Core Insights - The article discusses the challenges faced by patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and seasonal allergic rhinitis (SAR), highlighting the limitations of traditional treatments and the emergence of innovative therapies like Dupilumab [1][2][3] Group 1: Patient Challenges - Many patients with CRSwNP and SAR experience inadequate treatment outcomes, with about 50% of CRSwNP patients facing recurrence of symptoms despite standardized medical and surgical interventions [1] - A significant percentage of patients with moderate to severe SAR do not achieve effective symptom control even when using potent nasal corticosteroids and antihistamines [1][3] Group 2: Innovative Treatment Development - The approval of Supilumab (康悦达) by the National Medical Products Administration (NMPA) for CRSwNP in December 2024 marks a significant advancement in treatment options [2] - Supilumab is the first IL-4Rα biological agent approved for SAR, expanding its therapeutic applications [2][3] Group 3: Clinical Efficacy - In clinical trials, Supilumab demonstrated significant efficacy, with 72% of patients showing notable reduction in nasal polyps within two weeks of treatment, and 81% achieving at least a 50% reduction by 24 weeks [3][4] - For SAR, 52% of patients achieved nasal airflow within four days of treatment, and 84% reported mild or no nasal symptoms after four weeks [4] Group 4: Market Potential - The global market for IL-4Rα-targeted drugs is projected to grow significantly, with estimates reaching $12.2 billion by 2024 and $28.7 billion by 2030, reflecting a compound annual growth rate of 15.2% [5] - The competitive landscape is evolving, with domestic companies like 康诺亚 gaining traction in the IL-4Rα drug market, challenging established players [5][6] Group 5: Future Directions - 康诺亚 is actively exploring additional indications for Supilumab, including adolescent atopic dermatitis and nodular prurigo, aiming to address unmet clinical needs and reduce treatment costs [9][11] - The company is also developing a diverse pipeline of therapies, including second-generation bispecific antibodies and ADCs, to enhance treatment options for various diseases [10][11]

撰文丨王聪 编辑丨王多鱼 排版丨水成文 细胞内稳态的调节是一个精妙平衡的过程。在应对环境和病理生理压力时，哺乳动物细胞会启动适应性且可逆的生存策略，包括广泛的基因转录抑 制；全局性翻译抑制；某些特定且关键基因的表达上调；以及无膜细胞器的形成——例如细胞质中形成的 应激颗粒 和细胞核中形成的 核应激小体 （nSB） 。 标题：细胞自救黑科技：核内"应急指挥中心"如何为致命炎症踩刹车？ 2025 年 5 月 27 日， 中国科学院分子细胞科学卓越创新中心 陈玲玲 团队在国际顶尖学术期刊 Cell 上发表了题为： De novo assembly of nuclear stress bodies rearranges and enhances NFIL3 to restrain acute inflammatory responses 的研究论文 。 该 研究解析了 热休克 等刺激条件下 诱导产生的 无膜亚结构—— 核应激小体 （ nuclear stress body ， nSB ） 的精细层级结构 和 动态 组装过 程，并揭示其 通过 拉近 与基因的三维距离 ， 促进 NFIL3 等 基因的转录。 NFIL3 ...

Core Insights - The research reveals that metabolic factors, particularly gut health, play a significant role in the development of osteoarthritis, challenging the traditional view that it is primarily caused by local mechanical factors [1][2][3] - The study indicates a notable difference in gut microbiota composition and key metabolites between osteoarthritis patients and healthy individuals, suggesting a potential new direction for treatment [3][4] Group 1: Osteoarthritis Overview - Osteoarthritis is characterized by degeneration of joint cartilage and underlying bone, leading to pain, deformity, and functional impairment, significantly affecting patients' quality of life [2] - As of 2021, approximately 606 million people globally suffer from osteoarthritis, with around 152 million cases in China, reflecting a prevalence rate of 10.8% [2] Group 2: Research Findings - The research team conducted a large-scale study involving 4,080 community residents aged 50 and above, revealing a link between bile acid metabolism and osteoarthritis, influenced by gut microbiota [3][4] - A significant reduction in the abundance of specific gut bacteria (Bacteroides) was observed in osteoarthritis patients, correlating with abnormal bile acid metabolism [4][5] Group 3: Treatment Implications - The study suggests that supplementation with bile acids or GLP-1 analogs can significantly alleviate cartilage degeneration in osteoarthritis models, indicating a potential therapeutic pathway [5] - The findings highlight GLP-1 as a crucial mediator between gut health and joint protection, opening avenues for new treatment strategies [5] Group 4: Broader Implications of Gut Microbiota - Gut microbiota dysbiosis is linked to various diseases, including depression, diabetes, obesity, and cardiovascular diseases, emphasizing the importance of gut health in overall well-being [6][7] - The gut microbiome plays a critical role in immune regulation and systemic inflammation, with imbalances potentially leading to increased risks of autoimmune diseases and infections [7]

Core Insights - Inflammatory Bowel Disease (IBD) is on the rise in China, with an incidence rate of approximately 1.96-3.14 per 100,000 people, primarily affecting young adults [1][2] Group 1: Disease Overview - IBD includes Ulcerative Colitis (UC) and Crohn's Disease (CD), characterized by chronic inflammation of the gastrointestinal tract due to an uncontrolled immune response [2] - The peak age for UC in China is between 20-49 years, while for CD it is 18-35 years, with symptoms including persistent diarrhea, abdominal pain, and weight loss [2][3] Group 2: Misconceptions about IBD - Misconception 1: Diarrhea does not require concern; IBD symptoms can be severe and are often misdiagnosed [2][3] - Misconception 2: IBD is not solely caused by diet; it is linked to genetic susceptibility and immune dysregulation, although diet can exacerbate symptoms [3][4] - Misconception 3: IBD patients can marry and have children, but they may face additional challenges during pregnancy [4][5] - Misconception 4: Patients should not stop medication even if symptoms improve, as this can lead to rebound inflammation [4][5] - Misconception 5: Not all IBD patients will develop cancer; regular monitoring and treatment can mitigate risks [6][7] - Misconception 6: Surgery does not cure IBD; it is only for complications and requires ongoing medication [7][8] - Misconception 7: Patients can engage in moderate exercise, which can improve quality of life [8][9] - Misconception 8: IBD treatment is not limited to Western medicine; personalized treatment plans can include various therapies [9][10] - Misconception 9: IBD is not an incurable disease; with proper management, patients can lead normal lives [10] Group 3: Research and Development - There is rapid advancement in IBD research, with multiple innovative drugs entering clinical trials in China, indicating potential breakthroughs in treatment over the next decade [10]

5月19日是世界炎症性肠病日，这个好发于年轻人，却常被误认为"普通肠胃炎"的疾病背后，是数百万 中国患者与慢性肠道炎症的长期斗争。近年来，炎症性肠病（IBD）发病率在中国呈迅速上升趋势，目 前中国大陆地区发病率为1.96/10万-3.14/10万。北京大学人民医院消化内科主任、主任医师陈宁，从病 因、症状到治疗，带你科学认识这一"隐形流行病"，走出炎症性肠病的误区。 误区一：IBD只是拉肚子 炎症性肠病（简称IBD），包括溃疡性结肠炎（简称UC）和克罗恩病（简称CD），是一类常发生于青 壮年，主要损害胃肠道的慢性炎症。其核心是肠道免疫系统"失控"，导致黏膜反复溃疡、出血甚至穿 孔。 溃疡性结肠炎的炎症通常局限于黏膜表面，我国发病高峰年龄为20-49岁，男女性别差异不明显。常见 症状包括持续或反复发作的腹泻、大便混合黏液及血，伴随有腹痛、不停想要排便的感觉，此外还可能 出现发烧、全身乏力和体重下降等。 IBD需长期"维持治疗"，擅自停药可能导致病情反复。比如，使用生物制剂可快速控制炎症，突然停药 可能引发"反跳性炎症"，即导致肠道炎症反应在短期内急剧反弹，症状甚至比治疗前更严重的现象。研 究显示，规律用药可使溃 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 肌萎缩侧索硬化症 （ALS，也叫做 渐冻症 ） 是一种罕见的自主运动系统疾病，与大脑和脊髓中的运动神 经元丧失有关，会导致不可逆转的残疾和死亡，患者从出现症状到死亡，中位生存期仅为 2-3 年。 FDA批准的渐冻症治疗药物 利鲁唑 （ Riluzole ） 通常只能 延长几个月的生存期，，因此，目前仍迫切需 要更有效的渐冻症治疗方法。然而，由于对渐冻症相关靶点认识不足，以及渐冻症在临床和病理上的异质 性，更有效的渐冻症治疗方法的确定一直受到阻碍。 神经炎症被证明参与了广泛渐冻症表型，因此提供了一个有前景的治疗靶点，改变渐冻症发病机制中的炎 症成分，可以提高生存率并减缓功能恶化。 CD4 + FOXP3 + 调节性 T 细胞 （Treg） 是一种具有广泛免疫 调节功能的 T 细胞亚群，其数量和功能的损伤与渐冻症的严重程度、进展和生存率有关。Treg 的生成、激 活和存活都需要细胞因子白细胞介素-2 （IL-2） ，这为增强免疫耐受和抑制神经炎症提供了一条可行且可 测量的治疗途径。 近日，国际顶尖医学期刊《 柳叶刀 》 （The Lancet） 发表了一篇题为： Effic ...

Group 1 - Chronic inflammation is identified as a significant factor accelerating aging, linked to the dysfunction of calcium signaling in macrophage mitochondria [1][2][4] - The process is described as "mitochondrial calcium signaling dysfunction → chronic immune activation → inflammatory aging" [3] - Chronic inflammation negatively impacts various body systems, including the brain, muscles, and metabolic health, increasing risks for diseases like Alzheimer's and type 2 diabetes [5][6] Group 2 - Lifestyle adjustments can effectively regulate inflammation levels and promote healthier aging [6] - A multi-dimensional strategy is recommended, including dietary changes, regular exercise, adequate sleep, stress management, and maintaining a healthy weight [7][32] Group 3 - Anti-inflammatory foods include colorful fruits and vegetables, omega-3 fatty acids, whole grains, and spices like turmeric [9][10][11][12] - It is advised to avoid pro-inflammatory foods such as sugar, unhealthy fats, and processed meats [14][15][16] Group 4 - Regular exercise is emphasized as a powerful tool against inflammation, with both aerobic and strength training recommended [20][23] - Sleep quality is crucial, with a target of 7-9 hours per night to reduce inflammation markers [27][28] Group 5 - Chronic psychological stress is linked to increased inflammation, and stress management techniques like mindfulness and yoga are suggested [29][31] - Environmental factors, such as pollution and chemical exposure, should be minimized to reduce inflammation [34]

Financial Data and Key Metrics Changes - The net loss attributable to common stockholders for Q1 2025 was approximately $9.7 million, compared to approximately $11 million for the same period in 2024, indicating an improvement [26] - Research and development expenses totaled approximately $7.6 million for Q1 2025, down from approximately $8.7 million in Q1 2024 [26] - General and administrative expenses remained stable at approximately $2.3 million for both Q1 2025 and Q1 2024 [26] - As of March 31, 2025, the company had cash and cash equivalents of approximately $19.3 million, which is expected to fund operations through Q3 2025 [27] Business Line Data and Key Metrics Changes - The company is preparing to report top-line results from the MINDFUL phase two trial in early Alzheimer's disease, expected in mid to late June 2025 [6][27] - The market opportunity for EXPAREL in early Alzheimer's disease has increased to nearly 70% of early AD patients, up from the previously estimated 40% [7][8] - The safety profile of EXPAREL remains excellent, with no reports of adverse events in the ongoing trial [9] Market Data and Key Metrics Changes - The approval of mecanumab in the EU and UK excludes patients with two copies of the APOE4 gene, creating an unmet need for EXPAREL therapy in this subgroup [10][11] - The evolving biomarker landscape in Alzheimer's disease, particularly the significance of p-tau217, is expected to enhance the company's market position [12] Company Strategy and Development Direction - The company is focused on targeting neuroinflammation in Alzheimer's disease, positioning itself as a leader in this area [81][82] - Plans for the Kordstrom program include filing a Biologics License Application (BLA) in 2026 for the treatment of recessive dystrophic epidermolysis bullosa (RDEB) [17][24] - The company aims to transition manufacturing processes to optimize production for both Kordstrom and Inkmune, ensuring cost-effectiveness and regulatory compliance [24] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming MINDFUL trial results, believing they will significantly impact the treatment landscape for early Alzheimer's disease [16][81] - The company is optimistic about the regulatory environment for rare disease treatments, particularly following recent FDA comments [18][24] Other Important Information - The company has successfully transitioned its drug supply logistics for Inkmune to a US-based contractor, Cryoport, to ensure trial completion [21] - The company is also preparing for an IND submission for Kordstrom in the US, with manufacturing of a new batch of products using US-approved cord donors starting soon [73] Q&A Session Summary Question: Can you walk us through the next steps for the program assuming a positive readout in June? - Management indicated that they would defer specific timelines until after the FDA meeting, aiming to move quickly to open sites and enroll patients [32][33] Question: Can you comment on the FDA review team for your program? - Management believes that the FDA has remained on track and that the review team is stable, although they cannot predict future outcomes [36] Question: How do you think investors will react if EMAC hits but CDR is equivocal? - Management emphasized that EMAC is the primary driver for cognitive changes, and they expect correlations with CDR, which is a more blunt instrument [46][49] Question: Are APOE4 patients inherently inflammatory? - Management confirmed that APOE4 carriers tend to have earlier onset and faster progression of Alzheimer's disease, indicating a link to inflammation [62] Question: Are you still on track to initiate the twelve-month open-label trial for Cordstrom mid this year? - Management confirmed they are following FDA guidance and expect to submit an IND late this year, with plans for a follow-on trial in the US [73][74]

Financial Data and Key Metrics Changes - The net loss attributable to common stockholders for Q1 2025 was approximately $9.7 million, compared to approximately $11 million for the same period in 2024, indicating an improvement [27] - Research and development expenses totaled approximately $7.6 million for Q1 2025, down from approximately $8.7 million in Q1 2024 [27] - General and administrative expenses remained stable at approximately $2.3 million for both Q1 2025 and Q1 2024 [27] - As of March 31, 2025, the company had cash and cash equivalents of approximately $19.3 million, sufficient to fund operations through Q3 2025 [28] Business Line Data and Key Metrics Changes - The company is preparing to report top-line results from the MINDFUL trial, a Phase 2 trial in early Alzheimer's disease, expected in mid to late June 2025 [5][16] - The market opportunity for EXPAREL in early Alzheimer's disease patients has increased to nearly 70%, up from the previously estimated 40% [6][8] - The safety profile of EXPAREL remains strong, with no reports of adverse events in the MINDFUL trial [9] Market Data and Key Metrics Changes - The approval of mecanumab in the EU and UK excludes patients with two copies of the APOE4 gene, creating an unmet need for EXPAREL therapy in this subgroup [10][11] - The evolving biomarker landscape in Alzheimer's disease, particularly the significance of p-tau217, is expected to enhance the company's market position [12] Company Strategy and Development Direction - The company aims to position itself as a leader in targeting immune dysfunction that drives neuroinflammation in Alzheimer's disease [81][82] - Plans to file a Biologics License Application (BLA) for Cordstrom in 2026, with ongoing development for Inkmune in prostate cancer [17][29] - The company is focused on transitioning manufacturing processes to meet regulatory requirements and maximize production efficiency [25] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in reporting results that could change the care of patients with early Alzheimer's disease, highlighting substantial share ownership by management as alignment with investor interests [16][80] - The company anticipates an end-of-Phase 2 meeting with the FDA in Q4 2026 to discuss the design of a Phase 3 trial [29] Other Important Information - The company has successfully transitioned its drug supply logistics for Inkmune to a US contractor, ensuring readiness for trial completion [21] - The FDA has indicated a willingness to expedite the approval process for rare disease treatments, which bodes well for Cordstrom [18] Q&A Session Summary Question: What are the next steps for the program assuming a positive readout in June? - Management indicated that they would defer specific timelines until after the results and discussions with the FDA [35] Question: Can you comment on the turnover at the FDA and the receptivity at the ADPD conference? - Management believes the FDA remains on track and noted positive feedback from the ADPD conference regarding their approach to measuring cognition [39][44] Question: How many APOE homozygous patients are in the trial? - The trial includes approximately 9% of APOE homozygous patients, which is consistent with other studies [53] Question: What is the expected reduction in CDR for the trial? - Management expressed confidence in their power calculations based on previous studies, suggesting they are well-positioned to achieve statistically significant results [62] Question: Are you still on track to initiate the open-label trial for Cordstrom? - The company is following FDA guidance and expects to submit an IND later this year, with plans for a follow-on trial in the US [73]

Group 1 - The core viewpoint of the articles emphasizes the chronic nature of asthma as an airway inflammatory disease that requires ongoing management and treatment to prevent acute attacks and long-term complications [2][4][6] - The importance of adhering to prescribed inhalation therapies, particularly the combination of inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA), is highlighted as essential for controlling inflammation and alleviating symptoms [3][4] - A significant portion of asthma patients in China, approximately 55%-70%, are not effectively managing their condition, indicating a substantial unmet medical need [3] Group 2 - Severe asthma patients, constituting about 5% of the asthma population in China, face higher risks of complications and economic burdens due to frequent acute episodes and hospitalizations [5] - Innovative therapies, particularly biologics, are emerging as effective treatments for severe asthma, targeting specific inflammatory pathways and reducing reliance on corticosteroids [5][6] - The recent update to the bronchial asthma prevention and treatment guidelines introduces the concept of "clinical cure," offering hope for better management and quality of life for severe asthma patients [6]