中泰证券祝嘉琦：商业化时代来临 mRNA技术有望迎来黄金十年
Zhongtai Securities Zhu Jiaqi: Commercialization era is approaching mRNA technology is expected to usher in a golden decade
2020年两款mRNA疫苗的上市宣告mRNA技术正式进入商业化时代，旺盛的终端需求将带来整条产业链的景气机会， mRNA有望进入快速发展的黄金十年。由于mRNA技术在疫苗、药物等领域原理相通，本篇报告以mRNA疫苗为例，讨论mRNA技术的前景、关键壁垒以及产业链环节的价值量。
The launch of two mRNA vaccines in 2020 declares that mRNA technology has officially entered the era of commercialization. The strong end demand will bring the boom opportunities for the whole industry chain, and mRNA is expected to enter the golden decade of rapid development. Since the principle of mRNA technology is similar in vaccine, medicine and other fields, this report takes mRNA vaccine as an example to discuss the prospects, key barriers and value of the industrial chain of mRNA technology.
为什么mRNA技术前景可期？1)优势突出，应用广泛。mRNA通过“翻译”指导蛋白质的生产，广泛应用在预防疫苗、治疗疫苗、治疗药物等领域，代表新的生物技术方向。2)商业化时代来临。在递送技术、序列优化等不断积累下，实现从动物到人体的突破，随着首款mRNA疫苗上市，商业化应用将加快产业发展，有望开启黄金十年。3)市场空间扩阔。根据Pubmed预计2035年mRNA市场总规模230亿美金，其中非新冠产品有望达到180亿美金，2025-2035 GAGR 68%mRNA技术的壁垒体现在哪里？以mRNA疫苗为例探讨mRNA技术的核心壁垒。1)递送系统：专利保护和工艺参数铸就递送系统的高壁垒。mRNA的脆弱性使得递送成为关键，如何绕过专利壁垒并形成稳定的工艺参数成为企业亟待解决的问题。2)序列优化：分子修饰专利+高效率加帽构成较大难度。专利基本绕不开，需购买或开发更合适的修饰策略，但难度极大。不考虑专利壁垒，体外转录合成mRNA分子的关键在于高效率加帽。3)生产工艺：关键是将mRNA更好地搭载至递送载体上。另外纯化工艺贯穿整个流程，高效的纯化策略至关重要；稳定性也是重要的生产工艺课题。
Why is mRNA technology promising? 1) Outstanding advantages and wide application. MRNA guides protein production through "translation", and is widely used in preventive vaccines, therapeutic vaccines, therapeutic drugs and other fields, representing a new direction of biotechnology. 2) Commercialization era is coming. With the continuous accumulation of delivery technology, sequence optimization and other breakthroughs from animals to human beings, commercial application of the first mRNA vaccine will accelerate the development of the industry and is expected to open a golden decade. 3) Expanding market space. According to Pubmed, the total size of mRNA market is expected to reach 23 billion USD in 2035, among which non-COVID-19 products are expected to reach 18 billion USD. What are the barriers of GAGR 68%mRNA technology in 2025-2035? Take mRNA vaccine as an example to discuss the core barrier of mRNA technology. 1) Delivery system: patent protection and process parameters cast high barriers for delivery system. The vulnerability of mRNA makes delivery key. How to bypass patent barriers and form stable process parameters has become an urgent problem to be solved by enterprises. 2) Sequence optimization: the patent of molecular modification + high-efficiency capping is relatively difficult. Patents are basically inescapable, requiring the purchase or development of a more appropriate modification strategy, which is extremely difficult. Regardless of patent barriers, the key to in vitro transcriptional synthesis of mRNA molecules is efficient capping. 3) Production process: The key is to better carry the mRNA onto the delivery carrier. In addition, the purification process runs through the whole process, and efficient purification strategy is very important. Stability is also an important manufacturing process issue.
mRNA产业链的核心价值量？以mRNA疫苗为例详细拆分整个生产工艺流程：分为DNA质粒模板的制备、mRNA原液的制备、制剂的生产。单剂mRNA疫苗生产成本大约1-3美金，其中原材料占比(41.70%-55.90%)最高，其次是设备/耗材(23.90%-31.70%)。原材料中，帽子类似物占比最高达到46%，其次是工具酶(包括T7 RNA聚合酶、无机焦磷酸酶、RNA酶抑制剂)占比29%，占据产业链较大价值量。
What is the core value of mRNA industry chain? Taking mRNA vaccine as an example, the whole production process is divided into the preparation of DNA plasmid template, the preparation of mRNA raw solution and the production of preparations. The production cost of a single dose of mRNA vaccine is approximately US $1-3, with the highest proportion of raw materials (41.70%-55.90%), followed by equipment/consumables (23.90%-31.70%). In raw materials, hat analogues account for up to 46%, followed by tool enzymes (including T7 RNA polymerase, inorganic pyrophosphatase and RNA enzyme inhibitors) account for 29%, which occupies a large value in the industrial chain.
建议关注标的：mRNA技术商业化前景无限，有望迎来黄金十年，看好提前布局mRNA技术相关标的及产业链。
It is suggested to pay attention to the target: the commercialization of mRNA technology has unlimited prospects and is expected to usher in a golden decade. It is expected to lay out the target and industrial chain related to mRNA technology in advance.
mRNA疫苗：目前疫苗企业跑马圈地，积极布局mRNA技术平台，关注新冠mRNA疫苗进度靠前的沃森生物/艾博生物/蓝鹊生物、复星医药、艾美疫苗/丽凡达生物等，同时康希诺、石药集团、康泰生物/嘉晨西海、智飞生物/深信生物、瑞科生物/瑞吉生物、安科生物、斯微生物、厚存纳米等也积极布局，处于临床早期阶段。
MRNA vaccines: At present, vaccine companies are actively setting up the mRNA technology platform and paying attention to the advanced progress of THE NOVEL coronavirus mRNA vaccine, such as Worthen bio, AbBIO, Blue Magpie, Foxing Pharma, And Imet vaccine/Rivanda Bio. At the same time, Consino, Shiyao Group, Kangtai Bio/Jiachen Xihai, Zhifei Bio/Xinsheng Bio, Ruike Bio/Regi Bio, Anke Bio, Si Microbiome, Houcun Nano and other active distribution, in the early stage of clinical.
上游原料企业：诺唯赞、近岸蛋白、上海兆维
Upstream raw material enterprises: Novazan, nearshore protein, Shanghai Zhaowei
上游设备/耗材企业：东富龙、楚天科技、纳微科技、迈安纳
Upstream equipment/consumable enterprises: East Fulong, Chutian Technology, Nano Technology, Maianna
质粒CDMO企业：金斯瑞、博腾股份
Plasmid CDMO enterprises: Kingsley, Botten shares
风险提示：研发进度不及预期，临床推进不及预期，产品销售不及预期；研报使用信息更新不及时的风险；报告中关于各家公司mRNA技术及其进展等信息是根据公开资料梳理、翻译得到，存在与实际情况有偏差的风险
Risk warning: r&d progress is not as expected, clinical progress is not as expected, product sales is not as expected; Risk of not updating information in time; The information about each company's mRNA technology and its progress in the report is obtained by combing and translating public information, and there is a risk of deviation from the actual situation
（文章来源：中泰证券研究）
(Source: Zhongtai Securities Research)
