China needs genuine innovative drugs!

This is the insight gained by He Xun after deepening his involvement in the pharmaceutical industry for 30 years.

He Xun, a graduate of Tsinghua University, has worked his way up from the grassroots level of pharmaceutical companies, from group leader to workshop director, then to production and research and development department manager, chief engineer, deputy general manager, and general manager. He Xun has a profound understanding and accumulation of biopharmaceutical research and development, production, and sales, and has successfully turned several companies from deficits to profits.

However, the longer he has worked in the industry, the stronger He Xun's perception of the industry's pain points has become: "After 2015, with the continuous advancement of policies such as the introduction of overseas high-level talent, consistency evaluation, and the 4+7 bulk procurement, China has stepped into an era of rapid follow-up of innovative drugs from the era of generic drugs. The key to new drug development is whether we can screen out the best lead compounds with the fastest speed and lowest cost. Drug screening has always been the biggest challenge for China to move into the era of innovation at the source of new drugs."

In order to break through the key common technological bottlenecks in the industry chain, promote the transformation of results, and build a collaborative innovation ecosystem, in 2019, He Xun initiated and served as the general manager of the Guangdong Small Molecule New Drug Innovation Center, which was officially established.

In 2021, the Guangdong Small Molecule New Drug Innovation Center incubated its first project—NewDEL Biotech, with He Xun serving as chairman.

Currently, NewDEL Biotech's technology platform and product pipeline have been established. Leveraging the independently innovative DNA-encoded compound library (DEL) technology for innovative drug development and technical services can significantly improve the success rate of drug screening. The company has also completed an angel round of financing led by Tongchuang Weiye, totaling tens of millions of yuan.

"AI technology combined with drug discovery might be the best approach."

In 2016, He Xun met Professor Li Xiaoyu for the first time, initiating his exposure and understanding of DEL technology, and he became very optimistic about it.

DEL technology was proposed by American molecular biologists Professor Sydney Brenner and Professor Richard Lerner in 1992. Professor Li Xiaoyu has been researching in the field of DEL for nearly 20 years and is one of the academic leaders in the global DEL technology field. He has been repeatedly selected for Elsevier's list of highly cited scholars in China. He has used DEL technology to screen target lead compounds for many large pharmaceutical companies at home and abroad, achieving a series of breakthrough research results in the DEL field.

The most crucial link in the innovative drug industry chain is research and development. Approximately one-third of the total cost of new drug development is used for drug discovery and preclinical stages, which usually takes three to six years. Drug discovery and development are characterized by long lead times and high risks. The entire process from discovering lead compounds to bringing innovative drugs to market often requires testing tens of thousands of compounds. Therefore, improving the success rate of new drug discovery is crucial for drug development.

DEL technology brings hope to solve the problems of low success rate and efficiency in drug discovery.

DEL technology is a novel high-throughput drug screening technology that combines the advantages of combinatorial chemistry and high-throughput screening technology to efficiently find small molecules with high affinity for target proteins. It can greatly increase the probability of successful drug development, reduce development costs, and shorten development cycles. With the rapid accumulation of drug development data and the accelerated development of artificial intelligence technology (AI), AI applications in new drug discovery are increasing, and its advantages are also becoming increasingly prominent.

He Xun explained, "DEL technology is a breakthrough from 0 to 1, conducting 'needle in a haystack' screening quickly and inexpensively, with great hope of developing First-in-class drugs; AI technology is a leap from 1 to 2, based on existing big data, using machine learning to model and predict, further modifying and optimizing the structures of target candidate molecules."

DEL technology requires DNA encoding and then identification of the unique DNA sequences of screened small molecules through DNA sequencers. Previously, the widespread application of high-throughput sequencers was limited due to long sequencing times and high costs, which restricted the use of DEL technology. After 2010, with the revolution of second-generation sequencing technology, DEL technology developed rapidly. The top 20 international pharmaceutical companies have established DEL screening departments or cooperated with DEL biotechnology companies for research. Among them, GSK acquired Praecis' DEL technology platform, and the newly developed drugs are already in clinical stages.

On the basis of existing DEL technology, NewDEL Biotech has developed DEL 2.0 technology, which can be used for cell-based screening. Compared to the previous generation of technology's biochemical models, DEL 2.0 technology's screening is closer to the real in vivo environment, resulting in higher quality target lead compounds and higher conversion rates.

Currently, NewDEL Biotech is refining the DEL 3.0 technology platform. He Xun stated, "DEL 3.0 technology combines DEL with AI, achieving complementarity. DEL provides high-quality big data for AI model construction, and in turn, AI can help build higher-quality DNA-encoded compound libraries, further improving the efficiency and drug-likeness of new drug screening."

The competition in the field of anti-tumor immunotherapy is fierce, with a determination to develop First-in-class drugs.

Based on the proprietary DEL technology, NewDEL Biotech is establishing an innovative drug lifecycle system focused on First-in-class drug design, research, and industrialization to address unmet clinical needs.

In its business layout, NewDEL Biotech not only has its own R&D pipeline but also supplements existing pipelines through joint development with partners and collaboration with research institutions. Additionally, it provides technical services to assist research units and pharmaceutical companies in screening active compounds. With the increasing number of DEL screening target projects, it will have numerous new drug projects available for licensing out in the future.

In its self-developed pipeline, NewDEL Biotech has screened more than 10 lead compounds using DEL technology, focusing on multiple drug pipelines in the field of anti-tumor immunity, including novel tumor immune checkpoint inhibitors.

"Anti-tumor immunity is a huge, unsatisfied market. While the competition in this field is fierce, most drugs are the result of fast following. NewDEL Biotech has the innovative DEL 3.0 technology platform, focusing on the origin of new drug development, with the potential to screen First-in-class drugs. Therefore, we are not afraid of competition; we are fully confident," said He Xun.

Currently, NewDEL Biotech has achieved fruitful results through collaboration with research institutions and joint development with enterprises. In December last year, it signed a technology transfer agreement with Jinan University, collaborating with Professor Dingke's team to jointly develop a new generation of targeted anti-tumor drugs, with a total contract value exceeding 300 million yuan. It has also reached a new drug development cooperation agreement with Heridas Lead and Nanjing Jingzhunda, targeting new targets for the development of tumor immune therapy drugs.

"To develop drugs, differentiation is essential. The previous 'mindless' follow-up innovation is no longer feasible. The trend of Chinese new drug development is increasingly focusing on original innovation. Without original innovation, there is still a prospect for improved innovation, but it requires a large amount of R&D resources and funding for basic research. In other words, innovative drug companies need foundational technology to continuously enrich their pipelines through foundational technology to have room for survival."

According to He Xun, the DEL 3.0 technology platform will be completed in the first half of 2022, and in the first half of 2023, NewDEL Biotech will apply for an IND for a drug, entering the clinical stage. In the future, the company will continue to improve the DEL technology platform, explore DEL+PROTAC, DEL+allosteric site drug development, and other DEL+X technology application areas, promote ongoing pipelines, and actively cooperate with top domestic and foreign pharmaceutical companies and institutions for long-term cooperation, using differentiated technology to create a globally leading innovative drug company.