In the past 20 years, patients with rheumatoid arthritis (RA), Crohn's disease (CD), and other immune diseases have witnessed the impact of a great treatment advance with the availability of biological TNFα inhibitors. With 5 approved anti-TNFα biologics on the market and soon available biosimilars, patients have more treatment options and have benefited from understanding the biology of TNFα. Nevertheless, many unmet needs remain for people living with TNFα-related diseases, namely some side effects and tolerance of current anti-TNFα biologics and resistance to therapies. Furthermore, common diseases such as osteoarthritis and back/neck pain may respond to anti-TNFα therapies at early onset of symptoms. Development of new TNFα inhibitors focusing on TNFR1 specific inhibitors, preferably small molecules that can be delivered orally, is much needed.

在过去的 20 年中，类风湿性关节炎 (RA)、克罗恩病 (CD) 和其他免疫疾病患者见证了随着生物 TNFα 抑制剂可用性的巨大治疗进步的影响。市场上有 5 种批准的抗 TNFα 生物制剂和即将上市的生物仿制药，患者有更多的治疗选择，并从了解 TNFα 的生物学中受益。然而，对于 TNFα 相关疾病患者，仍有许多未满足的需求，即一些副作用和对当前抗 TNFα 生物制剂的耐受性以及对治疗的抗性。此外，骨关节炎和背部/颈部疼痛等常见疾病可能在症状出现早期就对抗 TNFα 治疗产生反应。开发专注于 TNFR1 特异性抑制剂的新型 TNFα 抑制剂，优选可口服递送的小分子，