HCAb-Based Immune Cell Engagers (HBICE®) are advanced T Cell Engagers (TCEs) developed by Nona Biosciences to enhance the immune system’s ability to target and eliminate cancer cells by directly linking T cells to tumor cells. These bispecific and multispecific antibodies target both a pan T cell marker (often CD3) and tumor-associated antigens (TAAs), promoting T cell activation and precise tumor lysis through the formation of an immunologic synapse.
Figure 1: Novel HBICE®
The diagrams below depict illustrative scenarios: by circumventing the conventional T-cell activation pathway, typically mediated by the TCR-MHC interaction, HBICE® molecules with CD3-targeting capabilities can induce a broad T-cell response that is not restricted by MHC, effectively overcoming immune escape mechanisms like antigen presentation downregulation. Within the tumor microenvironment (TME), T cells often lack essential costimulatory signals for optimal functionality. HBICE® antibodies, designed to target tumor-associated antigens (TAAs) and provide the essential costimulatory signal for full T cell activation in TAA-dependent manner. This mechanism results in the effective eradication of tumors and an enhanced safety profile.
T-cell engagers are bispecific antibodies designed to simultaneously bind to the antigens on target cells and CD3 receptors on T-cells. This dual binding brings T-cells into proximity with the target cells, activating the T-cells to attack and eliminate the target cells.
Nona Biosciences’ T-cell engager technology, powered by the HBICE® platform, offers a promising approach for the treatments of cancer and other indications.
T-cell engagers bridge T-cells and target cells, unleashing targeted immune responses. Key benefits include:
Direct T-cells to specific target cells, minimizing off-target effects.
Demonstrated clinical efficacy in hematological malignancies and solid tumors, with potential applications in non-oncology indications.
Flexible geometries for different therapeutic needs, including bi- and multi-specific formats.
Optimized to balance cytotoxicity and cytokine release, reducing adverse effects.
Each 20K OptoSelect chip has 20,000 individual NanoPen chambers and can separate and screen up to 20,000 cells within a single run.
With real-time fluorescent microscopy technology, different assays could be performed in-chip for plasma cell screening, including:
All these advantages make SBC platform to become highly efficient and robust antibody discovery platform.
Opto-electro positioning (OEP) technology precisely manipulates and unloads cells to 96-well plates preloaded with single-cell sequencing reagents.
Opto-electro positioning (OEP) technology precisely manipulates and unloads cells to 96-well plates preloaded with single-cell sequencing reagents.
Our CD3 HBICE® variants are designed to adjust binding activity to human T cells, striking a balance between cytotoxicity and cytokine release. This ensures effective tumor targeting while minimizing off-target effects.
Functional Assessment of BCMA x CD3 suggests a balanced profile of efficacy and safety.
BCMA x CD3 depletes BCMA-positive cells with limited cytokine release. No off-target killing on BCMA-negative HL-60 cells (A). No T cell activation for CD4+ or CD8+ cells (B). Strong cytotoxicity to BCMA-high NCI-H929 cells (C). Lower cytokine release (IL6, TNF-α) compared to control TAB3 (D).
CD3 HCAbs offer diverse and flexible formats to fit various therapeutic geometries, providing a robust platform for creating effective TAA×CD3 engagers (‘2+1’ HBICE®). Our technologies ensure the potent killing of TAA-positive tumor cells while maintaining safety and specificity.
Leveraging our proprietary HBICE® platform, we can enhance the immune response by activating T cells within tumor microenvironment (TME), focusing on targeting tumor-associated antigens (TAAs) to deliver a potent and precise attack against cancer cells.
Our HBICE® platform is designed to provide robust T cell activation through a dual signal mechanism. This involves the engagement of both the primary TCR (T-cell receptor) signal and the co-stimulatory signal, essential for effective T cell activation, proliferation, and memory formation.
The HBICE® engages the TCR-CD3 complex on T cells, initiating the primary signal essential for T cell activation.
The HBICE® simultaneously delivers a co-stimulatory signal, enhancing T cell activation and promoting a sustained immune response. This dual engagement is crucial for effective anti-tumor immunity.
Our 4-1BB HBICE® selectively activates T cells in the presence of TAAs, ensuring targeted and controlled immune responses. Key benefits include:
Activates T cells only with TAAs, minimizing off-target effects and reducing toxicity.
Combines with CD3 HBICE® to provide both TCR and co-stimulatory signals, boosting T cell proliferation and sustained cytotoxicity against tumors.
4-1BB HCAb-based HBICE can rapidly generate tumor-specific bispecific antibodies from existing anti-TAA H2L2 sequences.
Extends to other immune cells (NK, macrophages, dendritic), enabling a comprehensive cancer immunotherapy approach.
In vivo studies show that our B7H4×4-1BB HBICE® significantly inhibited tumor growth and improved survival in syngeneic mouse models.
The B7H4×4-1BB HBICE® activates T cells in the presence of tumor cells, increasing cytokine production and cytotoxic activity. Its effectiveness is dependent on high B7H4 expression levels on tumor cells.
The 4-1BB HBICE® was well tolerated in preclinical toxicity studies, with no significant adverse effects observed at therapeutic doses.
Pioneering the next generation of engagers for enhanced delivery and efficacy.
Mimicking T-cell receptors for an even more precise targeting approach.
Opening new avenues for neurological therapies by shuttling brain-targeted antibodies across BBB.
Having questions? Contact us at BD@nonabio.com
Beacon® single B cell screening
Display technology
CAR-function based functional screening
Hybridoma
HCAb direct cloning screening
TCR Mimic Antibody
Functional characterization
Binding / Affinity
Antibody production
In vitro functional assay
Developability
Protein
Cell line
DNA
mRNA
Target assessment
Recombinant protein
Recombinant cell-line
Affinity maturation ▶
Humanization▶
Fc-Engineering▶
Structure-Based Protein Design
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Stable cell line
Process development
Manufacture
PK / PD
Efficacy
ADA
TOX
Dr. Jingsong Wang is Chairman of Nona Biosciences. Prior to that, Dr. Wang served as Head of China R&D and Head of Translational Medicine, Asia Pacific, at Sanofi. He is a former attending physician and clinical fellow at Harvard Medical School. Dr. Wang received his Ph.D. in Molecular Pharmacology from China Pharmaceutical University and has also completed a Molecular Immunology Research Fellowship at Dr. Laurie Glimcher’s laboratory at the Harvard School of Public Health.
Dr. Yiping Rong is our Chief Scientific Officer. He is a well-recognized scientist with about 20 years’ experience of biomedical research and drug discovery. Dr. Rong used to work at Sanofi, JNJ and Roche and built strong expertise in cancer biology and pharmacology. He led and contributed to >15 programs entering clinical trials. He is also involved in translational research work for a few drugs. Multiple mAb or bispecific antibodies generated from his team were out licensed to MNCs. Some highly innovative first-in-class projects are in clinical trials. He worked on apoptosis, epigenetics, immuno-oncology, and cancer cell signaling fields and led the drug discovery projects including kinase, enzyme, receptor/ligand, protein-protein-interaction targets by small molecules or monoclonal antibodies. Dr. Rong received his Ph.D. degree in Pharmacology from Case Western Reserve University (Cleveland, Ohio). He is the member of American Association of Cancer Research and has more than twenty publications in cancer research field, including Nature Genetics, Molecular Cell, PNAS papers. He is also the inventor of dozens of patents in drug discovery field.
Dr. Jiyong Zhang leads business development at Nona Biosciences, bringing vision and dedication to strategic growth and client satisfaction. With 15 years of experience in biotherapeutic research and development, Dr. Zhang’s understanding of market dynamics and ability to identify mission-aligned opportunities are evident.
Before overseeing business development at Nona, Dr. Zhang played key roles at Alexion and Abbvie, contributing to antibody discovery, engineering, and bispecific antibody R&D. His scientific experiences and knowledge in biotherapeutic innovation makes him a forward-thinking strategist focused on enhancing service offerings to meet evolving client needs.
With Dr. Zhang and his team driving business development, Nona Biosciences is poised to offer innovative solutions and unparalleled service. This solidifies the company’s position as a trusted and client-focused drug discovery partner in the dynamic landscape of biotherapeutic innovation.
Dr. Joe Zhao is Vice President and Head of External Innovation of Nona Biosciences. Joe holds a BS from Fudan University and a PhD from University of Delaware, followed by postdoctoral trainings at Lankenau Medical Center and Zeneca Pharmaceuticals. Prior to joining Harbour BioMed, he was in small biotechs (Pharmacopeia and Ligand Pharmaceuticals) and large MNC (BMS). Joe has 25 years of combined experience in drug discovery of both small molecules and biologics in therapeutic areas of immuno-oncology, immunology, and genetic diseases.
Mr. Louis Liu is Senior Vice President and Head of Scientific Operation of Nona Biosciences. He graduated from Bethune Medical University with Bachelor Degree of Medicine. He has over 30 years’ experience in antibody technology platform establishment, antibody discovery and discovery team management experience. Previously he worked in Syntron Bioresearch Inc as R&D manager, Strategic Diagnostic Inc as product development supervisor, Rockland Immunochemical Inc as Manager of Monoclonal Antibody service and product development, GenScript Ltd as vice president of Antibody Division, Shanghai ChemPartner as vice president of Biologics Discovery.
Dr. Yun He is Chief Technology Officer of Nona Biosciences. Before Nona Biosciences spun off from Harbour BioMed, Dr. He served as Head of Antibody Technology at Harbour BioMed. During his tenure there, Dr. He contributed to multiple discovery programs and led the team in establishing HBICE® platform. Prior to joining Harbour BioMed, Dr. He was an Investigator at Biologics Center in Novartis, where he was responsible for antibody engineering and bioinformatics. Prior to that, Dr. He was the group leader of Bioinformatics at GenScript. Dr. He received his Ph.D. from the Chinese Academy of Sciences, with a focus on molecular biology and bioinformatics.
Dr. Musheng Bao earned his Ph.D. in China and completed his postdoctoral training at MD Anderson Cancer Center and Baylor Institute for Immunology Research. Beginning his professional journey as a Scientist II at MedImmune, Dr. Bao later transitioned to Sanofi, where he served as a Principal Scientist. Following this, he joined Harbour BioMed, where he led a team dedicated to therapeutic antibody development utilizing the Harbour Mice® platform. Presently, Dr. Bao has taken on the role of Head of Biology at Nona Biosciences.
Dr. Arkinstall has demonstrated remarkable competence throughout his career. He is a respected leader in drug discovery with substantial roles under his belt, including Research Head, Chief Scientific Officer (CSO), and Chief Executive Officer (CEO) positions at various pharmaceutical or biotech companies. Dr. Arkinstall served as CEO of Elstar Therapeutics and Revitope Oncology, companies advancing novel classes of multi-specific antibody-based cancer drugs. He previously was also the CSO of Kymab, an antibody therapeutics company founded in Cambridge, UK, prior to which he spent 16 years in progressively senior research leadership roles at EMD (Merck) Serono, and its associated entities across Europe and the United States.
Dr. Grosveld is Co-founder and CSO of Harbour Antibodies and the inventor of Harbour Mice®, Professor and former Head of Department of Cell Biology and Department of Clinical Genetics at Erasmus University Medical Center, Rotterdam, a fellow of Royal Society and a member of Royal Netherlands Academy of Arts and Sciences. Dr. Grosveld’s research on the control of globin gene expression has been selected as one of the top ten achievements of Medical Research Council (UK) (MRC) in the 20th century by Higher Education and Research Opportunities in the U.K. Dr. Grosveld was awarded the Louis-Jeantet Prize for Medicine in 1991, the Spinozapremie (Spinoza Prize) in 1995.
Dr. Kamen is a Venture Partner at Third Rock Ventures. In 2005, he co-founded BioAssets Development Corporation and served as its Chairman. He currently serves as an independent non-executive Director of Harbour BioMed and a director of Jounce Therapeutics (NASDAQ:JNCE). He was previously a director of Neon Therapeutics and Harbour Antibodies. Earlier in his career, he was senior vice president of scientific affairs at the pioneering biotechnology firm named Genetics Institute, Inc. Dr. Kamen received his bachelor’s degree in biophysics from Amherst College, a Ph.D. in biochemistry and molecular biology from Harvard University Graduate School of Arts and Sciences. During his academic scientific career, he worked at the Imperial Cancer Research Fund.
Dr. Kramer serves as CSO of Portage Biotech Inc. Dr. Kramer previously served as Vice President and Head of Discovery for Oncology Therapeutics at Janssen Research & Development, LLC (the Pharmaceutical Division of Johnson and Johnson), where he was responsible for leading Global Discovery, focusing on aberrant signaling cascades in tumor cells, as well as epigenetic reprogramming and tumor immunology using both small molecule and protein-based large molecule approaches. Prior to joining Janssen Research & Development, LLC, Dr. Kramer served as VP Drug Discovery and Research for Bristol-Myers Squibb (BMS), where he provided scientific leadership and strategic oversight for many pre-clinical Oncology and Immunology programs and projects that entered development. Dr. Kramer was previously an Assistant Professor at Harvard Medical School. Dr. Kramer received his Ph.D. in pharmacology from the University of Vermont and completed his post-doctoral fellowship in Oncology at the National Cancer Institute, National Institutes of Health.
Peter Moesta, Ph.D., oversaw the development, production and worldwide launch of important medicines, such as Humira, Yervoy and Opdivo. Dr. Moesta previously served in executive roles at Bristol-Myers Squibb.
Dr. Tian is an academician of Chinese Academy of Engineering, a member of Academia Europaea and a medical immunologist. Currently, he is a professor at University of Science and Technology of China (USTC), where he also works as Dean at School of Basic Medical Sciences, and Director at Institute of Immunology. He is also the Director of the Key Lab of Innate Immunity and Chronic Diseases of Chinese Academy of Science.
Dr. Tian was awarded with the National Science Fund for Distinguished Young Scholars. He is the academic leader of Chang Jiang Scholars Program as well as the Innovation Research Program of National Natural Science Foundation of China. Dr. Tian is Head of National Science and Technology Major Project and Chief Scientist of National Major Research Plan Program.
Dr. Tian’s laboratory is credited with seminal discoveries regarding basic knowledge and clinical study of natural killer (NK) cells, particularly liver-resident NK cells, cytokine-producing NK cells, and NK cell-based immunotherapy.
