neurodegenerative disease target and complex membrane protein for the discovery of monoclonal antibodies by employing HTP automation process. 1. Explored novel format of antigens (protein and/or peptide) to boost antigen-specific immune responses to difficult targets such as sodium ion channel, complex membrane protein antigen in various animal species including mouse, rat, and hamster. 2. Developed strategies to break immune tolerance to improve immune responses to highly conserved protein antigens in animal species. 3. Employed hybridoma and B cell cloning platforms to develop monoclonal antibody against difficult targets such as complex membrane protein sodium ion channel etc. 4. Optimized selection of antigen-specific B cells, and designing protein- and/or cell-based binding and functional activity screening strategies. 5. HTP automation: Clonepix, Biocel, Hamilton STAR, Tecan M1000 Pro, Biacore system and Wasatch microfluidics system etc.

Acted as principal investigator leading projects to discover monoclonal antibod-mediated Immunotherapies for autoimmune disease through understanding the role of innate immunity, T and B Cell Biology, MDSCs in autoimmunity. 1. Developed combined immunotherapy of anti-CD20 and oral anti-CD3 for autoimmune diabetes, which showed improved efficacy for the prevention and reversal of diabetes development in animal model. 2. Developed combined immunotherapy of anti-CD20 and GAD for autoimmune diabetes, which showed improved efficacy for the prevention and reversal of diabetes development in animal model. 3. Demonstrated NLRP3 inflammasome pathway promote autoimmune diabetes in animal model. 4. Demonstrated that immunoglobulin play an important role in the development of high fat diet-induced obesity and insulin resistance (type 2 diabetes patients). 5. Managed projects, grants and junior lab personnel. Selected Publication 1. Changyun Hu, Ding H, Li Y, Pearson JA, Zhang X, Flavell RA, Wong FS, Wen L. NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets. Proc Natl Acad Sci U S A. 112(36):11318-23 (2015) 2. Changyun Hu, Ding H, Zhang X., Wong FS and L. Wen. Combined treatment with anti-CD20 and oral anti-CD3 prevents and reverses type 1 diabetes in NOD mice. Diabetes. 62(8):2849-58 (2013) (with accompanying commentary By Dr. Lucienne Chatenoud). 3. Changyun Hu, Wei Du, Xiaojun Zhang, S.F. Wong and Li Wen. The role of Gr1+CD11b+ cells after B cell depletion in type 1 diabetes. J. Immunol. 188(1):294-301 (2012)

As leading scientist to investigate innate immunity and B cell-targeted Immunotherapies for autoimmune disease, and innate immunity of invertebrate by functional genomics studies. 1. Developed anti-CD20 mediated B cell depletion therapy in preclincal model, which was tested in the clinical trial of rituximab for autoimmune diabetes patients. 2. Demonstrated that TLR signaling pathway, in particular MyD88, is responsible for the modulation of gut flora and thus the prevention of autoimmune diabetes. 3. Demonstrated that B cell depletion can prolong the survival of islet graft in non-obese diabetic mice. 4. Developed RNA interference technique in tsetse fly to study the role of innate immunity in parasite transmission. 5. Managed projects and grants. Selective Publication 1. Changyun Hu, Daniel Rodriguez, Wei Du, Anupama. Ahuja, F.Susan Wong, Mark Shlomchik, and Li Wen. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J. Clin. Invest. 117:3857–3867 (2007) (with accompanying commentary by Dr. Jeffery Bluestone). 2. Li Wen, Ruth E. Ley, Pavel Yu. Volchkov, Peter B. Stranges, Lia Avanesyan, Austin C. Stonebraker, Changyun Hu, F. Susan Wong, Gregory L. Szot, Jeffrey A. Bluestone, Jeffrey I. Gordon & Alexander V. Chervonsky. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature. 455, 1109-1113 (2008)