Soquelitinib

Announced data from cohort 4 of soquelitinib atopic dermatitis Phase 1 trial demonstrating positive safety and efficacy results, including in patients who have received prior systemic therapy Initiated soquelitinib atopic dermatitis Phase 2 trial Completed public offering raising net proceeds of $189 million, extending cash runway into the second quarter of 2028 Conference call and webcast today at 4:30 p.m. ET / 1:30 p.m. PT SOUTH SAN FRANCISCO, Calif., March 12, 2026 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, today provided a business update and reported financial results for the fourth quarter and year ended December 31, 2025. “We believe the recent cohort 4 data from our Phase 1 atopic dermatitis trial demonstrate that soquelitinib has the potential to be an important new medicine for a broad range of patients with atopic dermatitis and other immune diseases,” said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. “The data also highlight the unique mechanism of action with ITK inhibition, regulating multiple T cell functional pathways that leads to an immune system resetting that may be effective in treating many diseases. Our near-term focus is the ongoing enrollment of our registration Phase 3 peripheral T cell lymphoma (PTCL) trial, getting off to a strong start with our recently initiated Phase 2 atopic dermatitis trial, and reporting additional data from the Phase 1 trial at the Society of Investigative Dermatology (SID) meeting. We are also advancing our plans to initiate two additional Phase 2 trials in asthma and hidradenitis suppurativa later this year. Our recent financing will enable us to advance all of these programs through key data readouts, providing significant opportunity to further demonstrate the value of soquelitinib’s pipeline-in-a-product potential.” Business Update and Strategy Soquelitinib (Corvus’ selective ITK inhibitor) for Immune Diseases On January 20, 2026, Corvus reported data from cohort 4 of the randomized, blinded, placebo-controlled Phase 1 trial evaluating soquelitinib in patients with moderate-to-severe atopic dermatitis (data as of January 15, 2026). Cohort 4 data demonstrated positive safety and efficacy results, including additional clinical benefit observed following longer 8-week treatment. Efficacy highlights: 75% of soquelitinib patients in cohort 4 achieved EASI 75, 25% achieved EASI 90 and 33% achieved IGA 0/1. This compares to 20%, 0% and 0%, respectively, for the placebo group. Across cohorts 1-4 of the Phase 1 trial, positive efficacy results were achieved in patients who have received prior systemic therapy, including patients who are treatment resistant to approved therapies such as dupilumab and JAK inhibitors. New long-term data for cohort 3 show maintenance or improvement in EASI out to three months beyond the treatment period associated with an increase of circulating Treg cells. Safety highlights: No new safety signals were observed. No severe or serious adverse events were reported. No significant lab abnormalities were seen. Soquelitinib has now been administered to over 150 patients with T cell lymphoma, autoimmune lymphoproliferative syndrome and atopic dermatitis involving over 14,000 patient treatment days. No patient has required dose modification or treatment related drug discontinuation in any of these clinical trials. Corvus initiated its Phase 2 randomized placebo-controlled atopic dermatitis clinical trial during Q1 2026. The trial is anticipated to enroll approximately 200 patients with moderate-to-severe atopic dermatitis that have failed at least one prior topical or systemic therapy. This includes four cohorts of 50 patients each, with soquelitinib doses of 200 mg once per day, 200 mg twice per day and 400 mg once per day, along with a placebo group. The treatment period is 12 weeks with a 90-day follow-up period with no treatment. Angel Pharmaceuticals, Corvus’ partner in China, is enrolling a Phase 1b/2 clinical trial evaluating soquelitinib in patients with moderate-to-severe atopic dermatitis. This is a blinded, placebo-controlled trial that is planned to evaluate a 12-week treatment regimen in 48 patients utilizing soquelitinib doses of 100 mg twice per day, 200 mg once per day, 200 mg twice per day and 400 mg once per day. The patient eligibility and endpoints are similar to those used previously by Corvus. Depending on the results from the Phase 1b portion of the study, an additional 60-90 patients will be enrolled in the Phase 2 portion of the study. The trial is open at several leading dermatology centers in China who have been involved in global registration trials. The study is conducted in close collaboration with Corvus. Results from the initial cohorts are anticipated late this year. Corvus also continues to advance its next-generation ITK inhibitor preclinical product candidates, which are designed to deliver precise T-cell modulation that is designed for specific immunology and oncology indications. Collaboration with National Institute of Allergy and Infectious Diseases (NIAID) Patient enrollment continues in the Autoimmune Lymphoproliferative Syndrome (ALPS) Phase 2 clinical trial, which is being conducted under a clinical research and development agreement with NIAID. The Phase 2 clinical trial ( NCT06730126 ) is anticipated to enroll up to 30 patients aged 16 or older with confirmed ALPS based on genetic testing. Soquelitinib for T Cell Lymphoma Corvus continues to enroll patients in a registrational Phase 3 clinical trial of soquelitinib in patients with relapsed/refractory PTCL at multiple clinical sites. This randomized controlled trial is anticipated to enroll a total of 150 patients with relapsed/refractory PTCL and is evaluating soquelitinib versus physicians’ choice of either belinostat or pralatrexate chemotherapies. The primary endpoint of the trial is progression free survival. There are no FDA fully approved agents for the treatment of relapsed/refractory PTCL, and the FDA has granted soquelitinib Orphan Drug Designation for the treatment of T cell lymphoma and Fast Track designation for treatment of adult patients with relapsed or refractory PTCL after at least two lines of systemic therapy. In December, Corvus presented the final data from the Company’s Phase 1/1b clinical trial evaluating soquelitinib in patients with T cell lymphoma in an oral presentation at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition. The data showed that patients in the 200 mg BID cohort had median progression free survival of 6.2 months and median overall survival of 28.1 months, comparing favorably to results with other therapies. The data support Corvus’ ongoing registration Phase 3 trial in relapsed/refractory PTCL and soquelitinib’s potential in immune and inflammatory diseases, including atopic dermatitis. Soquelitinib has been well tolerated with no patient requiring dose modification or discontinuation of the drug. Some of these patients have been on therapy for over 2 years. Over 30 lymphoma patients had Epstein Barr Virus (EBV) detected in blood at baseline prior to soquelitinib administration. No patient, including those with EBV at baseline, experienced viral reactivation or associated illness. Financial Results As of December 31, 2025, Corvus had cash, cash equivalents and marketable securities of $56.8 million as compared to $52.0 million as of December 31, 2024. Cash, cash equivalents and marketable securities as of December 31, 2025 does not include approximately $189.4 million in net proceeds received in a financing completed on January 23, 2026. Based on its current plans, Corvus expects its cash to fund operations into the second quarter of 2028. Research and development expenses for the three months and year ended December 31, 2025 totaled $9.9 million and $33.7 million, respectively, compared to $6.0 million and $19.4 million for the same periods in 2024. The increase in research and development expenses of $3.9 million and $14.3 million for the three months and year ended December 31, 2025, respectively, was primarily due to higher clinical trial and manufacturing costs associated with the development of soquelitinib as well as an increase in personnel related costs. Net loss for the three months ended December 31, 2025 was $12.3 million compared to a net loss of $12.1 million for the same period in 2024. Included in net loss for the three months ended December 31, 2025 and 2024 were non-cash losses of $0.7 million and $2.2 million, respectively, from Corvus’ equity method investment in Angel Pharmaceuticals and a non-cash loss of $2.3 million in the three months ended December 31, 2024 associated with a change in fair value of the Company’s warrant liability. Total stock compensation expense for the three months ended December 31, 2025 was $1.6 million compared to $0.8 million for the same period in 2024. Conference Call Details Corvus will host a conference call and webcast today, Thursday, March 12, 2026, at 4:30 p.m. ET (1:30 p.m. PT), during which time management will provide a business update and discuss the fourth quarter and full year 2025 financial results. The conference call can be accessed by dialing 1-800-717-1738 (toll-free domestic) or 1-646-307-1865 (international) or by clicking on this link for instant telephone access to the event. The live webcast may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days. About Corvus Pharmaceuticals Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company pioneering the development of ITK inhibition as a new approach to immunotherapy for a broad range of immune diseases and cancer. The Company’s lead product candidate is soquelitinib, an investigational, oral, small molecule drug that selectively inhibits ITK. Soquelitinib is being evaluated in a registration Phase 3 clinical trial for relapsed/refractory PTCL and in a Phase 2 clinical trial for the treatment of atopic dermatitis. Its other clinical-stage candidates are being developed for a variety of cancer indications. For more information, visit or follow the Company on LinkedIn . About Soquelitinib Soquelitinib (formerly CPI-818) is an investigational small molecule drug given orally designed to selectively inhibit ITK (interleukin-2-inducible T cell kinase), an enzyme that is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell immune function. Soquelitinib has been shown to affect T cell differentiation and induce the generation of Th1 helper cells while blocking the development of both Th2 and Th17 cells and production of their secreted cytokines. Th1 T cells are required for immunity to tumors, viral infections and other infectious diseases. Th2 and Th17 helper T cells are involved in the pathogenesis of many autoimmune and allergic diseases. The Company believes the inhibition of specific molecular targets in T cells may be of therapeutic benefit for patients with cancers, including solid tumors, and in patients with autoimmune and allergic diseases. Recent third-party studies have demonstrated that ITK controls a switch between the differentiation of Th17 proinflammatory cells and T regulatory suppressor cells. Inhibition of ITK leads to a shift toward T regulatory cell differentiation, which has the potential to suppress autoimmune and inflammatory reactions. Based on interim results from a Phase 1/1b clinical trial in patients with refractory T cell lymphomas, which demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies, the Company has initiated a registration Phase 3 clinical trial ( NCT06561048 ) of soquelitinib in patients with relapsed/refractory PTCL. Soquelitinib is also now being investigated in a randomized placebo-controlled Phase 2 clinical trial in patients with atopic dermatitis. A publication describing the chemistry, enzymology and biology of soquelitinib appeared in npj Drug Discovery in December 2024 and is available online at the Nature website and on the Publications and Presentations page of the Corvus website. About Peripheral T Cell Lymphoma Peripheral T cell lymphoma is a heterogeneous group of malignancies accounting for about 10% of non-Hodgkin’s lymphomas (NHL) in Western populations, reaching 20% to 25% of NHL in some parts of Asia and South America. The most common subtypes are PTCL-not otherwise specified (PTCL-NOS) and T follicular helper cell lymphoma. First line treatment for these diseases is typically combination chemotherapy; however, approximately 75% of patients either do not respond or relapse within the first two years. Patients in relapse are treated with various chemotherapy agents but have poor overall outcomes with median progression-free survival in the three to four month range and overall median survival of six to 12 months. There are no approved drugs in relapsed/refractory PTCL based on randomized trials. PTCL is a disease of mature helper T cells that express ITK, often containing numerous genetic mutations and frequently associated with viral infection. Most often the malignant cells of PTCL express a Th2 phenotype. About Atopic Dermatitis Atopic dermatitis, also called eczema, is a chronic disease that can cause inflammation, redness, scaly patches, blisters and irritation of the skin. It affects up to 20% of children and up to 10% of adults, and treatments include topical therapies, oral therapies and systemic injectable biologic therapies. It is frequently associated with other allergic disorders such as food allergies and asthma. Atopic dermatitis, like asthma and allergy, involves the participation of Th2 lymphocytes which secrete cytokines that result in inflammation. Soquelitinib has been shown in preclinical studies to inhibit cytokine production from Th2 lymphocytes. About Autoimmune Lymphoproliferative Syndrome (ALPS) ALPS is a rare genetic disease affecting children that manifests with lymphadenopathy, splenomegaly, cytopenias (low blood counts), proteinuria and autoimmunity. The disease is caused by a mutation in the Fas gene, which provides instructions for making a signaling protein involved in the induction of apoptosis. The mutation results in immune dysregulation due to abnormally high levels of “double negative” T cells (CD4 and CD8 double negative), which infiltrate the blood, spleen and lymphoid tissues. Fas signaling is regulated by ITK and T cell receptor signaling and patients with ALPS have an imbalance in this regulation resulting in a failure of T cells to undergo apoptosis and an accumulation of abnormal T cells. About Angel Pharmaceuticals Angel Pharmaceuticals is a privately held biopharmaceutical company developing a pipeline of precisely targeted investigational medicines for cancer, autoimmune, infectious and other serious diseases in China. Angel Pharmaceuticals was launched through a collaboration with Corvus and investments from investors in China. Angel Pharmaceuticals licensed the rights to develop and commercialize Corvus’ three clinical-stage candidates – soquelitinib, ciforadenant and mupadolimab – in greater China and obtained global rights to Corvus’ BTK inhibitor preclinical programs. Under the collaboration, Corvus currently has a 49.7% equity stake in Angel Pharmaceuticals excluding 7% of Angel’s equity reserved for issuance under the Angel employee stock ownership plan, and Corvus has designated three individuals on Angel’s five-person Board of Directors. For more information, visit . Forward-Looking Statements This press release contains forward-looking statements, including statements related to the potential safety and efficacy of the Company’s product candidates; the potential use of soquelitinib to treat a variety of hematological cancers and autoimmune diseases; the Company’s leadership position; clinical strategy and the design of clinical trials, including the timeline for initiation, target or expected number of patients to be enrolled, dose levels, number of sites and other product development milestones; and the amount of cash to fund operations into the second quarter of 2028. All statements other than statements of historical fact contained in this press release are forward-looking statements. These statements often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,” “will,” “may” or similar expressions. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to, risks detailed in the Company’s Annual Report on Form 10-K for the year ended December 31, 2025, filed with the Securities and Exchange Commission on or about the date hereof, as well as other documents that may be filed by the Company from time to time with the Securities and Exchange Commission. In particular, the following factors, among others, could cause results to differ materially from those expressed or implied by such forward-looking statements: the Company’s ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of its product candidates; the accuracy of the Company’s estimates relating to its ability to initiate and/or complete preclinical studies and clinical trials and release data from such studies and clinical trials; the results of preclinical studies and interim data from clinical trials not being predictive of future results; the Company’s ability to enroll sufficient numbers of patients in its clinical trials; the unpredictability of the regulatory process; regulatory developments in the United States and foreign countries; the costs of clinical trials may exceed expectations; the Company’s ability to accurately estimate the cash on hand providing funding into the second quarter of 2028 and the Company’s ability to raise additional capital. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those projected in the forward-looking statements. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise. The Company’s results for the fourth quarter and year ended December 31, 2025 are not necessarily indicative of its operating results for any future periods. CORVUS PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (in thousands, except share and per share data) Three Months Ended December 31, Year Ended December 31, 2025 2024 2025 2024 (unaudited) Operating expenses: Research and development $ 9,939 $ 5,974 $ 33,719 $ 19,385 General and administrative 2,278 2,131 9,252 8,163 Total operating expenses 12,217 8,105 42,971 27,548 Loss from operations (12,217 ) (8,105 ) (42,971 ) (27,548 ) Interest income and other expense, net 603 512 2,505 1,824 Gain from sale of property and equipment - 1 - 5 Change in fair value of warrant liability - (2,347 ) 27,141 (33,377 ) Loss before equity method investment (11,614 ) (9,939 ) (13,325 ) (59,096 ) Loss from equity method investment (707 ) (2,174 ) (1,958 ) (3,197 ) Net loss $ (12,321 ) $ (12,113 ) $ (15,283 ) $ (62,293 ) Net loss per share, basic $ (0.15 ) $ (0.18 ) $ (0.19 ) $ (1.02 ) Net loss per share, diluted $ (0.15 ) $ (0.18 ) $ (0.53 ) $ (1.02 ) Shares used to compute net loss per share, basic 82,960,560 68,347,016 78,964,842 60,985,165 Shares used to compute net loss per share, diluted 82,960,560 68,347,016 79,742,685 60,985,165 CORVUS PHARMACEUTICALS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (in thousands) December 31, December 31, 2025 2024 Assets Cash, cash equivalents and marketable securities $ 56,750 $ 51,964 Operating lease right-of-use asset 839 1,177 Other assets 2,539 3,226 Investment in Angel Pharmaceuticals 10,991 12,540 Total assets $ 71,119 $ 68,907 Liabilities and stockholders' equity Accounts payable and accrued liabilities and other liabilities $ 8,977 $ 6,307 Operating lease liability 937 1,122 Warrant liability - 28,910 Stockholders' equity 61,205 32,568 Total liabilities and stockholders' equity $ 71,119 $ 68,907 INVESTOR CONTACT: Leiv Lea Chief Financial Officer Corvus Pharmaceuticals, Inc. +1-650-900-4522 llea@corvuspharma.com MEDIA CONTACT: Sheryl Seapy Real Chemistry +1-949-903-4750 sseapy@realchemistry.com

在自身免疫与炎症（自免）疾病领域，过去两年无疑是“小分子药物”的“高光时刻”。当生物制剂（大分子）在靶点覆盖上逐渐触及天花板，小分子药物凭借其口服便利性、中枢神经系统（CNS）渗透性以及蛋白降解等颠覆性技术，正在重塑自免治疗的格局。这不仅是一场关于“疗效”的竞争，更是一场关于“机制”与“便利”的深度博弈。 01机制升维：攻克“不可成药”靶点 传统的药物研发逻辑是“抑制”蛋白的活性，但对于一些缺乏明确活性口袋的转录因子或支架蛋白，这一策略往往失效。近两年，蛋白降解技术（PROTAC/分子胶）在自免领域的应用，实现了从“抑制”到“清除”的跨越，让许多“不可成药”靶点成为可能。 STAT6降解剂（KT-621）：重塑Th2疾病治疗格局KT-621是全球首个进入临床的STAT6靶向PROTAC降解剂。STAT6是Th2型炎症（如特应性皮炎、哮喘）的核心驱动因子，传统上极难靶向。数据亮点：2025年12月公布的1b期临床数据显示，在22例中重度特应性皮炎（AD）患者中，口服KT-621（100mg/200mg QD）治疗29天后，实现了血液中STAT6中位降解率98%，皮损组织中STAT6中位降解率94%的深度靶点清除。临床疗效方面，所有患者平均湿疹面积和严重度指数（EASI）评分降低63%，EASI-50和EASI-75应答率分别达76%和29%，峰值瘙痒NRS评分平均降低40%。更值得注意的是，在合并哮喘的AD患者亚组中，中位部分呼出一氧化氮（FeNO）水平下降56%，显示出跨器官获益潜力。KT-621以口服给药形式，实现了与度普利尤单抗（Dupixent）皮下注射相当的生物标志物抑制效果（如TARC降低74%），且耐受性良好，未报告治疗相关严重不良事件或结膜炎病例。其2b期研究（BROADEN2）已启动，预计2027年年中读出数据。IRAK4降解剂（KT-485/SAR447971）：先天免疫的“总开关”IRAK4是Toll样受体（TLR）和IL-1信号通路的关键节点，兼具激酶活性和支架功能。降解IRAK4能同时阻断其双重功能，实现更彻底的抗炎效果。作为赛诺菲与Kymera合作开发的第二代IRAK4降解剂，其临床前数据显示出比第一代KT-474更高的选择性和效力。尽管KT-474在II期研究中因短暂QTc间期延长信号而停止开发，但赛诺菲已决定转向推进KT-485，预计于2026年进入I期临床试验。百济神州的BGB-45035作为全球唯一进入II期临床的IRAK4降解剂，正在类风湿关节炎患者中开展研究。 VAV1分子胶（MRT-6160）：T/B细胞通吃的“双杀”去年，诺华斥资超22亿美元收购的First-in-Class VAV1分子胶降解剂。VAV1是T细胞和B细胞受体信号传导的核心分子，靶向它有望同时抑制T细胞和B细胞的异常活化。数据亮点：在健康志愿者的I期研究中，MRT-6160实现了外周血T/B细胞中VAV1蛋白降解超过90%，并显著抑制了TCR诱导的IL-2、IFN-γ、IL-17A以及BCR依赖的IgG分泌。在自发性狼疮模型（MRL-Fas^lpr小鼠）中，口服1 mg/kg QD的MRT-6160显著抑制了淋巴结肿大、皮肤损伤、蛋白尿和抗dsDNA抗体产生，疗效与泼尼松相当甚至更优。诺华计划针对干燥综合征、系统性红斑狼疮和类风湿关节炎等多个适应症同时启动广泛的II期临床开发。02ITK: T细胞“上游调控者” 在Th2型炎症领域，ITK（IL-2诱导的T细胞激酶）抑制剂正凭借其独特的“上游调控”机制，成为挑战现有格局的“新玩家”。1. Soquelitinib（CPI-818）：Corvus Pharmaceuticals开发的首创口服ITK抑制剂。其核心机制是在T细胞受体（TCR）信号网络上游，通过抑制ITK来影响T细胞的激活阈值和分化走向。数据亮点：2026年1月公布的1期临床试验队列4数据显示，12例中重度AD患者接受200mg BID治疗8周后，75%的患者达到EASI 75，25%达到EASI 90，33%达到研究者总体评估（IGA）0/1分。尤为关键的是，在既往对度普利尤单抗或JAK抑制剂应答不足的患者中，仍有60%达到EASI 75，显示出覆盖难治人群的潜力。和剂药业已在中国启动针对中重度AD的1b/2期临床试验（CTR20253869），计划入组138名患者。2. ATI-2138（共价ITK和JAK3双重抑制剂）：在2025年Aclaris Therapeutics第三季度更新中，展示了强劲的疗效和清晰的后续开发路径。特应性皮炎2a期数据：在2025年欧洲皮肤病与性病学会（EADV）大会上公布的最新数据显示，治疗第4周（n=9），患者的湿疹面积和严重程度指数（EASI）评分下降77%，体表面积（BSA）评分下降64%，峰值瘙痒数字评定量表（PP-NRS）评分下降45%，且改善持续至治疗结束。基于积极的2a期数据，Aclaris计划在2026年上半年启动ATI-2138针对扁平苔藓、瘢痕性脱发和斑秃等新适应症的2期试验。这标志着ITK抑制剂正从AD向更多T细胞介导的炎症性皮肤病进军。 03 呼吸与皮肤炎症的“老靶点，新突破” 磷酸二酯酶4（PDE4）作为经典的抗炎靶点，其抑制剂因胃肠道副作用长期受限。近两年，通过亚型选择性（PDE4B）、双重靶向（PDE3/4）和剂型创新（吸入/外用），该领域迎来了“第二春”。1. Ensifentrine（全球首款）：由Verona Pharma开发的吸入性PDE3/4双重抑制剂，已于2024年6月获FDA批准，2025年在中国完成III期临床（ENHANCE-CHINA）。数据亮点：该研究纳入526例中国COPD患者，结果显示治疗12周后，主要终点FEV1 AUC 0-12h较安慰剂改善110mL，24周内中重度急性加重风险降低28%，患者生活质量（SGRQ）评分显著改善。其2025年第一季度销售额达7630万美元，环比增长95%。2. ITQC3721（国产领跑者）：正大天晴研发的吸入性PDE3/4抑制剂，全球研发进度第二。数据亮点：其II期数据显示，治疗4周即可显著改善患者肺功能，FEV1峰值较安慰剂组最高提升147mL，在已使用长效抗胆碱能药物（LAMA）的亚组中，提升幅度达239mL。该药于2025年7月被CDE纳入突破性治疗品种，III期临床已启动。3. Nerandomilast（BI 1015550）：勃林格殷格翰开发的口服选择性PDE4B抑制剂，于2025年10月获FDA批准用于特发性肺纤维化（IPF），成为十多年来该领域首个新机制药物。数据亮点：其关键III期研究（FIBRONEER-IPF）显示，治疗52周后，18mg BID组患者用力肺活量（FVC）下降-106 mL，显著优于安慰剂组的-170 mL，相当于将肺功能衰退速度减缓约37%。尽管腹泻发生率较高（18mg组41.3%），但因其选择性抑制PDE4B，胃肠道副作用已较传统泛PDE4抑制剂大幅改善。4. 外用剂型（罗氟司特乳膏）：Arcutis公司的ZORYVE（罗氟司特）乳膏0.05%于2025年10月获FDA批准用于2至5岁儿童轻度至中度特应性皮炎。该系列产品2025年全球销售额达3.721亿美元，同比增长123%，在外用皮肤病药物市场中占据45%的份额。华东医药已引进该产品的大中华区权益，并提交了多项适应症的上市申请。 04中枢渗透：BTK抑制剂的“跨界革命” 多发性硬化症（MS）等神经免疫疾病的治疗长期受限于血脑屏障（BBB），大分子药物难以进入中枢。近两年，可穿透血脑屏障的BTK抑制剂在MS领域取得了里程碑式的突破，实现了从“外周免疫抑制”到“中枢神经保护”的转变。同时，2025年更被业界称为BTK抑制剂的“自免元年”，诺华与赛诺菲的产品相继获批，标志着该靶点正式从血液肿瘤跨界到自免领域。1. Fenebrutinib（罗氏）：PPMS的“破冰者”数据亮点：2025年11月，罗氏宣布其非共价、可逆性BTK抑制剂Fenebrutinib在两项关键III期研究中达到主要终点。在针对复发型多发性硬化（RMS）的FENhance 2研究中，与特立氟胺相比，Fenebrutinib显著降低了患者的年化复发率（ARR）。更关键的是，在针对原发进展型多发性硬化（PPMS）的FENtrepid研究中，Fenebrutinib在至少120周的治疗期内，疗效非劣于目前PPMS唯一获批疗法奥瑞珠单抗（Ocrevus）。这不仅抑制外周B细胞，还能进入大脑抑制小胶质细胞的活化，直接靶向中枢神经系统内的慢性炎症。2. Remibrutinib（诺华）：全球首个CSU口服BTK抑制剂2025年10月1日，诺华的Remibrutinib（商品名：Rhapsido/瑞普多）获FDA批准，用于治疗H1抗组胺药控制不充分的成人慢性自发性荨麻疹（CSU），成为全球首个获批该适应症的BTK抑制剂。该批准基于两项关键III期全球多中心临床试验REMIX-1和REMIX-2（分别纳入470和455例患者）的积极结果。数据亮点：研究表明，使用二代抗组胺药物治疗后仍有症状的CSU患者，使用Remibrutinib（25mg，每日两次）治疗后最快一周即可达到显著的具有临床意义的改善，且作用持续至第52周。在第52周评估时，接近半数患者完全没有瘙痒和荨麻疹症状（UAS7=0），这在以往的CSU治疗中难以实现。除了CSU，诺华正积极推进Remibrutinib在化脓性汗腺炎（HS）、全身型重症肌无力（gMG）、食物过敏及多发性硬化症（MS）等适应症的III期临床试验。公司预测其年销售额峰值有望超过30亿美元。2. Rilzabrutinib（赛诺菲）：全球首个ITP口服BTK抑制剂2025年8月29日，赛诺菲的Rilzabrutinib（商品名：Wayrilz）获FDA批准，用于治疗对既往治疗没有充分响应的持续性或慢性免疫性血小板减少症（ITP）成人患者，成为全球首个在自免领域获批的BTK抑制剂。数据亮点：批准基于关键III期LUNA 3研究（n=202）。结果显示，第25周时，Rilzabrutinib组23%的患者达到持久血小板应答（即在没有挽救治疗的情况下，患者在24周双盲治疗期的最后12周中至少有8周血小板计数≥50000/μL），而安慰剂组为0%（p<0.0001）。Rilzabrutinib组首次血小板应答时间仅36天，应答持续时间达7周，远优于安慰剂组的0.7周，并能显著改善患者生活质量。该药已获得FDA针对温抗体型自身免疫性溶血性贫血（wAIHA）的突破性疗法认定，相关III期研究（LUMINA）已启动。同时，针对IgG4相关性疾病（IgG4-RD）等适应症的临床试验也在中国获批开展。3. 国产力量：奥布替尼（诺诚健华）在SLE的突破2025年12月，诺诚健华宣布其BTK抑制剂奥布替尼在治疗系统性红斑狼疮（SLE）的IIb期临床研究中达到主要终点，并获CDE批准启动III期注册临床试验。数据亮点：在IIb期研究中，奥布替尼75mg QD剂量组的SRI-4应答率达到57.1%，显著优于安慰剂组的34.4%。在病情较重的亚组（BILAG评分≥1A或≥2B且临床评分≥4）中，校正后率差高达43%，展现出治疗难治性SLE的巨大潜力。 五、 总结与展望 近两年的进展表明，自免小分子药物已不再满足于做生物制剂的“廉价替代品”或“补充疗法”，而是通过机制创新（降解技术）、组织分布优势（CNS渗透）、上游免疫调控（如ITK抑制）以及靶点与剂型优化（如PDE4B选择性、PDE3/4双靶点、外用/吸入剂型），正在成为某些疾病领域的主导疗法。 从具体数据看，KT-621以口服形式实现了与生物制剂相当的STAT6深度降解与临床疗效；Soquelitinib在难治性AD患者中展现出高达75%的EASI 75应答率；Ensifentrine作为20年来首个新机制COPD吸入制剂，已证明其降低急性加重风险的临床价值；Nerandomilast则以选择性PDE4B抑制成功打入IPF市场，打破了十余年的新药荒。而BTK抑制剂在2025年的集中爆发（Remibrutinib用于CSU，Rilzabrutinib用于ITP，Fenebrutinib在MS取得突破）更是标志着该靶点成功完成了从肿瘤到自免的战略跨界。 未来，随着更多降解剂、ITK抑制剂和优化后的PDE抑制剂进入临床后期，自免小分子有望在治疗便利性、疗效深度、安全性和疾病修饰（Disease Modification）方面实现全面超越，真正开启自免治疗的“口服时代”与“精准局部治疗时代”。然而，挑战依然存在，如PROTAC分子的口服吸收难题、BTK抑制剂的肝毒性风险、以及ITK抑制剂在更广泛适应症中的长期安全性验证等，这需要全球科学家持续攻坚。