Ustekinumab biosimilar (Alvotech)

▎Helixbro 在当今全球免疫与炎症（I&I）疾病的治疗格局中，炎症性肠病（Inflammatory Bowel Disease, IBD），特别是溃疡性结肠炎（UC）和克罗恩病（CD），正面临着严峻的临床挑战。尽管过去二十年来，生物制剂和小分子靶向药物的涌现极大地改变了IBD的治疗轨迹，但临床上单一靶点药物的有效性正在触及不可逾越的“天花板” 。随着对单一生物制剂原发性无应答（发生率高达30%）和继发性失应答（发生率约40%）现象的日益普遍，寻找能够打破这一僵局的下一代治疗策略成为了整个行业的焦点 。 在这一背景下，强生（Johnson & Johnson）基于Guselkumab（抗IL-23p19单抗）和Golimumab（抗TNFα单抗）的联合给药方案，以及随后开发的固定剂量复方制剂JNJ-78934804（又称JNJ-4804），为“双重先进靶向疗法”（Dual Targeted Therapy, DTT）确立了关键的临床与商业基准 。一、 双通路阻断的分子病理机制与生物学原理 从免疫学和系统生物学的底层逻辑来看，炎症性肠病并非由单一的致病细胞因子所驱动，而是由多条相互交织、具有高度冗余性和代偿性的免疫级联反应网络共同介导。抗肿瘤坏死因子（Anti-TNFα）药物在诱导和维持IBD临床缓解方面曾取得巨大成功，但随之而来的免疫原性（如抗药抗体的产生）和靶向逃逸现象揭示了黏膜免疫网络的动态流动性 。当TNFα通路被长期阻断时，肠道局部微环境倾向于上调其他促炎旁路以维持炎症状态，其中IL-23/Th17轴的作用尤为核心 。1.1 TNFα与IL-23的协同放大效应与正反馈回路 IL-23是一种由活化的单核巨噬细胞和树突状细胞分泌的异二聚体细胞因子，由p19特异性亚基和p40共有亚基组成 。在IBD及其他免疫介导的炎症性疾病（如银屑病）中，IL-23是驱动初始T细胞向致病性Th17细胞分化并维持其存活的关键上游信号 。Th17细胞不仅分泌IL-17A、IL-17F和IL-22等效应因子，还在局部组织的免疫微环境中扮演着促炎与组织修复的复杂角色 。 基础生物学研究揭示，TNFα与IL-17A（由IL-23驱动产生）在靶细胞层面上存在深度的协同作用。在对人类原代细胞（如角质形成细胞）的研究中发现，TNFα和IL-17A的联合刺激能够显著诱导细胞自身产生大量的IL-23 。这一过程的分子机制被证明受到表观遗传控制（如H3K9二甲基化）以及EGFR信号传导通路的调控 。由于IL-23对Th17细胞的激活至关重要，靶组织在TNFα和IL-17A刺激下分泌的IL-23又会反过来进一步激活Th17细胞，促使其分泌更多的IL-17A和TNFα 。这种细胞因子之间的串扰形成了一个极具破坏性的“正反馈回路”（Positive Feedback Loop），解释了为何慢性炎症能够在局部黏膜中持久维持并演变为难治性病理状态 。1.2 协同阻断的免疫重塑学基础 单独阻断IL-17A在IBD治疗中已被证明具有潜在的恶化病情风险，这主要是因为IL-17A在肠道中同时具有介导宿主保护性免疫防御（抵抗细胞外细菌）和维持上皮屏障完整性的功能 。然而，靶向位于更为上游的IL-23p19亚基，不仅能够精准下调致病性Th17克隆的扩增，还能保留其他非致病性IL-17的生理功能 。 当同时使用Guselkumab阻断IL-23p19并使用Golimumab阻断TNFα时，治疗策略实现了对炎症级联反应的空间与时间双重拦截。TNF抑制剂通过下调内皮细胞黏附分子（如e-选择素、ICAM-1、VCAM-1）来阻断循环白细胞向肠道黏膜的浸润，并诱导表达跨膜TNF的炎症细胞发生凋亡 。与此同时，IL-23抑制剂则从源头上切断了Th17细胞的维持信号，瓦解了局部的细胞因子正反馈网络 。转录组学（RNAseq）数据表明，这种双重阻断能够在分子水平上引发更为深刻的重塑，不仅显著下调IL-23通路模块，还广泛抑制了干扰素应答模块以及炎症性上皮和髓系细胞的转录状态 。二、 药物开发形式的路径抉择：双抗与固定剂量复方的博弈 在确立了TNFα与IL-23双重阻断的生物学合理性后，药物研发领域面临着一个重大的技术分水岭：是开发单一的双特异性抗体（Bispecific Antibody），还是采用两种单克隆抗体的固定剂量复方（Co-formulation）？顶尖药企在这两条路径上的探索揭示了现代抗体工程的技术局限与商业考量。2.1 双特异性抗体在炎症靶向中的物理化学及临床药理学挑战 双特异性抗体虽然在肿瘤免疫治疗（如T细胞接合器，TCE）中取得了显著成功，但在系统性炎症疾病的细胞因子阻断中却面临着难以逾越的药代动力学（PK）、药效动力学（PD）以及化学、制造与控制（CMC）障碍 。 强生公司曾大力推进一款名为JNJ-61178104的靶向TNFα与IL-17A的人源化单价双特异性抗体 。在体外细胞实验和鼠类肺部中性粒细胞浸润模型中，JNJ-61178104表现出了强效的靶点中和能力，甚至优于二价亲本抗体的联合使用 。然而，当该药物进入食蟹猴和人类的体内靶标占有率（Target Engagement）定量评估环节时，研究人员惊讶地发现，双抗分子在体内的表观结合亲和力远低于预期，且显著弱于具有等摩尔剂量的二价亲本抗体 。这一现象的底层原因是双抗分子结构中的空间位阻效应，以及体内循环系统中高浓度、大分子量靶抗原（特别是形成多聚体的TNFα）对单价结合位点的竞争性干扰 。 此外，免疫原性（ADA）是导致双特异性抗体在非肿瘤领域折戟的另一大元凶。同时结合两种不同的可溶性细胞因子极易形成巨大的、不可预测的高分子量免疫复合物。例如，另一款靶向TNF和TL1A的双抗AMG-966在I期临床中导致高达98%的受试者产生中和性抗药抗体，直接造成药物在体内暴露量的灾难性丧失 。同时，双特异性抗体在CMC扩大生产阶段常常面临链错配、热稳定性下降和高聚集倾向等成药性（Developability）挑战，导致药物审批过程中的完整回应函（CRL）签发率居高不下 。2.2 固定剂量复方与口服纳米抗体的创新突围 基于上述严酷的科学现实，强生的研发战略发生了务实的转向。通过将已经历广泛临床验证的Guselkumab和Golimumab结合为固定剂量复方制剂JNJ-78934804，强生不仅彻底规避了新分子实体的CMC风险，保留了两种药物原有的二价高亲和力结合特性，还能够根据临床需求灵活调整两种抗体的剂量比例 。 与此同时，针对口服给药的创新双抗策略也在Biotech界引起了广泛关注。例如，Sorriso Pharmaceuticals开发的V56B2是一种新型的双特异性纳米抗体（Domain Antibody），融合了靶向IL-23p19的V900和靶向TNFα的V565 。其精妙之处在于，V56B2包含一个中央蛋白酶敏感的连接肽 。当药物口服进入小肠后，肠道内的胰蛋白酶会切割连接肽，将双抗分解为两个完全独立的单体纳米抗体 。这种设计既实现了口服给药的便利性与靶向递送，又完美避免了在黏膜局部产生由于双靶点同时结合而导致的空间干扰与高分子聚合物风险 。小鼠模型和IBD患者结肠活检的体外培养研究证实，这种在肠道原位释放的单体组合能够深度抑制组织磷蛋白水平，并实现极高的粪便药物浓度，为未来改善患者依从性提供了颠覆性的技术选项 。三、 突破疗效天花板：VEGA与DUET临床数据的多维解构 对双重靶向策略的临床信心，建立在强生开展的一系列设计严谨的随机、双盲、对照临床试验数据之上。VEGA（Phase 2a）和DUET（Phase 2b）研究的数据不仅确立了联合疗法在初治患者中的压倒性优势，也为其在多重耐药患者中的挽救性应用提供了坚实证据。3.1 VEGA试验：第12周诱导期的断层式临床响应 VEGA是一项具有里程碑意义的2a期概念验证研究，共招募了214名对常规免疫抑制剂或皮质类固醇反应不足、且未曾使用过生物制剂（Biologic-naïve）的中重度活动性UC成人患者 。受试者被均等随机分配至三个研究臂：Guselkumab + Golimumab联合诱导组、Guselkumab单药组（TREMFYA）以及Golimumab单药组（SIMPONI）。 在第12周的主要终点评估中，联合疗法打破了长期以来UC治疗中约20%-30%临床缓解率的统计学瓶颈。基于修正意向治疗人群的分析揭示了联合疗法跨越所有关键维度的优效性： 第12周疗效评估核心指标 Guselkumab + Golimumab 联合治疗组 Guselkumab 单药组 Golimumab 单药组 临床应答率 (Clinical Response, Mayo) 83.1% 74.6% 61.1% 临床缓解率 (Clinical Remission, mMayo) 47.0% 24.0% 25.0% 内镜改善率 (Endoscopic Improvement) 49.0% 30.0% 25.0% 组织学缓解率 (Histologic Remission) 56.0% 49.0% 32.0% 组织学-内镜复合缓解 41.0% 27.0% 15.0% 粪便钙卫蛋白中位数 (FCP, mg/kg) 117.5 397.5 505.0 (数据来源：VEGA Phase 2a 研究，Feagan等，2023 ) 这些数据表明，通过同时扑灭TNF驱动的急性炎症招募和IL-23驱动的Th17持续活化，联合治疗在短短12周内不仅将临床应答率推高至惊人的83.1%，其在客观炎症标志物（如粪便钙卫蛋白大幅下降至117.5 mg/kg）和黏膜愈合上的表现更是实现了对单药组的降维打击 。3.2 VEGA试验：第38周维持期的深度组织学重塑 IBD治疗的终极目标不仅是短期症状的控制，更是实现长期的无皮质类固醇缓解和深度的黏膜组织学愈合，这直接关联到结直肠癌风险的降低和远期手术率的下降。在VEGA试验中，联合组在完成12周的联合诱导后，转换为Guselkumab单药维持治疗，并随访至第38周 。 在第38周的维持期数据中，联合诱导所建立的深度响应态势得到了完美延续： 临床缓解持久性：基于改良Mayo评分，联合组的临床缓解率维持在47.9%，显著优于Guselkumab单药组的31.0%和Golimumab单药组的20.8% 。 无皮质类固醇临床缓解：极为难得的是，在第38周达到临床缓解的联合组患者中，有100%（31/31）的患者在过去60天内完全摆脱了对皮质类固醇的依赖，这在改善患者长期生活质量和降低代谢毒性方面具有无可估量的价值 。 金标准：Geboes组织学评估：VEGA研究采用了极其严苛的Geboes评分系统来定义组织学缓解，要求黏膜固有层和上皮中完全无中性粒细胞浸润、无隐窝破坏、无糜烂或溃疡以及无肉芽组织形成 。在这一严苛标准下，联合组在第38周实现了24%的组织学缓解与内镜正常化复合终点，是Guselkumab单药组（13%）的近两倍，是Golimumab单药组（6%）的四倍 。伴随活检RNAseq揭示的炎症转录模块的长效下调，证实了双重诱导能够产生长期的“免疫学记忆”与疾病修饰（Disease Modification）效应 。3.3 DUET试验：攻克多重耐药壁垒的2026年最新进展 如果说VEGA试验确立了联合疗法在初治患者中的理论上限，那么正在进行的DUET-UC和DUET-CD（Phase 2b）研究则直指当前IBD治疗中最棘手的痛点——难治性与多重耐药群体 。 DUET项目评估了三种不同剂量梯度（高、中、低）的JNJ-78934804复方制剂的效力 。尤为关键的是，该研究中约有一半的参与者属于既往对两种或两种以上全身性治疗类别（例如抗TNF、抗整合素或JAK抑制剂）反应不足的高度难治性亚群 。根据在2026年美国消化疾病周（DDW）会议上公布的最新突破性进展：在DUET-CD的第48周主要终点分析中，针对这一高度难治性克罗恩病亚组，JNJ-4804展示出了颠覆性的挽救疗效。其临床缓解率达到了表现最佳对照组的近两倍，而内镜应答率比对照组高出60%以上 。 这一数据不仅巩固了强生在IBD管线上的统治地位，更从实质上宣告了JNJ-78934804具备成为所有现有疗法失败后的终极“超级挽救疗法”的潜力。四、 安全性监控与药政监管路径的前瞻性研判 在临床疗效大幅跃升的背后，顶尖临床专家和药政监管机构（如FDA和EMA）对双重免疫抑制可能引发的严重感染和肿瘤风险抱有高度的警惕性。对于将两种强效细胞因子阻断剂合二为一的复方制剂，其安全窗和监管审评路径相较于单药有着本质的差异。4.1 安全性图谱：机会性感染的微弱信号与整体耐受性 整体而言，VEGA试验跨越50周的安全性数据出人意料地呈现出高度的平稳性。联合治疗组发生任何不良事件（AEs）的比例为63%，不仅未出现预期的不良事件叠加效应，反而低于Golimumab单药组的76%和Guselkumab单药组的65% 。这种现象的潜在解释是，快速且深度的黏膜愈合本身减少了因疾病活动性引起的系统性炎症和继发性并发症。此外，各组间严重不良事件（SAEs，均为6%）和严重感染（均为3%）的发生率均保持一致且处于较低水平 。 然而，针对特定机制的机会性感染不容忽视。在VEGA联合治疗组中，临床医生报告了1例在第18周确诊的结核病（TB）以及1例在第14周确诊的巨细胞病毒（CMV）结肠炎 。TNFα在人体内是维持结核分枝杆菌肉芽肿稳定、防止潜伏感染激活的关键细胞因子；而IL-23在宿主抵抗细胞外病原体（包括真菌和特定细菌）中发挥着屏障防卫作用 。双通路的联合压制削弱了机体的双重防线。对强生多项大规模临床试验（如GALAXI、GRAVITI、QUASAR以及VEGA）的汇总分析也强调了以100人年（Patient-years）为单位严密监测活性结核发生率的必要性 。未来在真实世界临床实践中，更为严格的潜伏结核和慢性病毒基线筛查，以及在治疗周期内的高频病原学监测，将是使用此类双重疗法的先决条件。4.2 药政监管框架：FDA指南与复方制剂的批准门槛 从药政监管的视角来看，联合疗法在不同地区的审批面临着截然不同的法规挑战。FDA在关于双特异性抗体及多特异性产品开发的工业指南（FDA-2019-D-0621）中虽然主要聚焦双抗，但也对化学、制造与控制（CMC）以及多靶点干预的脱靶效应提出了严格要求 。 更为重要的是，FDA和EMA对固定剂量复方制剂（Fixed-Dose Combinations, FDCs）有一项核心的监管原则：必须提供确凿的证据证明复方中的每一个活性成分（Contribution of Components）都对最终的疗效或安全性做出了实质性的独立贡献 。这也是为何DUET试验必须设计复杂的6个研究臂（包含安慰剂、单药对照以及三种不同剂量的复方）的根本原因 。强生需要通过庞大且昂贵的剂量探索研究矩阵，向FDA证明Guselkumab和Golimumab的联合绝不是简单的叠加，且无法通过提高任何一种单药的剂量来达到同等的疗效水平 。 此外，在全球化开发战略中，EMA对共同包装（Copackaging）的严厉限制也迫使药企必须推进真正的固定剂量复方研发，而非简单地将两支单抗打包销售 。FDA肿瘤学卓越中心负责人理查德·帕兹杜尔（Richard Pazdur）博士等人在讨论组合疗法审批时也曾强调，组合策略不仅是新药审批的重点，更是伴随诊断和精准医疗（防止无反应患者暴露于高风险组合）不可或缺的组成部分 。五、 商业估值、卫生经济学与竞争性市场格局 JNJ-78934804不仅仅是一个临床突破，更是捍卫企业在免疫与炎症领域核心商业版图的战略性武器。面对日益拥挤的单药市场和来势汹汹的生物类似药，双靶点疗法的商业逻辑正在被重塑。5.1 全球IBD市场的宏大增量与生物类似药冲击 随着工业化进程、饮食结构改变以及人口老龄化，全球溃疡性结肠炎和克罗恩病的患病基数正处于爆发式增长期。权威市场研究机构的预测数据显示，全球UC市场规模将从2024年的约73亿美元稳步攀升，预计到2030至2035年间将突破108亿美元至153亿美元，其复合年增长率（CAGR）将强劲维持在5.7%至8.5%的区间 。如果将体量相仿的CD市场计算在内，这是一个总体量超过300亿美元的巨型蓝海市场。 然而，这个庞大的市场正遭遇生物类似药（Biosimilars）的剧烈洗牌。目前，抗TNF类药物（英夫利西单抗、阿达木单抗）早已面临大量低成本竞争；更为严峻的是，针对强生自身重磅炸弹Stelara（乌司奴单抗，靶向IL-12/23）的多款生物类似药（如Wezlana、Otulfi、Selarsdi、Yesintek）已经获批，正以极具破坏性的共同保险（Co-insurance）价格折扣（预估共同保险费用低至840-1696美元）疯狂蚕食市场份额 。在此背景下，Tremfya（Guselkumab）的单药迭代和JNJ-78934804的复方升维，构成了强生构筑新专利护城河、维持高价值产品线生命周期的唯一防线 。5.2 卫生经济学与结果研究（HEOR）：支撑高昂定价的底层逻辑 双重靶向疗法的商业化面临的最尖锐矛盾在于“定价上限”。现有的单一先进生物制剂年治疗费用普遍高达5万至10万美元，如果按单药价格的简单叠加来为联合疗法定价，必将彻底击穿全球绝大多数医保支付系统（如美国Medicare、欧洲HTA及中国国家医保目录）的承受底线。 因此，双靶点复方制剂的定价必须高度依赖于具有说服力的卫生经济学（HEOR）证据链。通过马尔可夫模型（Markov Model）等高级统计工具进行的系统性评价显示，虽然组合疗法大幅推高了初始用药成本，但在针对重度难治性CD患者的长期经济学评估中，这种投资是具有高度成本效益的 。例如，在一项基于中国医疗体系视角的成本效益分析中，以人均GDP的1倍（2024年约为13444.68美元）作为意愿支付阈值，包含阿达木单抗和乌司奴单抗序贯或联合使用的治疗策略（ADA-UST）产生了最高的绝对净货币效益（NMB），达到35850.93美元，并展现出极佳的增量成本效益比（ICER），即每增加一个质量调整生命年（QALY）的成本为2285.38美元 。 这一经济学优势的核心在于“手术规避”（Surgery Avoidance）。对于多线生物制剂失败的难治性患者而言，如果缺乏有效挽救手段，只能被迫接受全结肠切除术、小肠切除术及永久性造口手术。这些侵入性干预带来的高昂外科及住院费用、持续的术后护理成本、短肠综合征的静脉营养开销，以及患者终身劳动力丧失所引发的社会经济损失，其综合成本极其惊人 。JNJ-78934804凭借其将临床缓解率翻倍和实现深层黏膜愈合的能力，能够有效阻断疾病向不可逆的外科终点演进。强生完全可以通过收集长期的无激素缓解和手术规避数据，与全球支付方谈判签订“基于价值的定价（Value-Based Pricing）”和“按疗效付费（Outcomes-based）”协议，从而理直气壮地获取双重靶向带来的商业溢价 。六、投资人的资本配置逻辑与战略重构 JNJ-78934804的数据发布以及各大MNC在2026年摩根大通（JPM）医疗健康大会上的战略表态，正在驱动资本向免疫与炎症领域的特定赛道重新集结 。

Alvotech (NASDAQ US: ALVO, ICELAND: ALVO, STOCKHOLM: ALVO SDB) Financial Highlights A supplemental long‑form earnings release providing additional operational details and business update for Q1 2026 is available at: https://investors.alvotech.com/earnings-calendar under “Q1 2026 Earnings Call”. The supplemental document is provided solely for reference and is not part of this SEC Form 6‑K. The Form 6‑K should not be read together with, or construed as referring to, the supplemental long‑form release. Q1 2026 Highlights Total revenues1 were $105.9m compared to $132.8m in the same period last year Adjusted EBITDA1 was $24.4m with Gross Margin of 57% Post-period end: Submitted a Marketing Authorization Application to the European Medicines Agency for AVT16 and AVT80, proposed biosimilars to Entyvio® (vedolizumab) Commenced a pivotal efficacy and safety study for AVT29 for Eylea HD® in support of a submission in the US in 2028 Entered into a strategic manufacturing agreement with FUJIFILM Biotechnologies, establishing a U.S.-based second source of commercial supply Comments by Lisa Graver, CEO: “During the quarter, we continued to execute across multiple strategic priorities, including progressing the FDA resubmission process, expanding our commercial portfolio, advancing high-value pipeline programmes, and further strengthening our manufacturing platform. “In recent months, we have implemented several important improvements across our quality systems and operations. Importantly, we have deliberately taken additional time to substantially de-risk future operational and regulatory disruption and to ensure that when we resubmit to the FDA, we do so with a package that fully addresses the agency’s requirements and supports the long-term growth and value of the company. “Both revenues and EBITDA were impacted in the quarter by a slowdown in production related to these facility improvements. We expect a recovery in product revenues as normal operations resume. “Commercially, we continue to see strong underlying demand for biosimilars across our marketed portfolio, including continued momentum for our Humira biosimilar in the U.S. market. “At the same time, we advanced several important pipeline programmes, including a marketing submission to the European Medicines Agency for our proposed biosimilar to Entyvio, and continued progress with our programme for high-dose Eylea, where the first patients have now been enrolled in a pivotal clinical study. “In addition, we have today announced a strategic manufacturing agreement with FUJIFILM Biotechnologies covering multiple products in our portfolio. This is an important step to further strengthen and diversify our manufacturing network that supports the next phase of commercial launches. “We remain highly focused on resubmitting our BLAs pending approval with the U.S. FDA in the second quarter. Actions taken since last year strengthen not only the packages for resubmission but also our operational platform more broadly, supporting future pipeline execution. With these improvements, we believe the company is well positioned for its next phase of growth.” Outlook for 2026 Management anticipates total revenues to be in the range of $650-$700 million and adjusted EBITDA to be in the range of $180-220 million in 2026. The lower end of the revenue range assumes no revenues from new launches into the U.S. market in 2026. Invitation to Q1 2026 management presentation: Join us to listen to the live audio webcast at 8:00 AM EST (12:00 GMT, 13:00 CET) on Thursday, May 7, 2026. The audio webcast will be accessible via the following link: https://edge.media-server.com/mmc/p/ppckxq33 To participate via telephone in the Q&A session, please register using this link to obtain your PIN: https://register-conf.media-server.com/register/BIdfe56c21c8d448efb09f3c30405bb00d Presentation slides for the webcast and other materials are available under “Q1 2026 Earnings Call” at: https://investors.alvotech.com/earnings-calendar For further information, please contact: Media – alvotech.media@alvotech.com Benedikt Stefansson Sarah MacLeod Investors - alvotech.ir@alvotech.com Dr. Balaji V Prasad Benedikt Stefansson The information was submitted for publication through the agency of the contact persons. Financial calendar: Annual or interim results will be released on the dates specified below, after the close of U.S. markets. An earnings call is held on the following day, after release of the results. Please note that all dates are subject to change. About Alvotech Alvotech is a biotechnology company, founded by Robert Wessman, focused solely on the development and manufacture of biosimilar medicines for patients worldwide. Alvotech seeks to be a global leader in the biosimilar space by delivering high-quality, cost-effective products and services, enabled by a fully integrated approach and broad in-house capabilities. Five biosimilars are already approved and marketed in multiple global markets, including biosimilars to Humira® (adalimumab), Stelara® (ustekinumab), Simponi® (golimumab), Eylea® (aflibercept) and Prolia®/Xgeva® (denosumab). The current development pipeline includes nine disclosed biosimilar candidates aimed at treating autoimmune disorders, eye disorders, osteoporosis, respiratory disease, and cancer. Alvotech has formed a network of strategic commercial partnerships to provide global reach and leverage local expertise in markets that include the United States, Europe, Japan, China, and other Asian countries and large parts of South America, Africa and the Middle East. For more information, please visit https://www.alvotech.com. None of the information on the Alvotech website shall be deemed part of this press release. For more information, please visit our investor portal, and our website or follow us on social media on LinkedIn, Facebook, Instagram, and YouTube. Forward Looking Statements Certain statements in this communication may be considered “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements include, for example, Alvotech’s expectations regarding competitive advantages, business prospects and opportunities including pipeline product development, future plans and intentions, regulatory submissions, review and interactions, the potential approval and commercial launch of its product candidates, the timing of regulatory approval, market launches and financial projections. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by Alvotech and its management, are inherently uncertain and are inherently subject to risks, variability, and contingencies, many of which are beyond Alvotech’s control. Factors that may cause actual results to differ materially from current expectations include, but are not limited to factors set forth in the sections entitled “Risk Factors” and “Cautionary Note Regarding Forward-Looking Statements” in documents that Alvotech may from time-to-time file or furnish with the SEC. There may be additional risks that Alvotech does not presently know or that Alvotech currently believes are immaterial that could also cause actual results to differ from those contained in the forward-looking statements. These forward-looking statements are provided for illustrative purposes only and are not intended to serve as, and must not be relied on by an investor as, a guarantee, assurance, prediction or definitive statement of a fact or probability. Alvotech does not undertake any duty to update these forward-looking statements or to inform the recipient of any matters of which any of them becomes aware of which may affect any matter referred to in this communication. Alvotech disclaims any and all liability for any loss or damage (whether foreseeable or not) suffered or incurred by any person or entity as a result of anything contained or omitted from this communication and such liability is expressly disclaimed. Non IFRS Financial Measures This Presentation may include projections of certain financial measures not presented in accordance with International Financial Reporting Standards (“IFRS”) including, but not limited to, Adjusted Revenues, EBITDA and certain ratios and other metrics derived therefrom. These non-IFRS financial measures are not measures of financial performance in accordance with IFRS and may exclude items that are significant in understanding and assessing the Company’s financial results. Therefore, these measures should not be considered in isolation or as an alternative to net income, cash flows from operations or other measures of profitability, liquidity or performance under IFRS. You should be aware that the Company’s presentation of these measures may not be comparable to similarly-titled measures used by other companies. The Company believes these non-IFRS measures of financial results provide useful information to management and investors regarding certain financial and business trends relating to the Company’s financial condition and results of operations. The Company believes that the use of these non-IFRS financial measures provide an additional tool for investors to use in evaluating ongoing operating results and trends and in comparing the Company’s financial measures with other similar companies, many of which present similar non-IFRS financial measures to investors. These non-IFRS financial measures are subject to inherent limitations as they reflect the exercise of judgments by management about which expense and income are excluded or included in determining these non-IFRS financial measures. Due to the high variability and difficulty in making accurate forecasts and projections of some of the information excluded from these projected measures, together with some of the excluded information not being ascertainable or accessible, the Company is unable to quantify certain amounts that would be required to be included in the most directly comparable IFRS financial measures without unreasonable effort. Consequently, no disclosure of estimated comparable IFRS measures is included and no reconciliation of the forward-looking non-IFRS financial measures is included. For the same reasons, the Company is unable to address the probable significance of the unavailable information, which could be material to future results. 1 Figures are adjusted to exclude items that are not indicative of our ongoing operating performance. See disclaimer on ‘Non IFRS Financial Measures’ at the end of this press release. As a foreign private issuer, Alvotech is not required to, and does not, prepare or file quarterly financial statements under IFRS or with the SEC. The financial information included in this Form 6-K reflects management’s current estimates and is presented for the purpose of providing an interim business update.