Reply to the letter on the implementation of the opinions of the municipal Party committee meeting on the science and Innovation Board of Shanghai aopumai Biotechnology Co., Ltd. on the initial public offering of shares and listing on the science and Innovation Board
Sponsor (lead underwriter)
April, 2002
Shanghai Stock Exchange:
We have received the letter of implementation of the opinions of the municipal Party committee meeting on the science and Innovation Board on the initial public offering and listing of Shanghai aopumai Biotechnology Co., Ltd. on the science and Innovation Board (hereinafter referred to as the "inquiry letter") issued by your office on April 14, 2022. Shanghai aopmai Biotechnology Co., Ltd. (hereinafter referred to as "aopmai", "issuer", "company") and Haitong Securities Company Limited(600837) (hereinafter referred to as " Haitong Securities Company Limited(600837) " and "sponsor"), Beijing Jinchengtongda law firm (hereinafter referred to as "Jinchengtongda", "issuer's lawyer") Lixin Certified Public Accountants (special general partnership) (hereinafter referred to as "Lixin certified public accountants", "reporting accountants") and other relevant parties have checked the questions listed in the inquiry letter item by item, and now the reply is as follows, please review.
The explanations on the interpretation, format, supplementary and updated disclosure of the reply are as follows:
Unless otherwise specified, the abbreviations or terms in this reply report have the same meanings as those in the prospectus. Font of this reply report:
The questions listed in the inquiry letter are in bold (BOLD)
Answer to question Arial
catalogue
catalogue 3 question 1: Question 4: nine
Question 1:
Please explain to the issuer:
(1) Whether the issuer's cdmo business description is accurate, and whether the current cdmo business only includes contract R & D and sample production;
(2) the future development route of CDMO business and the embodiment of other advanced technologies related to CMC besides the construction of cell strain.
(3) The commercial rationality of large cdmo transactions with the immune ark, and the matching with the immune Ark's own business scale and real needs.
The sponsor is requested to explain the verification procedures and results of the authenticity of these transactions, and express clear opinions on the above matters.
Question reply:
1、 Issuer's Description:
(I) whether the issuer's cdmo business description is accurate, and whether the current cdmo business only includes contract R & D and sample production
The cdmo business of the issuer is mainly protein antibody drug cdmo, and the technical services provided include cell line construction, upstream cell process development, downstream purification process development, preparation development, pilot production, quality analysis, etc., which are consistent with the cdmo technical services of Companies in the same industry, such as YaoMing biology and Kingsley, and the description of cdmo business is accurate.
According to the industry practice, the biological drug cdmo business generally includes the service contents of contract R & D, sample production and commercial production. At present, the issuer has established a biological drug cdmo technical service platform and a 200L / 500L GMP stock solution production line, which can carry out GMP production, support the application for clinical trial (ind) of new drugs and support the pilot production of clinical phase I & II, However, phase III and commercial production have not been arranged yet. Therefore, from the above definition, up to now, the issuer's cdmo business does not include commercial production, but only contract R & D and sample production. The scope of business belongs to the process related to biological drug production, which is a standard biological drug cdmo business.
To sum up, the issuer's cdmo business description is accurate.
(II) the future development of CDMO business and the embodiment of other advanced technologies related to CMC besides the cell building services.
1. Future development route of cdmo business
Based on many years of experience in cell culture medium development and several implemented cdmo projects, oppmai has a deep understanding of the key technical links of protein antibody drug production such as cell culture and antibody expression. The products and technical processes related to cell culture have formed the technical core of the company. By the end of 2021, the issuer has completed 63 independent cell line construction projects, 19 culture medium and process customization development projects and 9 CMC projects. Based on its technical advantages and successful experience in cell culture such as cell line construction and culture medium customization development, the issuer can gain customer trust in the market competition of antibody drug cdmo and successively undertake the whole process cdmo projects for specific new drug research and development. By the end of February 2022, the amount of orders in hand for the company's cdmo business was 933158 million yuan, and the revenue is expected to be 809934 million yuan within one year.
"Integration and one-stop" is the overall development trend of biological drug cdmo industry. In the future, the development of the company's cdmo business will be carried out in both vertical and horizontal aspects. In terms of vertical development, the company will take this IPO as an opportunity to extend the cdmo service to the "integration" direction through the development of fund-raising and investment projects, so as to form the whole process cdmo service capacity covering the commercial production stage; In terms of horizontal development, the company will also give full play to the experience and advantages accumulated in the cdmo field of protein antibody drugs in the future, further expand the scope of antibody drugs to the development of antibody coupled drugs (ADC) and multifunctional antibodies, and further enrich the service types of antibody drugs. At the same time, the company continues to promote and give full play to the business cooperation between culture medium sales and cdmo services. When meeting the conditions, the company tries to layout the cdmo technical service platform of recombinant protein drugs / vaccines and gene therapy / cell therapy technical service platform, closely follow the development trend of the industry, and create a comprehensive cdmo technical service system of macromolecular drugs.
2. Besides the construction of cell strain, the other CMC related technology is advanced.
In addition to the platform for building cell lines, the other core technologies and advanced characterization of issuers in CDMO business are as follows:
Technology platform core technology advanced characterization
The use quality of upstream cell culture comes from design (QBD), which can efficiently complete the R & D process of antibody laboratory scale, and can customize the culture medium for customers based on the concept of process development platform and experimental design (DOE)
Other R & D methods
Technology platform core technology advanced characterization
Adjust the amplification process according to the different characteristics of cell lines and expression products, and comprehensively consider various factors such as the linear speed of agitator blade end and the removal of CO ν
The purified and developed products meet the quality standards of the pharmaceutical industry, and the purity of downstream protein can reach more than 99% of the detection standard
The development platform technology has wide practicability and can be applied to protein drugs such as proteins, enzymes, virus like particles, monoclonal antibodies, polyclonal antibodies of different types of biological drug products and recombinant proteins. The corresponding purification process platform has been developed and has wide applicability
In the field of cell culture process development, the issuer independently developed CHO-K1 suspension acclimation medium and acclimation method, and obtained invention patent, which reduced the acclimation time of adherent medium from 5-10 months to less than 2 months.
At the same time, it can solve the problems of easy cell agglomeration, low survival rate and long doubling time. It is also one of the CDMO business platforms, which is the embodiment of the advanced technology of the upstream cell culture process development platform.
(III) the commercial rationality of the large amount cdmo transaction with the immune ark, and the matching with the immune Ark's own business scale and real needs
1. The transaction between the two parties has a reasonable business background
In 2021, the issuer realized cdmo business income of 13.945 million yuan for immune ark, mainly from the project of imm0071703 new drug CMC pre clinical development (hereinafter referred to as "opm2025 project"). The project was signed by the issuer and immune ark on November 25, 2020, with a total contract amount of 15.795 million yuan. In 2021, the contract project was successfully promoted, The milestone was completed in the current year and the corresponding revenue was 12.895 million yuan, accounting for 92.47% of the cdmo business revenue of the immune ark in the current year.
According to the public information of immune ark, immune ark was established in May 2017. It is a biotechnology company focusing on innovative antibody drug discovery. The company has established technical platforms such as high-throughput reporting cell screening platform based on simulated immune cell response, antibody display library platform based on HEK293, xfab multi-specific antibody molecule construction platform, CD3 humanized mouse and other pharmacological and pharmacodynamic research platforms, Opm2025 project is the 41bb-cd40 bispecific antibody drug development project independently developed by the immune ark based on the above technical platform, and has been in the pre ind stage.
The founder and CEO of immune ark Gao Xin is a doctor of science majoring in molecular biology. He focuses on tumor immune agonist antibodies and is fully responsible for the company's strategic development and operation planning. He has successively worked in the Academy of Military Medical Sciences and the national protein drug research and Engineering Center, and has 25 years of experience in the research and development of recombinant protein drugs; Pan Xiujie, chief scientific officer of immune ark, is a doctor majoring in medical physiology. He has been engaged in immunotoxicology research for a long time and is fully responsible for the scientific evaluation and management of the company's projects. He has worked in the Academy of Military Medical Sciences, a member of the immunotoxicology Professional Committee of the Chinese Toxicology Society, a CNAs accredited and CMA qualified testing & verifier, and has 20 years of medical research experience.
The immune ark belongs to an innovative drug development enterprise, and the main personnel are R & D personnel. Therefore, the personnel scale is small and in line with the characteristics of the industry. As an innovative drug development enterprise, the main business of immune Ark at present is antibody drug research and development. With the official launch of the drug marketing license holder system (MAH system) at the national level, small and medium-sized pharmaceutical companies without production capacity are allowed to apply for drug listing. In the process of drug application for ind, corresponding cdmo services are required. Therefore, the business needs of immune ark are consistent with its own development stage and industry practice.
2. The main project progress of the cooperation between the two sides is consistent with the milestone delivery progress of the issuer
By the end of 2021, the issuer had completed 13 delivery milestones for the main project of cooperation between the two sides - opm2025 project, promoting the project to enter the ind pre communication link. At the end of December 2021, the immune ark, together with the cooperation unit of the new drug R & D project, submitted a pre ind communication application to the drug evaluation center of the State Drug Administration. The specific application contents include clinical protocol, pharmacy, pharmacology and toxicology, a total of 34 reports, and completed the relevant communication work. At present, the feedback from the drug evaluation center has been obtained, and the project is in the normal process of promotion.
Therefore, the progress of the above projects is consistent with the milestone delivery of the issuer, and the relevant projects are the real business needs of the immune ark.
The sponsor is requested to explain the verification procedures and results of the authenticity of such transactions, and express clear opinions on the above matters
2、 Verification of the sponsor
(I) verification procedure
1. Obtained the main cdmo business contracts signed between the issuer and immune ark, analyzed the rationality of milestone setting, terms and prices, and compared with other similar project contracts;
2. Visited the immune ark to understand its new drug project development and overall business development, interviewed its actual controller, Gaoxin, to understand its production and operation plan, and whether the signing of large amount cdmo contract is consistent with the development stage of the enterprise; The amount of business transactions between the immune ark and the issuer was confirmed by letter; 3. Obtain the milestone report of the Issuer on the delivery of opm2025 project, check the experimental records during the project promotion, obtain the confirmation email of the customer on the delivery, and obtain the payment collection document; Obtained the pre ind pre communication application form submitted by the immunization ark to the drug evaluation center of the State Drug Administration, checked the professional feedback content of the drug evaluation center, and checked the matching with the issuer's project implementation progress in combination with the promotion progress of relevant new drug research and development;
4. Search the public data of the immunization ark, verify the relationship between the immunization ark and its main shareholders (including external investor shareholders) and the issuer and its actual controller, and obtain the information of the issuer and its actual controller, the immediate relatives of the actual controller, directors (excluding external directors), supervisors (excluding external supervisors) and senior managers, Verify that there are no abnormal capital transactions with the immune ark and its major shareholders; (II) verification opinions
After verification, the sponsor believes that the large amount cdmo transaction between the issuer and the immune ark is a common transaction type under the MAH system, which is in line with industry practice. As a new drug development enterprise, the related R & D pipeline of immune ark plans to apply for ind, so it has the procurement demand of corresponding cdmo business, has commercial rationality, matches the business scale and real demand of immune ark, and the project implementation progress matches the new drug development progress fed back by the drug evaluation center of the State Drug Administration; There is no significant difference between the issuer and the immune ark in terms of contract terms, project gross profit margin, etc. compared with the issuer in the same period and similar businesses, and the relevant transaction price is fair. In conclusion, the transaction between the issuer and the immune ark is authentic.
Question 2:
Please explain to the issuer:
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