Exclusive Interview with Lang Guojun, founder of Sanyou Bio: The Key to Breaking the Bottleneck of New Drug Innovation--The Past and Future of the Super-Trillion Molecule Library

SHANGHAI, Oct. 17, 2024 /PRNewswire/ -- In the ninth year since the establishment of Sanyou Bio, Lang Guojun believes that the time is perfect to unveil the world's largest super-trillion molecule library. During the interview with Tongxieyi, he frankly and confidently expressed, "Nine years of hard work have gone to sharpen a sword, and now, the moment has come for the meticulously crafted 'super-trillion molecule library sword' to be unsheathed."

Over the years, Sanyou Bio has always been customer-centric and focused on new drug R&D, supporting the discovery and optimization of hundreds of innovative drug projects. Among them, more than 10 innovative drug projects have already entered clinical trials, with numerous research outcomes published in top journals. However, Lang Guojun believes this is just the beginning, because Sanyou Bio harbors a far greater vision – to help more people and more companies collaborate and leverage innovative biologics to improve the quality of human life. The application expansion of the super-trillion molecule library is a crucial step in realizing this vision.

Tongxieyi: Under what circumstances did Sanyou Bio choose to create an innovative molecule library?

Lang Guojun: During my PhD studies, I began exploring hybridoma monoclonal antibody research. In 2010, I officially entered the pharmaceutical industry, focusing on phage display antibody libraries. By around 2012, our team successfully built a fully human Fab antibody library with a scale of hundred-billion (10¹⁰), which demonstrated excellent performance in the screening of various targets, positioning us as industry leaders at that time.

However, by 2014, we began to conceive of building an even larger antibody library. Unfortunately, the overall environment in the pharmaceutical industry was not ideal back then. The strategic focus of the original pharmaceutical company was on R&D of drug variety, so this idea could not be implemented.

The turning point came around 2015. With the introduction of a series of policies aimed at promoting the development of the innovative drug industry, the overall industry landscape has greatly improved. Against this backdrop, I had in-depth discussions with family and close friends, and received their financial and resource support. It was with such support that Sanyou Bio was born.

Combined with our team's extensive experience in antibody molecule libraries, Sanyou Bio entered the market from the perspective of molecule libraries. Our initial mission was to create an outstanding innovative molecule library to fully address the challenges in discovering innovative molecules and to widely apply it in new drug development and scientific research.

Tongxieyi: Please introduce the history and reasons of Sanyou Bio's establishment of super-trillion molecule library.

Lang Guojun: Sanyou Bio's super-trillion molecule library originated in 2015 and has gone through 9 years of continuous development and innovation.

In 2015, to establish clear intellectual property rights, we first constructed a phage display plasmid vector with independent intellectual property and unique sequences.

In 2016, we integrated hybridoma and phage display technologies and successfully constructed a mouse immune antibody library, which combines the advantages of mouse immunization and phage display. After the successful development of this technology, we promoted its commercialization. We became the first company in China to commercialize mouse immune library.

In 2017, we completed the concept verification of the 100 billion fully human antibody library. The verification results indicated that upgrading from 10 billion library to 100 billion library had a very significant importance.

In 2018, we successfully constructed the first 100 trillion-level molecule library – the 100 billion fully human antibody library. Compared with the 10 billion antibody library, the number of molecules in this library increased severalfold. At the same time, with the significant increase in library capacity, the number of preferred lead molecules also saw a significant increase. In January of the same year, Ablynx, a company focusing on single-domain antibodies, was acquired by Sanofi for €3.9 billion. However, according to literature reports, the largest single-domain antibody library in the world at that time was only more than 4 billion. Given the technological advantages of Sanyou Bio's platform, we decided to start the construction of a single-domain antibody library. By the end of the year, we successfully completed the construction of a natural library of 100-billion-level alpaca single-domain antibodies and a series of immune libraries. That year, we also completed the concept verification of a billion-level fully human common light chain antibody library, laying a solid foundation for the subsequent development of a super-trillion level common light chain antibody library.

In 2019, we successfully constructed the second 100 billion level molecule library – the 100 billion synthetic single-domain antibody library. In the same year, we completed the concept verification of the trillion-level fully human antibody library. The results showed that the trillion-level library achieved a qualitative leap compared to the 100-billion level library.

In 2020, we successfully constructed the first super-trillion fully human antibody library, and simultaneously advanced the concept verification of both the trillion-level fully human semi-synthetic antibody library and the trillion-level humanized single-domain antibody library. The trillion-level fully human semi-synthetic antibody library is an upgrade based on the trillion-level fully human antibody library through gene recombination in the CDR regions. The trillion-level humanized single-domain antibody library, on the other hand, is a synthetic antibody library constructed by precise directional synthesis based on a highly humanized single-domain antibody framework, referring to the characteristics of CDR sequences in nature. During this time, we also completed the concept design of the trillion-level common light chain antibody library.

In 2021, we built the second and third trillion-level molecule libraries – the super-trillion fully human semi-synthetic antibody library and the super-trillion single-domain antibody library. In the same year, we successfully completed the screening and validation of the first trillion-level molecule library. The results demonstrated that, for a single target protein, not only was the average number of lead molecules in the hundreds, but also the diversity was extremely high.

In 2022, we successfully constructed the fourth trillion-level molecule library – the super-trillion common light chain antibody library. This library can effectively address the issue of light and heavy chain mismatch in the construction of "Two-in-One" bispecific antibodies, and is suitable for the development of bispecific antibodies, dual-target antibodies, or dual-epitope ADCs. By this point, the cumulative capacity of Sanyou Bio's four trillion-level libraries had reached an impressive 7 trillion. On June 3 of the same year, we integrated the super-trillion level molecule libraries and related technologies into a single platform, which we named the Sanyou Super-Trillion Innovative Antibody Drug Discovery Platform (STAL), and officially released it to the public. Additionally, we successfully constructed and validated the 100-billion cyclic peptide molecule library.

In 2023, we successfully completed the construction and validation of the fifth trillion-level library – the super-trillion peptide molecule library, with a library capacity of 3 trillion. This brought the total library capacity of Sanyou Bio's super-trillion molecule libraries to over 10 trillion. In October of the same year, we systematically summarized and publicly launched the Sanyou Super-Trillion Innovative Biologics Discovery Platform. By the end of the year, we had also constructed and validated 100-billion level new Anti-Calin molecule library successfully.

While using super-trillion single-domain antibody library, we also identified areas for improvement in both the super-trillion single-domain and the super-trillion peptide molecule libraries. Therefore, we took the lead in launching the concept verification of the second-generation super-trillion single-domain antibody library, and completed the construction and validation of the concept of the second-generation super-trillion single-domain antibody library in October 2024. At present, the second-generation super-trillion single-domain antibody library is under construction, and we are also actively advancing the development of the second-generation super-trillion peptide library.

Overall, from 2015 to the present, through more than nine years of continuous effort, we have gradually built a comprehensive series of molecule libraries, including fully human antibodies, fully human semi-synthetic antibodies, fully human common light chain antibodies, 2C/4C single-domain antibodies, targeted peptides, targeted Anti-Calin small proteins, mouse immune libraries, rabbit immune libraries, camelid immune libraries, and canine immune libraries – forming ten major types of molecule libraries. The total capacity of these libraries exceeds ten trillion, collectively establishing our "Sanyou Super-Trillion Molecule Library" (STAL). The screening and validation across dozens of targets have demonstrated that the STAL platform is capable of developing monoclonal antibodies, bispecific antibodies, multi-specific antibodies, antibody-drug conjugates (ADC) drugs, antibody-oligonucleotide conjugates (AOC) drugs, radiolabeled antibody drugs, peptide-drug conjugates (PDC) drugs, and Chimeric Antigen Receptor T (CAR-T) immunotherapies, supporting the development of these mainstream therapeutic molecules.

Tongxieyi: What are the core points of the super-trillion molecule library?

Lang Guojun: Firstly, the key factor is the consolidation of core technologies and team expertise. In terms of library building capabilities, to establish the super-trillion molecule library, we developed the Super-Trillion Innovation Biologics Discovery Platform, which enables us to construct a trillion-level library within a few months. Throughout this process, Sanyou Bio has formed a specialized and professional R&D team that continues to develop and iterate in the field of innovative molecule libraries. Our team has accumulated extensive engineering design knowledge and experience in this field, and formed a series of core technology accumulation.

Secondly, the supporting infrastructure has been crucial to the construction of the super-trillion molecule library. Over the course of the company's growth and development, we have received substantial capital and external support. To further advance the R&D of the super-trillion molecule library, Sanyou Bio has established the world's top integrated R&D platform for innovative biologics. The platform has more than 1,200 pieces of equipment with investments exceeding 15 million US dollars in facilities and equipment, including highly sophisticated equipment clusters such as automated antibody library screening systems, multicolor flow cytometry analysis systems, SPR and BLI affinity kinetic analysis systems, single-cell printing and imaging systems, mammalian cell culture bioreactors, AKTA purification systems, lyophilization systems, high-performance liquid chromatography (HPLC) systems, ultra-performance liquid chromatography (UPLC) systems, capillary electrophoresis analyzers, component analysis systems, and more, fully supporting the various needs of the sustainable development of molecule library.

Finally, customer demand also plays a crucial role. After more than nine years of accumulation, Sanyou Bio has established strong business relationships with more than 1,200 customers worldwide. The alignment with customer needs and the practical experience from various projects have been a driving force behind the construction and development of the molecule library.

Tongxieyi: What innovative molecule libraries does Sanyou Bio have so far? How many categories are these molecule libraries divided into?

Lang Guojun: At present, super-trillion molecule libraries constructed by Sanyou Bio can be divided into four categories:

The first category is the fully human antibody libraries, which include the super-trillion fully human antibody library, super-trillion fully human semi-synthetic antibody library, and the super-trillion common light chain antibody library, with a total library capacity of 3 trillion.

The second category is the single-domain antibody libraries, which comprise the 2C-type and 4C-type single-domain antibody libraries, with a total library capacity of approximately 4 trillion.

The third category consists of peptides and other novel molecule libraries, including the cyclic peptide library and the Anti-Calin small protein library, with a total library capacity of over 3 trillion.

The fourth category is the immune antibody libraries, which include four sub-categories: mouse, rabbit, camel, and canine immune antibody library. These immune libraries are highly specific antibody library for specific individual targets, with a single library typically having a capacity in the range of hundreds of millions. To date, hundreds of such immune libraries have been successfully constructed.

Tongxieyi: What are the applications of the super-trillion molecule library in different fields?

Lang Guojun: Sanyou Bio's  super-trillion molecule library has a broad range of applications, and can be categorized into four main areas.

In the field of therapeutic treatment, the super-trillion molecule library is suitable for antibody discovery targeting tumor cell therapy, cellular immunotherapy, and gene therapy, covering antibody-related technologies such as monoclonal antibodies, bispecific antibodies, ADCs, and CAR-T. It also supports cutting-edge therapies like cell and gene therapies (CGT) and oncolytic viruses.

In the field of scientific research, the super-trillion molecule library is widely used in both exploratory research on innovative target drugs and basic scientific research. It enables the discovery of molecules targeting peptides, membrane proteins, transmembrane proteins, and GPCRs, which are popular but challenging targets in the drug discovery field.

In the field of diagnosis, Sanyou Bio collaborates with diagnostic companies for developing and discovering diagnostic products related to immune diagnosis, nucleic acid molecular diagnosis, and tumor biomarkers. These include products like histopathological diagnostics (HDC), (CDx) companion diagnostics, and chemiluminescence systems.

In the field of detection, the super-trillion molecule library is applied in various detection methods such as enzyme-linked immunosorbent assay (ELISA), radioimmunoassay, immunohistochemistry, immunoprecipitation, flow cytometry, and biosensors.

Tongxieyi: What are the essential differences between the super-trillion molecule library and other libraries on the market? What core problems have been solved?

Lang Guojun: The key differences are mainly reflected in three aspects. First, Sanyou's library offers the widest diversity in the industry. As mentioned earlier, in terms of the type of library, Sanyou Bio's super-trillion molecule library encompasses a wide range of types, including fully human monoclonal antibodies, common light chain bispecific antibodies, single-domain antibodies, novel proteins, peptides, and species-specific antibodies from mice, rabbits, camels, and dogs. Second, the library capacity is leading and unrivaled in the industry. At present, the library capacity of Sanyou Bio's library has exceeded 10 trillion. Compared with the library capacity of the second-tier companies, ours is dozens of times larger, and no company in the industry can reach the library capacity level of Sanyou Bio. Third, the accumulation of experience and high-throughput screening technology platform are also the leading level in the industry.

Sanyou Bio's super-trillion molecule library mainly addresses two core challenges in the field. First, it solves the problem of high-throughput screening of antibodies. We have effectively integrated phage display technology with eukaryotic expression systems, thereby improving the quality and throughput of functional antibody screening. At present, Sanyou Bio has achieved high-throughput automated antibody screening, significantly improving efficiency. Second, it solves the problem of diverse molecular configurations and super-trillion library capacity. Sanyou Bio's molecule libraries are diverse, including fully human antibody library, common light chain antibody library, single-domain antibody library, and peptide library. Through a modular library construction strategy, we were able to successfully build a trillion-level molecule library within just a few months. At this stage, customers have successfully advanced and applied for IND for more than 10 projects through our super-trillion molecule library, including monoclonal antibodies, bispecific antibodies, trispecific antibodies, ADCs, and CAR-T, all making significant progress and results.

Tongxieyi: What opportunities will the application of AI bring to the super-trillion molecule library?

Lang Guojun: Firstly, we are deeply integrating intelligent technologies into the construction and operation of our super-trillion molecule library to promote the comprehensive upgrade of the molecule library and the significant improvement of screening throughput. By incorporating advanced AI algorithms and machine learning techniques, we are building a dual-drive platform of "AI + Super-trillion molecule library" to achieve intelligent, automated, and highly efficient molecule screening. Specifically, with cutting-edge AI screening tools, we can efficiently screen the huge molecule library at unprecedented speeds. This not only shortens the screening cycle but also allows us to rapidly identify promising candidate molecules, thereby accelerating the process of new drug R&D.

Secondly, the integration of dry and wet lab experiments will generate vast amounts of data by screening, which will serve as a valuable "compass" for optimizing and upgrading the next-generation antibody libraries. By deeply analyzing the data and models from the AI screening process, we can gain a deeper understanding of molecular characteristics. These characteristics are more likely to result in favorable biological activity or pharmacokinetic performance, which in turn guides us to design more efficient and targeted antibody libraries and promotes the continuous optimization and innovation of our molecule libraries.

Tongxieyi: What are your plans for the future of the super-trillion molecule library?

Lang Guojun: After nine years of hard work and accumulation, Sanyou Bio has laid a solid foundation for the "super-trillion molecule library". However, this foundation is merely the beginning, the expansion and application journey of the super-trillion library has just commenced, and the future journey is full of infinite possibilities and challenges.

Firstly, we can move beyond the limitations of protein targets to develop against novel targets such as DNA, coding mRNA, non-coding RNA, proteins, and small peptides. At the same time, we can also explore development around intracellular targets, cell membrane surface targets, and extracellular targets. The goal is to create multifunctional innovative molecules that can simultaneously target different cellular locations. This opens new pathways for new drug R&D and provides possibilities for the treatment of more diseases.

Secondly, we will develop high-challenging molecular forms to adapt various diseases and targets, particularly in cutting-edge areas such as bispecific antibodies, multi-specific antibodies, large-molecule conjugated small molecules, large-molecule conjugated nucleic acids, and cell connectors. Through continuous technological innovation and R&D, we aim to provide our clients with more diversified and personalized solutions to meet the growing market demands.

Finally, for challenging diseases, we plan to expand the application scope of the super-trillion molecule library. Through screening, we can identify lead molecules that differentiate and recognize disease biomarkers and therapeutic targets. These lead molecules can not only be used for validating disease targets, but also serve as candidate drugs, providing innovative molecular therapies for intractable diseases. On Sanyou Bio's open platform, we continuously promote collaboration with professional teams to jointly advance drug development for challenging diseases.

The super-trillion molecule library finally comes out after nine years of hard work, just like a sword out of its sheath. In this long and tenacious journey of scientific research, we have witnessed countless attempts and breakthroughs. Each effort is akin to a craftsman meticulously carving, all for that moment of brilliant splendor.

Now, this sword, condenses wisdom and sweat, has finally broken out of its sheath with unimaginable power, its edge points directly to the vast landscape of new drug R&D, unleashing the potential and hope of a trillion-level library.

Let the super-trillion molecule library be the sword that opens up a bright future for new drug R&D.

About Sanyou Bio

Sanyou Biopharmaceuticals Co., Ltd. is a world-leading high-tech biotechnology enterprise focusing on R&D and services of innovative biologic drugs. Sanyou has built the 4C business patterns that integrate "differentiated CRO, integrated CDO, innovative CPO and characteristic CRS", to accomplish the mission "to make the R&D easy for innovative biologics".

Sanyou has established an integrated innovative biologic drug R&D laboratory with advanced facilities, and has a professional team with the majority holding a Ph.D. or master degree. Sanyou has built three industry-leading innovative technology platforms featured by "super-trillion, integration, and intelligence" , which are comprised of more than 50 sub-platforms with the core innovative super-trillion phage display platform, and supported by platforms of material preparation, biologics discovery, molecule optimization, in vitro and in vivo efficacy, production cell line construction, upstream and downstream process development, preclinical R&D, industrialization development, etc.

Sanyou's business network has expanded to all parts of the world, including Asia, US and Europe, and established branches in Boston, Philadelphia, San Diego and London. Sanyou has established friendly business relationships with more than 1000 pharmaceutical companies, drug R&D institutions and diagnostics companies worldwide. Sanyou received National-level certification as a high-tech enterprise and a Specialized and Sophisticated enterprise, and passed the ISO9001 quality assurance certification and GB/T intellectual property management system certification.

 

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