Sufentanil Citrate

官方公众号 点击蓝字关注我们 通信作者：叶颖江 教授 从“多模式”到“精准多模式”：腹部手术围手术期疼痛管理指南（2025版）解读 鞠辉   沈凯   叶颖江 北京大学人民医院麻醉科 北京大学人民医院胃肠外科 引用本文: 鞠辉, 沈凯, 叶颖江. 从“多模式”到“精准多模式”：腹部手术围手术期疼痛管理指南（2025版）解读[J]. 中华普通外科杂志, 2025, 40(11): 833-838. DOI: 10.3760/cma.j.cn 113855-20251011-00523. 长按识别下图二维码，阅读本刊更多内容： 摘要 腹部手术围手术期疼痛管理指南（2025版）发布，标志着对疼痛管理进一步的规范化和精确化。本解读从多模式镇痛的角度对指南推荐意见涉及的镇痛药物和非药物性策略在围手术期的联合应用进行了详细的分析，有助于涉及疼痛管理的围手术期医护团队更好地了解疼痛管理的方法策略。    2005年以来，加速康复外科（enhanced recovery after surgery，ERAS）指南的发布，使ERAS医疗模式在全球得到广泛推荐和应用 ［ 1 ］ 。ERAS指采用一系列有循证医学证据支持的围手术期处理优化措施，以有效降低手术患者机体应激反应，达到快速康复的目的。核心是以患者为中心，促进短期和长期预后，其中围手术期镇痛占有重要的地位，通过多种方式方法减轻应激反应。 横断面调查研究揭示：腹部手术后中重度急性疼痛的发生率高达40%~50% ［ 2 ］ 。疼痛控制不佳与术后并发症增加有关，对生活质量和功能的恢复产生负面效应，也是持续疼痛和长期服用阿片药物的危险因素。尽管近年来急性疼痛的治疗手段明显增加，急性疼痛发生的绝对数量和程度仍是临床医师要应对的巨大挑战。阿片类药物单次或患者自控镇痛泵的使用仍然是疼痛治疗的基础手段，但其显著的不良反应限制了临床应用。 腹部手术后急性疼痛包括体表切口导致的躯体痛，内脏器官损伤导致的内脏痛以及组织损伤、局部炎症反应导致的炎性痛 ［ 3 , 4 ］ ，炎性痛可造成痛觉超敏、促进急性疼痛向慢性疼痛转变 ［ 5 ］ 。疼痛性质不同，减少疼痛和降低疼痛程度的方法也不同。本指南始终围绕这一点撰写，为围手术期腹部手术镇痛提供了指导意见。微创术式包括多孔腹腔镜技术和单孔腹腔镜技术、达芬奇手术的广泛开展，减少了切口大小，降低了疼痛的程度，与开放手术相比也改变了麻醉和镇痛方式方法的选择。针对不同的腹部手术可以采用超声引导下区域神经阻滞技术、硬膜外阻滞、鞘内吗啡、静脉镇痛药物等多种方法。临床医师根据经验，采取各种组合，以达到最佳治疗效果，减少并发症的发生。近年来随着超声引导神经阻滞的发展和普及，以及微创术式的开展，躯体痛已逐步得到有效控制，硬膜外阻滞的使用率亦有明显下降 ［ 6 ］ ，内脏痛及炎性痛成为急性疼痛管理的主要矛盾，是近年来疼痛管理的关注焦点，也是疼痛药物研发的靶点。尽管阿片类药物仍是疼痛治疗的基本药物，但由于多模式镇痛理念的普及以及新型镇痛药物的问世，传统阿片类药物用量逐步下降。 指南的制订也体现了疼痛管理的重要性。疼痛管理是国务院办公厅关于推动公立医院高质量发展中的重要一环，国家卫生健康委指引下，各级医院探索建立医院疼痛综合管理制度，规范医院疼痛综合管理流程，提升疼痛综合管理医疗服务质量和安全。腹部手术数量多，围手术期疼痛的预防和处理需要外科和麻醉科的共同参与来实施规范化、精准化围手术期疼痛管理，促进腹部手术患者术后快速康复。中华医学会外科学分会、中华医学会麻醉学分会组织多领域专家撰写本指南，对接受腹部手术的成人患者围手术期疼痛涉及的医护人员提供了参考依据，对具体措施采取了强推荐（明确显示干预措施利大于弊或弊大于利）和弱推荐（不能确定干预措施的利弊），特别指出指南不具有强制性，不作为医疗事故鉴定和医学责任认定依据。 一、 围手术期疼痛管理目标和原则 一项国际共识明确在临床研究中围手术期疼痛管理的六大终点指标 ［ 7 ］ ：24 h疼痛程度（静息痛和动态痛），术后恶心呕吐发生，术后恢复质量指数（QoR Score or QoR-15），胃肠道功能恢复时间，下地活动时间和睡眠质量。其他观察指标还包括呼吸功能：包括咳嗽、深呼吸功能恢复，减少术后阿片类药物的使用和不良反应，减少各种镇痛措施可能引起的伤害如神经损伤和重要脏器损害，减少慢性痛的发生等。近年来也关注疼痛给患者带来的心理影响。 围手术期镇痛贯穿于术前、术中和术后康复的全过程，要实现这些目标就需要系统化干预减轻患者疼痛，包括个体化镇痛、全程动态评估、多模式镇痛等。 二、 围手术期疼痛术前影响因素和评估工具 术前焦虑、抑郁、疼痛灾难化等心理状态、疼痛敏感性较高、有慢性疼痛史、睡眠障碍、年轻患者、女性、肥胖、吸烟等均是术后急性疼痛的危险因素，与术后疼痛的强度和持续时间、镇痛药物使用量密切相关 ［ 8 ］ 。基因多态性可能影响阿片类药物代谢效率，导致镇痛效果差异 ［ 9 ］ 。文化背景和教育水平也会影响疼痛管理的效果。 疼痛评分是围手术期疼痛治疗重要的追踪指标，一方面观察镇痛的效果，另一方面偏离常规治疗曲线的异常，可能提示术后并发症的发生 ［ 10 ］ 。 视觉模拟评分（visual analogue scale，VAS）、数字评定量表（numerical rating scale，NRS）是目前临床实践和科研中最常用的单维度评估工具。语言障碍或认知功能受限的人群常采用面部表情疼痛量表（faces pain scale，FPS），理解力及语言能力低的患者则可以采用语言评价量表（verbal rating scale，VRS）。需要注意的是这些疼痛评分可能受情绪、睡眠和其他药物等多重因素影响，要谨慎对待，避免过度镇痛 ［ 11 ］ 。 多维度评估工具常用的量表包括简明疼痛量表（brief pain inventory，BPI）、McGill疼痛问卷（McGill pain questionnaire，MPQ）及其简化版（SF-MPQ）、整体疼痛量表（global pain scale，GPS）、健康调查简表（the 36-item short form health survey，SF-36）、临床调整疼痛评估工具（clinically aligned pain assessment tool，CAPA）等。这些多维度评估量表除了评估疼痛的性质、强度外，还关注疼痛对于患者情绪、心理、睡眠及日常行为/生活质量的影响。 基于功能的评分得到越来越多的重视，但目前临床实践没有公认的对围手术期基于功能的动态痛的评估方法 ［ 12 ］ 。 三、 多模式镇痛常用的方法 （一）术前宣教和非药物性策略 术前宣教是强推荐的策略之一，有助于改善围手术期焦虑、降低疼痛评分、减少术后阿片类药物用量，可以采用标准化和个体化视听教育、心理干预等方法，使患者熟悉手术流程，对疼痛有一定预期，也建立疼痛能得到很好治疗的信心，避免实际疼痛程度和预期疼痛完全缓解之间产生巨大的差异 ［ 13 ］ 。虚拟现实技术通过其独特的沉浸式体验和注意力分散效果，可以起到相似的作用 ［ 14 ］ 。 此外，ERAS中涉及的术前准备措施包括戒烟戒酒、改善营养状态和锻炼，对术后疼痛评分也有积极的作用。非药物性策略还包括认知行为疗法、针灸、电刺激等。 （二）术前预防性镇痛 对于术前预防性镇痛，指南均为弱推荐。包括术前预防性使用加巴喷丁或普瑞巴林以及阿片类药物和非甾体类抗炎药（non-steroidal anti-inflamamm atory drugs，NSAIDs），包括选择性环氧化酶-2（cyclooxygenase-2，COX-2）抑制剂，需要注意药物相关不良反应，如加巴喷丁可能增加术后嗜睡发生风险 ［ 15 ］ 以及NSAIDs类常见的出血等不良反应 ［ 16 ］ 。 （三）区域阻滞 近年来区域阻滞技术被认为是多模式镇痛的核心组成部分，包括硬膜外阻滞、筋膜平面阻滞和局部切口浸润。 腹部手术种类多，切口部位多，可以根据切口的部位选择不同方式的不同入路的阻滞方法。指南中为强推荐级别的方法包括腹横肌平面（TAP）阻滞、髂腹下/髂腹股沟神经阻滞、伤口局部浸润。腰方肌阻滞（quadratus lumborum block，QLB）、椎旁阻滞和硬膜外阻滞均为弱推荐。此外，竖脊肌阻滞是2016年首次报道的新型筋膜间平面阻滞技术，有研究表明其在腹部手术中镇痛的有效性，由于循证证据尚不充分，暂未列入本次指南 ［ 17 ］ 。 1.TAP阻滞（推荐级别：强；证据分级：中）：常用入路包括肋缘下入路和腋中线入路。TAP阻滞的镇痛效果与阻滞入路、手术切口位置密切相关。对于肝胆、胰脾、胃等上腹部手术，建议采用肋缘下TAP阻滞 ［ 18 ］ 。对于结直肠、阑尾和疝等下腹部手术，建议采用腋中线入路TAP阻滞 ［ 19 ］ 。 2.腹直肌鞘阻滞（推荐级别：弱；证据等级：中）：腹直肌鞘阻滞可以有效降低腹部手术后（包括胆囊切除术、疝修补术等）疼痛评分，尤其适用于正中切口的腹部开放手术（包括开腹胃、结肠、肠系膜血栓等手术）（推荐级别：弱）。对于腹腔镜胆囊切除术，腹直肌鞘阻滞的作用存在争议。 3.QLB（推荐级别：弱；证据等级：中）：QLB（推荐级别：弱）是将局部麻醉药注入到腰方肌邻近的筋膜间隙内，阻滞在其内行走的胸腰神经而发挥镇痛作用，穿刺路径主要包含前路、后路、外侧入路，肌内入路因其有效性和并发症使用少。QLB前路穿刺阻滞范围可达T 6~L 1，适用全腹部手术 ［ 20 ］ ，缓解内脏痛的效果优于其他入路，腰丛阻滞概率大。目前常使用0.2%~0.5%的罗哌卡因单侧0.2~0.4 ml/kg或15~30 ml。外侧入路和后侧入路适用于脐下腹部手术。与TAP阻滞相比，QLB具有更长的镇痛时间，效果更好 ［ 21 ］ ，但对操作者的技术要求较高。 4.椎旁阻滞和硬膜外阻滞（推荐级别：弱；证据等级：中）：这两种阻滞在指南中也是弱推荐，单次和连续椎旁阻滞可减轻多种腹部手术后疼痛，在开放腹股沟疝手术、腹腔镜胆囊切除术和开放肝脏手术、开放胰腺癌根治术和开放胆囊切除术患者中有良好的镇痛效果，并降低术后恶心呕吐的发生风险 ［ 22 ］ 。硬膜外阻滞镇痛和抗应激作用确切，促进胃肠道恢复和减少阿片药物使用，对死亡率可能影响不大。鞘内吗啡的使用指南未提及，在某些国家有不同程度使用。椎旁阻滞和硬膜外阻滞更具侵入性并具有更大的不良反应风险，表现为低血压、恶心呕吐、尿潴留、下肢运动/感觉异常和操作相关的失败率，这是硬膜外阻滞在全球范围使用比例下降的原因。在腹部手术患者中，筋膜平面内神经阻滞与硬膜外阻滞对术后早期疼痛评分的影响可能相似 ［ 23 ］ ，外周神经阻滞操作的安全性高于硬膜外穿刺，后者越来越多地被筋膜间隙平面阻滞和（或）手术部位浸润所替代。 5.髂腹下/髂腹股沟神经阻滞（推荐级别：强；证据等级：中）：髂腹下/髂腹股沟神经阻滞可以减轻腹股沟疝修补术后疼痛，优于TAP阻滞 ［ 24 ］ 、不劣于QLB的镇痛效果。 6.伤口局部浸润（推荐级别：强；证据等级：高）：局部伤口浸润（单次给药或连续给药）镇痛效果确切，促进早期活动和缩短住院时间，在腹部手术患者中效果尤其明显 ［ 25 ］ ，在切口痛更突出的开放腹部手术中优势更大。采用右美托咪定或地塞米松作为局部麻醉药佐剂可延长局部伤口浸润的镇痛时间。 7.竖脊肌阻滞：竖脊肌平面阻滞是将局部麻醉药注射在竖脊肌和横突尖端之间的筋膜平面，药物扩散到脊神经而发挥作用。根据注射部位的不同，可向上下扩散2~5个平面，广泛用于胸腹手术的镇痛。其安全性高、操作简单、扩散范围广 ［ 26 ］ 。 硬膜外阻滞、椎旁阻滞和竖脊肌阻滞、QLB对躯体痛和内脏痛均有效果，但TAP和腹直肌鞘阻滞对内脏痛没有减轻作用。 肝肾功能不全的患者接受单次区域阻滞时可以使用正常浓度和剂量的局部麻醉药；若重复给药或行连续区域阻滞，应根据患者情况减少局部麻醉药用量。 （四）围手术期全身镇痛药物选择 指南中作为强推荐级别使用的药物包括κ受体激动剂、NSAIDs、右美托咪定和艾司氯胺酮。 1.利多卡因：静脉利多卡因有镇痛、抗炎、抗肿瘤等多重作用，对伤口愈合和结直肠手术后胃肠道功能的早期恢复可能也有积极作用，目前研究正在进行 ［ 27 ］ 。ERAS指南建议使用利多卡因作为多模式镇痛的组成部分，但尚需更多证据。常用的策略为负荷剂量应≤1.5 mg/kg，持续10~20 min；静脉输注应≤1.5 mg·kg -1·h -1，累计输注时间≤24 h，累积剂量不应超过120 mg/h。围手术期静脉输注利多卡因常规治疗窗内全身毒性反应事件少见且多表现为轻微不良反应，如嗜睡、头晕、口唇麻木、耳鸣和心动过缓，无需特殊治疗；此外不应与其他局部麻醉药相关措施同时或在其作用时间内使用，应随时备有20%的脂质乳剂。 2. κ受体激动剂：κ受体（尤其是胃肠道内高表达）参与感受内脏伤害性刺激，κ受体激动剂作为指南强推荐级的药物，是近年来研究针对内脏痛的热点药物，可有效缓解腹部手术后疼痛，较μ受体激动剂更具优势（推荐级别：强；证据等级：高）。κ受体激动剂包括非选择性κ受体激动剂（如羟考酮、纳布啡等）和选择性κ受体激动剂（如安瑞克芬），作用部位分为外周选择性（如安瑞克芬）和非外周选择性，外周选择性κ受体激动剂在有效镇痛的同时可减少呼吸抑制、镇静等中枢神经系统不良反应。羟考酮、布托啡诺和纳布啡在腹腔镜手术后的镇痛尤其内脏痛的优势已得到证实。安瑞克芬是全球首个获得镇痛适应证的高选择性外周κ阿片受体激动剂，通过降低脊髓背根神经节和外周神经末梢的兴奋性发挥外周性止痛和止痒作用，其外周选择性强，脑/血浆浓度比值为0.001，可避免呼吸抑制、镇静、成瘾等中枢不良反应，用于腹部手术患者术后镇痛不仅疗效优异，同时安全性好，术后恶心呕吐的发生率低于安慰剂组 ［ 28 ］ 。后续的研究应进一步探索安瑞克芬减少恶心呕吐的作用机制。此外安瑞克芬还具有止痒作用，是否可减少围手术期瘙痒的发生有待进一步验证。 3. NSAIDs：NSAIDs包括非选择性COX抑制剂和选择性COX-2抑制剂，是控制炎性疼痛的重要手段 ［ 29 ］ ，选择性COX-2抑制剂优于非选择性COX抑制剂，可缩短择期腹部手术患者术后排气、排便及耐受饮食时间，降低胃肠手术后恶心呕吐发生率和肠梗阻风险。NSAIDs是术后镇痛的基础用药，在多模式镇痛中发挥重要作用。 4.右美托咪定：围手术期静脉使用右美托咪定包括镇痛泵复合使用减少腹部手术后24 h内的阿片类药物用量并改善镇痛效果 ［ 30 ］ ，且术后恶心呕吐和瘙痒发生率更低、患者满意度更高，同时还具有抗炎、免疫保护和改善胃肠道抗微循环作用，可能对内脏痛也有效果。在围手术期应用优势明显，但需注意心动过缓、低血压和过度镇静等不良事件的发生风险。指南建议对于2 h以内的手术，可以仅给予0.5~1.0 μg/kg负荷量，注意给药时间尽量在15 min以上；对于长时间手术，可考虑持续以0.2~0.7 μg·k -1·h -1的速率输注右美托咪定，建议手术结束前至少1 h停药以避免影响麻醉苏醒。与阿片类药物复合用于术后自控静脉镇痛时，右美托咪定的常用背景输注剂量为0.03~0.05 μg·kg -1·h -1、单次按压剂量0.06~0.10 μg/kg。 5.艾司氯胺酮：围手术期应用艾司氯胺酮可减少腹部手术后24 h内的阿片类药物用量、降低术后24 h疼痛评分，且不增加中枢神经系统不良反应及恶心呕吐发生风险（推荐级别：强），不良事件的发生率更低 ［ 31 ］ 。其抗抑郁的作用近年在围手术期领域研究也得到关注。艾司氯胺酮是氯胺酮的右旋体，效价比约为2∶1。用作全身麻醉辅助用药时，单次静脉注射剂量一般为0.2~0.3 mg/kg，维持输注时速率不超过0.3 mg·kg -1·h -1；需注意停药时间，避免苏醒延迟。艾司氯胺酮常与阿片类药物联合使用于自控静脉镇痛，48 h的镇痛泵艾司氯胺酮剂量为0.5~2.0 mg/kg，背景输注速率0.010～0.033 mg·kg -1·h -1；单次按压的剂量通常每次不超过0.5 mg，间隔时间不少于15 min。 四、 精准多模式镇痛的实施 多模式镇痛才能实现疼痛管理目标，有效的多模式镇痛要使患者的应激反应、疼痛强度和疼痛带来的痛苦最小化，避免大剂量单一药物带来的不良反应，加速患者早期下地活动和恢复生活能力 ［ 32 ］ 。 在术前评估和全程动态评估的基础上通过多模式镇痛，联合使用不同作用机制的药物，通过多种给药途径包括静脉、区域神经阻滞和神经轴阻滞等以及非药物手段，针对疼痛产生的多个环节进行干预，从而达到更全面、更安全的疼痛管理方式，并根据手术方式和患者情况进行个体化镇痛。 多模式镇痛的核心组成部分是区域神经阻滞，尤其是筋膜平面内神经阻滞和局部伤口浸润，选择最佳技术的挑战在于日常临床实践中的实用性，建议采用较少数量的多功能、有效且易于执行的方法，如TAP。 在术前策略的基础上，针对腹部手术疼痛的三个来源，常选择筋膜平面内神经阻滞或伤口浸润阻滞（单次或持续）+κ受体激动剂（分次或自控镇痛，优先外周选择性κ受体激动剂）+NSAIDs+静脉镇痛药物（如右美托咪定、艾司氯胺酮、利多卡因）组合使用。对于开放性腹部手术，硬膜外阻滞+NSAIDs也是可选方案，但需注意并发症 ［ 33 , 34 , 35 ］ 。 五、 结语 腹部手术术式广泛，患者群体多样，疼痛的程度和对镇痛的需求差异很大，镇痛策略需要考虑多种相关因素。 规范化的多模式、精准镇痛不仅可改善腹部手术患者的疼痛管理效果、提高患者满意度，更有助于减少术后并发症、缩短住院时间、降低慢性疼痛发生风险、提升患者术后康复质量，为患者尽早回归正常的生活和工作提供基础保障。本指南基于国内外最新的循证医学证据，为腹部手术患者的围手术期疼痛管理提供了指导。 参考文献 （在框内向上滑动手指即可浏览全部参考文献） [1] Ljungqvist O ,Scott M ,Fearon KC . Enhanced recovery after surgery: a review[J]. JAMA Surg, 2017,152(3):292-298. DOI: 10.1001/jamasurg.2016.4952 .  返回引文位置Google Scholar  百度学术  万方数据 [2] Liu Y ,Xiao S ,Yang H ,et al. Postoperative pain-related outcomes and perioperative pain management in China: a population-based study[J]. Lancet Reg Health West 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Business development: Secures royalty economic interests in two early stage partnered assets through XOMA Royalty’s announced expected acquisition of LAVA Therapeutics. Company acquisitions: •Completed XOMA Royalty’s acquisitions of Turnstone Biologics and HilleVax; • announced acquisitions of LAVA Therapeutics and Mural Oncology; • acted as structuring agent for XenoTherapeutics’ acquisition of ESSA Pharma. Key Pipeline advancements: • Zevra Therapeutics submitted a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) seeking marketing approval for arimoclomol as a treatment for Niemann-Pick Type C; • Rezolute Bio reconfirmed its expectations to announce topline data in December from its Phase 3 ersodetug trial in patients with congenital hyperinsulinism (HI) and announced alignment with FDA on streamlined design for ongoing Phase 3 trial of ersodetug in tumor HI; •Gossamer Bio expects topline results from PROSERA, its Phase 3 trial of seralutunib in pulmonary atrial hypertension (PAH), in February 2026. Cash receipts: In the first nine months of 2025, XOMA Royalty received $43.9 million in royalties and milestones from its partners, including $14.3 million from royalties during the third quarter. EMERYVILLE, Calif., Nov. 12, 2025 (GLOBE NEWSWIRE) -- XOMA Royalty Corporation (NASDAQ: XOMA), the biotech royalty aggregator, reported its 2025 third quarter and year to date financial results and highlighted recent actions that have the potential to deliver additional shareholder value. “We continue to execute on innovative ways to increase optionality within our portfolio while maintaining a healthy cash balance and limiting dilution to our shareholders,” stated Owen Hughes, Chief Executive Officer of XOMA Royalty. “Growing royalty receipts reflect solid commercial execution on the part of our partners. We look forward to several clinical readouts over the coming months and quarters that, if positive, can meaningfully shape our business trajectory.” Royalty and Milestone Acquisitions CompanyAsset and Transaction DetailLAVA TherapeuticsXOMA Royalty will secure an economic interest in PF-08046052, which is being developed by Pfizer, and JNJ-89853413, which is being developed by Johnson & Johnson, upon closing its acquisition of LAVA. Company Acquisitions CompanyTransaction DetailsTurnstone BiologicsXOMA Royalty acquired Turnstone for $0.34 in cash per share of Turnstone common stock plus one non-transferable contingent value right (CVR). HilleVaxXOMA Royalty acquired HilleVax for a cash payment of $1.95 per share plus a non-transferable CVR that entitles holders to receive certain potential payments. LAVA TherapeuticsXOMA Royalty will acquire LAVA for (i) an initial cash amount per share of $1.04 plus (ii) a non-transferable CVR per share representing the right to receive certain cash payments, including (A) the previously announced rights to receive, among other things, 75% of the net proceeds related to LAVA’s two partnered assets plus 75% of any net proceeds from any out license or sale of LAVA’s unpartnered programs, plus (B) a new right to receive up to approximately $0.23 per CVR depending on the final determination after closing of certain potential liabilities.Mural OncologyXOMA Royalty will acquire Mural Oncology through its wholly owned subsidiary XRA 5 Corp. for between $2.035 and $2.24 in cash per share. The acquisition is expected to close in the fourth quarter of 2025.1,2XenoTherapeutics Acquisition of ESSA PharmaXOMA Royalty acted as structuring agent for XenoTherapeutics’ completed acquisition of ESSA Pharma. Pipeline Partner Updates through November 10, 2025 PartnerEventRezoluteIn September, Rezolute announced it had achieved alignment with FDA on a significantly streamlined clinical development path for its ongoing Phase 3 study (upLIFT) of ersodetug for the treatment of tumor HI. Topline results are expected in the second half of 2026.3TakedaThe first patient was dosed in Takeda’s Phase 3 clinical trial investigating mezagitamab as a treatment for adults with IgA Nephropathy.Zevra TherapeuticsOn July 28, Zevra announced it had submitted an MAA to EMA for the evaluation of arimoclomol for the treatment of Niemann-Pick Disease Type C (NPC)4.Gossamer BioActivated first clinical site for the global, registrational Phase 3 SERANATA study examining seralutinib in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD) in the fourth quarter of 20255.Daré BiosciencesAnnounced positive interim safety and efficacy results from its ongoing Phase 3 clinical trial evaluating the contraceptive effectiveness, safety, and acceptability of Ovaprene®, an investigational monthly, hormone-free intravaginal contraceptive.6 Anticipated Partner Events of Note through Mid-2026 PartnerEventRezoluteAnnounces topline data in December 20257 from sunRIZE Phase 3 clinical trial, which is investigating ersodetug in infants and children with congenital HI.Gossamer BioPublishes topline results from the Phase 3 PROSERA Study evaluating seralutinib in Functional Class II and III PAH patients5.Daré BioscienceMakes DARE to PLAY™ Sildenafil Cream available commercially via prescription in the fourth quarter of 2025 as a compounded drug under Section 503B of the Federal Food, Drug, and Cosmetic Act.8Commences one of two registrational Phase 3 clinical trials investigating Sildenafil Cream, 3.6%, for the treatment of female sexual arousal disorder9. Discussions with FDA regarding endpoint assessment for Phase 3 clinical studies of Sildenafil Cream, 3.6% continue8.Day One BiopharmaceuticalsPer the Day One conference call held on November 4, 2025, Ipsen, Day One’s partner outside the U.S., expects to receive EMA regulatory decision on its application to commercialize tovorafenib in the European Union. 1 https://investors.xoma.com/news-events/press-releases/detail/482/mural-oncology-announces-entry-into-agreement-to-be 2 http://ml.globenewswire.com/Resource/Download/538d82a8-0fae-4d41-8687-71845b9b67c2 3 https://ir.rezolutebio.com/news/detail/361/rezolute-announces-alignment-with-fda-on-streamlined-design-for-ongoing-phase-3-trial-of-ersodetug-in-tumor-hyperinsulinism 4 https://investors.zevra.com/news-releases/news-release-details/zevra-therapeutics-submits-marketing-authorization-application 5 https://ir.gossamerbio.com/news-releases/news-release-details/gossamer-bio-announces-third-quarter-2025-financial-results-and 6 https://ir.darebioscience.com/news-releases/news-release-details/positive-interim-phase-3-results-highlight-potential-ovaprener 7 https://ir.rezolutebio.com/news/detail/366/rezolute-reports-first-quarter-fiscal-2026-financial-results-and-provides-business-update 8 https://ir.darebioscience.com/news-releases/news-release-details/dare-bioscience-reports-second-quarter-2025-financial-results 9 https://ir.darebioscience.com/news-releases/news-release-details/dare-bioscience-announces-phase-3-plans-sildenafil-cream-36 Third Quarter and Year to Date 2025 Financial Results Tom Burns, Chief Financial Officer of XOMA Royalty, commented, “In the first nine months of 2025, we have received $43.9 million in cash from partners, of which $30.3 million were royalty payments related to commercial sales and $13.6 million in milestone payments and fees. In the third quarter, we received $14.3 million in cash from our partners’ commercial sales. With well-executed commercialization efforts by our partners and the emergence of new commercial opportunities from within our portfolio, XOMA Royalty has the potential to become a self-sustaining entity from royalties alone over the near term.” Income and Revenue: Income and revenue for the three and nine months ended September 30, 2025, were $9.4 million and $38.4 million, respectively, as compared with $7.2 million and $19.8 million for the corresponding periods of 2024. The increase in both periods presented was primarily driven by increased income related to VABYSMO and OJEMDA. Research and Development (R&D) Expenses: R&D expenses for the three and nine months ended September 30, 2025, were $69 thousand and $1.4 million, respectively, compared with $0.8 million and $2.0 million for each of the corresponding periods of 2024. R&D expenses in the first quarter of 2025 and the three- and nine-month periods of 2024 were related to the clinical trial costs incurred subsequent to XOMA Royalty’s acquisition of Kinnate in April 2024 related to KIN-3248 and the associated wind-down activities. General and Administrative (G&A) Expenses: G&A expenses for the three and nine months ended September 30, 2025, were $9.7 million and $25.7 million, respectively, as compared with $8.0 million and $27.5 million for the corresponding periods of 2024. The increase of $1.7 million for the three months ended September 30, 2025, as compared to the same period in 2024, was primarily due to an increase in business development and deal-related costs, partially offset by a decrease in stock-based compensation expense. For the nine months ended September 30, 2025, the decrease of $1.8 million, as compared to the same period in 2024, was primarily due to costs related to exit packages for Kinnate senior leadership in the second quarter of 2024 and a decrease in stock-based compensation expense, partially offset by an increase in business development and deal-related costs. XOMA Royalty’s G&A expenses included non-cash stock-based compensation expenses during the three and nine months ended September 30, 2025, of $1.8 million and $5.4 million, respectively, as compared to $2.6 million and $8.1 million for the corresponding periods of 2024. The 2024 periods reflect non-cash stock-based compensation related to the appointment of Mr. Hughes to full-time Chief Executive Officer and issuance of performance stock units. Credit Losses on Purchased Receivables: During the nine months ended September 30, 2024, XOMA Royalty recorded one-time, non-cash credit losses on purchased receivables associated with the Aronora and Agenus assets. To date, there have been no credit losses in 2025. Amortization of Intangible Assets: Amortization of intangible assets relates to the IP acquired in the Company’s acquisitions of Pulmokine in November 2024 and the mezagitamab economics from the BioInvent transaction in May 2025. Amortization of non-cash intangible assets were $0.9 million and $2.1 million for the three and nine months ended September 30, 2025. Gains on Acquisitions: In the third quarter of 2025, XOMA Royalty recorded gains on acquisitions of $17.9 million for HilleVax and $1.8 million for Turnstone. Interest Expense: For the three and nine months ended September 30, 2025, interest expense was $3.3 million and $10.0 million, respectively, as compared with $3.5 million and $10.4 million for the corresponding periods of 2024. Interest expense relates to the Blue Owl Loan established in December 2023. Other Income, net: For the three and nine months ended September 30, 2025, other income, net was $0.7 million and $8.5 million, respectively, as compared with $1.9 million and $5.9 million for the corresponding periods of 2024. Net Income: XOMA Royalty reported net income of $14.1 million and $25.6 million for the three and nine months ended September 30, 2025, as compared to net losses of $17.2 million and $9.9 million in the corresponding periods of 2024. Cash Position: On September 30, 2025, XOMA Royalty had cash and cash equivalents of $130.6 million, including $85.4 million in restricted cash. The restricted cash balance included $43.3 million related to the assumed HilleVax lease, $39.9 million reserved to fund the Mural acquisition, and $2.2 million related to the Blue Owl Loan. Cash and cash equivalents of $106.4 million as of December 31, 2024, included $4.8 million in restricted cash related to the Blue Owl Loan. In the third quarter of 2025, XOMA Royalty received $14.3 million in cash receipts from royalties and commercial payments and paid $1.4 million in dividends on the XOMA Royalty Perpetual Preferred stocks. In the first nine months of 2025, XOMA Royalty received $43.9 million in cash receipts, including $30.3 million in royalties and commercial payments and $13.6 million in milestone payments and fees. During the first nine months of 2025, XOMA Royalty deployed $25.0 million to acquire additional assets for its royalty and milestone portfolio, repurchased approximately 108,510 shares of its common stock for a cost of $2.4 million, and paid $4.1 million in dividends on the XOMA Royalty Perpetual Preferred stocks. About XOMA Royalty CorporationXOMA Royalty is a biotechnology royalty aggregator playing a distinctive role in helping biotech companies achieve their goal of improving human health. XOMA Royalty acquires the potential future economics associated with pre-commercial and commercial therapeutic candidates that have been licensed to pharmaceutical or biotechnology companies. When XOMA Royalty acquires the future economics, the seller receives non-dilutive, non-recourse funding they can use to advance their internal drug candidate(s) or for general corporate purposes. The Company has an extensive and growing portfolio of assets (asset defined as the right to receive potential future economics associated with the advancement of an underlying therapeutic candidate). For more information about the Company and its portfolio, please visit www.xoma.com or follow XOMA Royalty Corporation on LinkedIn. Forward-Looking Statements/Explanatory NotesCertain statements contained in this press release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, including statements regarding the timing and amount of potential commercial payments to XOMA Royalty and other developments related to VABYSMO® (faricimab-svoa), OJEMDA™ (tovorafenib), MIPLYFFA™ (arimoclomol), XACIATO™ (clindamycin phosphate) vaginal gel 2%, IXINITY® [coagulation factor IX (recombinant)], DSUVIA® (sufentanil sublingual tablet), and Sildenafil Cream, 3.6%; the potential occurrences of the events listed under “Anticipated 2025 Events of Note”; the anticipated timings of regulatory filings and approvals related to assets in XOMA Royalty’s portfolio; and the potential of XOMA Royalty’s portfolio of partnered programs and licensed technologies generating substantial milestone and royalty proceeds over time. In some cases, you can identify such forward-looking statements by terminology such as “anticipate,” “intend,” “believe,” “estimate,” “plan,” “seek,” “project,” “expect,” “may,” “will”, “would,” “could” or “should,” the negative of these terms or similar expressions. These forward-looking statements are not a guarantee of XOMA Royalty’s performance, and you should not place undue reliance on such statements. These statements are based on assumptions that may not prove accurate, and actual results could differ materially from those anticipated due to certain risks inherent in the biotechnology industry, including those related to the fact that our product candidates subject to out-license agreements are still being developed, and our licensees may require substantial funds to continue development which may not be available; we do not know whether there will be, or will continue to be, a viable market for the products in which we have an ownership or royalty interest; and if the therapeutic product candidates to which we have a royalty interest do not receive regulatory approval, our third-party licensees will not be able to market them. Other potential risks to XOMA Royalty meeting these expectations are described in more detail in XOMA Royalty's most recent filing on Form 10-Q and in other filings with the Securities and Exchange Commission. Consider such risks carefully when considering XOMA Royalty's prospects. Any forward-looking statement in this press release represents XOMA Royalty's beliefs and assumptions only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. XOMA Royalty disclaims any obligation to update any forward-looking statement, except as required by applicable law. EXPLANATORY NOTE: Any references to “portfolio” in this press release refer strictly to milestone and/or royalty rights associated with a basket of drug products in development. Any references to “assets” in this press release refer strictly to milestone and/or royalty rights associated with individual drug products in development. As of the date of this press release, the commercial assets in XOMA Royalty’s milestone and royalty portfolio are VABYSMO® (faricimab-svoa), OJEMDA™ (tovorafenib), MIPLYFFA™ (arimoclomol), XACIATO™ (clindamycin phosphate) vaginal gel 2%, IXINITY® [coagulation factor IX (recombinant)], and DSUVIA® (sufentanil sublingual tablet). All other assets in the milestone and royalty portfolio are investigational compounds. Efficacy and safety have not been established. There is no guarantee that any of the investigational compounds will become commercially available. XOMA ROYALTY CORPORATION CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited) (in thousands, except share and per share amounts) Three Months Ended September 30, Nine Month Ended September 30, 2025 2024 2025 2024 Income and Revenues: Income from purchased receivables under the EIR method$6,962 $5,423 $19,039 $9,985 Income from purchased receivables under the cost recovery method 1,857 1,040 9,125 1,910 Revenue from contracts with customers 225 25 9,250 6,050 Revenue recognized under units-of-revenue method 307 709 978 1,828 Total income and revenues 9,351 7,197 38,392 19,773 Operating expenses: Research and development 69 817 1,431 2,011 General and administrative 9,734 8,020 25,682 27,485 Credit losses on purchased receivables - 14,000 - 23,000 Amortization of intangible assets 878 - 2,077 - Total operating expenses 10,681 22,837 29,190 52,496 Income (Loss) from operations (1,330) (15,640) 9,202 (32,723) Other income (expense) Gains on acquisitions 18,004 - 18,004 19,316 Change in fair value of embedded derivative related to RPA - - - 8,100 Interest expense (3,301) (3,493) (10,004) (10,446) Other income, net 727 1,890 8,456 5,900 Net income$14,100 $(17,243) $25,658 $(9,853) Income tax expense$(49) $- $(49) $- Net income (loss)$14,051 $(17,243) $25,609 $(9,853) Net income (loss) available to (attributable to) common stockholders, basic$8,981 $(18,611) $15,192 $(13,957) Basic net income per share available to common stockholders$0.74 $(1.59) $1.26 $(1.20) Weighted average shares used in computing basic net income per share available to common stockholders 12,137 11,712 12,038 11,645 Net income (loss) available to (attributable to) common stockholders, diluted$12,683 $(18,611) $21,505 $(13,957) Diluted net income per share available to common stockholders$0.70 $(1.59) $1.20 $(1.20) Weighted average shares used in computing diluted net income per share available to common stockholders 18,141 11,712 17,932 11,645 XOMA ROYALTY CORPORATION CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited) (in thousands, except share and per share amounts) September 30, December 31, 2025 2024 ASSETS Current assets: Cash and cash equivalents$45,189 $101,654 Short-term restricted cash 45,288 1,330 Investment in equity securities 1,521 3,529 Trade and other receivables, net 3,573 1,839 Short-term royalty and commercial payment receivables under the EIR method 13,269 14,763 Short-term royalty and commercial payment receivables under the cost recovery method 900 413 Prepaid expenses and other current assets 967 2,076 Total current assets 110,707 125,604 Long-term restricted cash 40,076 3,432 Property and equipment, net 24 32 Operating lease right-of-use assets 272 319 Long-term royalty and commercial payment receivables under the EIR method 4,678 4,970 Long-term royalty and commercial payment receivables under the cost recovery method 57,864 55,936 Exarafenib milestone asset 3,500 3,214 Investment in warrants 595 - Intangible assets, net 44,556 25,909 Other assets - long term 879 1,861 Total assets$263,151 $221,277 LIABILITIES, CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable$2,654 $1,053 Accrued and other liabilities 4,134 5,752 Contingent consideration under RPAs, AAAs, and CPPAs - 3,000 Operating lease liabilities 2,508 446 Unearned revenue recognized under units-of-revenue method 1,320 1,361 Preferred stock dividend accrual 1,368 1,368 Current portion of long-term debt 14,345 11,394 Contingent value rights liabilities - current portion 1,976 - Total current liabilities 28,305 24,374 Unearned revenue recognized under units-of-revenue method – long-term 3,473 4,410 Exarafenib milestone contingent consideration 3,500 3,214 Long-term operating lease liabilities 20,678 483 Long-term debt 94,382 106,875 Contingent value rights liabilities - long-term 4,807 - Deferred tax liability 49 - Total liabilities 155,194 139,356 Convertible preferred stock, $0.05 par value, 5,003 shares authorized, issued and outstanding as of September 30, 2025 and December 31, 2024 20,019 20,019 Stockholders’ equity: 8.625% Series A cumulative, perpetual preferred stock, $0.05 par value, 984,000 shares authorized, issued and outstanding as of September 30, 2025 and December 31, 2024 49 49 8.375% Series B cumulative, perpetual preferred stock, $0.05 par value, 3,600 shares authorized, 1,600 shares issued and outstanding as of September 30, 2025 and December 31, 2024 — — Common stock, $0.0075 par value, 277,333,332 shares authorized, 12,310,300 and 11,952,377 shares issued and outstanding as of September 30, 2025 and December 31, 2024, respectively 92 90 Additional paid-in capital 1,301,542 1,298,747 Accumulated other comprehensive income 121 73 Accumulated deficit (1,213,866) (1,237,057) Total stockholders’ equity 87,938 61,902 Total liabilities, convertible preferred stock and stockholders’ equity$263,151 $221,277 XOMA ROYALTY CORPORATIONCONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS(unaudited)(in thousands) Nine Months Ended September 30, 2025 2024 Cash flows from operating activities: Net income$25,609 $(9,853)Adjustments to reconcile net income to net cash provided by (used in) operating activities: Adjustment for income from EIR method purchased receivables 627 (9,985)Stock-based compensation expense 5,358 8,136 Gains on acquisitions (18,004) (19,316)Credit losses on purchased receivables — 23,000 Gain on sale of equity securities (3,663) — Income tax expense 49 — Common stock contribution to 401(k) 141 118 Amortization of intangible assets 2,077 — Depreciation 8 8 Accretion of long-term debt discount and debt issuance costs 1,136 996 Non-cash lease expense 47 45 Change in fair value of equity securities (1,230) (624)Change in fair value of available-for-sale debt securities classified as cash equivalents 49 104 Change in fair value of derivatives 10 — Changes in assets and liabilities: Trade and other receivables, net (1,187) (41)Prepaid expenses and other assets 1,839 (72)Accounts payable and accrued liabilities (3,248) (1,348)Operating lease liabilities (268) (185)Unearned revenue recognized under units-of-revenue method (978) (1,828)Net cash provided by (used in) operating activities 8,372 (10,845) Cash flows from investing activities: Net cash acquired in Kinnate acquisition — 18,926 Net cash, cash equivalents and restricted cash acquired in Turnstone acquisition 3,943 — Net cash, cash equivalents and restricted cash acquired in HilleVax acquisition 46,832 — Payments of consideration under RPAs, AAAs, and CPPAs (8,000) (37,000)Receipts under RPAs, AAAs, and CPPAs 3,139 26,263 Payment for BioInvent contract-based intangible asset (20,725) — Payment of contingent consideration related to Kinnate IP asset (550) — Purchase of property and equipment — (17)Purchase of equity securities (99) — Sale of equity securities 6,999 — Net cash used in investing activities 31,539 8,172 Cash flows from financing activities: Principal payments – debt (10,598) (6,902)Debt issuance costs and loan fees paid in connection with long-term debt (80) (740)Payment of preferred stock dividends (4,104) (4,104)Repurchases of common stock (2,395) (13)Proceeds from exercise of options and other share-based compensation 3,422 4,127 Taxes paid related to net share settlement of equity awards (2,019) (2,429)Net cash used in financing activities (15,774) (10,061) Net increase (decrease) in cash, cash equivalents, and restricted cash 24,137 (12,734)Cash, cash equivalents, and restricted cash at the beginning of the period 106,416 159,550 Cash, cash equivalents, and restricted cash at the end of the period$130,553 $146,816 Supplemental Cash Flow Information: Cash paid for interest$11,906 $9,985 Cash paid for taxes$277 $— Non-cash investing and financing activities: Accrual of contingent value rights liability in the Turnstone acquisition$1,110 $— Accrual of contingent value rights liability in the HilleVax acquisition$5,673 $— Right-of-use assets obtained in exchange for operating lease liabilities in the HilleVax acquisition$22,525 $— Relative fair value basis reduction of right-of-use assets in the HilleVax acquisition$(22,525) $— Transaction costs in connection with the Turnstone acquisition included in accounts payable$92 $— Transaction costs in connection with the HilleVax acquisition included in accounts payable and accrued expenses$449 $— Excise tax accrual due to stock repurchases$24 $— Preferred stock dividend accrual$1,368 $1,368 Estimated fair value of the Exarafenib milestone asset$— $2,922 Estimated fair value of the Exarafenib milestone contingent consideration$— $2,922 Right-of-use assets obtained in exchange for operating lease liabilities in the Kinnate acquisition$— $824 Relative fair value basis reduction of rights-of-use assets in the Kinnate acquisition$— $(824)Accrual of contingent consideration under the Affitech CPPA$— $3,000 Accrual of contingent consideration under the LadRX AAA$— $1,000 Investor contact:Media contact:Juliane SnowdenKathy VincentXOMA Royalty CorporationKV Consulting & Management+1-646-438-9754kathy@kathyvincent.com juliane.snowden@xoma.com