The SIMM-Servier partnership for drug discovery: looking back, looking forward





Jian DING, PhD PhD



Yang YE, PhD
Shanghai Institute of Materia Medica (SIMM)/Chinese Academy of Sciences, Shanghai
P. R. CHINA

The SIMM-Servier partnership for drug discovery: looking back, looking forward

by J . Ding and Y. Ye, China

The Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences (CAS), evolved from the Institute of Materia Medica of Peking Academy of Sciences, founded in 1932 by Professor Zhao Chenggu (T. Q. Chou). SIMM has developed and commercialized over 100 new drugs in the past 60 years. With the implementation of a high-end talent program in 1998, SIMM has successfully recruited and trained a group of domestic and overseas leading talents, forming a structured, professional, open-minded, and innovative research team. Collaboration between SIMM and Servier in 1996 has resulted in various projects in the fields of oncology, neurodegenerative disease, and diabetes. In the last three years, SIMM has set up new strategic world-class centers; the research capabilities of such new centers will soon be involved in the ongoing SIMM-Servier collaborative research programs. Both parties trust that new technologies in each other’s laboratories, a joint laboratory, and talented people from both sides will help identify either novel lead compounds targeting currently untreated diseases, or new, previously unobserved mechanisms of drug actions.

Medicographia. 2014;36:400-404 (see French abstract on page 404)


The Institute

The Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences (CAS), has the longest history as a comprehensive research institution for drug discovery in China. SIMM has evolved from the Peking Institute of Materia Medica, Academia Sinica, founded in 1932 by Professor Zhao Chenggu (T. Q. Chou; Figure 1) in Beijing.

Professor Zhao was the first Chinese person in history to receive a PhD degree in chemistry. He received his PhD degree from the University of Geneva in 1914, under the supervision of Professor Amé Pictet, a famous Swiss chemist studying organic natural products. In 1916, Professor Zhao became a researcher in the French company ROC. He became fluent in French and married a Frenchwoman, with whom he had one daughter.

In 1933, the institute was relocated to 395 Wu Kang Road, Shanghai, which was a French concession at that time. In 1953, the institute moved to 319 Yue Yang Road, the residence of the former Consulate General of France in Shanghai. Since 2003, the institute has been based at 555 Zu Chong Zhi Road, Zhang Jiang Hi-Tech Park, Pudong New Area, Shanghai (Figure 2).


Figure 1
Figure 1. Bronze bust of Professor Zhao
Chenggu (T. Q. Chou). © SIMM.



In line with the mission of “discovering new drugs to relieve patients’ suffering from various diseases,” SIMM has developed and commercialized over 100 new drugs in the past 60 years. Among them, a number of innovative drugs such as artemether (antimalarial), dimercaptosuccinic acid (antidote for heavy metal poisoning), and huperzine A (Alzheimer’s disease) gained recognition both nationally and abroad. SIMM has also developed some novel drugs in recent years, including depside salts (angina), a modern Traditional Chinese Medicine (TCM), and antofloxacin hydrochloride, a novel fluoroquinolone antibacterial agent. SIMM currently has a series of drug candidates in clinical stages.

Since the implementation of the Knowledge Innovation Program of CAS, developing novel drugs has become a paramount research focus of SIMM. In line with frontiers in life sciences, with the aim of solving key scientific problems in drug discovery, SIMM carries out both basic and applied studies, and develops new theories, methods, and technologies. Research priorities are given to treat major diseases, such as oncology, cardiovascular, neuropsychiatric, metabolic, autoimmune, and infectious diseases. SIMM also pays high attention to the development of modern TCM.

There are 4 national research centers in SIMM (State Key Laboratory of Drug Research, National Center for Drug Screening, National Engineering Laboratory for TCM Standardization Technology, and Chinese National Compound Library); 5 research departments (Medicinal Chemistry, Natural Products Chemistry, Pharmacology I, II, and III, and CAS Key Laboratory of Receptor Research); 11 technological platforms and research centers; and 4 institutional service and logistic departments, including a United Editorial Officer responsible for the publication of two academic journals (Acta Pharmacologica Sinica and Asian Journal of Andrology).


Figure 2
Figure 2. Bird’s eye view of SIMM campus on Zu Chong Zhi Road, Shanghai. © SIMM.


With the implementation of a high-end talent program in 1998, SIMM has successfully recruited and trained a group of domestic and overseas leading talents, forming a structured, professional, open-minded, and innovative research team. SIMM currently has 850 employees; among them 92 are professors and 50 are associate professors, including 6 academicians. The graduate education department has more than 600 masters and PhD students, as well as 40 postdoctoral fellows.

SIMM enjoys a wide range of international partnerships around the world. The SIMM-AstraZeneca alliance project, focused on the joint establishment of a Center for Drug Safety Evaluation and Research, has become the first organization in China to be accredited by in terms of compliance with the Organization for Economic Cooperation and Development (OECD) Principles of Good Laboratory Practice (GLP). Based on the transfer of Novo Nordisk 0.5 million small molecule compounds, the number of compounds collected in the Chinese National Compound Library has now exceeded 1.3 million.

SIMM has established an innovative partnership with the World Health Organization (WHO) for drugs against poverty-related diseases. SIMM has established dynamic scientific collaborations with universities and institutions in North America, Europe, the Middle East, and Asia.

Through several generations’ efforts, SIMM has become one of the leading interdisciplinary centers of excellence in drug discovery in China. It is recognized worldwide for its outstanding achievements and distinguished research team.

The SIMM-Servier joint laboratory

The initial contact between Servier and SIMM started in 1996 when Professor Paul Vanhoutte and Dr Pierre Renard made the groundbreaking visit to SIMM in the campus of Yue Yang Road, thus starting the long-lasting partnership of 18 years (Figures 3 and 4).


Figure 3
Figure 3. Herbarium at SIMM. © SIMM.


Figure 4
Figure 4. Group photo recording the first visit of Servier to SIMM. © SIMM.


Trust each other: develop together
Over these 18 years, scientists working at SIMM and Servier have established various collaborative projects in the areas of oncology, central nervous system disease, and diabetes, sparing no effort to identify drug leads, drug candidates, or new mechanisms of drug action and drug targets. Along with the trust the collaborative teams have built up through the years, the management teams from both sides have established an increasingly constructive, productive structure of the collaboration. Collaboration goals between SIMM and Servier are gradually shifting from focusing on the identification of single projects limited by one compound series or one target, to multilevel cooperation programs involving, for example, medicinal chemistry, chemical proteomics, pharmacology, and structural biology. Both parties hope that such multilevel partnerships will facilitate innovative discovery thanks to optimized interactions among the team, thus saving time and accelerating each step involved.

In 2013, the collaboration of SIMM and Servier entered into a new era by the fact that the rights of the first SIMM clinical candidate lucitanib were licensed to Servier. Lucitanib is a kinase inhibitor that targets fibroblast growth factor receptors 1 and 2 (FGFR1-2) and vascular endothelial growth factor receptors 1-3 (VEGFR-1-3). It has specific antitumor activity in FGFR1- 2–dependent tumors and a strong antiangiogenic effect. SIMM and Servier are co-owners of the marketing authorizations for China. In addition, SIMM will conduct specific research in biomarkers and support Servier regarding the participation of China in international clinical studies.


Figure 5
Figure 5. Servier experts giving on-site training to joint laboratory team membersat SIMM. © SIMM.


Figure 6
Figure 6. SIMM-Servier project discussion meeting at SIMM in 1998. © SIMM.


Figure 7
Figure 7. SIMM-Servier project discussion meeting at Servier in 2011. © SIMM.


Trust innovation: building new drug discovery technology platforms together
In the last four years, SIMM has set up new strategic world class centers, such as the Center for Structure and Function of Drug Targets, where scientists are focusing on the elucidation of G protein– coupled receptor structures, and the Center for Chemical Proteomics, where scientists are focusing on the identification of new posttranslational modifications. The research capabilities of such new centers will soon be involved in the ongoing research collaborative programs between SIMM and Servier.

Moreover, in 2012, SIMM and Servier agreed to enter into a new agreement in order to establish a joint discovery and biopharmaceutical research laboratory. Advanced technology platforms in pharmacokinetics, metabolism, and in vitro toxicology have been successfully transferred and have become operational at SIMM. The joint laboratory serves not only the SIMM-Servier joint research programs, but also SIMM’s own discovery programs (Figure 5).

Trust natural products: exploiting treasures from folk medicine together
The first collaborative project between Servier and SIMM in 1997 was already focusing on a famous cluster of natural products represented by artemisinine. Throughout the years, the enthusiasm of scientists from both sides remains, with current programs in the areas of oncology, neurodegenerative disease, and diabetes. Both parties trust that new technologies in each other’s laboratories, a joint laboratory, and talented people from both sides could help us to identify either novel lead compounds targeting currently untreated diseases, or new, previously unobserved mechanisms of drug actions (Figures 6 and 7).

Conclusion

Drug discovery research is a long and complex journey where we always need state-of-the-art skills as well as talented people. The long-lasting partnership between Servier and SIMM reflects the inspiration of recognizing, trusting, and sharing each other’s knowledge, skills, and expertise, according to the needs of drug discovery programs. SIMM has full confidence and expectations, through joint efforts with Servier’s expertise, to continue delivering successful results in our long-lasting and ongoing collaborative projects.


Keywords: diabetes; drug discovery; neurodegenerative diseases; oncology; SIMM (Shanghai Institute of Materia Medica)