Relatlimab

来源：Nat Med 药学基础研究第12期（总第52期） —————————————————————————————— 本期Nature Medicine（Volume 32, Issue 7, July 2026）聚焦肿瘤免疫治疗、神经退行性疾病基因治疗、RNA靶向疗法、心血管再生医学及代谢药物联合策略等多个药学前沿领域。精选5篇与药理机制、靶点、信号通路及临床转化密切相关的研究，涵盖帕金森病双靶点基因治疗（TH+AADC）、SOD1肌萎缩侧索硬化症siRNA偶联物（RAG-17）、心梗后心力衰竭microRNA-132抑制剂（CDR132L）、肥胖患者tirzepatide联合抗肌生成素抗体apitegromab保留瘦体重，以及复发性胶质母细胞瘤anti-LAG-3/anti-PD-1联合免疫检查点治疗。这些研究体现了从靶点发现到临床转化的完整链条，为创新药物研发提供了重要循证依据。 ▎本期目录 · Contents 1. 帕金森病双靶点基因治疗I期试验 Dual-target gene therapy in Parkinson's disease: a multicenter phase 1 trial 2. SOD1肌萎缩侧索硬化症siRNA偶联物I期试验 Oligonucleotide–siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial 3. 心梗后心衰microRNA-132抑制剂CDR132L II期试验 The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: a randomized phase 2 trial 4. Tirzepatide联合抗肌生成素抗体apitegromab保留瘦体重II期试验 Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial 5. 复发性胶质母细胞瘤anti-LAG-3联合anti-PD-1 I期试验 Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial —————————————————————————————— ▎临床试验·Clinical Trials Dual-target gene therapy in Parkinson's disease: a multicenter phase 1 trial Nat Med 丨 2026-06 丨 Article（多中心、开放标签、剂量递增I期临床试验） ▍帕金森病双靶点基因治疗I期试验 研究背景 帕金森病（PD）的核心病理机制为黑质多巴胺能神经元进行性丢失，导致纹状体多巴胺合成不足。既往基于腺相关病毒（AAV）的芳香族L-氨基酸脱羧酶（AADC）单基因治疗仍依赖外源性左旋多巴补充，而多基因共递送受限于AAV包装容量。酪氨酸羟化酶（TH）和AADC是多巴胺合成通路中的两个关键限速酶，同时靶向二者可实现多巴胺自主合成。本研究旨在评估新型AAV载体BBM-P002共递送组成型活性TH和AADC基因在帕金森病患者中的安全性和耐受性。 核心发现 • BBM-P002采用新型AAVT42载体共递送组成型活性TH和AADC两个限速酶基因，实现多巴胺自主合成策略，突破了既往单基因治疗依赖外源性左旋多巴的局限。 • 10例中晚期帕金森病患者接受双侧壳核内灌注，设4个剂量队列（4.0×10¹¹至1.2×10¹² vg），12个月内主要终点为安全性和耐受性。 • 试验达到主要终点：未出现剂量限制性毒性或药物相关严重不良事件；23例不良事件均被判定与BBM-P002无关，且主要为轻度、一过性事件。 • 未观察到系统性毒性或具有临床意义的免疫原性反应，表明基因治疗载体在脑内局部递送具有良好的生物安全性。 • 研究结果支持BBM-P002继续推进临床开发，为下一步有效性评估和剂量优化奠定基础。 领域意义 本研究是全球首个靶向TH和AADC双限速酶基因的帕金森病基因治疗临床试验，展示了AAVT42载体在脑内局部基因递送的安全可行性。该'双靶点'策略有望实现多巴胺自主合成，减少对外源性左旋多巴的依赖，为帕金森病病因学治疗开辟了新路径。 英文摘要 (Abstract) Restoring striatal dopamine synthesis is a promising gene therapy strategy for Parkinson's disease. Previous adeno-associated virus-mediated aromatic L-amino acid decarboxylase (AADC) monotherapies remain dependent on exogenous levodopa, whereas multigene delivery is constrained by strict adeno-associated virus packaging limits. A 'dual approach' targeting the two rate-limiting enzymes, tyrosine hydroxylase (TH) and AADC, offers the potential for autonomous dopamine synthesis. We report the 12-month primary safety and tolerability outcomes of a multicenter, open-label, dose-escalation, phase 1 trial evaluating BBM-P002, a new adeno-associated virus vector—AAVT42—codelivering constitutively active TH and AADC. Ten participants with moderate-to-advanced Parkinson's disease were enrolled and received bilateral intraputaminal infusions across doses of 4.0 × 10¹¹ vg (Cohort 1; n = 1), 6.0 × 10¹¹ vg (Cohort 2; n = 2), 1.0 × 10¹² vg (Cohort 3; n = 2) and 1.2 × 10¹² vg (Cohort 4; n = 5). The trial achieved its primary outcome, as BBM-P002 demonstrated a favorable safety and tolerability profile within 12 months post-treatment. No dose-limiting toxicities or drug-related serious adverse events occurred. A total of 23 adverse events were reported, all judged unrelated to BBM-P002 and primarily mild and transient. Systemic toxicity and clinically meaningful immunogenicity were absent. In conclusion, intraputaminal delivery of BBM-P002 was safe and well tolerated in this phase 1 trial, supporting continued clinical development. ClinicalTrials.gov registration: NCT05822739. DOI: 10.1038/s41591-026-04436-0 丨 ClinicalTrials.gov: NCT05822739 —————————————————————————————— Oligonucleotide–siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial Nat Med 丨 2026-07 丨 Article（首次人体、开放标签、剂量递增I期临床试验） ▍SOD1肌萎缩侧索硬化症siRNA偶联物I期试验 研究背景 肌萎缩侧索硬化症（ALS）是一种致死性神经退行性疾病，部分由超氧化物歧化酶1（SOD1）功能获得性突变引起。目前针对SOD1-ALS的精准治疗手段有限，小干扰RNA（siRNA）可通过RNA干扰机制特异性沉默突变基因表达。然而，siRNA的中枢神经系统（CNS）递送一直是技术瓶颈。本研究开发了RAG-17，一种利用辅助寡核苷酸偶联平台增强CNS递送的siRNA靶向SOD1疗法，在临床前模型中验证疗效后开展了首次人体试验。 核心发现 • RAG-17采用辅助寡核苷酸偶联平台技术，显著增强了siRNA向中枢神经系统的递送效率，在SOD1(G93A) ALS啮齿动物模型中挽救了运动神经元退行性变、延缓疾病进展并延长生存期，即使晚期给药仍有效。 • 在食蟹猴中，鞘内注射RAG-17实现了剂量依赖性且持久的CNS中SOD1 mRNA和脑脊液中SOD1蛋白水平降低，验证了跨物种的药效学一致性。 • 首次人体试验纳入6例SOD1-ALS患者，设两个剂量队列（初始60 mg和90 mg，逐步递增至维持剂量150 mg或180 mg），主要安全性终点达标。 • 治疗中出现的不良事件（TEAEs）发生率33%（2/6），均为轻中度，包括肌束颤动（2例）和丙氨酸氨基转移酶升高（1例），均可自行缓解，无严重不良事件。 • 关键次要终点显示脑脊液SOD1蛋白分别降低69%（队列1，第240天）和56%（队列2，第210天），血浆神经丝轻链（NfL）分别降低62%和52%，且研究结束时无患者需要机械通气或死亡。 领域意义 本研究展示了寡核苷酸-siRNA偶联技术在CNS药物递送中的突破性潜力，RAG-17在SOD1-ALS患者中实现了显著的靶蛋白降低和神经退行性生物标志物改善。该策略为其他神经退行性疾病的RNA靶向治疗提供了可借鉴的技术平台和临床转化范式。 英文摘要 Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease partly caused by gain-of-function mutations in superoxide dismutase 1 (SOD1). Here we developed RAG-17, an siRNA-targeting SOD1, using an accessory oligonucleotide conjugate platform for enhanced central nervous system (CNS) delivery. Preclinically, RAG-17 rescued motor neuron degeneration, delayed disease progression, preserved motor function and extended survival in SOD1(G93A) ALS rodents, even with advanced-stage treatment. In cynomolgus monkeys, intrathecal RAG-17 led to dose-dependent, durable reductions in SOD1 mRNA (CNS) and protein (cerebrospinal fluid (CSF)). In a first-in-human trial in patients with SOD1-ALS (n = 6), participants were assigned to two cohorts—cohort 1 (n = 3) received an initial 60 mg dose (seven doses total) and cohort 2 (n = 3) received an initial 90 mg dose (six doses total). The dose was escalated in 30 mg steps to maintenance doses of 150 mg (n = 5) or 180 mg (n = 1). Thus, the primary safety endpoint was met, showing acceptable safety and tolerability. Treatment-emergent adverse events (TEAEs) occurred in 33% of participants (two of six). All TEAEs were mild to moderate, including muscle tremor (two patients) and elevated alanine aminotransferase (one patient), all of which resolved. No serious adverse events were reported. Furthermore, no other clinically meaningful changes were observed in laboratory parameters, vital signs, the ALS Functional Rating Scale-Revised score, physical or neurological examinations or ECG. The key secondary endpoints showed CSF SOD1 reductions of 69% (cohort 1, day 240) and 56% (cohort 2, day 210), and plasma neurofilament light chain reductions of 62% (cohort 1) and 52% (cohort 2), from baseline; no patient required invasive mechanical ventilation or died by the end of the study. These results demonstrate a favorable safety outcome, supporting the continued clinical evaluation of RAG-17 for SOD1-ALS. ClinicalTrials.gov registration: NCT05903690. DOI: 10.1038/s41591-026-04491-7 丨 ClinicalTrials.gov: NCT05903690 —————————————————————————————— The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: a randomized phase 2 trial Nat Med 丨 2026-05 丨 Article（多国、随机、双盲、安慰剂对照II期临床试验，HF-REVERT试验） ▍心梗后心衰microRNA-132抑制剂CDR132L II期试验 研究背景 心肌梗死后不良心室重塑是导致心力衰竭进展的关键病理过程。MicroRNA-132（miR-132）已被证实为不良心脏重塑的中心调控因子，通过调控多种下游靶基因参与心肌肥厚、纤维化和凋亡等病理通路。CDR132L是一种人工合成的反义寡核苷酸类miR-132抑制剂，在临床前模型中可逆转不良心室重塑。本研究（HF-REVERT试验）旨在评估CDR132L在心肌梗死后左心室收缩功能障碍患者中的安全性、耐受性和有效性。 核心发现 • CDR132L是全球首个进入II期临床试验的microRNA靶向心脏病治疗药物，采用多国、随机、双盲、安慰剂对照设计，纳入294例心梗后3-14天内左心室收缩功能障碍患者。 • 患者随机分配接受CDR132L 5 mg/kg、10 mg/kg或安慰剂，每4周静脉给药一次共3次，联合指南推荐的标准药物治疗，280例患者纳入改良意向性治疗分析。 • CDR132LS安全性和耐受性良好，未出现肝毒性、肾毒性、血液学毒性或心脏毒性信号，不良事件发生率与安慰剂组相当。 • 主要终点（6个月时左心室收缩末期容积指数百分比变化）在所有组别均有改善，但CDR132L组与安慰剂组间无统计学显著差异；次要终点（LVEF、整体纵向应变、NT-proBNP）亦无显著差异。 • 预设的探索性分析提示，基线时存在重度不良重塑的患者可能从CDR132L治疗中获益，支持在慢性心力衰竭人群中进一步评估该药物。 领域意义 尽管HF-REVERT试验的主要终点未达到统计学显著性，但本研究首次在临床层面验证了microRNA靶向治疗在心血管疾病中的安全性和靶点调控能力。探索性亚组分析结果为后续在慢性心力衰竭和特定高风险表型患者中的精准化研究提供了重要方向，推动了RNA靶向疗法在心血管领域的临床转化。 英文摘要 MicroRNA-132 (miR-132) is a central regulator of adverse cardiac remodeling. Here we evaluated CDR132L, a synthetic antisense oligonucleotide miR-132 inhibitor, in a multinational, randomized, double-blind, placebo-controlled phase 2 trial (HF-REVERT) in patients with recent myocardial infarction (MI) and left ventricular (LV) systolic dysfunction. Within 3–14 days after MI, 294 patients were randomized to receive CDR132L 5 mg kg−1, CDR132L 10 mg kg−1 or placebo as three intravenous doses at 4-week intervals plus guideline-directed therapy. In total, 280 patients (245 men and 35 women) who received at least one dose of the study drug were included in the modified intention-to-treat population. CDR132L was well tolerated, with no hepatic, renal, hematologic or cardiac toxicity signals. The primary endpoint—the percentage change in LV end-systolic volume index at 6 months—improved in all groups but did not differ significantly between the CDR132L groups (5 mg kg−1 and 10 mg kg−1) and the placebo group. Secondary endpoints, including LV ejection fraction, global longitudinal strain and N-terminal pro B-type natriuretic peptide, were also not significantly different between the CDR132L and placebo groups. Prespecified exploratory analyses suggested potential benefits of CDR132L treatment in patients with advanced adverse remodeling at baseline, supporting further evaluation of CDR132L, including in chronic heart failure conditions. ClinicalTrials.gov: NCT05350969. DOI: 10.1038/s41591-026-04408-4 丨 ClinicalTrials.gov: NCT05350969 —————————————————————————————— Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial Nat Med 丨 2026-06 丨 Article（随机、双盲、安慰剂对照II期临床试验，EMBRAZE研究） ▍Tirzepatide联合抗肌生成素抗体apitegromab保留瘦体重II期试验 研究背景 肠促胰岛素类似物如tirzepatide（替尔泊肽）在实现显著减重的同时，会导致瘦体重（lean mass）与总体重成比例丢失，可能对健康和功能产生不良影响。肌生成素（myostatin）是骨骼肌质量的负调控因子，抑制其激活可增加肌肉质量。Apitegromab是一种研究性全人源单克隆抗体，可选择性抑制肌生成素激活。本研究（EMBRAZE试验）旨在评估tirzepatide联合apitegromab在减重过程中保留瘦体重的疗效和安全性。 核心发现 • EMBRAZE研究是全球首个评估GLP-1/GIP双受体激动剂联合抗肌生成素抗体在减重中保留瘦体重的概念验证性临床试验，纳入102例超重或肥胖成人，1:1随机分配接受tirzepatide联合apitegromab（10 mg/kg）或tirzepatide联合安慰剂。 • 第24周时，apitegromab组瘦体重丢失较安慰剂组减少1.9 kg（80% CI: 1.2-2.7 kg，P=0.001），而两组间总体重下降幅度相似，表明apitegromab选择性保留了瘦体重。 • apitegromab使瘦体重保留率达到54.9%（相对于安慰剂组），即超过一半的瘦体重流失被有效阻止。 • 药代动力学分析显示apitegromab trough浓度和总潜伏态肌生成素（药效学标志物）均随时间升高并在约16周后达到平台期，证实了持续的靶点调控。 • 不良事件发生率在apitegromab组（76%）和安慰剂组（71%）间总体相似，严重不良事件各组均为1例（2%），表明联合治疗安全可耐受。 领域意义 本研究开创性地证明了在肠促胰岛素类减重药物中联合靶向肌生成素通路可有效保留瘦体重，为解决GLP-1类药物减重中肌肉流失这一临床难题提供了精准联合策略。该概念验证结果支持apitegromab在肥胖和肌肉减少症等适应症中的进一步开发，体现了从靶点机制到临床转化的完整路径。 英文摘要 Loss of lean mass in proportion to total weight loss is observed with incretin mimetic therapies such as tirzepatide and has the potential to adversely affect health and function. Apitegromab is an investigational, fully human monoclonal antibody that selectively inhibits myostatin activation and is, thereby, capable of increasing muscle mass. In the randomized, double-blind, placebo-controlled phase 2 EMBRAZE study, adults with overweight or obesity (n = 102) were randomized 1:1 to receive tirzepatide plus apitegromab (10 mg kg−1) or tirzepatide plus placebo. At week 24, apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2−2.7) kg less lean mass loss than placebo (P = 0.001), despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo. In participants receiving apitegromab, trough concentrations of apitegromab and total latent myostatin, a pharmacodynamic marker, both increased over time and reached a plateau after approximately 16 weeks. Incidence of adverse events (AEs) (% (95% CI)) was generally similar across apitegromab-treated participants and placebo-treated participants, with 39 of 51 (76% (63−86%)) and 36 of 51 (71% (57−81%)) participants experiencing an AE, respectively. Serious adverse events (SAEs) were balanced and experienced by one of 51 (2% (0−10%)) participants in each arm. In summary, this proof-of-concept study demonstrated that selective targeting of myostatin by apitegromab was well tolerated and effective in preserving lean mass when combined with tirzepatide. ClinicalTrials.gov identifier: NCT06445075. DOI: 10.1038/s41591-026-04440-4 丨 ClinicalTrials.gov: NCT06445075 —————————————————————————————— Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial Nat Med 丨 2026-07 丨 Article（多中心、开放标签、序贯分配I期临床试验） ▍复发性胶质母细胞瘤anti-LAG-3联合anti-PD-1 I期试验 研究背景 胶质母细胞瘤（GBM）是最致命的原发性脑肿瘤之一，免疫检查点抑制剂在GBM中的单药治疗效果有限。淋巴细胞激活基因3（LAG-3）是参与T细胞耗竭的免疫检查点分子，在GBM免疫抑制微环境中发挥重要作用，是潜在的治疗靶点。Relatlimab是抗LAG-3单克隆抗体，nivolumab是抗PD-1单克隆抗体，两者联合可能通过双重检查点阻断协同恢复抗肿瘤免疫。本研究旨在评估relatlimab单药或联合nivolumab在复发性GBM中的安全性和初步抗肿瘤活性。 核心发现 • 本研究采用多中心、开放标签、序贯分配I期设计，纳入46例复发性GBM患者（每组23例），评估抗LAG-3抗体relatlimab单药或联合抗PD-1抗体nivolumab的安全性和初步疗效。 • 主要终点安全性达标：单药组最大耐受剂量为relatlimab 800 mg，联合组为relatlimab 160 mg/nivolumab 240 mg；联合组6/23例出现3-4级治疗相关不良事件，单药组未观察到。 • 新辅助给药（手术前给药）与两种治疗方案均关联瘤内CD8+ T细胞浸润增加，提示LAG-3阻断可改善GBM免疫抑制微环境中的T细胞浸润。 • 探索性分析发现基线干扰素信号升高和T细胞克隆性增加的肿瘤在联合治疗中获得持久反应的可能性更高，揭示了预测性生物标志物。 • 12个月总生存率在relatlimab单药组为34.8%，联合治疗组为52.2%，尽管该研究设计不以疗效评估为目的，但联合治疗展示了有前景的临床信号。 领域意义 本研究首次在胶质母细胞瘤中系统评估了LAG-3免疫检查点阻断的策略，证明其安全可行并提供了免疫学和临床疗效的初步证据。新辅助给药策略结合生物标志物探索为GBM精准免疫治疗提供了新思路，支持LAG-3/PD-1双重阻断在GBM中的进一步临床开发。 英文摘要 Lymphocyte activation gene 3 (LAG-3) is an immune checkpoint implicated in T cell exhaustion and a potential therapeutic target in glioblastoma (GBM). We conducted a multicenter, open-label, phase 1 study with sequential allocation to evaluate the safety and preliminary activity of the anti-LAG-3 antibody relatlimab, administered alone or with the anti-programmed cell death protein 1 (PD-1) antibody nivolumab, in patients with recurrent GBM. Forty-six patients were treated (23 per cohort). The primary endpoint of safety was met, with maximum tolerated doses of 800 mg relatlimab for monotherapy and 160 mg relatlimab/240 mg nivolumab for combination therapy. Treatment-related grade 3–4 adverse events occurred in 6 of 23 patients receiving combination therapy and were not observed with monotherapy. Neoadjuvant administration was associated with increased intratumoral CD8+ T cell infiltration for both monotherapy and combination therapy. Exploratory analyses suggested that tumors with elevated baseline interferon signaling and increased T cell clonality were enriched among patients with durable responses to combination therapy. Twelve-month overall survival was 34.8% with relatlimab alone and 52.2% with combination therapy; however, this study was not designed to assess efficacy. These findings demonstrate an acceptable safety profile and provide preliminary immunologic and clinical signals supporting further evaluation of LAG-3 blockade in GBM. ClinicalTrials.gov identifier: NCT02658981. DOI: 10.1038/s41591-026-04475-7 丨 ClinicalTrials.gov: NCT02658981 —————————————————————————————— —————————————————————————————— ▎参考文献·References [1] Dual-target gene therapy in Parkinson's disease: a multicenter phase 1 trial. Nat Med. 2026 (2026-06). DOI: 10.1038/s41591-026-04436-0 ClinicalTrials.gov: NCT05822739. https://doi.org/10.1038/s41591-026-04436-0 [2] Oligonucleotide–siRNA conjugate for SOD1 amyotrophic lateral sclerosis: a phase 1 trial. Nat Med. 2026 (2026-07). DOI: 10.1038/s41591-026-04491-7 ClinicalTrials.gov: NCT05903690. https://doi.org/10.1038/s41591-026-04491-7 [3] The microRNA inhibitor CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: a randomized phase 2 trial. Nat Med. 2026 (2026-05). DOI: 10.1038/s41591-026-04408-4 ClinicalTrials.gov: NCT05350969. https://doi.org/10.1038/s41591-026-04408-4 [4] Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial. Nat Med. 2026 (2026-06). DOI: 10.1038/s41591-026-04440-4 ClinicalTrials.gov: NCT06445075. https://doi.org/10.1038/s41591-026-04440-4 [5] Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial. Nat Med. 2026 (2026-07). DOI: 10.1038/s41591-026-04475-7 ClinicalTrials.gov: NCT02658981. https://doi.org/10.1038/s41591-026-04475-7 —————————————————————————————— 关注我们，追踪药学前沿

Immunocore reports second quarter financial results and provides a business update KIMMTRAK® (tebentafusp-tebn) net revenues of $115.9 million in Q2 2026, growing by 18% year-over-year Enrollment in Phase 3 TEBE-AM trial for previously treated advanced cutaneous melanoma nearing the target of 540 patients – Data could come as early as end of 2026 Oral presentation of five-year overall survival data showing KIMMTRAK doubles likelihood of being alive at five years for patients with HLA-A*02:01 positive metastatic uveal melanoma Promising Phase 1 brenetafusp monotherapy clinical activity in heavily pretreated HLA-A*02:01-positive patients with advanced melanoma, presented at ASCO, supports selected dose for Phase 3 PRISM-MEL-301 trial in first-line advanced melanoma Cash, cash equivalents and marketable securities of $880 million as of June 30, 2026 Conference call today, August 6 at 8:00 AM ET, 1:00 PM BST (OXFORDSHIRE, England & RADNOR, PA. & GAITHERSBURG, MD., US, 6 August 2026) Immunocore Holdings plc (Nasdaq: IMCR) (“Immunocore” or the “Company”), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, today announced its financial results for the first half ended June 30, 2026, and provided a business update. "The five-year overall survival data for KIMMTRAK underscores the lasting impact of our medicine for patients with metastatic uveal melanoma and reinforces our confidence in the potential of our platform," said Bahija Jallal, CEO of Immunocore. "With enrollment in our Phase 3 TEBE-AM trial nearing target completion and continued progress across our pipeline, we remain focused on our mission: delivering innovative transformative medicines to improve outcomes for patients with serious diseases." Second Quarter and First Half Highlights (including post-period) Financial Results For the second quarter ended June 30, 2026, total net product revenue (or ‘net sales’) arising from the sales of KIMMTRAK was $115.9 million, compared to $98.0 million for the same period in 2025. Q2 2026 sales were $74.9 million in the United States, $34.1 million in Europe, and $6.9 million in international regions. The increase in net product sales was primarily due to increased volumes in the United States and international regions. Research and development (R&D) expenses for Q2 2026 were $73.9 million, compared to $69.0 million for Q2 2025. This increase was primarily due to advancement of our clinical programs, including our three Phase 3 studies. Selling, general and administrative (SG&A) expenses for Q2 2026 were $43.9 million, compared to $42.8 million for Q2 2025. Net loss for Q2 2026 was $0.8 million ($0.02 loss per share) compared to $10.3 million ($0.20 loss per share) for Q2 2025. Net income for the six months ended June 30, 2026, was $12.2 million ($0.23 income per share) compared to a net loss for the six months ended June 30, 2025, of $5.3 million ($0.11 loss per share). Cash, cash equivalents and marketable securities were $880.2 million as of June 30, 2026, as compared to $864.2 million as of December 31, 2025. The Company expects to pay, in the second half of 2026, approximately $120 million in sales-related rebate accruals. KIMMTRAKThe Company’s lead product, KIMMTRAK® (tebentafusp), is approved in 39 countries and has been launched in over 30 countries globally to date for HLA-A*02:01 positive people with unresectable or metastatic uveal melanoma (mUM). KIMMTRAK continues to be the standard of care in all major markets where it is launched. The Company sees three key growth areas in the fifth year since the launch of KIMMTRAK as it plans to expand patient reach, including continued US community and global market penetration in mUM, the potential expansion into 2L+ advanced cutaneous melanoma (CM), and the potential expansion into adjuvant uveal melanoma. Metastatic uveal melanoma KIMMTRAK net product sales were $115.9 million and $222.6 million for the three and six months ended June 30, 2026, representing increases of 18% and 16% respectively, as compared to the same periods in 2025.17% year-over-year quarterly sales growth in the United States with mean duration of treatment of 14 months.21% year-over-year quarterly sales growth combined in Europe and International, driven by increased demand.Five-year overall survival (OS) data, from the Phase 3 trial of KIMMTRAK in patients with unresectable or mUM, were presented at the AACR 2026 meeting, representing the longest follow-up reported for any T cell engager in a solid tumor.KIMMTRAK doubled the likelihood of being alive at five years with an OS rate of 16% versus 8% in the control arm (HR 0.67), and a median OS of 21.6 vs. 16.9 months, respectively.The OS benefit with KIMMTRAK was observed regardless of known baseline characteristics including poor prognostic factors (high tumor burden; elevated lactate dehydrogenase [LDH]) or tumor location.Data also confirmed OS benefit was primarily driven by KIMMTRAK rather than subsequent therapies. 2L+ advanced cutaneous melanoma Enrollment in the registrational Phase 3 TEBE-AM trial, evaluating tebentafusp as monotherapy, and in combination with pembrolizumab, versus a control arm in patients with previously treated advanced CM, is nearing the target of 540 patients. The trial is event driven and topline data could come as early as the end of 2026.There is great unmet need in second- and later-line CM, with no therapy having shown an OS improvement post checkpoint inhibitors in a randomized clinical trial to date. The Company estimates there are up to 4,000 previously treated advanced HLA-A*02:01 positive CM patients in the US and Europe. Adjuvant uveal (or ocular) melanoma The European Organisation for Research and Treatment of Cancer (EORTC) continues to expand the site footprint of the Phase 3 Adjuvant Trial in Ocular Melanoma (ATOM), with patients now enrolling in the United States. The Company estimates the HLA-A*02:01 positive, high-risk adjuvant uveal melanoma patient population could represent up to 1,200 patients in the US and Europe. PRAME portfolio Brenetafusp is the Company’s lead PRAME-A02 ImmTAC bispecific candidate. Brenetafusp is being evaluated in combination with nivolumab in a Phase 3 registrational trial (PRISM-MEL-301) in patients with first-line, advanced cutaneous melanoma, and in a Phase 1/2 clinical trial as monotherapy and in combination across multiple tumor types, including ovarian cancer and non-small cell lung cancer (NSCLC). PRISM-MEL-301 – First PRAME Phase 3 clinical trial with brenetafusp in first-line advanced cutaneous melanoma The Company continues with 1:1 randomization of HLA-A*02:01 positive, first-line, advanced or metastatic cutaneous melanoma patients to brenetafusp 160 mcg + nivolumab or a control arm of either nivolumab or nivolumab + relatlimab.Despite approved therapies, there remains an unmet need for improved progression-free survival and OS in the first-line setting where there is the potential to address an estimated 10,000 HLA-A*02:01 positive patients across US and Europe. Phase 1/2 clinical trials of brenetafusp and IMC-P115C (PRAME-A02 Half-Life Extended) in multiple solid tumors Melanoma The Phase 1/2 data, presented at the 2026 ASCO meeting, showed improved clinical activity of brenetafusp monotherapy, in patients with heavily-pretreated advanced melanoma, with an overall response rate (ORR) of 17% and a disease control rate (DCR) of 67%, in the 160 mcg versus 40 mcg cohort (ORR 6% and DCR 56%), despite patients on the high dose having less favorable prognostic factors. These data support the selected dose for the ongoing Phase 3 PRISM-MEL-301 trial in first-line advanced melanoma.The median OS for brenetafusp monotherapy of 14.3 months was similar to other Phase 1/2 trials of combination therapies in heavily pre-treated patients with advanced melanoma, including studies with autologous cell therapies.Brenetafusp in combination with pembrolizumab (n=6) demonstrated promising clinical activity with ORR of 33% and DCR 67% in patients with PD1 primary resistance (defined as progressive disease within 6 months of starting first PD1-based regimen).Brenetafusp was generally well tolerated as monotherapy and in combination with pembrolizumab. Other tumors and IMC-P115C After observing an initial brenetafusp monotherapy signal in platinum-resistant ovarian cancer (PROC), the Company is evaluating, as part of an ongoing Phase 1/2 trial, combination therapy with bevacizumab in earlier lines, including platinum-sensitive ovarian cancer (PSOC). In the same trial, the Company continues signal detection across multiple metastatic non-small cell lung cancer (NSCLC) cohorts, including combinations with standards of care in earlier-line NSCLC.The Company is enrolling patients in the Phase 1 dose escalation trial evaluating IMC-P115C in patients with multiple solid tumors.The Company expects to present Phase 1/2 data from both trials in the second half of 2026. ImmTAV candidates for a functional cure in infectious diseases The Company’s bispecific TCR technology platform has the potential to offer a new approach for the treatment of certain chronic infections by eliminating evidence of remaining virus in circulation after the patient stops taking medication – known as a ‘functional cure’. The Company is studying an investigational candidate for people living with human immunodeficiency virus (HIV). Phase 1/2 trial of IMC-M113V (Gag-A02) for people living with HIV In July 2026, at the International AIDS Society meeting in Rio de Janeiro, the Company presented translational data, from the first three cohorts of the multiple ascending dose part of the Phase 1/2 trial, demonstrating that IMC-M113V induces robust type I and II interferon-associated immune programs, with stronger induction in participants who maintained viral control after treatment interruption.The data also showed that, in addition to previously demonstrated direct killing of HIV-infected cells, IMC-M113V redirection of T cells results in induction of a robust interferon-associated immune program that may contribute to post-treatment viral control.The Company completed enrollment of additional patients at higher dose cohorts, up to 1200 mcg, as part of the multiple ascending dose (MAD) part of the Phase 1/2 trial. Analysis of the new data is ongoing with results planned to be shared early next year. Tissue-specific down modulation of the immune system for autoimmune diseasesThe key differentiator of the ImmTAAI platform is down modulation of the immune system in a tissue-specific manner. The candidates achieve this by suppressing pathogenic T cells via PD1 receptor agonism only when tethered to the target tissue. Clinical trial sites for the Phase 1 trial with IMC-S118AI are open, and the Company expects the first type 1 diabetes patient to be dosed in the coming weeks.The Company, in collaboration with the University of Florida, published preclinical data in Science Advances demonstrating that in live human pancreas tissue slices from a recent-onset type 1 diabetes donor, IMC-S118AI selectively binds to HLA-A*02:01-positive beta cells and suppresses autoreactive T cell activity around islets, helping protect beta cells and preserve insulin secretion.IMC-S118AI is designed to bind pre-pro-insulin on beta cells of the pancreas and deliver a PD-1 agonist signal to nearby auto-reactive T cells thereby protecting the pancreatic beta cells from T cell attack while preserving beta cell mass.The Company plans to file a CTA or investigational new drug (IND) application in the second half of 2026 for its second autoimmune program, IMC-U120AI (CD1a x PD1), which is designed to target a variety of dermatological diseases including atopic dermatitis. ### About ImmTAC® molecules for cancerImmunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune “cold” low mutation rate tumors. About ImmTAV® molecules and infectious diseases ImmTAV (Immune mobilizing monoclonal TCRs Against Virus) molecules are novel bispecifics that are designed to enable the immune system to recognize and eliminate virally infected cells. Immunocore is advancing a clinical candidate, aiming to achieve sustained control of HIV after people living with HIV stop anti-retroviral therapy (ART), without the risk of virological relapse or onward transmission. This is known as ‘functional cure’. About ImmTAAITM molecules and autoimmune diseases ImmTAAI (Immune mobilizing monoclonal TCRs Against AutoImmune disease) molecules are novel bispecifics that are designed for tissue-specific down modulation of the immune system. When tethered to the tissue of interest, ImmTAAI candidates suppress pathogenic T cells via PD1 receptor agonism. The Company is currently advancing two candidates for autoimmune diseases, including type 1 diabetes and inflammatory dermatological diseases. About TEBE-AM – Phase 3 registrational trial with tebentafusp in previously treated advanced cutaneous melanoma The trial is randomizing patients with second-line or later advanced cutaneous melanoma who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a BRAF kinase inhibitor. Patients are randomized to one of three arms, including tebentafusp – as monotherapy or in combination with an anti-PD1 – or a control arm. The primary endpoint is overall survival. About PRISM-MEL-301 (NCT06112314) – Phase 3 trial with brenetafusp (IMC-F106C, PRAME-A02) in 1L advanced cutaneous melanoma The Phase 3 registrational trial is randomizing HLA-A*02:01-positive patients with previously untreated, advanced or metastatic cutaneous melanoma, to brenetafusp 160 mcg + nivolumab or a control arm of either nivolumab or nivolumab + relatlimab. The primary endpoint of the trial is progression free survival (PFS) by blinded independent central review (BICR), with secondary endpoints of overall survival (OS) and overall response rate (ORR). About the ATOM Phase 3 trial The EORTC-sponsored Phase 3 clinical trial is randomizing HLA-A*02:01-positive patients with high-risk primary uveal melanoma after definitive treatment, by surgery or radiotherapy, and no evidence of metastatic disease on imaging. The trial will randomize patients 1:1 to one of two arms: tebentafusp as monotherapy or observation. The primary endpoint of the trial is relapse-free survival (RFS), with secondary objectives of overall survival and safety and tolerability of tebentafusp. Exploratory objectives include the comparison of the health-related quality of life between the treatment arms and the evaluation of the role of circulating tumor DNA (ctDNA) as a biomarker for the presence of residual disease. About the IMC-F106C-101 Phase 1/2 trial IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumors, including non-small cell lung and ovarian cancers, evaluating brenetafusp in combination arms with standards-of-care. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C (brenetafusp), a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. About Uveal Melanoma Uveal melanoma is a rare and aggressive form of melanoma, which affects the eye. This is the most common primary intraocular malignancy in adults and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK. About Cutaneous Melanoma Cutaneous melanoma (CM) is the most common form of melanoma. It is the most aggressive skin carcinoma and is associated with the vast majority of skin cancer-related mortality. The majority of patients with CM are diagnosed before metastasis but survival remains poor for the large proportion of patients with metastatic disease. Despite recent progress in advanced melanoma therapy, there is still an unmet need for new therapies that improve first-line response rates and duration of response as well as for patients who are refractory to first-line treatments. About KIMMTRAK® KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform, designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom. IMPORTANT SAFETY INFORMATION Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK, with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS. Skin Reactions Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions. Elevated Liver Enzymes Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity. Embryo-Fetal Toxicity KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose. The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate. For more information, please see full Summary of Product Characteristics (SmPC) or full U.S. Prescribing Information (including BOXED WARNING for CRS). About KIMMTRAKConnect Immunocore is committed to helping patients who need KIMMTRAK obtain access via its KIMMTRAKConnect program. The US program provides services with dedicated nurse case managers who provide personalized support, including educational resources, financial assistance, and site of care coordination. To learn more, visit KIMMTRAKConnect.com or call 844-775-2273. About Immunocore Immunocore is a commercial-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, autoimmune diseases and infectious diseases. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including clinical and pre-clinical programs​ in oncology, infectious diseases, and autoimmune diseases. The Company’s most advanced oncology TCR therapeutic, KIMMTRAK, has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom. Forward Looking Statements This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as “may”, “will”, “believe”, “expect”, “plan”, “anticipate”, “aim”, “continue”, “target” and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, statements regarding the Company’s ability to reach more patients for KIMMTRAK, including continued U.S. community and global market penetration in mUM, the potential expansion into 2L+ advanced cutaneous melanoma, and the potential expansion into adjuvant uveal melanoma; the Company’s ability to grow and advance its clinical pipeline; the estimated size of the patient populations for the Company’s product candidates; expectations regarding the design, progress, timing, enrollment, randomization, scope, expansion, and results of the Company’s and its collaborators’ existing and planned clinical trials; the timing and sufficiency of clinical trial outcomes to support potential approval of any of the Company’s product candidates or those of, or combined with, its collaboration partners; the expected submission of clinical trial applications or investigational new drug applications; the potential regulatory approval, and expected clinical benefits and availability of the Company’s product candidates; and expectations regarding the timing and amount of sales-related rebate payments. Any forward-looking statements are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual events or results to differ materially and adversely from those set forth in or implied by such forward-looking statements, many of which are beyond the Company’s control. These risks and uncertainties include, but are not limited to, the impact of worsening macroeconomic conditions, including as a result of health epidemics or pandemics, war in Ukraine, the conflict in the Middle East, or global geopolitical tension, on the Company’s business, financial position, strategy and anticipated milestones, including the Company’s ability to conduct ongoing and planned clinical trials; the Company’s ability to obtain a clinical supply of current or future product candidates or commercial supply of KIMMTRAK or any future approved products; the Company’s ability to obtain and maintain regulatory approval of KIMMTRAK and its other product candidates; the Company’s ability and plans in continuing to establish and expand a commercial infrastructure and to successfully launch, market and sell KIMMTRAK and any future approved products; the Company’s ability to successfully expand the approved indications for KIMMTRAK or obtain marketing approval for KIMMTRAK in additional geographies in the future; the delay of any current or planned clinical trials, whether due to patient enrollment delays or otherwise; the Company’s ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; competition with respect to market opportunities; unexpected safety or efficacy data observed during preclinical studies or clinical trials; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or future regulatory approval; the Company’s need for and ability to obtain additional funding, on favorable terms or at all, including as a result of worsening macroeconomic conditions, including changes in inflation and interest rates and unfavorable general market conditions, and the impacts thereon of the war in Ukraine, the conflict in the Middle East, and global geopolitical tension; the Company’s ability to obtain, maintain and enforce intellectual property protection for KIMMTRAK or any of its product candidates it or its collaborators are developing; and the success of the Company’s current and future collaborations, partnerships or licensing arrangements. These and other risks and uncertainties are described in greater detail in the section titled "Risk Factors" in the Company’s filings with the Securities and Exchange Commission, including the Company’s most recent Annual Report on Form 10-K for the year ended December 31, 2025 filed with the Securities and Exchange Commission on February 25, 2026, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the SEC. All information in this press release is as of the date of the release, and the Company undertakes no duty to update this information, except as required by law. Contact Information Immunocore Sébastien Desprez, VP CommunicationsT: +44 (0) 7458030732E: sebastien.desprez@immunocore.comFollow on LinkedIn: @Immunocore Investor RelationsRyan Baker, VP Investor RelationsT: +1 (617) 771 5001 E: ir@immunocore.com Immunocore Holdings plcCondensed Consolidated Statement of OperationsComparison of the Quarters and Year to Date Ended June 30, 2026 and 2025 (In thousands, except share and per share data)(Unaudited) Quarter Ended Year to Date June 30,2026 June 30,2025 June 30,2026 June 30,2025Revenue from sale of therapies, net $115,927 $97,964 $222,604 $191,845Total revenue 115,927 97,964 222,604 191,845Cost of revenue from sale of therapies (1,088) (1,040) (1,522) (1,871)Research and development expense (73,945) (69,008) (135,058) (125,476)Selling, general, & administrative expense (43,890) (42,791) (81,740) (82,989)Income (loss) from operations (2,996) (14,875) 4,284 (18,491)Interest income 3,582 4,271 7,000 8,447Interest expense (3,062) (3,045) (6,113) (6,070)Foreign currency gain (loss) (1,108) (738) 2,741 2,342Other income, net 3,070 4,693 4,846 10,162Net income (loss) before income taxes (514) (9,694) 12,758 (3,610)Income tax expense (294) (606) (595) (1,667)Net income (loss) $(808) $(10,300) $12,163 $(5,277) Basic net income (loss) per share $(0.02) $(0.20) $0.24 $(0.11)Basic weighted-average number of shares outstanding 50,973,830 50,294,205 50,868,252 50,191,018 Diluted net income (loss) per share $(0.02) $(0.20) $0.23 $(0.11)Diluted weighted-average number of shares outstanding 50,973,830 50,294,205 52,903,203 50,191,018 Immunocore Holdings plcCondensed Consolidated Balance SheetsAs of June 30, 2026 and December 31, 2025(In thousands)(Unaudited) June 30, 2026 December 31, 2025ASSETS Current assets Cash and cash equivalents$484,920 $467,709Marketable securities 395,291 396,444Accounts receivable, net 95,350 73,977Prepaid expenses and other current assets 67,692 51,870Inventory, net 7,791 6,742Total current assets 1,051,044 996,742Property and equipment, net 12,863 11,462Operating lease right of use assets, net 37,020 38,783Other non-current assets 18,495 20,282Total assets$1,119,422 $1,067,269 Liabilities and shareholders’ equity Current liabilities Accounts payable$26,319 $24,364Accrued expenses and other current liabilities 206,400 219,744Deferred revenue, current 573 583Operating lease liabilities, current 1,906 2,006Total current liabilities 235,198 246,697Accrued expenses, non-current 26,883 —Deferred revenue, non-current 4,490 4,858Operating lease liabilities, non-current 38,847 41,556Interest-bearing loans and borrowings 394,206 393,125Total liabilities$699,624 $686,236 Shareholders' equity Ordinary shares 138 136Deferred shares 1 1Additional paid-in capital 1,273,101 1,240,255Accumulated deficit (819,112) (831,275)Accumulated other comprehensive loss (34,330) (28,084)Total shareholders' equity 419,798 381,033Total liabilities and shareholders' equity$1,119,422 $1,067,269 Immunocore Holdings plcSummary Condensed Consolidated Statements of Cash FlowsFor the Six Months Ended June 30, 2026 and 2025(In thousands)(Unaudited) 2026 2025 Cash and cash equivalents at beginning of period $467,709 $455,731Net cash provided by operating activities 2,153 26,399Net cash provided by (used in) investing activities 3,433 (20,712)Net cash provided by financing activities 17,141 6,221Net foreign exchange difference on cash held (5,516) 20,294Cash and cash equivalents at end of period $484,920 $487,933