Revisit the Perspectives of Bispecific Antibodies under the COVID-19 Pandemic

Kedan Lin, PhD

Dr. Lin has served as Vice President of Clinical Development and US Operation in Innovent Biologics since 2018. She is responsible for the strategy and execution of US clinical development, US IND filing and site operation. In addition, she also supervises the Non-Clinical Group, which support over 20 assets in various stages of development. Over the past 20 years, Dr. Lin has built extensive expertise in translational and clinical development across a broad range of therapeutic areas, including oncology, metabolic diseases and ophthalmology. Prior to coming to Innovent, Dr. Lin served as Director of Clinical Pharmacology at NGM Biopharmaceuticals, leading both preclinical and clinical quantitative pharmacology efforts. She also spent ten years at Genentech as Senior Scientist, Group Leader and Pharmacology Team Leader for various BioOncology programs including antibody drug conjugates and T cell dependent bispecific antibodies. She successfully led several programs from target validation, molecule selection, IND enabling to phase 2 development. Prior to Genentech, she was a staff scientist at Celera and scientist at Exelixis, where she conducted target identification, screening and ADME characterization on small molecule discovery programs. Dr. Lin received her PhD in molecular pharmacology from University of California, San Francisco, and she also holds a MSc. degree from Ohio State University as a University Fellow.

Mitchell Ho, PhD

Chairperson's Remarks

Dr. Mitchell Ho is a Senior Investigator, the Deputy Chief of the Laboratory of Molecular Biology and the Director of the Antibody Engineering Program the National Cancer Institute (NCI), National Institutes of Health (NIH). Dr. Ho is also the Chair of the Department of Biochemistry for FAES Graduate School at the NIH. He is a member of the Board of Directors for the Antibody Society and the Chair of the Scientific Advisory Board for the Chinese Antibody Society, and the Editor-in-Chief of Antibody Therapeutics (Oxford University Press). Dr. Ho received his Ph.D. from the University of Illinois at Urbana-Champaign. Dr. Ho’s laboratory studies the biology of cancer driven by cell surface proteins, such as glypicans (e.g. GPC3, GPC2) and mesothelin, in broad scientific fields of molecular biology with focus on ligand/receptor interactions, antibody/protein engineering, and cancer immunotherapy. He has received many honors including the APAO Scientific Achievement Award, NIH DDIR Innovation Award, and NCI Director's Innovation Award.

Audrey Jia, MD, PhD

Regulatory Challenges and opportunities for biological products

Dr. Jia holds a Master degree in Bioscience Regulatory Affairs from Johns Hopkins University, and a Ph.D. degree in Microbiology and Molecular Genetics from Emory University. Prior to that, Dr. Jia obtained her Bachelor degree of Medicine from Peking University.

Dr. Jia has 20 years of combined experience in biologic drug development and regulatory review. Dr. Jia spent 10 years from year 1999 to year 2009 in the biopharmaceutical companies working on monoclonal antibody engineering, humanization, affinity maturation, expression, and purification. During her time in US FDA from year 2009 to 2015, Dr. Jia was a full time CMC reviewer for IND/BLA review of biological products including antibody fragments, fusion proteins, antibody drug conjugate, combination products, and radiolabeled antibodies. She performed numerous IND reviews, BLAs (including post approval reviews), and several US and international cGMP pre-approval inspections (PAIs). She is specialized in both novel proteins/antibodies and biosimilar products reviews.

Dr. Jia currently works as the principal consultant for regulatory and CMC of drug and biologic products. She has helped many companies filed their US INDs/BLAs successfully

Audrey贾博士，北京大学医学学士，通过美国医生执照考试。约翰霍普金斯大学生物法规硕士，埃默里大学微生物分子遗传学博士。贾博士在生物药物开发和监管审查方面拥有20年的综合经验。贾博士曾在Pfizer, AbbVie和PDL BioPharma从事单克隆抗体的工程、人源化、亲和力成熟、工艺开发长达十年。在美国FDA期间，贾博士是评估生物制品的全职CMC评审员，她进行过大量IND评审，BLA评审，以及美国和国际cGMP上市申报核查。她的专长是新型蛋白质、抗体和生物仿制品的评审。贾博士也是FDA在突破性治疗政策发展方面的重要成员，对于快速通道，突破性疗法的法规要求，及通过快速途径开发药物都非常熟悉。2016至今，贾博士作为中美知名法规咨询公司DataRevive的总裁，成功为许多亚美欧公司申报美国的临床IND和上市申报

Ting Xu, PhD

Development of KN046 - a PD-L1/CTLA-4 BsAb

Dr. Xu has more than 20 years of experience in pharmaceutical research and development. Dr. Xu worked at Archemix, Serono and Biogen as Principal Investigator or Project Leader. In 2008, Dr. Xu founded several biopharmaceuticals companies including Suzhou Alphamab and Jiangsu Alphamab. In 2019, Dr. Xu led Alphamab Oncology’s successful Initial Public Listing on the Main Board of Hong Kong Stock Exchange (stock code: 9966 HK).

Dr. Xu has extensive experiences in protein engineering, antibody drug screening and engineering. After returning to China, he has established several proprietary protein and antibody engineering platforms, successfully developed more than 20 innovative biological drug candidates and more than 30 biosimilar drug candidates. He is leading the R&D and clinical development of Alphamab Oncology's 7 innovative biological drug candidates to advance to commercialization.

Dr. Xu obtained his bachelor’s degree in biochemistry from Nanjing University, doctoral degree from the Institute of Biophysics of the Chinese Academy of Sciences, was a post-doctoral fellow at Harvard University.

Yue Liu, PhD

Combining Computer Aided Design and Traditional Antibody Discovery and Engineering Technologies to Develop Multi-Specific Antibodies

Coming soon!

Paul Parren, PhD

Bispecific γδ-T cell Engagers for Cancer Immunotherapy.

Prof. Paul W.H.I. Parren, (Lava therapeutics and Leiden University Medical Center, the Netherlands) is dedicated to translate antibody biology and immunotherapy knowledge into innovative therapeutics and technologies. Prof. Parren studied Biology at the University of Amsterdam where he obtained a M.Sc. in Experimental Oncology (cum laude) in 1987 and a PhD in 1992. Next, he was a Postdoc, Assistant Professor and Associate Professor in the department of Immunology at The Scripps Research Institute in La Jolla, California, where he interrogated the human antibody response in protection against viral infections. From 2002-2017, he served in the positions of Vice President, Senior Vice President and Scientific Director at the biotechnology company Genmab in Utrecht, where he headed preclinical R&D leading to the development of the approved therapeutic antibodies ofatumumab (Arzerra) and daratumumab (DARZALEX), and several clinically translated technologies aimed at improving antibody therapy including bispecific and effector-function enhanced antibodies. He is a tenured Professor of Molecular Immunology at the Leiden University Medical Center in Leiden. Since 2018, he is EVP and head of R&D at the start-up biotech Lava Therapeutics where he develops novel bispecific T-cell engagers for cancer therapy. He also provides drug development, patent and investment advice as an independent biotech consultant.

Teresa Lavoie, PhD

Patent Protection Strategies for Bispecific Antibodies

Teresa Lavoie, Ph.D., is a Principal at Fish & Richardson P.C. In her practice, she helps early-stage life sciences companies succeed by protecting and maximizing the value of their crucial intellectual property through patent counseling, prosecution, and portfolio development. Her work delivers the value necessary for her clients to accomplish a wide range of goals, such as getting pharmaceutical products to market or building attractive patent portfolios for investment, partnership, and acquisition. Over the past six years alone, Dr. Lavoie and her team have developed, managed, and overseen the sale of pharmaceutical and diagnostic patent portfolios with an aggregate value exceeding $33 billion.

Dr. Lavoie’s practice is international in scope and focuses on strategic patent counseling, prosecution, and portfolio development, including patent opinions, due diligence, freedom-to-operate analyses, and lifecycle management strategies. She has significant scientific expertise in the fields of small-molecule and biologic pharmaceuticals (including antibody technologies and immunotherapies, such as CAR-T therapies), drug formulation and delivery technologies, diagnostics, clean and alternative food technologies, protein biochemistry and engineering, cell systems engineering, nanotechnologies, plant biotechnology and genomics, and green/environmental chemistries. She also has extensive experience in IP licensing, including sponsored research, feasibility, and development and commercialization agreements.

Her clients are located in major innovation clusters around the country and the world, including San Francisco, Boston/Cambridge, and San Diego. Representative clients include Array BioPharma, Avanir Pharmaceuticals, Carmot Therapeutics, Cell Design Labs, Compass Therapeutics, Concert Pharmaceuticals, Cocoon Biotech, IFM Therapeutics (prior to acquisition by BMS for $2.3 billion), IFM Tre (prior to acquisition by Novartis for $1.575 billion), Loxo Oncology (prior to acquisition by Eli Lilly and Company for $8 billion), Melinta Therapeutics, Samumed, and Onyx Pharmaceuticals (prior to acquisition by Amgen for $9.7 billion).

Jizu Yi, PhD

CMC Challenges and Strategies for Bispecific Antibody Development

Dr. Jizu Yi, Senior Vice President of WuHan YZY Biopharma Co. Ltd., has over 20 years of working experience in Biopharm/Biotech industrials, focusing on new biologic and technological development. His expertise includes biologic CMC, specifically in cell line development and analytical development, QC, QA, manufacture and quality management system in biopharmaceutical industry, and IND filings. Prior to joining YZY Dr. Yi was Director II of WuXi Biologics (Shanghai), Principal Scientist of Becton Dickinson & Company, Assistant Professor of Mount Sinai School of Medicine, and Postdoctoral Researcher at Fox-Chase Cancer Center-UPENN.

Dr. Yi has over 50 scientific research articles published on international journals and books, awarded multiple international patents.He holds Ph.D. of Biochemistry from Rutgers, the State University of New Jersey.

David Ho, MD

Potent Neutralizing Monoclonal Antibodies Directed to Multiple Epitopes on the SARS-CoV-2 Spike.

David D. Ho is the Founding Scientific Director of the Aaron Diamond AIDS Research Center and the Clyde and Helen Wu Professor of Medicine at Columbia University Irving Medical Center. He received his degrees from California Institute of Technology and Harvard Medical School.


Dr. Ho has been at the forefront of AIDS research for 39 years, publishing over 450 papers. His elegant studies unraveled the dynamic nature of HIV replication in vivo and revolutionized our basic understanding of this horrific disease. This knowledge led him to champion combination antiretroviral therapy that resulted in unprecedented control of HIV in patients. An automatic death sentence has been transformed into a manageable disease, and over 25 million worldwide are currently on such therapy. Dr. Ho’s research team is now devoting considerable efforts on vaccine and antibody research in order to halt or slow the spread of the AIDS epidemic. Recently, he is devoting a considerable effort to develop novel strategies to diagnose, treat and prevent Covid-19 infection.


Dr. Ho has received fourteen honorary doctorates. He was named Time Magazine’s Man of the Year in 1996 and the recipient of a Presidential Medal from Bill Clinton in 2001. He was also inducted into the California Hall of Fame. Dr. Ho was also recognized by the Kingdom of Thailand with the Prince Mahidol Award in Medicine, and given the Distinguished Alumni Award by Caltech. He is a member of the US National Academy of Medicine as well as the Chinese Academy of Engineering.

Jijie Gu, PhD

Next Wave of Innovation of Drug Discovery Driven by Antibody-based Multispecific and Functional Drugs

Dr. Jijie Gu is the Chief Scientific Officer and Executive Vice President at WuXi Biologics. In this role, He is responsible for leading and expanding biologics discovery service business in WuXi Biologics, building up core competencies in antibody and biologics platform technologies and discovery of biologic drugs, and taking the lead to drive WuXi Biologics to be a global leading service provider for biologics drug discovery and technology innovation.

Dr. Gu Jijie brings in more than 20 years of experience including 18 years in pharmaceutical industry in target discovery and drug discovery and early drug development and in building and management of several function areas. Prior to joining WuXi Biologics, he was a director and a function head leading target validation and lead discovery in Immunology Therapeutic Area for both small molecule and large molecule drugs at AbbVie Cambridge Research Center. Before that, he was a function head of Oncology Biologics in Global Biologics at AbbVie Bioresearch Center. Dr. Gu has deep expertise in target discovery, therapeutic design, antibody generation, protein engineering, biologic drug discovery, preclinical and early clinical development. He has made critical contributions to building Abbott/AbbVie antibody platform technologies including yeast display, mRNA display, hybridoma, antibody humanization automation, human IgG transgenic animals and single domain antibody. He has been leading building novel biologics platform technologies at Abbott/AbbVie for a long period of time, including Fc engineering, ADC technology, TCR technology, bispecific and multispecific antibody technologies, and T cell engagers, etc. Dr. Gu is experienced in leading projects in multiple therapeutic areas including Oncology, Immunology, Immuno-Oncology, Metabolic disease, Neuroscience and Ophthalmology. As a project leader or a function head, he has track record of delivering multiple NBEs into clinical development and contributed broadly to building AbbVie Biologics portfolio. He is a co-inventor for more than 20 filed and issued US patents. He is also on editorial board for peer reviewed journals mAbs and Antibody Therapeutics.

Dr. Gu received his Ph.D. in Molecular Biology and Biochemistry from Peking Union Medical School, and had his postdoctoral training in Tumor Immunology at Dana Farber Cancer Institute at Harvard Medical School and in Cancer Cell Biology at Harvard School of Public Health.

顾继杰博士现任药明生物首席科学官兼执行副总裁，负责领导药明生物生物新药发现服务业务，打造生物新药发现技术平台和项目研发的核心能力，领导和推动药明生物成为全球领先的一体化生物新药发现服务平台。

顾继杰博士有超过20年的工作经验，包括18年在制药行业的靶点发现和药物发现和早期临床开发经验，及建立和管理多个功能部门的经验。在加入药明生物前，顾继杰博士是艾伯维剑桥研发中心的主任和部门负责人，负责领导小分子和大分子药物在免疫治疗领域的靶点验证和先导药物发现工作。此之前，他是艾伯维生物研究中心全球生物制药部肿瘤生物药物发现部门负责人。顾博士在靶点选择、药物设计、抗体生成、蛋白工程、生物药物的发现、临床前和早期临床开发方面拥有丰富的专业知识。他为构建雅培和艾伯维抗体平台技术做出了重要贡献，参与包括酵母展示、mRNA展示、杂交瘤、抗体人源化、人IgG转基因动物和单域抗体等平台技术的建立。他也一直在雅培和艾伯维领导构建新型生物平台技术，包括Fc改造、ADC技术、TCR技术、双特异性和多特异性抗体技术、双特异T细胞募集抗体等。顾博士在肿瘤学、免疫学、免疫肿瘤学、代谢性疾病、神经科学、眼科学等多个治疗领域具有领导项目研发的经验。作为项目负责人或部门负责人，他已将多个NBEs推进到临床开发，并为艾伯维生物药管线做出了广泛贡献。他是20多个美国专利的共同发明人，也是mAbs和Antibody Therapeutics专业期刊的编辑委员会成员.

顾继杰博士在北京协和医学院获得分子生物学和生物化学博士学位，并曾在哈佛医学院Dana-Farber癌症研究所和哈佛公共卫生学院分别从事肿瘤免疫学和癌细胞生物学领域的博士后研究工作。

Jijie Gu, PhD

Chairperson's Remarks

Mitchell Ho, PhD, Sr. Investigator, LMB, NCI

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Next Wave of Innovation of Drug Discovery Driven by Antibody-based Multispecific and Functional Drugs

Jijie Gu, PhD, CSO/EVP, WuXi Biologics

The first wave of drug discovery innovation, to apply empirical pharmacology to discover drugs with defined structure without knowing the actual target for action, started modern pharmaceutical industry in 1900. The second wave of innovation started in 1970s marked by discovery of drugs with defined small molecular structure and a defined target for modulation. The third wave of innovation started in 1980s marked by proteins, especially antibodies, as drugs. With the maturation of technologies to discover small molecules and antibodies to a defined target, the fourth wave innovation is on the way recent years driven by using small molecules, antibodies, peptides, oligonucleotides, and other target or effector moieties as building blocks to construct complex multi-specific drugs to enable novel therapeutic concepts otherwise impossible by using single target approach. Multispecific antibodies and antibody drug conjugates are antibody-based multifunctional drugs at the central stage of this wave of innovation. In this presentation I will discuss the principles and key considerations in discovery and development of multispecific antibody drugs illustrated by some examples. Despite of the emergence of new therapeutic modalities such as cell, gene and RNA therapy, next decade will witness clinical success of multispecific antibodies employing some novel mechanisms of action.

Development of KN046 - a PD-L1/CTLA-4 BsAb

Ting Xu, PhD, Founder/CEO, Alphamab Oncology

1. Origin of KN046, from the structure and function aspects
2. The MOA of KN046, the benefit of colocalize PD-L1 and CTLA-4 antagonists
3. The clinical read out in multiple solid tumors

CMC Challenges and Strategies for Bispecific Antibody Development

Jizu Yi, PhD, SVP, YZY Biopharma

Key topics will include：
•Expression System and Stability
•Impurity Complication and Control
•Immunogenicity
•Requirement Differences for NMPA and FDA IND filing

Bispecific γδ-T cell Engagers for Cancer Immunotherapy.

Paul Parren, PhD, Executive VP, Lava Therapeutics

Bispecific T cell engagers (bs-TCE) are a promising class of immune-oncology agents in targeted cancer immunotherapy. Classical bs-TCE designs consist of a tumor antigen-binding domain combined with a binding domain against the CD3 T-cell receptor-signaling complex. Irrespective of the bispecific antibody format used, CD3-based bs-TCEs have a number of disadvantages, which in part are explained by the fact that they activate all T-cells irrespective of lineage, which associates with serious adverse events as a result of exaggerated T cell activation and cytokine release in some patients, and limited efficacy due to T suppressor cell activation in others.

The development of bs-TCEs with increased tumor selectivity to widen the therapeutic window has high potential. Lava Therapeutics’ platform is based on the selective recruitment of Vγ9Vδ2 T cells for tumor targeting. This  T cell subset has been shown to display powerful innate anti-tumor immune effector activity with an ability to infiltrate human tumors in which its abundance in tumor-infiltrating lymphocytes has been shown to positively correlate with patient survival. This presentation will discuss a novel class of bsTCEs designed to engage Vγ9Vδ2-T cells for the development of efficacious and safe cancer immunotherapies.

Potent Neutralizing Monoclonal Antibodies Directed to Multiple Epitopes on the SARS-CoV-2 Spike.

David Ho, MD, Director, AIDS Center, Columbia Univ.

The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. We have reported the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease (Liu et al, Nature 2020). Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are quite immunogenic. Cyro-electron microscopy structures on a dozen of these antibodies bound to the spike have been solved. We have also selected resistant viruses using 6 of our neutralizing monoclonal antibodies in vitro. Lastly, we have constructed over 60 bispecific antibodies, several of which have IC50 near 0.1 ng/mL and IC90 of 2 ng/mL. A number of our antibodies are now in clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.

Regulatory Challenges and opportunities for biological products

Audrey Jia, MD, PhD, Principal Consultant, DataRevive

This presentation will discuss the regulatory challenges especially for foreign companies that wish to develop their product in the US market. The focus will be on regulatory and CMC

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CAS Staff, , The Chinese Antibody Society

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Patent Protection Strategies for Bispecific Antibodies

Teresa Lavoie, PhD, Principal, Fish & Richardson

Bispecific antibodies emerge as a new generation of therapeutic antibody therapies by combining two antigen-binding sites into a single construct. From the patent perspective, bispecific antibodies share many characteristics with monoclonal antibodies. As the first-generation antibody patents have been challenged in court, the scope of protection that can be obtained for therapeutic antibodies has evolved. This has a similar impact on patent protection strategies for bispecific antibodies. This presentation will discuss why we need to build a strong patent portfolio for bispecific antibodies and the patent protection strategies of building a strong patent portfolio in view of the recent case law. This presentation will also briefly discuss some special considerations for filing applications in US and China, and the USPTO pilot programs that are offered this year because of the COVID-19 pandemic.

Combining Computer Aided Design and Traditional Antibody Discovery and Engineering Technologies to Develop Multi-Specific Antibodies

Yue Liu, PhD, Founder/CEO, Ab Studio and Ab Therapeutics

Multiple-specific antibody targeting more than one antigen or epitope has unmet needs for treating cancer and other diseases. In order to improve the discovery efficacy and reduce R&D cost for making a multi-specific therapeutic antibody, we created a unique strategy by combining computer aided design with traditional antibody discovery and engineering technologies. Taking development of a humanized tri-specific antibody neutralizing SARS-CoV-2 virus as an example, by panning a naïve llama VHH phage library and a computer designed humanized llama VHH phage library, we were able to quickly fish out high affinity viral S protein binders with function to block virus/host cell interaction. Applying in silicon analysis of 3D models built up with leading VHH sequences, we were able to select leading VHHs with better developability features. After epitope bin and antigen-VHH docking analysis, we were able to select VHHs binding to different epitopes and link them together in a reasonable orientation to assemble a tri-specific antibody with great efficacy and manufacture-ability and limited safety concerns. While many bispecific antibody platforms focus on the application of a unique protein structure, we believe no matter which protein structure is applied, selection and optimization of each monoclonal antibody component’s sequence in order to enable the successful assembly of a multi-specific antibody is also critical. We believe our strategy could help resolve this concern and significantly speed up the process of therapeutic multi-specific antibody development.