I. focus this week – mRNA based transient car-t cell technology
In the cover article of the latest issue of science, the research team of Perelman School of medicine at the University of Pennsylvania creatively used an mRNA injection to achieve car-t treatment in mice with heart failure, and successfully repaired the function of mouse heart. The mRNA of car targeting fibroblast activating protein is packaged in lipid nanoparticles (LNP) targeting T cells (CD5) and injected into mice to produce car-t cells with therapeutic effect in mice, so as to eliminate pathogenic activated fibroblasts and reduce cardiac fibrosis, and then the mRNA will be diluted during cell division, Thus, the instantaneous car-t treatment technology is realized. This week, we used 21 charts to interpret in detail the latest frontier progress in the direct generation of car-t cells by mRNA injection in vivo.
What are the car-t and mRNA of precision medical tools? Car-t cell therapy has precise targeting and strong lethality; MRNA drugs use target / antigen coding RNA to make cells absorb and express the encoded antigen through a specific delivery system, so as to cause humoral and cell-mediated immune response at the same time. Using the temporary copy of genetic information that can be carried by nucleoside modified mRNA, a more controllable transient car-t treatment technology with shorter effect duration is carried through LNP.
MRNA technology linkage broke the treatment dilemma, and the first battle of instantaneous car-t therapy was won. In the treatment of myocardial fibrosis, in order to solve the negative impact of the infinite persistence of T cells on the work of normal fibroblasts in car-t cell therapy, the instantaneous anti fibrosis car-t therapy is developed by using nucleoside modified mRNA technology, and the targeted antibody is modified on the surface of LNP to meet the dual needs of efficacy and safety:
It can deliver enough mRNA to produce functional car-t cells in vivo, successfully show phagocytosis in vivo and effectively improve cardiac function;
After the treatment of functional cells, the mRNA restricted in the cytoplasm can be diluted during cell division, so as to ensure the normal healing function of fibroblasts.
Where is the way of cell therapy from LNP carrying car-t: cell therapy has broad prospects. On the one hand, the superposition of mRNA technology is conducive to promote car-t therapy to solve the problems of complex process, long cycle and high price; On the other hand, building functional T cells in vivo is expected to greatly extend the application prospect of the platform. Biontech has taken the lead in the layout of car tmRNA vaccine, and carvac has achieved positive results in the early clinical treatment of solid tumors.
II. Market review of innovative medicine stocks in the pharmaceutical sector:
This week Huadong Medicine Co.Ltd(000963) , Sichuan Kelun Pharmaceutical Co.Ltd(002422) , Yifan Pharmaceutical Co.Ltd(002019) , Livzon Pharmaceutical Group Inc(000513) , Sunshine Guojian Pharmaceutical(Shanghai) Co.Ltd(688336) ranked the top 5 in the rise and fall of Shanghai and Shenzhen pharmaceutical innovative drugs. The last 5 are Shanghai Junshi Biosciences Co.Ltd(688180) – u, Jenkem Technology Co.Ltd(688356) , Staidson(Beijing) Biopharmaceuticals Co.Ltd(300204) , Brightgene Bio-Medical Technology Co.Ltd(688166) , Frontier Biotechnologies Inc(688221) – U. The top 5 gainers and losers in the pharmaceutical innovation sector of Hong Kong stocks this week were Geli pharmaceutical-b, China biopharmaceutical, Lizhu pharmaceutical, stone Pharmaceutical Group, Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co.Ltd(688505) . The last 5 are Shanghai Junshi Biosciences Co.Ltd(688180) , Rongchang biology-b, kangfang biology-b, Xinda biology and jiakesi-b.
III. medium and long term perspective of innovative pharmaceutical industry:
In recent years, with the influx of capital stimulated by policies, China has ushered in a gale of innovation. China’s innovation market has strong policy attributes. On October 8, 2017, the two offices jointly issued the opinions on deepening the reform of review and approval system and encouraging innovation of drugs and medical devices, which opened the first wave of innovation. With the revision of drug registration management measures, drug negotiation and the introduction of medical insurance dynamic adjustment mechanism, the top-level design of the policy has completely solved the problem of insufficient innovation power in history due to limited R & D resources, non-standard Review & slow progress, low bidding efficiency, high difficulty in admission and difficult connection of medical insurance. Under the stimulation of Programmatic Policies, combined with the promotion of the science and innovation board and the registration system in recent years, the capital of innovative medicine racetrack swarmed, and the financing of innovative medicine enterprises accelerated, which also led China’s innovative medicine investment into the gale mouth era. Driven by a good policy environment and capital, China’s innovation rise has accelerated. Domestic innovative drugs have entered the harvest period one after another, and more heavy innovative products will be approved and listed in China in the next few years.
It can not be ignored that the time window for “general innovation” given by the policy is becoming shorter and shorter, the cost control of medical insurance is becoming stricter, and the track is becoming more and more crowded. We have slowly entered the moment of “selected high-quality innovation”. At present, the homogenization of innovative drug research and development in China is more serious, and the homogenization of targeted drugs is the most serious. The era of “blockbuster” when innovative drugs are listed has slowly passed, and the time window period of “general innovation” given by the policy is becoming shorter and shorter. We believe that China’s innovative drug market has slowly entered the moment of “selected high-quality innovation” from “general innovation”. In the future, the homogenization competition of McAb hot targets will continue to be intense, and the homogenized products will gradually lose their competitiveness. New technologies, scarce technology platforms, differentiated treatment fields and innovative drug delivery methods may bring a better competitive pattern to enterprises, and companies with technology precipitation are expected to stand out.
Risk tips: 1) negative policies continue to exceed expectations; 2) The growth rate of the industry was lower than expected.
