CSPC Pharmaceutical Group has reached a blockbuster BD again. Recently, CSPC Pharmaceutical announced that it has reached a BD agreement with BeiGene on the group's new methionine adenosyltransferase 2A (MAT2A) inhibitor, SYH2039, and will grant BeiGene the rights to develop and commercialize the pipeline globally.

The BD amount this time is also very impressive: CSPC Pharmaceutical Group will receive a total of US$150 million in advance payments, and is entitled to receive up to US$135 million in potential development milestone payments and up to US$1.55 billion in potential sales milestone payments, as well as tiered sales commissions calculated based on the annual net sales of the product. It is worth mentioning that the compound was screened by CSPC Pharmaceutical through AI technology. Previously, CSPC Pharmaceutical also BD a preclinical pipeline screened by AI technology to AstraZeneca at a high price.
CSPC Pharmaceutical AI exploded.

▍Why CSPC Pharmaceutical?
The molecule of this BD transaction is a MAT2A inhibitor, which is also a relatively new targeted drug. Methionine adenosyltransferase (MAT) is involved in the key transformation of S-adenosylmethionine (SAM), which plays an important role in the methylation of proteins and DNA. Imbalance in the methionine cycle metabolism process has been found to be a potential pathogenesis of cancer, which is manifested by the increase of related indicators detected in most cancers, among which MAT2A is a typical example.

MAT2A is the catalytic subunit of MATII (an isomer of MAT) and plays an extremely critical role in the above biochemical reaction process. More importantly, high expression of MAT2A has been observed in many cancers: such as liver cancer, colon cancer, gastric cancer and non-small cell lung cancer. By inhibiting this target, "precise" death of cancer cells can be caused. In addition, MAT2A inhibitors have a synergistic effect when used in combination with PRMT5 inhibitors.

Therefore, the inhibition of MAT2A has become a new development direction for small molecule targeted drugs. The current typical pipeline under development is IDEAYA's IDE397, which just announced positive clinical phase II data in non-small cell lung cancer and urothelial carcinoma this year. SYH2039, a CSPC inhibitor with the same target, was approved for clinical trials in China and the United States in March and April this year, respectively. Preclinical trials have shown that the molecule can effectively inhibit the growth of various MTAP-deficient tumor cells such as non-small cell lung cancer, glioma, gastroesophageal cancer, pancreatic cancer and bladder cancer.

Why did BeiGene take this drug? As mentioned above, the combination of MAT2A inhibitors and PPMT5 inhibitors will theoretically have a very good synergistic effect. BeiGene currently has a pipeline of PPMT5 inhibitors. In September this year, the clinical trial application of its related pipeline BGB-58097 was accepted by the CDE. At present, the relevant pipelines with faster progress are all in the United States, and the fastest progress in China is only CSPC, so this BD will occur between CSPC and BeiGene.

In addition, the amount of this BD is also very interesting: the advance payment amount reached US$150 million, but the milestone payment for research and development was only US$135 million, and the large potential milestone payments were all in commercialization. In other words, this transaction overdrew most of the expected R&D progress in advance, which can be understood as spending most of the milestone expenses that should be spent during R&D in advance payments.

The reason may be that the molecule is indeed very effective, and on the other hand, it may be the current scarcity of the molecule. It is the only one in China that has entered clinical trials, and it is jointly promoted by China and the United States, which is very consistent with BeiGene's own strategy. In the future, handing over the commercialization of the drug in the United States to BeiGene is also a win-win cooperation.

▍High-quality AI platform
As we all know, in terms of AIDD (AI drug design), the development speed of small molecules is much faster than that of large molecules, and there are many companies that discover small molecule drugs. There are two main categories: one is mainly outsourcing R&D through its platform, and the main representative is Jingtai Technology. Of course, Jingtai Technology does not limit its business to the pharmaceutical field. The other is AIDD companies with their own pipelines, which can be understood as biotech, and the most typical one is Insilicon Valley. Of course, Insilicon Valley currently also has a part of its own income from licensing cooperation with its technology platform.

CSPC has signed a cooperation agreement with Insilicon Intelligence and Jingtai Technology. In August last year, CSPC Pharmaceutical Group, Jingtai Technology and Insilicon Intelligence announced a strategic cooperation. Based on the cooperation agreement, CSPC Pharmaceutical Group will combine its own drug development experience with Insilicon Intelligence and Jingtai Technology's leading AI technology platform, focus on strategic products with high clinical needs, use AI to assist drug design, improve the efficiency and success rate of new drug screening, and jointly promote the development of innovative drugs.

pharmaAI consists of three parts: Biology42, Chemistry42 and Medicine42.
Biology42 conducts target discovery and prioritization, and consists of three parts: PandaOmics, Generative Biologics and Life Star 1.
PandaOmics: A cross-data type of systems biology research, which is used to promote the discovery of new targets or prioritize established targets for diseases of interest, and provide target identification and biomarker identification from the molecular characteristics and clinical data correlation.
Generative Biologics: Use generative models to design and evaluate proteins, predict protein interactions and generate protein sequences, and perform protein generation for selected targets.
Life Star 1: Analyze the input cell line samples, and the generated data is then analyzed using PandaOmics' algorithms to identify potential candidate targets, compounds, and biomarkers. In addition, Life Star 1 can further promote the maintenance and testing of these cell line samples to determine whether the desired effects can be achieved through selected targets, compounds, and biomarkers.
Chemistry42 - Generate new small molecules and determine the characteristics of small molecules. Four parts: Generative Chemistry, Golden Cubes, ADMET Predictors, and Alchemistry.
Medicine42 - Prediction of clinical trial results. Consists of inClinico application data. Use AI algorithms to analyze publicly available data, including the chemical structure of drugs, past clinical data, past clinical plans, public publications, subsidies, and patents. The goal is to build a knowledge graph, which is then used to train machine learning models. Use the model to predict the probability of trial success and evaluate the impact of specific trial design features on the overall success rate.

Not only CSPC, but also Insilicon Intelligence's Pharma.AI platform has been favored by other large pharma companies.

▍CSPC AI has exploded
For AIDD small molecules, the future trend is bound to significantly shorten the drug discovery process, thereby greatly accelerating its entry into the clinical stage. According to Insilicon Intelligence's prospectus, Insilicon Intelligence's PandaOmics platform can quickly discover new targets through multi-omics data comparison. In the preclinical stage, its AI technology shortens the R&D cycle to 11-18 months, with a total investment of less than US$2.7 million, while traditional methods often require 5 years and hundreds of millions of dollars.

The shortened preclinical time and cost have greatly accelerated the development of small molecule drugs, turning them into factories for mass production of innovative drug molecules, and the increase in molecules also means an increase in BD opportunities. The future trend is likely to be that AIDD companies will "batch" BD of pipelines.

This trend was first realized in CSPC, a pharma. The first was the BD with AstraZeneca a few months ago: to promote the development of a preclinical innovative small molecule lipoprotein (a) (Lp(a)) inhibitor - YS2302018. According to the terms of the agreement, CSPC Pharmaceutical Group will receive an advance payment of US$100 million and is entitled to receive potential development milestone payments of up to US$370 million and sales milestone payments of up to US$1.55 billion, totaling US$2.02 billion. Then came the BD between CSPC Pharmaceutical and BeiGene. CSPC Pharmaceutical has become the first pharmaceutical company to initially implement the model of "batch BD of AIDD". A traditional Chinese pharma has achieved this achievement, which is one of the successful examples of traditional pharmaceutical companies turning from imitation to innovation.

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