Obefazimod

2026年1月，法国媒体《La Lettre》报导，美国制药巨头礼来正评估收购法国生物技术公司Abivax的可能性，拟出价约150亿欧元，约合175亿美元。2025年7月以来，Abivax股价累计暴涨近15倍。  Abivax成立于2013年，其发展历程围绕核心候选药物Obefazimod（ABX464）展开，该药物最初用于HIV研究，后来因其显著的抗炎作用而转向炎症疾病领域。 ABX464的研发可追溯至2009年，由Abivax、法国国家科研中心（CNRS）和居里研究所共同发现，最初定位为HIV治疗候选药物，其发现过程是一种经典的化学生物学方式。 1、化学生物学 化学生物学（Chemical Biology）是用化学的方式去理解、操控和重新设计生命过程。具体在新药研发领域，科研人员利用化学合成和筛选技术，发现具有生物活性的小分子化合物，作为潜在药物候选物或工具分子，用于干预疾病相关生物过程，同时探索小分子与生物靶点的相互作用机制，为药物研发提供新靶点和新策略。 化学生物学起源于上世纪90年代，由美国哈佛大学的Stuart Schreiber教授及Scripps研究所的Peter Schultz教授率先提出并推动发展。其中，Schreiber教授是Vertex（福泰制药）的科学创始人，而Vertex的多款囊性纤维化（CF）药物（如Ivacaftor）正是通过化学生物学方式发现的，为其成为千亿美元市值公司奠定了基础。 这种研发的起点不是先锁定某个已知靶点去“设计”分子，而是更偏向细胞水平的表型筛选（phenotypic screening）：在HIV感染的细胞模型里筛选化合物库，寻找能明显抑制病毒复制、且细胞毒性可接受的候选药物。 ABX464最初并不是为了治疗炎症性疾病而设计，而是作为一种抗HIV的小分子候选药物。在初筛获得先导化合物后，研发人员通过复测抗病毒活性（不同细胞系/不同病毒株）；评估耐药风险、药代性质（口服可行性、暴露量等）；结构优化以提高效力与安全性等方式对化合物进行迭代优化，最终形成了开发候选物ABX464。 随后的机制研究显示，ABX464并非典型的蛋白酶/逆转录酶/整合酶抑制剂，而是作用在病毒RNA生物合成过程上（图1）。 图1. ABX464作用机制示意图 ABX464与宿主细胞的RNA加工相关复合体（尤其是cap-binding complex，CBC）特异性结合，从而改变HIV RNA的剪接/输出过程（HIV的某些RNA需要Rev等机制才能输出并用于产生结构蛋白），最终抑制病毒复制（图1）。 2、miR-124 在HIV研究过程中，研究人员观察到ABX464对免疫系统产生了意料之外的抗炎效果。进一步研究发现，ABX464能选择性增强miR‑124的表达（图2）。 图2. ABX464调控miR-124示意图 miR-124是一种重要的微小RNA（microRNA），属于长度约为22个核苷酸的非编码RNA家族，不编码蛋白质，但可通过与靶基因的mRNA结合，抑制其翻译或促进其降解，从而精准调控基因表达，在生物体内发挥着多种关键的调控作用。 在免疫系统中，miR-124是炎症反应的负调节因子，能抑制多条炎症通路，包括NF‑κB、STAT3、TLR信号通路。它还可通过抑制巨噬细胞的活化和促炎因子（如TNF-α、IL-6等）的产生，促进巨噬细胞向抗炎型（M2型）极化，从而减轻炎症反应，维持免疫稳态（图3）。 图3. miR-124调控机制 在溃疡性结肠炎等炎症性疾病中，miR-124的表达下调可能导致炎症反应失控。而通过上调miR-124的表达，可抑制炎症细胞的活化和促炎因子的释放，缓解炎症症状（图4）。 图4. miR-124在IBD中的作用机制 此外，miR‑124通过抑制TGF‑β/SMAD、STAT3、NF‑κB、成纤维细胞活化和ECM（细胞外基质）生成，阻止炎症向纤维化进展，是一种天然的抗纤维化microRNA。 TGF‑β是所有器官纤维化（肠道、肝、肺、肾）的核心驱动因子。miR‑124通过靶向SMAD4、TGF‑βR1/TGF‑βR2、RhoA来抑制TGF‑β信号，使成纤维细胞不易被激活、胶原蛋白（COL1A1、COL3A1）减少、ECM沉积下降。 3、IBD ABX464是Abivax临床管线中唯一产品，用于治疗活动性溃疡性结肠炎（UC；临床3期）及克罗恩病（CD；临床2期）。仅凭一款未上市产品，Abivax市值可达百亿美元，再次凸显炎症性肠病（IBD）在MNC心目中的地位。 IBD之所以成为MNC争相进入的核心赛道，是因为它同时具备巨大市场规模+高未满足需求+多机制创新空间+长期商业价值的罕见组合。 IBD全球患者数超过700–800万，并且呈持续上升趋势。增长原因包括城市化、饮食西化、肠道微生物变化、遗传易感人群扩大。对于MNC来说，这意味着：长期、稳定、不断扩大的市场。 IBD药物市场已经超过300–400亿美元，并预计在未来十年持续增长。驱动因素包括：生物制剂价格高、患者需要长期治疗（终身疾病）、新机制药物不断进入市场、适应症扩展。这对于MNC来说是典型的高价值、可持续、可迭代的商业赛道。 尽管已有TNF抑制剂、α4β7抗体、IL‑23抗体、JAK抑制剂、S1P调节剂获批上市，但IBD仍存在巨大的未满足需求：约30–40%患者对现有药物无应答、约50%患者在1–2年内失去应答、纤维化（尤其是克罗恩病）无药可治、安全性问题（感染、肿瘤风险）仍存在。这意味着，任何新机制药物都有机会成为“first‑in‑class”或“best‑in‑class”。 IBD是免疫学最复杂、最前沿的疾病之一。许多新机制药物会先在IBD中验证，再扩展到其它疾病：TL1A → 纤维化、哮喘、特应性皮炎；JAK → 风湿、皮肤病；S1P → 多发性硬化；microRNA → 多系统炎症。因此IBD对于MNC来说是：战略性平台疾病（platform disease）。 4、miR-124 vs. TL1A 如果对比miR-124及TL1A，可以看到在“诱导期缓解率”这个单一指标上，TL1A路线（Duvakitug）的数字，确实是肉眼可见的比miR‑124路线（Obefazimod）“更猛一个量级”（表1）。 表1. miR-124及TL1A对比 但是，两个临床试验在时间点、方案设计、人群构成、既往用药、评分基线等方面均不相同，并不具备跨试验比较的意义。 TL1A像是“重炮”，miR‑124更像“系统调音台”。数字上重炮更炸眼，但调音台在某些组合、长期安全性、合并纤维化/多系统炎症场景里，可能有它独特的位置。 我们可能要等到临床3期结果公布，才能在诱导缓解、深度缓解（内镜+组织学）、维持率、激素停用、安全性（感染、肿瘤、实验室异常），这些更具“临床真实”的维度上，做一场真正有意义的对比。

Abivax Presents First Evidence of Anti-Fibrotic Activity for Obefazimod Alongside New Clinical Efficacy and Safety Analyses in Inflammatory Bowel Disease at ECCO 2026 22 abstracts presented at European Crohn’s and Colitis Organization’s (ECCO) 21st Annual Congress illustrate the depth and breadth of data supporting obefazimod’s potential in inflammatory bowel diseaseAnti-fibrotic effects of obefazimod were observed in both a preclinical human fibroblast model and in an in vivo animal model, suggesting potential to address a major unmet need in Crohn’s diseaseA pooled analysis of safety data from ABTECT-1 and ABTECT-2 induction trials demonstrates a favorable safety profile with rates of serious treatment emergent adverse events and study discontinuation similar to placeboSymptomatic response of obefazimod was observed as early as week 1 (first time point evaluated) with symptomatic remission observed at week 2 (nominally significant p-value <0.05) in a pooled analysis of ABTECT-1 and ABTECT-2Biomarker data from ABTECT-1 and ABTECT-2 induction trials indicate upregulation of miR-124 and reduction of key inflammatory cytokines (IL-17A and IL-6) toward homeostatic levels PARIS, France – February 21, 2026 – 12:00 PM CET – Abivax SA (Euronext Paris: FR0012333284 – ABVX / Nasdaq: ABVX) (“Abivax” or the “Company”), a clinical-stage biotechnology company focused on developing therapeutics that harness the body’s natural regulatory mechanisms to stabilize the immune response in patients with chronic inflammatory diseases, today announced novel preclinical and clinical data for obefazimod as part of the presentations at The European Crohn’s and Colitis Organization’s (ECCO) 21st Annual Congress. These data further expand the evidence base supporting development of obefazimod for inflammatory bowel disease, highlighting its anti-fibrotic potential in Crohn’s disease (CD), a favorable safety and tolerability profile, rapid onset of symptomatic relief, and additional evidence supporting its mechanism of action in restoring immune balance through upregulation of miR-124. Marc de Garidel, MBA, Chief Executive Officer of Abivax, commented: "The robust data presented at ECCO this week reinforce obefazimod's unique and differentiated profile. The anti-fibrotic findings, taken together with the additional clinical efficacy, safety, and biomarker data presented, strengthen our confidence in obefazimod’s potential across UC and CD. As we look toward the upcoming Phase 3 maintenance trial readout in Q2 2026 and the Phase 2b ENHANCE-CD trial readout in Q4 2026, we remain focused on translating this data into real-world benefits for patients with IBD." Fabio Cataldi, MD, Chief Medical Officer of Abivax, added: “The emerging preclinical evidence of anti-fibrotic activity is particularly compelling, as fibrosis remains an area of profound unmet need. Combined with the favorable safety and tolerability profile of obefazimod, we believe this growing evidence base positions obefazimod as a compelling oral therapy with the potential to address multiple dimensions of disease not yet fully managed by current therapies.” HIGHLIGHTED PRESENTATIONS: The 22 abstracts presented at ECCO 2026, including subgroup analyses from the Phase 3 ABTECT induction trials illustrating obefazimod’s clinical activity across a wide range of patient subpopulations, can be accessed at: https://www.abivax.com/publications/congress-publications Obefazimod shows first evidence of anti-fibrotic activity in preclinical models of inflammatory bowel disease (Danese S et al. OP30, ECCO 2026) In an in vitro human fibroblast model, obefazimod led to a ~50% reduction in a biomarker of active fibrosis (Pro-C3) (p < 0.0001) and a ~30% reduction in a fibroblast activation marker (⍺SMA) (p < 0.0001)In an in vivo animal model, obefazimod exhibited dual anti-inflammatory and anti-fibrotic effects leading to rapid improvement in markers of disease activity Obefazimod demonstrated anti-inflammatory effects when initiated as a fibrosis preventative (day 5) or fibrosis treatment (day 20): ~25% (p<0.0001) and ~50% (p<0.0001) reduction in Disease Activity Index, with late (day 20) and early (day 5) treatment, respectively~35% (p<0.0001) and ~65% (p<0.0001) reduction in histologic ulceration and inflammation scores, with late and early treatment, respectively Obefazimod demonstrated anti-fibrotic effects when initiated as a fibrosis preventative (day 5) or fibrosis treatment (day 20): ~45% (p<0.0001) and ~55% (p<0.0001) reduction in Collagen Deposition (fibrosis marker), with late and early treatment, respectively~40% (p<0.0001) and ~50% (p<0.0001) reduction in ⍺SMA (fibroblast activation marker), with late and early treatment, respectively ~60% (p<0.0001) and ~90% (p<0.0001) reduction in histologic Fibrosis Score, with late and early treatment, respectively Integrated summary of safety of obefazimod in Phase 3 ABTECT induction trials (Seidler U et al. P0712, ECCO 2026) Of the 1,272 patients randomized and treated with Obe-50mg, Obe-25mg, or placebo (PBO), the overall rates of serious treatment emergent adverse events (TEAEs) was comparable across all groups (Obe-50mg: 3.1%; Obe-25mg: 2.2%; PBO: 3.2%)TEAEs leading to study discontinuation occurred at similar rates across all groups (Obe-50mg, 4.7%; Obe-25mg, 1.9%; PBO, 4.1%)Headaches were one of the most frequent TEAEs and were reported to be mild, transient, and short in duration (median: 2-3 days) and rarely leading to discontinuation (0-1.1%) Early symptomatic improvements with obefazimod in patients with moderately to severely active ulcerative colitis (Armuzzi A et al. P0923, ECCO 2026) A greater proportion of patients receiving obefazimod (50mg or 25mg) versus PBO achieved symptomatic response from week 1 and symptomatic remission from week 2 increasing through week 8In a pooled analysis of the Phase 3 ABTECT-1 and ABTECT-2 induction trials, both Obe-50mg and Obe-25mg produced reductions in rectal bleeding subscores and stool frequency subscores versus PBO starting from week 1 and reaching a nominally significant difference by week 2 (p-value <0.05)Improvement in symptoms consistently increased through week 8 Obefazimod enhances miR-124 expression in blood and colon tissue and reduces the key inflammatory cytokines IL-17A and IL-6 in serum of patients with moderately to severely active ulcerative colitis (Siegmund B et al. P0868, ECCO 2026) In both Phase 3 ABTECT induction trials, Obe-25mg and Obe-50mg significantly enhanced expression of miR-124 in blood (unadjusted p < 0.0001 vs. PBO) and in rectal and sigmoidal tissue (unadjusted p < 0.0001 vs. PBO) at week 8At week 8, Obe-25mg and Obe-50mg significantly reduced IL-17A levels in serum (unadjusted p < 0.0001 vs. PBO); Obe-25mg (p=0.0150 vs. PBO) and Obe-50mg (p=0.0039 vs. PBO) decreased IL-6 levels in serummiR-124 mechanism of action allows for partial reduction of inflammatory cytokines IL-17 and IL-6 toward homeostatic levels without completely blocking these pathways Professor Silvio Danese, Director of the Gastroenterology and Digestive Endoscopy Unit of the IRCCS San Raffaele Hospital, added: “For patients living with inflammatory bowel disease, long-term disease control and preservation of bowel function are critical. Seeing data that address not only clinical response and safety, but also biological activity and fibrosis, is encouraging. If these findings continue to translate clinically, they may represent a meaningful advancement for patients who currently have limited options.” About Abivax Abivax is a clinical-stage biotechnology company focused on developing therapeutics that harness the body’s natural regulatory mechanisms to stabilize the immune response in patients with chronic inflammatory diseases. Based in France and the United States, Abivax’s lead drug candidate, obefazimod (ABX464), is in Phase 3 clinical trials for the treatment of moderately to severely active ulcerative colitis. Contact: Patrick MalloySVP, Investor Relations Abivax SApatrick.malloy@abivax.com+1 847 987 4878 Media Contacts: LifeSci CommunicationsJon PappasSVP, Head of Media RelationsLSC_ABIVAX@lifescicomms.com FORWARD-LOOKING STATEMENTS This press release contains forward-looking statements, forecasts and estimates, including those relating to the Company’s business. Words such as “anticipate,” “expect,” “potential” and variations of such words and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements concerning the potential therapeutic benefit of obefazimod and the expected availability and timing of results from the Phase 3 maintenance trial and Phase 2b ENHANCE-CD trial of obefazimod. Although Abivax’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks, contingencies and uncertainties, many of which are difficult to predict and generally beyond the control of Abivax, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. A description of these risks, contingencies and uncertainties can be found in the documents filed by the Company with the French Autorité des Marchés Financiers pursuant to its legal obligations including its universal registration document (Document d’Enregistrement Universel) and in its Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on March 24, 2025 under the caption “Risk Factors.” These risks, contingencies and uncertainties include, among other things, the uncertainties inherent in research and development, future clinical data and analysis, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug candidate, as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, and the availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements. Special consideration should be given to the potential hurdles of clinical and pharmaceutical development, including further assessment by the Company and regulatory agencies and IRBs/ethics committees following the assessment of preclinical, pharmacokinetic, carcinogenicity, toxicity, CMC and clinical data. Furthermore, these forward-looking statements, forecasts and estimates are made only as of the date of this press release. Readers are cautioned not to place undue reliance on these forward-looking statements. Abivax disclaims any obligation to update these forward-looking statements, forecasts or estimates to reflect any subsequent changes that the Company becomes aware of, except as required by law. Information about pharmaceutical products (including products currently in development) that is included in this press release is not intended to constitute an advertisement. This press release is for information purposes only, and the information contained herein does not constitute either an offer to sell or the solicitation of an offer to purchase or subscribe for securities of the Company in any jurisdiction. Similarly, it does not give and should not be treated as giving investment advice. It has no connection with the investment objectives, financial situation or specific needs of any recipient. It should not be regarded by recipients as a substitute for exercise of their own judgment. All opinions expressed herein are subject to change without notice. The distribution of this document may be restricted by law in certain jurisdictions. Persons into whose possession this document comes are required to inform themselves about and to observe any such restrictions. Attachment 20260221_Abivax_PR_Presents New Data at ECCO 2026