ADC welcome "official guidance", local enterprises actively layout

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I don't know if my friends have felt the surging cold wave. After a night of autumn rain, the temperature is like a roller coaster, falling all the way. This cold wave not only brought us down, but also brought a chill to the biopharmaceutical industry. Judging from the investment and financing data, the financing events and amount from January to August this year decreased by 12.6 and 45.2 respectively compared with the same period last year, and the financing amount was nearly halved.

the general environment is cold, ADC drugs have gone up against the trend, with 14 ADC drugs approved worldwide, 4 ADCs approved in China, and dozens of ADC drugs approved for clinical research. In addition, there are frequent actions at the regulatory level. Following the release of the "Technical Guidelines for Non-clinical Research of Antibody Conjugated Drugs (Draft for Comments)" (hereinafter referred to as non-clinical principles) by the Drug Administration on July 6, the "Technical Guidelines for Clinical Research and Development of Anti-tumor Antibody Conjugated Drugs (Draft for Comments)" (hereinafter referred to as clinical principles) was issued again on September 15, pointing out that ADC drug research and development is oriented to clinical needs, encourage research and development personnel to explore its design features in depth. What are the main points of these two guiding principles that deserve our attention?

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states in the Non-Clinical Principles that, in addition to the need for holistic consideration of the ADCfor its various components and the composition after releaseresearch. For example, in the pharmacology section, it is proposed that "in addition to the overall pharmacological/pharmacodynamic effects of ADC, the pharmacological effects of its various components need to be studied"; In the pharmacokinetics section, it is proposed that "the coupling structure characteristics of ADC lead to various in vivo processes, so it is necessary to select and establish appropriate detection methods, and complete the corresponding analytical methodology verification."

In addition to the consideration of the individual components, the Non-Clinical Principles emphasizethe importance of selected animal species, for example, in general toxicology, it is mentioned that "if ADC toxicity studies are carried out in both rodent and non-rodent species, rodents are preferred for the separate investigation of the toxicity of free small molecular compounds, unless there is no activity in rodents."; In reproductive toxicity, it is mentioned that "if the target binding animal species is non-human primate or no related animal species, rats or rabbits can usually be considered first to carry out reproductive toxicity tests to investigate the reproductive toxicity of free small molecule compounds."

In addition, in the Non-Clinical Principles, ADC drugs are alsoPart of the Experimentmake recommendations, such as in the pharmacokinetics section, "In general, tissue distribution of ADCs is not necessary, but for ADCs to be targeted to specific tissue lesions (e. g., ADCs targeted to the brain), tissue distribution studies are needed."; In general toxicology, it is mentioned that "for linkers, there is generally no need for separate toxicity evaluation. In general, it is not necessary to conduct safety studies on naked antibodies."

"The development of ADC drugs should be based on the principle of clinical value-oriented, with the goal of solving clinical needs., actively carry out research on the mechanism of action, and on this basis, carefully design ADC, so that the benefits outweigh the risks." Around this original intention, the five core elements of target antigen, antibody, linker, payload and coupling method are discussed in the Clinical Principles.

The Clinical Principles also state that, on the basis of following the general principles and laws of drug development, ADC drugs are used in the clinical development process.should pay attention to the differences in the efficacy of the same target antigen between different drugs, the differences in the efficacy of the same drug for different target antigen expression states, the exploration of the best dosing regimen, the safety risk of off-target, and the exploration of combination treatment strategies. The clinical needs should be taken as the starting point, combined with molecular structure and mechanism characteristics, in-depth exploration and analysis of their own clinical advantages, and reasonable development strategies.

According to Jost Sullivan, the global antibody-coupled drug market is expected to reach $6.2 billion billion in 2022, with a compound growth rate of 30.6 percent from 2019 to 2024. In 2030, the global antibody conjugate drug market size is expected to reach $20.7 billion, China's market size is expected to reach $4.2 billion.

The domestic ADC drug capital market is hot.leading enterprises have entered the harvest period. Take Rongchang Biology as an example. According to the prospectus submitted by Rongchang Biology on February 18, 2022 in Shanghai Stock Exchange, it is estimated that the sales volume of vidicetuzumab will reach 0.4 billion yuan in 2022, and many investment and financing events will continue to be born in ADC field.

Figure 1. Investment and Financing of ADC Drug Market in China

Table 1. Partial financing events in the domestic ADC sector in 2021

's first ADC has been listed, a number of enterprises actively layout.June 2021, the conditional approval of the listing of Rongchang Bio's vidisituzumab, China's first independent research and development of domestic ADC drugs. Therefore, 2021 is also known as the first year of domestic ADC drugs. According to the data of Yazhi Network, as of September, ADC of domestic pharmaceutical companies had 52 clinical trial information. Rongchang Bio, Duoxi Bio, Hengrui Pharmaceuticals, Korenbotai and other research and development in the number of high.

Figure 2. The pipeline quantity distribution of the top 10 domestic ADC clinical research and development enterprises

ADC drugs are widely distributed in the field of tumors, with a focus on hot targets.Compared with foreign countries, in the total number, the total number of local research pipelines is less, indications, target distribution is more concentrated, popular target HER2 accounted for more than 30%. In addition, some enterprises are already exploring innovative targets, which have not yet formed a clear competitive pattern and still have great potential for development.

R & D progress is dominated by early projects., although ADC has gradually attracted the attention of enterprises and the popularity continues, the current research and development level in our country is still in the primary stage. There are 31 drugs under research in clinical phase I, accounting for over 60%. The second and third phase projects with slightly faster progress include RC108 in Rongchang, MRG003, MRG002 in Meiyake, BAT8001 in Baiaotai, etc.

in the domestic policy environment of encouraging independent innovation of pharmaceutical enterprises and accelerating the introduction of drugs that meet clinical unmet needs, ADC drugs will occupy more of the Chinese market in the future, and also drive the development of CDMO field. High-quality targets in the ADC field will also continue to receive the attention of the capital market, pharmaceutical companies not only seek financing in the domestic primary and secondary markets, some enterprises are also actively seeking ADC overseas license out, to achieve the early realization of the project.