Live Review： What is the next magic medicine in the field of inflammation？

foreword

Inflammatory diseases, as the second largest therapeutic field after cancer, have attracted much attention in drug research and development.

On May 26th, Academician of Chinese Academy of Sciences, President of Shanghai Institute of Immunotherapy Innovation and Chairman of BiG-Chen Dong,Researcher, Tsinghua Peking University Life Center/Director of Department of Internal Medicine and Rheumatology, Changzheng Hospital, Naval Medical University-Xu Huji,Co-founder and Senior Vice President of Connaught-Wang Changyu,Senior Investment Manager of Sinopharm Zhongjin-He yanran, visiting the BiG round table,From the perspective of scientists, entrepreneurs, clinicians and capital, this paper discusses the next magic medicine on the inflammatory drug track.!

　Part 1‍

Clinical drive

How to treat the next magic medicine in the field of inflammation?

▌ Q1.How to treat the next magic medicine in the field of inflammation?

Wang Changyu:According to different pathogenesis and pathogenesis.There will be different magic drugs in different fields.CM310, the target drug of IL-4α in Th2 promoted by Connaught, may rival TNFα in Th1 in the future.

　

Fig. 1 PD-1 antibody drugs and CTLA-4 antibody drugs (source: kangantu)

Xu Huji:Judging from the treatment law of rheumatic immune diseases, because the process of drug research and development is very tortuous, it is not easy to predict the future magical drugs, butBased on the pathogenic mechanism of rheumatic diseases, small molecular compounds may be the next magic medicine.!

Fig. 2 Information comparison of disease-relieving anti-rheumatic biological agents (bDMARD) and targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARD) approved by China and the United States.

(Source: antpedia)

He Yan ran:Autoimmune diseases are caused by many factors,How to effectively identify the intervention pathway that plays a role in disease treatment in human body needs more efforts on the scientific level.!

▌Q2.What are the unmet clinical needs of inflammatory diseases?

Xu Huji:At present, the first clinical problem isDiagnosis of inflammatory diseases. At present, early diagnosis is a part promoted by the medical field to help early treatment and drug research and development.The second problem is that none of the current drugs can100%treat a patientDifferences in disease heterogeneity lead to differences in drug research and development. The third question isMany diseases have no good diagnosis and treatment standards., making many clinical trials unable to advance smoothly.Understanding the pathogenesis of diseases promotes drug research and development.Need in the future.Drug research and development based on the pathogenic mechanism of diseases. In addition, the currentClinical drugs also have some side effects to be solved..

Fig. 3 Professor Xu Huji’s team uses genetic data to construct a method model for early diagnosis of ankylosing spondylitis [1]

▌ Q3.What new discoveries in immunology in recent years are worth transforming?

Wang Changyu:With the rapid development of immunology,New mechanism, new means and new use of old drugs are all aspects worthy of technological transformation.. Including cell death, innate immunity and new cell types, may develop effective drugs. New means such as CAR-T also provide tools for drug research and development. New use of old drugs: Many targets that play a role in tumor treatment can also be applied to the treatment of inflammatory diseases, such as CTLA-4, PD-1/PD-L1, BTK, etc.

　

Fig. 4 CAR-Tregs cell therapy targets different types of antigens [2]

He Yan ran:Autoimmune patients will be accompanied by some changes caused by long-term chronic inflammatory reaction in the late stage. Is there any better drug intervention?It is also a lot of good treatment ideas.

Chen Dong:At present, the idea of vaccine research and development in COVID-19 is relatively old, and new knowledge such as immune regulation has not been applied to vaccine research and development, which is an attempt worthy of attention and transformation.

▌ Q4.What are the research and development hotspots of innovative pharmaceutical companies?

He Yan ran:From the perspective of capital market, the company needs to consider the pipeline with expected commercialization ability. At present, most of the pipelines of pharmaceutical companies in China are familiar and not very "trendy" targets. This is a step to prove the clinical value of the target.On the one hand, China pharmaceutical companies grasp the vast domestic market and fight with affordable drugs, on the other hand, they prove their R&D strength in the international market, even if they make positive and effective signals in rare diseases, it is also a good proof effect..

Wang Changyu:China enterprises also need to do it.cost control, can control the cost to a minimum, so as to launch effective, valuable and affordable drugs without losing quality.

Figure 5 Caijing cover: Innovative drugs break through (Source: sina)

　 ▌ 　Q5.How to find the best indications for new immunotherapy drugs 　 　

Xu Huji:Clinically, according to the doctor’s experience or the new use of old drugs, the best indications may be found, but at present, most drug research and development areThe selection of indications based on the mechanism of the disease needs the evidence of animal models and clinical trials to verify..

Wang Changyu:Clinical basis and animal model can help new immunotherapy drugs find the best indications.. In addition, it is a problem to be solved that how drugs related to basic research can play a therapeutic role and reduce side effects at the same time.

He Yan ran:Drugs with the same mechanism can be developed in different dosage forms.. in additionWhen choosing indications, it is also necessary to make clear which diseases are competitive in the market..

　Part 2　

Q1. Evaluate yourselfIs there any chance for the accompanying diagnosis mechanism of the therapeutic effect of immune diseases or the therapeutic effect of magical drugs?

Xu Huji: Opportunities must exist, ifWithout the standard of clinical diagnosis, it is difficult to push clinical drug research and development to a new height.At present, the diagnosis of rheumatoid arthritis is better, so the drug evaluation in clinical trials is also better, but for many other diseases with almost no evaluation standards, there is much room for improvement in evaluation. Q2. Will innate immunity become the target of future magic medicine? What are the possible innate immune targets?

Xu Huji:Inherent immunity will definitely become the target in the future.. In recent years, progress has been made in innate immunity, and Academician Shao Feng is at the forefront in this respect, includingInflammatory corpuscles and nucleic acid sensing targetsMany studies, including, have begun targeted therapy research.

Q3. How to evaluate TSLP target? Will it become the next magic medicine for asthma?

Wang Changyu:IScientists are developing the second TSLP antibody drug CM326 in the world.40%Asthma patients are not caused by normal eosinophilia.There are no good drugs at present,TSLPAntibody drugCan play a role in this part of patients, there areIt may be the next magic medicine for asthma.And it’sIndications may not be limited to asthma..

Fig. 6 Mechanism of TSLP targeting monoclonal antibody tezepelumab [3]

Q4. Why is the drug sales in the domestic autoimmune disease market far inferior to those in overseas markets?

Xu Huji:At present, the number of patients with autoimmune diseases in China far exceeds that of doctors and researchers.In the future, on the one hand, it is necessary to expand the influence and number of rheumatologists, on the other hand, it is necessary to increase the education of grassroots doctors so that biological agents can bring more benefits to patients..

He Yan ran:Make some supplements,The doctor’s recommendation ability and the patient’s willingness to pay lead to the difficulty of accessibility..

Q5. With the maturity of pharmaceutical properties of siRNA, what impact will it have on antibody drugs?

Wang Changyu:In the short term, siRNA drugs need to solve the problems of drug stability and pharmacokinetics in the short term, soIt may not affect antibody drugs in the short term, but in the long run,After these problems are solved to some extent,May threaten the market of antibody drugs..

Q6. What do you think of the possibility that benvimod, an AHR agonist, will replace calcipotriol as the first-line drug for psoriasis?

He Yan ran:Benvimod’s drugThe advantage is that the mode of administration is external application.Some patients feel that the main problem is skin lesions and prefer local administration, and itIt is a unique drug from phenotype to mechanism, from China to the world.. At present, it is proved thatThe curative effect of this drug is close to that of carbotriol.,It has certain value as a skin drug..

　

Fig. 7 benvimod cream (source: miaoshou)

Q7.How to treatRORγtThe medicinal properties of?

Chen Dong:RORγt is a good target, and its sequence is similar to RORα and RORβ. Can it be developed?Highly specific targetingRORγtDrugs, which will be helpful to its security and effectiveness. in additionSmall molecule drug research and developmentIn the aspects of pharmacokinetics and pharmacodynamicsChallenging.RORγtThe medicinal properties of the drug need to be further seen..

Q8.Domestic ADC focuses on the application of tumor, and comments on its future in autoimmune diseases.

Wang Changyu:At present, ADC is basically a chemotherapy drug, and patients with autoimmune diseases may not tolerate large side effects, which may limit the role of ADC in autoimmune diseases.Its application scope may be to choose again when other drugs are not well treated.ADCTreatment, or life-threatening disease choice.ADCtreat.

Q9. Early prevention and intervention of autoimmune diseases is a good concept, but how to design such drugs in clinic?

Xu Huji:At present, it is generally believed that early intervention will prevent the onset, but whether intervention will involve ethical society and other factors..

Chen Dong:Make a supplement,It may be beneficial to find out the specific indexes of patients who can be cured after intervention, and on this basis, it may be beneficial to carry out early intervention on patients who can prevent the onset..

Q10. What is the most anticipated direction of drugs and drug research and development in the field of inflammation?

Wang Changyu:The future blockbuster drugs may be drugs with multiple indications.. Besides,The new mechanism may also become a better direction of drug research and development.

Xu Huji:Intervening in the pathogenesis of in-situ pathological tissue will have better fundamental treatment results..

He Yan ran:There are three directions to look forward to seeing progress. One isHow to develop better targeted therapy for diseases with high heterogeneity without standard treatment?. The second isMany patients with autoimmune diseases and tumors have great clinical needs for accompanying physiological processes.. The third isHow to better treat it from the pathogenesis.

Chen Dong:At present, the medication is basically lifelong medication, and some treatment methods like desensitization of allergic diseases are expected to appear.Patients with autoimmune diseases rebuild antigen-specific balance and restore tolerance, so that the body function can be restored to a steady state..