Highlights from the Inaugural Annual Conference of the Chinese Antibody Society 

May 10th, 2017

Boston, MA – The inaugural annual conference of the Chinese Antibody Society (CAS) was successfully held on Sunday, April 30th, in Cambridge, M.A. More than 400 professionals from industry, academia and government convened to bring forward the current progress and trends in therapeutic antibody R&D, as well as opportunities and challenges in global marketing of therapeutic antibodies developed in China.

The conference generated extensive media coverage through partnership with GEN and multiple Chinese news outlets. It kicked off with a welcome speech delivered by Dr. Yan Chen, the Head of Biotherapeutics Discovery at Juno Therapeutics and an advisor to CAS. As the Director of CMC Management at Wuxi Biologics and the founding president of CAS, Dr. Shouye Wang introduced the society’s development since its founding in April, 2016. CAS is the first and only global organization for Chinese professionals focusing on therapeutic antibodies. With a growing community of 600+ members and 6000+ followers on WeChat (as of May 10th, 2017), it serves as a gateway for the globalization of Chinese therapeutic antibodies, as well as a platform for collaboration of professionals in China, USA and the rest of the world. CAS is also an official endoser of several major biopharmaceutical conferences in China, including the 2017 Second China Pharmaceutical Innovation and Development Forum, and the upcoming 4th China BIoPh Outlook Summit. In addition, preparation for the launch of Antibody Therapeutics, the official journal of CAS, is well underway.

Dr. Mitchell Ho, senior Investigator at NIH and the chairman of CAS advisory board, presented a talk on Inhibitory Antibodies Targeting Cancer Cell Signaling. Dr. Ho’s lab is focusing on identifying novel therapeutic targets, mechanisms of inhibiting cancer signaling pathways, and technologies to target poorly immunogenic antigens or buried epitopes. He gave an overview of three antibodies (HN3, HS20, and YP7) developed in his lab that bind to different epitopes on glypican 3 (GPC3). HN3 and HS20 antibodies are capable of inhibiting the Wnt/Yap signaling in hepatocellular carcinoma cells, leading to reduced proliferation of the tumor cells. In addition, he described the work on LH7, a single domain antibody identified from a phage display library with specificity to GPC2. GPC2-directed CAR-T cells constructed based on the LH7 antibody fragment have demonstrated potent anti-tumor efficacy in mouse models. Dr. Ho also presented an update of the immunotoxins developed in the NIH immunotoxin program. Immunotoxin is an scFv-toxin fusion protein that induces protein synthesis inhibition upon internalizing into the cells. Several immunotoxins targeting CD22, CD19 and mesothelin are now in the clinical trials. In the recent years, Dr. Ho developed an anti-GPC3 immunotoxin HN3-PE38, which functions by dual mechanisms of inactivating Wnt/Yap signaling via the HN3 antibody and inhibiting protein synthesis via the PE38 toxin.

The talk from Dr. Weichang Zhou, CTO and SVP in the Biologics Development and Manufacturing of WuXi Biologics, focused on Establishing Integrated Platforms for Expediting Global Biologics Development from Concept to Commercialization. Dr. Weichang Zhou introduced the open-access integrated platform implemented by WuXi Biologics to facilitate process development from concept to commercialization. This platform contributed to the transformation of Callidus Biopharma from a startup company of only three employees to an important part of Amicus focusing on next-generation Pompe ERT and complementary enzyme targeting technologies.

Dr. Janice Reichert, Executive Director of the Antibody Society and Editor-in-Chief for mAbs journal, discussed the Antibody Therapeutics Development Metrics. She presented statistics on several important aspects of antibody therapeutics development, including the rates of clinical phase transition and approval, as well as lengths of the clinical development and review periods. She also analysed the variations of these statistics by therapeutic category, antibody format, origin of the antibodies, and regulatory agency designation.

The last speaker of the morning session was Prof. Zhiqiang An from University of Texas Health Science Center and an advisor of CAS., with a talk titled Academic Drug Discovery: Challenges and Opportunities. According to Prof. An, the major challenges of academic antibody drug discovery include the lack of novel antibody drug targets and biomarkers, development of drug resistance to therapeutic antibodies, and the need for technological breakthroughs such as novel methods to target intracellular proteins and deliver drugs across the blood-brain barrier. Other issues such as reproducibility of publications and decrease in government funding have further complicated the matter. Comparing the strength of academic research and industry development, he suggested that success in antibody drug discovery can be improved by an early collaboration of the academia and industry. Prof. An presented an overview of his research at Texas Therapeutics Institute, which involves identification of new immune checkpoint targets and tumor angiogenesis factors, and discovery of novel targets for breast cancer bone metastasis and brain injuries. He also underscored the importance of optimizing the dose of chemotherapies when they are used in combination with immunotherapies.

The afternoon session began with a talk from Dr. Michael Yu, CEO of Innovent Biologics and chair of CAS’ board of directors, on the Innovative Biologics in China: Opportunities and Challenges. As a co-inventor of Conbercept, Dr. Yu shared the stories behind its development as an anti-VEGF fusion protein into an approved biopharmaceutical in China for the treatment of wet age-related macular degeneration. He explained that while this drug was initially developed in China, global standards were applied to assess its therapeutic benefits. He highlighted that a visionary team guided by rigorous standards was the key to the success of this product on the international market.

Following this, Dr. Chengbin Wu, CEO of Epimab Biotherapeutics and an advisor of CAS., discussed the developmental landscape of bispecific antibodies in China. In his talk Biologics Innovation and Global Partnership: Bispecific Antibodies Rise Again, he introduced Epimab’s proprietary platform Fabs-In-Tandem Ig (FIT-Ig). FIT-Ig technology generates tetravalent bispecific monoclonal antibodies by re-arranging the DNA sequences of two parental antibodies into three constructs and co-expressing them in mammalian cells. He presented a case study of EMB-01, a bispecific antibody developed using the FIT-g platform that retained the biological function of its parental antibodies and demonstrated desirable physiochemical properties. He also pointed out the benefits of developing drugs in China , including access to local and global CRO and CMO, resources from major hospitals and clinical sites, a large pool of talents, access to onsite CFDA office, academic collaborations, and generous government funding.

Dr. Zhenping Zhu, President of R&D and Chief Science Officer at 3SBio Inc and an advisor of CAS, gave a talk on Research and Development of Therapeutic Biologics in China: A Reality Check. In recent years, many western pharmaceutical companies have turned to China to license new discoveries and sought business opportunities. The booming biopharma industry in China is a result of recruitment of talents, input from venture capitals, emergence of CRO companies, and CFDA regulatory reforms. However, biopharma companies in China are also confronted with increasing challenges, including lack of novel targets for drug development, need for an increase in industry R&D spending, shortage of resources for conducting clinical trials, and a relatively small share of the global market of antibody-based therapeutics. Dr. Zhu concluded that innovation on R&D is the key to address these issues. He shared his vision for the Chinese biopharmaceutical companies to become global leaders governed by global standards. This may be achieved through product license-in/out, collaborative partnerships, equity investment, merge/acquisition, etc.

The final speaker of the conference, Dr. Dane Wittrup, a professor at MIT, discussed key findings in his recent publication Biophysical Properties of the Clinical-Stage Antibody Landscape. (http://www.pnas.org/content/114/5/944.full.pdf) While target binding is an important property of an antibody, high affinity does not always guarantee the developability of the antibody. Factors contributing to the drug-like properties of an antibody include its specificity, solubility, covalent integrity, expression, aggregation etc. Dr. Wittrup and his colleagues constructed isotype-matched IgG1 antibodies from the sequences of 137 antibodies that are in clinical trials, and evaluated their biophysical properties in 12 assays. Using the metrics observed in these assays, they quantified the acceptable limits of drug-like behaviours and discovered that the developability risks, which were represented by red warning flags, decreased with the advancement of the drug towards approval.

The panel discussion focused on the do’s and don’ts of the regulatory path leading to a successful IND filing in the US. Moderated by Dr. Fubao Wang, Associate Vice President of Sanofi and a board member of CAS, the panel featured industry experts including Dr. Daotian Fu, Vice President & Managing Director of Livzon Pharmaceutical Group and an advisor of CAS., Dr. Audrey Jia, COO at DataRevive LLC and an advisor of CAS, Dr. Xin Du, Executive Director of Regulatory Affairs at Advaxis Inc, Dr. Yaning Wang, Senior Vice President at Qilu Pharmaceuticals PR&D, and Dr. Li Wan, Head and Director of Global Regulatory Affairs at Luye Pharma.

Dr. Wang discussed the trend of IND filings in the US from Chinese companies. He mentioned that over the past 3 years, 15 Chinese companies have received US IND clearance. This trend of increase in US IND applications from the Chinese pharmaceutical sector is largely due to the support from the Chinese government and the expansion of China’s pharmaceutical market.

Dr. Wan also confirmed that China has emerged as a drug innovation powerhouse. Many Chinese companies developing innovative therapies or biosimilars are seeking to enter the US market for the two reasons: 1) the United States has the largest healthcare industry in the world, 2) FDA approval is often recognized as the gold standard worldwide. However, to receive an FDA’s IND clearance is often a time-consuming and expensive process. Therefore, it is advisable for pharmaceutical companies to engage the FDA as a partner through effective communication and active discussion of product development strategies.

Dr. Du discussed the requirements for IND filing. IND requires full product/CMC information, pharmacology/toxicology studies, general investigational plan, investigator’s brochure, clinical protocols, etc. He suggested that companies should follow the requirements in eCTD, rather than simply following the CFR codes. It is wise for companies filing IND applications to keep the following advice in mind: 1) acquire complete information on the drug, 2) understand the difference between biologics and chemical drugs, and develop an effective CMC strategy, 3) enforce controls during process development and in clinical trials

Dr. Jia started by discussing the global strategy in the drug development. For example, is it a good idea to do a phase I clinical trial in Australia first, and then come back to the US for a phase II trial? According to Dr. Jia, if the company conducts clinical trials in Australia first, it may lose the opportunity to take advantage of the expedited review process offered by the US FDA. In addition, in some cases, it might be difficult to recruit enough patients in Australia. In term of conducting trials in China, companies should also recognize the difference of regulations between FDA and CFDA, and may consider preparing an individual version of application for each regulatory agency.

The conference concluded with a dinner reception sponsored by Qilu Pharmaceuticals. CAS is expected to host more conference programs and networking events in both China and US throughout this year. Dr. Chuan-Chu Chou, CEO of Qragen and an advisor of CAS, commented that “the inauguration conference of CAS marks a new milestone for integrating and sharing resources in the pharmaceutical industry. I hope our generation of professionals will collaborate closely and employ innovative thinking to tackle the challenges of the future drug R&D.”

Reported by Xin Yu, with contributions from Peng Lin, Xianchun Tang, Zhenyuan You, Jiacong Guo, Weihan Liu, and Baolong Wang.

 Photo credits: Cary Chu, Sun Chun, Daryl Luk