In the field of self-immunity, there is hope for the continued development of multiple FIC therapies. These targets may give birth to the next "drug king."

Over the past 30 years, targeting signaling pathways that regulate immune responses has become a very popular method for treating autoimmune diseases. According to the statistics of the pharmaceutical cube, in the TOP100 global drug sales in 2024, tumors and autoimmune diseases still dominate the market, with a total revenue of up to $99.885 billion in the autoimmune field alone. Dupixent surpassed Humira for the first time with sales of $14.179 billion, completing the transfer of the crown in the autoimmune drug market. Recently, an article titled "Trends in the drug target landscape for autoimmune diseases" was published in Nature Reviews Drug Discovery, analyzing the development trends of drug targets for autoimmune diseases from 2020 to 2024, focusing on the TOP15 targets of products in Phase II, Phase III clinical trials, and on the market in 2024, compared to 2020. The next drug king may emerge from these targets. Validating the heat and pipeline layout of Nature targets The paper statistically analyzed 92 autoimmune-related targets or target combinations under research in the past five years, finding that the number of autoimmune drugs under development increased by 47% from 131 in 2020 to 193 in 2024, showing a significant increase. Among these targets, the IL-1 receptor-associated kinase IRAK4 has received much attention from researchers. Because it has the potential to inhibit the entire IL-1 family (IL-1, IL-18, IL-33, and IL-36) and toll-like receptors with a single drug. According to the NextPharma database, there are currently a total of 62 drugs worldwide in active development towards this target, with a hot development status. Among them, there are 21 players in the IRAK4 inhibitor pathway and 20 players in the IRAK4 Protac pathway, with a growing number of players targeting multiple targets, such as the IRAK4/IRAK1 dual-target inhibitors, which currently have 6 players. In addition, using NextPharma's track ranking function, it can be clearly seen that the development stages and rankings of various pipelines in the track. Currently, Gilead's edecesertib is temporarily leading the IRAK4 inhibitor pathway, ranking first, while China's only Langcome Technology's MY004567 is catching up with MNC's pace, ranking fourth. However, in the Chinese research and development track rankings, Langcome Technology is leading the way, ahead of other companies. In addition, the pipelines of other domestic companies are still in the early preclinical stages. Reducing the risk of developing "first-in-class targets" By combining the academic forward-looking analysis of Nature with the relatively certain layout of the TOP20 MNC tracks, pharmaceutical companies can reduce the risk of developing "first-in-class targets" by focusing on areas where "MNCs have already placed their bets and domestic companies have not yet entered." The paper mentions opportunities for the development of IL-targeted FIC drugs including targets such as IL-4, IL-33, and IL-18. By using opportunity insight modules, enterprise researchers can quickly verify the competitive situation of these targets. For example, for the IL-18 target, there are already 4 companies in the TOP20 MNCs laying out for IL-18 monoclonal antibodies, recombinant IL-18, dual antibodies and other pathways, with the fastest progress being Novartis' IL-18/IL1 dual antibody MAS825, which has already entered Phase III clinical trials. There is only one domestic company, Xuzhou Medical University, developing the IL-18 oncolytic virus therapy ZD55-IL-18 for this target, which is still in the preclinical research stage. China has missed the first-mover advantage in the IL-18 target FIC opportunity, but there is still little competition intensity and room for layout. In addition, there are similar layout opportunities for the IL-33 target. Currently, Sanofi, Roche, AstraZeneca, and Pfizer, among the TOP20 MNCs, have already made layouts, but even in the most competitive IL-33 monoclonal antibody pathway, only two domestic companies, Quanxin Biotechnology and Sunshine Guojian Pharmaceutical, have made layouts, and their pipelines are still in the application for clinical trials. Other companies still have room to enter. In the coming years, there is expected to be a number of FIC therapies emerging in the autoimmune field. In dermatology, Amgen's rocatinlimab (OX40 monoclonal antibody) and Sanofi's amlitelimab (OX40L monoclonal antibody) are new drugs targeting the OX40/OX40L T cell activation axis, which are expected to address key upstream regulatory factors produced by IL-4 and IL-13. Patients with COPD are also expected to benefit from a new class of treatment drugs: IL-33 monoclonal antibodies itepekimab and tozorakimab are both in Phase III clinical trials. In addition, targeting the CD40/CD40L axis may bring new treatment options for systemic diseases, including dazodalibep (CD40L antagonist) for treating Sjgren's syndrome and dapirolizumab (CD40L monoclonal antibody) for treating systemic lupus erythematosus. This article is shared from the "Pharmaceutical Cube" WeChat public account, GMTEight Editor: Song Zhiying.