CPHI China · 2023 New Drug Development and Cooperation Congress

The "CPHI China · 2023 New Drug Development and Cooperation Congress" was held in Shanghai from October 31 to November 1, 2023. Dr. Yue Qian, Senior Director of Computational Chemistry at Viva Biotech, was an invited speaker. She shared a speech on the topic of "Computational Chemistry in the Research and Development of Small Molecule New Drugs".

Computer-aided drug design (CADD) has progressively evolved into Computer-driven drug discovery (CDDD), playing a significant role in the drug discovery process.

In recent years, with the continuous development of artificial intelligence (AI) technology and algorithms, as well as the accumulation of experimental data, Computer-aided drug design (CADD) has progressively evolved into Computer-driven drug discovery (CDDD), playing a significant role in the drug discovery process. Dr. Yue Qian started from this point and, using Viva's practical case, discussed the application of computational chemistry methods like Molecular Dynamics, Virtual Screening, Molecular Generator, and Free Energy Perturbation in various stages of drug discovery. Dr. Qian explained that in the initial stages of drug discovery, on the one hand, molecular dynamics can be used in conjunction with the known molecular structure to understand the protein conformation change, as well as the introduction of small molecules induced protein conformation changes, and cited the recent classic case of selective FGFR2 inhibitors to further illustrate the application of molecular dynamics in the drug design. On the other hand, in cases where the protein structure is known but the binding site and binding mode are unclear, molecular dynamics can also be used for exploration. Research can be based on existing fragment molecule interactions, allowing for outward expansion. Similarly, Viva's Crystal Soaking experimental method can also help in identifying binding sites and modes.

Moving on to the drug screening phase, once the binding model is clarified is binding pocket, the next step involves utilizing Structure-Based Drug Discovery (SBDD). In cases where certain protein characteristics limit the use of SBDD, an alternative virtual screening method can be employed, known as ligand-based drug design (LBDD). In this phase, the size of the compound library is crucial. Viva's computational chemistry technology can expand upon the compound library provided by the client or use its own library, combined with molecular generation to break through the existing chemical space, thereby identifying the most suitable compounds. Common molecular generative models currently in use include active learning, which initially involves a round of screening based on physicochemical models. After obtaining the screening results, training is conducted using machine learning, followed by re-ranking through scoring and returning to the original model for validation. This process can even use higher-precision physicochemical models. This iterative process significantly saves computational time. Moreover, virtual screening is highly compatible with ASMS and SPR technologies. By narrowing down the number of compounds to a few thousand through virtual screening, further validation can then be performed using ASMS and SPR.

After obtaining experimental data from the screening, we will use Free Energy Perturbation (FEP) studies to analyze the changes in the relative free energies of two compounds. This analysis aids in the optimization of lead compounds. Dr. Qian emphasized that compared to Schrödinger's module, Viva Biotech's own FEP shows a free energy change (dG) with an error within 1 kcal/mol, offering high reliability.

In the end, Dr. Qian noted that whether it's molecular dynamics simulations, FEP, or the currently popular machine learning, all these approaches require substantial computational power for support. Viva Biotech boasts a supercomputing cluster platform equipped with advanced A100GPU chips, providing powerful computational support and high-performance bioinformatics processing.

2023 SAPA-China Annual Conference

On November 3-4, the 2023 SAPA-China Annual Conference, co-hosted by the Sino-American Pharmaceutical Professionals Association (SAPA-China) was held in the Suzhou Industrial Park. Dr. Jianhua Cai, Senior Vice President of Viva Biotech, was invited to attend the roundtable forum on the challenges and future of small molecule drug discovery, where he shared some of the efforts and work Viva has made in addressing the challenges and future trends in the research and discovery of small molecule drugs.

Second from left: Dr. Jianhua Cai Senior Vice President of Viva Biotech

In the future, drug discovery based on the understanding of biological mechanisms is one of the necessary ways for domestic companies to win in the fierce global competition.

Dr. Cai pointed out that in addressing the challenges of drug discovery for undruggable targets, an important strategy for small molecule drugs is the development of degrading drugs. Viva Biotech has already established a complete PROTAC/Molecular Glue R&D platform, offering a comprehensive set of PROTAC/Molecular Glue screening and validation solutions. To date, Viva Biotech has studied over 50 E3 ligases for clients, delivering more than 110 E3 ligase-PROTAC-target protein ternary complex structures. Combining its proprietary affinity screening technology such as ASMS, Bioassay, SPR, chemical synthesis of E3 ligands and linkers, and complemented by CADD, Viva Biotech accelerates the drug discovery process for PROTAC/Molecular Glue. Additionally, he emphasized the significant value of SBDD and biophysics techniques in innovative drug discovery, sharing some of Viva's past successes and experiences with its SBDD platform. In response to the moderator's question about how China can stand out in the fierce competition of original drug innovation, Dr. Cai believes that there is still a considerable gap between Chinese biotechnology companies and their overseas counterparts in biological mechanism research. Overseas companies place great emphasis on the study of biological mechanisms, and for domestic companies to emerge victorious in the global arena, developing drugs from an understanding of biological mechanisms is a necessary path.

Dr. Han Dai, Chief Innovation Officer and Head of Viva BioInnovator, served as the moderator for Sub-Forum Nine, Theme Three, "Current Advantages, Challenges, and Future Expectations in Biopharmaceutical Investment." He engaged in an extensive and lively discussion with the guests present on topics such as biopharmaceutical investment, innovation, and outlook under the new circumstances.

During the exhibition, Viva Biotech staff received visiting guests at the booth, sharing with them Viva Biotech's successful experiences and professional insights in the field of new drug discovery and drug production. They also fully demonstrated Viva Biotech's PROTAC/molecular glue technology platform, protein production and preparation, structural research, membrane protein research, Cryo-EM, drug screening, Bioassay, drug metabolism, CADD, therapeutic antibody discovery, and other advanced technology platforms. The booth was bustling with many attendees, creating a lively atmosphere.

BIONNOVA Beijing Forum

BIONNOVA Beijing Forum 2023 was successfully held at Beijing Palace Garden Hotel & Resorts on 24th November, Dr. Jianhua Cai, Senior Vice President of Viva Biotech, was an invited speaker and delivered a speech on the topic of "The Application of Biophysics in Innovative Drug Discovery and Development". 

Biophysical Platform empowered the development of new drug discovery

Since the invention of X-ray crystallography in the early 20th century and its application in the life science field, biophysical techniques have rapidly developed, with methods including X-ray, NMR, MS, and Cyro-EM technology platforms winning numerous Nobel Prizes in Chemistry or Physiology/Medicine. Meanwhile, these biophysical techniques have found wide applications in the field of innovative drug discovery. Dr. Cai, starting from this point, comprehensively introduced the application of Viva Biotech's biophysical technology platform in the study of drug mechanism of action (MOA) and drug screening. Viva Biotech utilizes a series of biophysical techniques such as X-ray, Cryo-EM, HDX-MS, SPR, Intact-MS, and Native-MS for research into the protein tertiary structure, binding affinity, binding sites, binding kinetics, as well as for screening and identification in covalent and non-covalent binding.

In the aspect of drug screening, he noted that Viva has established a comprehensive drug screening platform. This platform is based on its own compound library, which includes a structurally diverse compound library of 200,000 compounds, a fragment compound library of 2,050 compounds, a fragment compound library of 960 compounds, a focused GPCR library of 6,500 compounds, a covalent compound library of 1,000 compounds, and client-provided compound libraries. Technologies like ASMS, SPR, Crystal soaking, and Intact-MS are used to develop affinity screening methods for specific targets, and he discussed specific case applications, particularly Viva's newly developed covalent compound screening method at the cellular level. He also emphasized that Viva's compound library is continuously updated and iterated. Additionally, to meet the market demand for screening traditionally challenging small molecule targets, Viva recently introduced a peptide library based on phage display technology. This includes two types: one is a commercially available linear peptide library of 7aa and 12aa, and a 7aa cyclic peptide library, with diversity reaching 109, and the other is a customizable peptide screening library, which can be internally constructed in 6-8 weeks with diversity higher than 109. The screening cycle for each library is approximately 4 weeks.

Dr. Cai illustrated various biophysical technologies, such as SEC-ASMS and SPR, and explored their roles in the discovery of molecular glues. Additionally, he showcased the practical application of Viva's biophysical technology in innovative drug discovery, highlighting the discovery of the first new mechanistic variant anticancer drug and a novel small molecule PCSK9 variant inhibitor. These successful cases effectively demonstrate Viva's robust capabilities in providing comprehensive one-stop services for new drug discovery.

During the exhibition, Viva Biotech hosted a booth to showcase its expertise in new drug discovery, development, and production. The team presented its core technological platforms, including PROTAC/molecular glue technology, protein production and preparation, structural research, cryo-electron microscopy, drug screening, bio-analytical method development platform, chemistry service, computer-aided drug design, and antibody/macromolecule drug development. The core technology platform was highly praised and recognized by the guests. The North China exhibition tour concluded successfully, marking a significant milestone for us. We established numerous industry connections and engaged in meaningful discussions about changes, collaborations, and prospects in the pharmaceutical field. Looking forward, we are excited to meet more like-minded professionals to explore new opportunities in drug development and manufacturing.