atopic dermatitis(AD)Introduction

Atopic dermatitis has a variety of clinical manifestations, ranging from mild symptoms such as pityriasis simplex (dry hypopigmented spots) or hand eczema to severe symptoms such as erythrodermic eczema. Atopic dermatitis can adversely affect the patient's quality of life and can create a lifelong social, academic and occupational burden for patients and their families.

atopic dermatitis(AD)Market

Atopic dermatitis is one of the most common chronic inflammatory pruritic diseases. Worldwide, atopic dermatitis affects up20% of children and adolescents and 1-5% of adults. GlobalThe incidence of atopic dermatitis in patients6.79 has been reached in 2022Hundreds of millions of people, including more than children and adolescents.50%，and estimatedFurther increase to 7.55 by 2030Billions of people. In all patients with atopic dermatitis, approximately25% to 30%Patients with moderate to severe illness. The global market for approved prescription products for atopic dermatitis drugs has grown rapidly in recent years2011of the year$4.4 billion to $12.2 billion in 2022, yearcompound growth rate15.8%。

Atopic Dermatitis Therapeutic Targets

IL-4RαTarget

Atopic Dermatitis TreatmentTh2 plays a key role. IL-4Rα is a common subunit of IL-4 and IL-13 receptors in the type 2 immune response mediated by Th2 cells, and is also one of the most developed targets. 

IL-4 is able to bind to two receptors, activating JAK1 and JAK3 in combination with type I IL-4R, while JAK1 and TYK2 are involved through type II IL-4R. Type I receptors bind only to IL-4, while type II receptors bind to both IL-4 and IL-13. Phosphorylation of the IL-4Rα cytoplasmic domain leads to recruitment and phosphorylation of the signaling and transcription factor Stat6. Therefore,Most of the functions of the IL-4 are performed through Stat6. IL-4Rα is a key component of type I receptor and type II receptor in type 2 inflammation pathway. Blocking IL-4Rα can simultaneously block two powerful regulators of type 2 immune response, IL-4 and IL-13, and block the central pathway of Th2 inflammation through type I receptor and type II receptor.IL-4/IL-13 Pathway and Its Signal Transduction

Jointly developed by Sanofi and Regeneron, Dupiumab is a fully human monoclonal antibody that works by actingIL-4Rα subunit specifically binds to inhibit IL-4 and IL-13 signaling, inSales reach 8.3 billion in 2022S. dollars. No doubt inAfter Humira and K drugs, a strong contender for the next drug king. Domestic aroundIL-4RαTarget-developed monoclonal antibody drugs have also been laid out. At present, there are 7 kinds of domesticIL-4RαThe drug is in clinical and above stages, among which, Conedor'sCBP-201and Connoah'sCM310Because of the progress of research and development, early data amazing, high-profile. However, ConradIIAfter the results were announced, share prices fell. . The reason is that the details are not released well, so that investors think that its efficacy is not as good as that of the former.Me-betteR became.me-worseAs soon as the news came out, the stock fell.57.72%.

JAK/STATpathway target

Soluble mediators of AD pathogenesis act by binding to specific transmembrane receptors and subsequently initiate intracellular signaling through the JAK signal transducer and activator of transcription (STAT) pathway.

Based onJAKFunctional characteristics and specific tissue distribution of each subtype in the kinase family,JAK1Widely found in various tissues and cells in the body, andIL-6,IFNThe activation of inflammatory factors is closely related to the immune, inflammatory and other diseases in the field of new targets;JAK2It has become an exact target for the treatment and prevention of blood system related diseases;JAK3It has become a hot target for the treatment of autoimmune diseases.

Compared to JAKOther family, JAK1The treatment of the target is optimal and the side effects are minimal.2022The size of the global JAK1 inhibitor market in102billion US dollars, which will grow to 30.5 billion US dollars in 2030,The compound annual growth rates for 2022 to 2024 and 2024 to 2030 are 28.4 per cent and 8.0 per cent, respectively.The market size of JAK1 inhibitors in China has grown rapidly since the first product was approved in 2017,2022Year and 2030 25billion yuan and 48.1 billion yuan,2022YearThe compound annual growth rates for 2024 and 2024 to 2030 are 92.2 per cent and 30.0 per cent, respectively.

Globally listedThere are 8 JAK1 inhibitors, among which Gilead's Filgotinib and AbbVie's Upadacitinib are selective JAK1 inhibitors, and other products are non-selective JAK inhibitors that can inhibit JAK1. Novartis's rucotinib is approved for use in tumor-related myelofibrosis and polycythemia vera, and other products are only approved for autoimmune disease-related indications.

A total of 3 JAK1 inhibitors have been approved for listing in China, namely baritinib jointly developed by Lilly and Inset Medical, Novartis's rucotinib and Pfizer's tofacitinib, all of which are non-selective JAK inhibitors that can inhibit JAK1, and domestic JAK1 inhibitors have not yet been approved for listing. However, the research and development of JAK1 inhibitors in China is becoming more and more popular, and the major domestic pharmaceutical companies are trying to occupy this blank market. There are a total of 12 JAK1 inhibitors under study in China, of which 2 have been submitted for listing, and 4 are in clinical phase III or key clinical trials; 3 in clinical phase II; and 3 in clinical phase I. Among them, selective JAK1 inhibitors include Pfizer's Abrocitinib, AbbVie's Upadacitinib, Hengrui Pharmaceutical's SHR0302 and Dizhe Pharmaceutical's DZD4205. For the treatment of atopic dermatitis, Hengrui innovatively launched JAK1External preparations reduce the side effects of oral drugs.

The new Henglida investment research team believes that:Atopic dermatitis as a chronic disease treatment is difficult, long cycle, domestic pharmaceutical companies have in the main target I.L-4α and JAK1Layout. With Sanofi's IL-4RAlpha and Pfizer's JAK1Inhibitors enter health insurance, and competition is getting fiercer. The future believes that if we can do it in a head-to-head experiment.Me-better, or such as Hengrui's improvement of the dosage form on JAK1 inhibitors, as well as the innovative development of new targets for atopic dermatitis and the courage to go overseas to improve the competitiveness of domestic drugs, will undoubtedly become the winner of this track.