IO-202

▎药明康德内容团队编辑 本期看点 1. 用于治疗继发性噬血细胞性淋巴组织细胞增生症（sHLH）的单克隆抗体疗法ELA026在1b期研究中的表现亮眼，用药后第4周时的总缓解率（ORR）为100%（12/12）。 2. RNA干扰（RNAi）药物ARO-CFB用于治疗补体介导疾病，在一项1/2a期临床研究中使正常健康受试者中目标蛋白的水平平均降低90%，且持续时间超过3个月。 3. 6个月内使用1-2次血浆激肽释放酶单克隆抗体抑制剂navenibart在早期临床试验中使遗传性血管性水肿（HAE）患者的每月发作率降低了90%-95%。 药明康德内容团队整理 ELA026：公布1b期临床试验的新数据 Electra Therapeutics公司公布了其单克隆抗体疗法ELA026用于治疗继发性噬血细胞性淋巴组织细胞增生症的1b期研究结果。sHLH是一种罕见的、危及生命的高炎症性疾病，目前尚无批准的治疗方法。它可以由癌症、感染、自身免疫性疾病或免疫疗法引发。sHLH与严重的炎症反应有关，患者需要立即干预。如果不进行治疗，患者可能会出现多器官衰竭和死亡。sHLH与病程早期的高死亡率相关，使用可用疗法的恶性肿瘤相关HLH（mHLH）患者在两个月时的死亡率约为50%。ELA026靶向髓系细胞和T淋巴细胞表面的SIRP-α/β1/γ，髓系细胞和T淋巴细胞是诱发sHLH细胞因子风暴和高炎症反应的主要病理免疫细胞。以SIRP为靶点选择性地清除致病性免疫细胞具有在免疫学、炎症和癌症领域广泛应用的潜力。 此次公布的研究结果表明，对于mHLH患者，在接受ELA026作为一线治疗的患者中，第4周时的ORR为100%（12/12），出院率为100%(11/11)，2个月生存率为92%（11/12）。安全性方面，ELA026的耐受性良好，不良事件可控。 ARO-CFB：公布1/2a期临床试验的中期数据 Arrowhead Pharmaceuticals公司公布了其靶向补体因子B（CFB）的在研RNAi药物ARO-CFB用于治疗补体介导疾病的1/2a期临床研究的中期结果。ARO-CFB旨在减少肝脏中CFB的表达，CFB在放大补体替代通路活化过程中起着重要的调节作用。ARO-CFB正被开发为补体介导的肾脏疾病的潜在治疗药物，如免疫球蛋白A肾病（IgAN）。此外，ARO-CFB还有望用于涉及补体激活的非肾脏疾病的临床治疗。 截至2024年11月15日的数据，ARO-CFB在正常健康受试者中实现了剂量依赖性的循环CFB蛋白水平降低，平均达90%，且持续时间超过3个月。此外，无论是单次还是多次给药，ARO-CFB几乎完全抑制了替代通路的活性。截至目前，ARO-CFB总体耐受性良好，安全性数据支持进一步的临床开发。 Navenibart（STAR-0215）：公布1b/2期临床试验数据 Astria Therapeutics公司公布了其用于治疗遗传性血管性水肿的血浆激肽释放酶单抗抑制剂navenibart的1b/2期临床试验数据。在该研究中，16名患者被分入三个队列接受STAR-0215皮下给药：队列1的4名患者接受了1剂450 mg剂量；队列2的6名患者先接受了1剂600 mg剂量，并在3个月后又接受了1剂300 mg剂量；队列3的6名患者先接受了1剂600 mg剂量，并在1个月后又接受了1剂600 mg剂量。 此次公布的结果显示，在6个月内给药1次或2次navenibart，3个队列患者的平均每月发作率降低了90%-95%，该结果支持每年仅给药2次或4次。此外，使用navenibart后，中度或严重HAE发作减少了约95%-96%，需要使用急救药物的发作减少了91%-94%。队列2和队列3患者6个月内的无发作率为67%。安全性方面，navenibart总体耐受性良好，无严重不良事件，无停药现象。 IO-202：公布1b期临床试验扩展队列的新数据 Immune-Onc Therapeutics公司公布了其1b期扩展队列的最新数据，该队列评估了其抗LILRB4抗体IO-202联用阿扎胞苷（AZA）治疗慢性粒单核细胞白血病（CMML）患者的疗效和安全性。IO-202是一款潜在"first-in-class"的IgG1抗体，可特异性、高亲和力地与LILRB4结合，并通过抗体依赖性细胞毒性和抗体依赖性细胞吞噬作用消除LILRB4阳性细胞。因此，IO-202是一种在血癌、自身免疫性和炎症性疾病方面具有广阔潜力的靶向疗法。 此次公布的结果显示，根据国际工作组2023缓解标准，在接受IO-202与AZA联合治疗的18名疗效可评估的CMML患者中，ORR为66.7%，完全缓解（CR）率为50%。在LILRB4高表达的CMML患者中，ORR为100%，CR率为83.3%。值得注意的是，过往获批疗法的CR率仅为7-17%。 ISB 2001：公布1期临床试验的新数据 Ichnos Glenmark Innovation公司公布了其三特异性抗体ISB 2001用于治疗复发/难治性多发性骨髓瘤（RRMM）的1期研究的新数据。ISB 2001同时靶向MM细胞上的BCMA和CD38，以及T细胞上的CD3，旨在增加对MM细胞的特异性结合，同时最大限度地减少脱靶效应。 截至2024年10月1日的数据，20名可评估疗效患者的ORR为75%（5/20），CR/严格的CR（sCR）率为20%。在接受活性剂量（0.05 mg/kg和更高剂量）治疗的18例患者中，ORR为83%，CR/sCR率为22%。安全性方面，在每周皮下注射剂量为1.2 mg/kg时未观察到剂量限制性毒性（DLT），大多数是轻度的细胞因子释放综合征（CRS），未报告神经毒性，也没有患者因不良事件而停药。 NX-5948：公布1a/1b期临床试验的新数据 Nurix Therapeutics公司公布了其布鲁顿酪氨酸激酶（BTK）降解剂NX-5948用于治疗复发或难治性慢性淋巴细胞白血病或小淋巴细胞淋巴瘤（CLL/SLL）的1a/1b期临床试验的新数据。NX-5948是一种口服、可穿越血脑屏障的小分子BTK蛋白降解剂。 截至2024年10月10日的数据，首次疾病评估时（治疗后第8周）49名疗效可评估的CLL/SLL患者的客观缓解率为75.5%，该数据在至少进行两次疾病评估（治疗后第16周时）的患者中增加至84.2%。无论患者既往治疗、基线突变、高危分子特征或中枢神经系统（CNS）受累如何，均观察到缓解。13名患者的缓解持续时间超过6个月，5名患者在治疗一年后仍在接受治疗并保持缓解。此外，NX-5948在所有评估的剂量中均具有良好的耐受性。 Enzomenib（DSP-5336）：公布1/2期临床试验的新数据 Sumitomo Pharma America公司公布了其在研口服小分子enzomenib用于治疗复发/难治性急性白血病的1/2期临床试验的新数据。Enzomenib可抑制menin与MLL蛋白的相互作用，并能降低白血病相关基因HOXA9和MEIS1的表达，增加带有MLL重排和NPM1突变的人类急性白血病细胞系中分化基因CD11b的表达。 此次公布的结果显示，在23例KMT2A重排患者中，客观缓解率为65.2%，达到CR加部分血液学恢复的完全缓解（CRh）的患者比例为30.4%。在接受300 mg每日两次（BID）治疗的15名KMT2A重排患者中，客观缓解率为73.3%，达到CR加CRh的比例为40%。在接受200 mg BID或300 mg BID治疗的17名NPM1突变患者中，客观缓解率为58.8%，达到CR加CRh的比例为47.1%。Enzomenib的耐受性良好，药物相关不良事件的总体发生率较低，没有报告DLT。10.7%的患者患上了分化综合征，但未导致患者死亡，也不需要永久停用enzomenib。 Evorpacept：公布1b/2期联合治疗试验数据 ALX Oncology公司公布了其CD47抑制剂evorpacept联用HER2靶向双特异性抗体zanidatamab治疗此前接受过大量治疗的HER2阳性和HER2低表达转移性乳腺癌患者的1b/2期临床试验数据。Evorpacept是一种下一代CD47阻断疗法，它将高亲和性CD47结合结构域与经特殊处理的Fc结构域相结合，因此无法激活Fc受体，有望降低CD47靶向抗体因激活Fc受体可能产生的毒副作用。此外，与其它抗CD47抗体相比，evorpacept的分子量更小，更容易渗透到实体瘤中，从而提高疗效。 此次公布的结果显示，evorpacept联用zanidatamab对经中央实验室评估确认为HER2阳性的患者（n=9）显示出最强的抗肿瘤活性。这些患者经确认的客观缓解率为55.6%，中位无进展生存期（PFS）为7.4个月。总体而言，队列1（HER2阳性的转移性乳腺癌患者）患者（n=21）的经确认的客观缓解率为33.3%，中位PFS为3.6个月，中位缓解持续时间（DOR）尚未达到。在队列2（HER2低表达的转移性乳腺癌患者）的患者（n=15）中也观察到了一定的缓解，经确认的客观缓解率为20.0%，中位PFS为1.9个月，中位DOR为5.5个月。 MDNA11：公布1/2期临床试验的新数据 Medicenna Therapeutics公司公布了正在进行的1/2期ABILITY-1研究的最新临床数据，该研究旨在评估其下一代长效IL-2超级激动剂MDNA11单药或联用PD-1抑制剂帕博利珠单抗治疗晚期实体瘤的疗效和安全性。MDNA11是一种通过静脉注射给药的长效“增强β而非α”的IL-2超级细胞因子（IL-2 Superkine），它能够优先激活负责杀伤癌细胞的免疫效应细胞（CD8阳性T细胞和自然杀伤细胞，即NK细胞），同时最小化或不刺激具有免疫抑制作用的调节性T细胞（Tregs）。 此次公布的结果显示，MDNA11单药治疗和联用帕博利珠单抗的疾病控制率（DCR）分别为55%（1例CR、4例部分缓解和6例疾病稳定）和78%（1例CR、1例部分缓解和5例疾病稳定）。1名70岁的晚期化疗难治性肛门癌患者在接受MDNA11联用帕博利珠单抗治疗时，在8周内达到了CR。单药治疗组中两名免疫检查点抑制剂耐药患者的所有肿瘤完全消失，1名获得CR的黑色素瘤患者在第63周时依然没有复发，1名微卫星不稳定性高（MSI-H）的胰腺癌患者在肝脏中实现了靶病灶和非靶转移灶的完全消除，在研究期间实现了20个月的持久缓解，并已持续停止抗癌治疗达11个月。 VGA039：公布1期临床试验的中期数据 Star Therapeutics公司公布了其在研单克隆抗体VGA039用于治疗血管性血友病（Von Willebrand Disease，VWD）的1期单剂量递增（SAD）研究的中期数据。VGA039靶向蛋白质S，旨在恢复血液凝固的平衡，有望作为一种适用于多种出血性疾病的通用止血疗法。 此次公布的数据显示，在3名高年出血率（ABR）VWD患者中，皮下注射VGA039与ABR的显著降低相关，单次注射使患者的ABR降低了75%-88%，且治疗浓度保持了约4周。该降幅与已获批准的VWD预防疗法在临床试验中观察到的降幅一致，但这些疗法需要每周进行多次静脉注射。在安全性可评估的7名患者中，VGA039安全且耐受性良好，未观察到注射部位反应。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料（可上下滑动查看） [1] Nurix Therapeutics Presents New Positive Data from Phase 1a/1b Clinical Trial of NX-5948 in Chronic Lymphocytic Leukemia at the 66th American Society of Hematology Annual Meeting. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/09/2994129/0/en/Nurix-Therapeutics-Presents-New-Positive-Data-from-Phase-1a-1b-Clinical-Trial-of-NX-5948-in-Chronic-Lymphocytic-Leukemia-at-the-66th-American-Society-of-Hematology-Annual-Meeting.html [2] Ichnos Glenmark Innovation (IGI) Presents First Clinical Data from Phase 1 Study of Trispecific TREAT™ Antibody, ISB 2001, Showing High Overall Response Rate (ORR) with Durable Responses and Favorable Safety Profile in Patients with Heavily Pretreated Multiple Myeloma. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/10/2994146/0/en/Ichnos-Glenmark-Innovation-IGI-Presents-First-Clinical-Data-from-Phase-1-Study-of-Trispecific-TREAT-Antibody-ISB-2001-Showing-High-Overall-Response-Rate-ORR-with-Durable-Responses-.html [3] Immune-Onc Therapeutics Presents Updated Data from Phase 1b Study of IO-202 Highlighting Promising Efficacy and Safety Data in CMML Patients at 2024 American Society of Hematology (ASH) Annual Meeting. Retrieved December 12, 2024, from https://www.immune-onc.com/pr-posts/immune-onc-therapeutics-presents-updated-data-from-phase-1b-study-of-io-202-highlighting-promising-efficacy-and-safety-data-in-cmml-patients-at-2024-american-society-of-hematology-ash-annual-meeting [4] Electra Therapeutics Presents Positive Clinical Results from Completed Phase 1b Study of ELA026 in Secondary Hemophagocytic Lymphohistiocytosis (sHLH) in an Oral Session at ASH 2024. Retrieved December 12, 2024, from https://electra-therapeutics.com/electra-therapeutics-presents-positive-clinical-results-from-completed-phase-1b-study-of-ela026-in-secondary-hemophagocytic-lymphohistiocytosis-shlh-in-an-oral-session-at-ash-2024/ [5] Star Therapeutics Presents Interim Clinical Data for VGA039 in Patients with Von Willebrand Disease (VWD) at ASH 2024. Retrieved December 12, 2024, from https://star-therapeutics.com/star-therapeutics-presents-interim-clinical-data-for-vga039-in-patients-with-von-willebrand-disease-vwd-at-ash-2024/ [6] Sumitomo Pharma America Presents New Data on Nuvisertib and Enzomenib at the 2024 American Society of Hematology Annual Meeting. Retrieved December 12, 2024, from https://www.prnewswire.com/news-releases/sumitomo-pharma-america-presents-new-data-on-nuvisertib-and-enzomenib-at-the-2024-american-society-of-hematology-annual-meeting-302326146.html [7] Arvinas and Pfizer Announce Initial Phase 1b Data from the TACTIVE-U Sub-Study of Vepdegestrant in Combination with Abemaciclib at 2024 San Antonio Breast Cancer Symposium. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/10/2994631/0/en/index.html [8] ALX Oncology Announces New Data Demonstrating Evorpacept in Combination with Zanidatamab Generates Promising Antitumor Activity in Advanced Breast Cancer. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/10/2994624/0/en/index.html [9] Arrowhead Pharmaceuticals Presents Interim Clinical Data on ARO-CFB for the Treatment of Complement Mediated Diseases. Retrieved December 12, 2024, from https://arrowheadpharma.com/news-press/arrowhead-pharmaceuticals-presents-interim-clinical-data-on-aro-cfb-for-the-treatment-of-complement-mediated-diseases/ [10] Astria Therapeutics Announces Positive Final Results from Target Enrollment in the ALPHA-STAR Phase 1b/2 Trial of Navenibart for HAE. Retrieved December 12, 2024, from https://ir.astriatx.com/news-releases/news-release-details/astria-therapeutics-announces-positive-final-results-target [11] C4 Therapeutics Presents Cemsidomide Phase 1 Data at the American Society for Hematology (ASH) Annual Meeting that Demonstrated Potential to Become Best-in-Class IKZF1/3 Degrader. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/08/2993401/0/en/C4-Therapeutics-Presents-Cemsidomide-Phase-1-Data-at-the-American-Society-for-Hematology-ASH-Annual-Meeting-that-Demonstrated-Potential-to-Become-Best-in-Class-IKZF1-3-Degrader.html [12] Medicenna Provides Clinical Update and Announces First Complete Responder in MDNA11 in Combination with KEYTRUDA® (pembrolizumab) Combination Dose Escalation Arm of the ABILITY-1 Study. Retrieved December 12, 2024, from https://ir.medicenna.com/news-releases/news-release-details/medicenna-provides-clinical-update-and-announces-first-complete [13] Disc Medicine Presents Positive Updated Results from Phase 1b Trial in Patients with Myelofibrosis (MF) and Anemia in an Oral Presentation at the 66th American Society of Hematology (ASH) Annual Meeting. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/09/2993429/0/en/Disc-Medicine-Presents-Positive-Updated-Results-from-Phase-1b-Trial-in-Patients-with-Myelofibrosis-MF-and-Anemia-in-an-Oral-Presentation-at-the-66th-American-Society-of-Hematology-.html [14] Rigel Highlights Initial Data from Ongoing Phase 1b Study Evaluating R289 in LR-MDS at the 66th ASH Annual Meeting and Exposition. Retrieved December 12, 2024, from https://www.prnewswire.com/news-releases/rigel-highlights-initial-data-from-ongoing-phase-1b-study-evaluating-r289-in-lr-mds-at-the-66th-ash-annual-meeting-and-exposition-302325895.html [15] OnKure Announces Encouraging Preliminary Safety, Tolerability, and Pharmacokinetic (PK) Data from its First-In-Human PIKture-01 Trial of OKI-219. Retrieved December 12, 2024, from https://investors.onkuretherapeutics.com/news-releases/news-release-details/onkure-announces-encouraging-preliminary-safety-tolerability-and [16] Prelude Therapeutics Presents Preliminary Results of Phase 1 Dose-escalation Study of PRT2527 as Monotherapy and in Combination with Zanubrutinib in Patients with Relapsed/Refractory Lymphoid Malignancies. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/11/2995306/0/en/Prelude-Therapeutics-Presents-Preliminary-Results-of-Phase-1-Dose-escalation-Study-of-PRT2527-as-Monotherapy-and-in-Combination-with-Zanubrutinib-in-Patients-with-Relapsed-Refracto.html [17] Enterome’s Immunotherapy EO2463 Shows Early Clinical Response in Newly Diagnosed Follicular Lymphoma Suggesting a Potential Alternative to ‘Watchful Waiting’. Retrieved December 12, 2024, from https://www.enterome.com/news-events/enteromes-immunotherapy-eo2463-shows-early-clinical-response-in-newly-diagnosed-follicular-lymphoma-suggesting-a-potential-alternative-to-watchful-waiting/ [18] CatalYm’s Visugromab Phase 1/2a Data Demonstrating Clinical Proof-of-Concept for Reversing Resistance to Checkpoint Inhibitors through GDF-15 Neutralization Published in Nature. Retrieved December 12, 2024, from https://www.catalym.com/catalyms-visugromab-phase-1-2a-data-demonstrating-clinical-proof-of-concept-for-reversing-resistance-to-checkpoint-inhibitors-through-gdf-15-neutralization-published-in-nature/ [19] Opna Bio Announces Interim Data from Phase 1 Combination Study of OPN-2853 with Ruxolitinib in Patients with Advanced Myelofibrosis. Retrieved December 12, 2024, from https://www.opnabio.com/opna-bio-announces-interim-data-from-phase-1-combination-study-of-opn-2853-with-ruxolitinib-in-patients-with-advanced-myelofibrosis/ [20] Recursion Reports Interim Phase 1 Clinical Data for REC-617 Monotherapy, a Potential Best-in-Class CDK7 Inhibitor, With Encouraging Patient Response and Favorable Tolerability. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/09/2994128/0/en/Recursion-Reports-Interim-Phase-1-Clinical-Data-for-REC-617-Monotherapy-a-Potential-Best-in-Class-CDK7-Inhibitor-With-Encouraging-Patient-Response-and-Favorable-Tolerability.html [21] Galapagos Announces Encouraging New Results from Ongoing Phase 1/2 Study of CD19 CAR T-Cell Therapy, GLPG5101, in Patients with Relapsed/Refractory Non-Hodgkin Lymphoma. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/07/2993348/0/en/Galapagos-Announces-Encouraging-New-Results-from-Ongoing-Phase-1-2-Study-of-CD19-CAR-T-Cell-Therapy-GLPG5101-in-Patients-with-Relapsed-Refractory-Non-Hodgkin-Lymphoma.html [22] Poseida Therapeutics Highlights Positive Interim Phase 1 Results for P-BCMA-ALLO1 and Preclinical Data for Dual CAR-T P-CD19CD20-ALLO1 at the 66th American Society of Hematology (ASH) Annual Meeting. Retrieved December 12, 2024, from https://www.prnewswire.com/news-releases/poseida-therapeutics-highlights-positive-interim-phase-1-results-for-p-bcma-allo1-and-preclinical-data-for-dual-car-t-p-cd19cd20-allo1-at-the-66th-american-society-of-hematology-ash-annual-meeting-302325606.html [23] Lyell Presents Positive Initial Clinical Data from the Phase 1-2 Clinical Trial of IMPT-314 for the Treatment of B-cell Lymphoma at the 2024 ASH Annual Meeting. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/10/2994158/0/en/Lyell-Presents-Positive-Initial-Clinical-Data-from-the-Phase-1-2-Clinical-Trial-of-IMPT-314-for-the-Treatment-of-B-cell-Lymphoma-at-the-2024-ASH-Annual-Meeting.html [24] Synthekine Presents Positive Initial Results from Phase 1 Clinical Trial of CD19 CAR-T (SYNCAR-001) and Orthogonal IL-2 (STK-009) Combination Therapy for Treatment of Hematologic Malignancies at ASH 2024 Annual Meeting. Retrieved December 12, 2024, from https://www.synthekine.com/news/synthekine-presents-positive-initial-results-from-phase-1-clinical-trial-of-cd19-car-t-syncar-001-and-orthogonal-il-2-stk-009-combination-therapy-for-treatment-of-hematologic-malignancies-at-ash-2/ [25] AAVantgarde presents safety data of the LUCE-1 study of AAVB-081 for RP related to Usher 1B. Retrieved December 12, 2024, from https://www.aavantgarde.com/en/news/aavantgarde-presents-safety-data-of-the-luce-1-study-of-aavb-081-for-rp-related-to-usher-1b/ [26] Neurona Therapeutics Presents Positive Clinical Update: New Data from NRTX-1001 Cell Therapy Trial in Drug-resistant Epilepsy Announced at 2024 Annual Meeting of the American Epilepsy Society. Retrieved December 12, 2024, from https://www.neuronatherapeutics.com/news/press-releases/120624/ [27] IN8bio Reports Continued Progression-Free Survival in Phase 1 Investigator-Sponsored Trial of INB-100 Allogeneic Gamma-Delta T Cells for Leukemias at the 2024 American Society of Hematology Annual Meeting. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/10/2994365/0/en/IN8bio-Reports-Continued-Progression-Free-Survival-in-Phase-1-Investigator-Sponsored-Trial-of-INB-100-Allogeneic-Gamma-Delta-T-Cells-for-Leukemias-at-the-2024-American-Society-of-H.html [28] Sonnet BioTherapeutics Announces Topline Safety Data Following Successful Completion of SON-1010 Monotherapy Dose Escalation in Phase 1 SB101 Trial. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/09/2993772/0/en/Sonnet-BioTherapeutics-Announces-Topline-Safety-Data-Following-Successful-Completion-of-SON-1010-Monotherapy-Dose-Escalation-in-Phase-1-SB101-Trial.html [29] CRISPR Therapeutics Presents Data at the 2024 American Society of Hematology (ASH) Annual Meeting. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/09/2993974/0/en/CRISPR-Therapeutics-Presents-Data-at-the-2024-American-Society-of-Hematology-ASH-Annual-Meeting.html [30] Monte Rosa Therapeutics Provides Development Progress Update for Ongoing MRT-2359 Phase 1/2 Study in Patients with MYC-driven Solid Tumors. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/05/2992220/0/en/Monte-Rosa-Therapeutics-Provides-Development-Progress-Update-for-Ongoing-MRT-2359-Phase-1-2-Study-in-Patients-with-MYC-driven-Solid-Tumors.html [31] Olema Oncology Announces FDA Clearance of Investigational New Drug Application for OP-3136, a Potent KAT6 Inhibitor. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/09/2993612/0/en/Olema-Oncology-Announces-FDA-Clearance-of-Investigational-New-Drug-Application-for-OP-3136-a-Potent-KAT6-Inhibitor.html [32] Theratechnologies Announces Preliminary Tolerability and Efficacy Data from Phase 1b, Dose-Ranging Trial of Sudocetaxel Zendusortide in Patients with Advanced Ovarian Cancer. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/09/2993661/0/en/Theratechnologies-Announces-Preliminary-Tolerability-and-Efficacy-Data-from-Phase-1b-Dose-Ranging-Trial-of-Sudocetaxel-Zendusortide-in-Patients-with-Advanced-Ovarian-Cancer.html [33] Artelo Biosciences Announces Presentation of Phase 1 Data with ART27.13 in Cancer-Related Anorexia. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/09/2993818/0/en/Artelo-Biosciences-Announces-Presentation-of-Phase-1-Data-with-ART27-13-in-Cancer-Related-Anorexia.html [34] Silence Therapeutics Presents Promising Phase 1 Data in Polycythemia Vera Patients at the American Society of Hematology (ASH) Annual Meeting. Retrieved December 12, 2024, from https://silence-therapeutics.com/investors/press-releases/press-releases-details/2024/Silence-Therapeutics-Presents-Promising-Phase-1-Data-in-Polycythemia-Vera-Patients-at-the-American-Society-of-Hematology-ASH-Annual-Meeting/default.aspx [35] AC Immune Reports Interim Safety Data from Phase 1b/2 ABATE Trial of ACI-24.060 in Down syndrome. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/10/2994352/0/en/AC-Immune-Reports-Interim-Safety-Data-from-Phase-1b-2-ABATE-Trial-of-ACI-24-060-in-Down-syndrome.html [36] Affimed Reports Promising Phase 1 Efficacy and Safety Data for AFM28 in Relapsed/Refractory Acute Myeloid Leukemia (R/R AML). Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/09/2994033/0/en/Affimed-Reports-Promising-Phase-1-Efficacy-and-Safety-Data-for-AFM28-in-Relapsed-Refractory-Acute-Myeloid-Leukemia-R-R-AML.html [37] PS3-08: Interim Overall Survival of Patients with Locally Advanced or Metastatic Triple-Negative Breast Cancer treated with First Line PM8002/BNT327 in Combination with Nab-Paclitaxel in Phase Ib/II Study. Retrieved December 10, 2024, from https://sabcs.org/Portals/0/Documents/Formatted_Abstracts%2011-27%20Without%20Embargoed.pdf?ver=qjVzk5LPNjOteEIvNEYJFw%3d%3d [38] Olema Oncology Presents Updated Clinical Results for Palazestrant in Combination with Ribociclib at the San Antonio Breast Cancer Symposium. Retrieved December 12, 2024, from https://ir.olema.com/news-releases/news-release-details/olema-oncology-presents-updated-clinical-results-palazestrant [39] Astria Therapeutics Announces FDA Clearance of IND Application for STAR-0310, a Monoclonal Antibody OX40 Antagonist for the Treatment of Atopic Dermatitis. Retrieved December 12, 2024, from https://ir.astriatx.com/news-releases/news-release-details/astria-therapeutics-announces-fda-clearance-ind-application-0 [40] Aptose Clinical Data Featured in Poster Presentation at the 2024 ASH Annual Meeting Support Tuspetinib Triple Drug Therapy for Newly Diagnosed AML. Retrieved December 12, 2024, from https://www.aptose.com/news-media/press-releases/detail/304/aptose-clinical-data-featured-in-poster-presentation-at-the [41] Biomea Fusion Announces Preliminary Data from Ongoing COVALENT-103 Study of Investigational Covalent FLT3 Inhibitor BMF-500 in Relapsed or Refractory Acute Leukemia. Retrieved December 12, 2024, from https://investors.biomeafusion.com/news-releases/news-release-details/biomea-fusion-announces-preliminary-data-ongoing-covalent-103 [42] NextCure Announces Acceptance of IND Application for LNCB74. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/10/2994522/0/en/NextCure-Announces-Acceptance-of-IND-Application-for-LNCB74.html [43] PureTech Founded Entity Seaport Therapeutics Presents Additional Data from Phase 1 Study of SPT-300 at ACNP Annual Meeting 2024. Retrieved December 12, 2024, from https://news.puretechhealth.com/news-releases/news-release-details/puretech-founded-entity-seaport-therapeutics-presents-additional 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

– Complete remission (CR) rate of 50% and overall response rate (ORR) of 66.7% in 18 evaluable patients with CMML treated with IO-202 in combination with azacitidine – – CR rate of 83.3% and ORR of 100% in CMML patients with high LILRB4 expression – PALO ALTO, CA, USA I December 09, 2024 I Immune-Onc Therapeutics, Inc. (“Immune-Onc”), a private clinical-stage biopharmaceutical company advancing novel therapies in immunology and oncology by targeting myeloid cell inhibitory receptors, today presented updated data from its Phase 1b expansion cohort evaluating IO-202, a first-in-class anti-LILRB4 antibody, in combination with azacitidine (AZA) in patients with chronic myelomonocytic leukemia (CMML). These new findings were highlighted in an oral presentation at the 2024 American Society of Hematology (ASH) Annual Meeting in San Diego, California. The updated results from this trial in hypomethylating agent-naïve CMML showed that IO-202, in combination with AZA, achieved a complete remission (CR) rate of 50.0% and an overall response rate (ORR) of 66.7% among the 18 efficacy evaluable patients based on the International Working Group (IWG) 2023 response criteria for higher-risk myelodysplastic syndromes. 1 Further analysis revealed that efficacy favors patients with high LILRB4 expression, who achieved a CR rate of 83.3% (5/6) and an ORR of 100% (6/6). Responses were observed in patients across all subgroups, including those with proliferative disease, elevated blast counts, unfavorable mutations, and high symptom scores. These findings underscore the potential of IO-202 to address an important unmet need in CMML, where the only approved treatment with hypomethylating agents yields modest CR rates of 7-17%. 2 There is a critical need for innovative therapies for CMML, as no new treatments with a novel mechanism of action have been approved in over 30 years. The prognosis for CMML patients remains poor, with a median survival of less than three years. Allogenic hematopoietic cell transplant (HCT) is the only potentially curative option, yet fewer than 15-20% of patients are eligible to undergo HCT. As a novel agent, IO-202 demonstrates promising clinical benefits, addressing a significant unmet need. In this study, treatment with IO-202 in combination with AZA enabled 38.9% of the patients to successfully bridge to HCT. Additionally, four out of six transfusion-dependent patients became transfusion-independent. IO-202 is well-tolerated at the preliminary recommended Phase 2 dose (60 mg/kg followed by 30 mg/kg every two weeks​) among 21 safety-evaluable patients. No dose-limiting toxicities were reported. “These results represent a positive advance in the treatment of CMML, a disease with very limited options and poor outcomes,” said Gabriel N. Mannis, M.D., IO-202 Phase 1 investigator and associate professor of medicine, division of hematology, Stanford Cancer Institute, Stanford University. “The favorable correlation between LILRB4 expression and treatment response underscores the contribution of IO-202 to efficacy consistent with its mechanism of action. Achieving a 50% complete response rate overall—and an 83% complete response rate in patients with high LILRB4 expression—demonstrates the potential of IO-202 as a highly impactful therapy. Additionally, the ability to bridge nearly 40% of patients to transplant and help most transfusion-dependent patients achieve independence offers new hope for improving outcomes in this challenging disease.” “We are encouraged by the promising clinical activity and tolerability of IO-202 in this trial,” said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. “These data support a pivotal study to evaluate IO-202 in combination with azacitidine as a frontline treatment for hypomethylating agent-naïve CMML. We look forward to working closely with regulators to bring this potentially life-changing therapy to patients.” ABOUT CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML) CMML is a rare form of blood cancer, with an overall incidence of 0.35 cases per 100,000 population in the United States. 3 CMML is characterized by persistent elevation of peripheral blood monocytes (≥0.5×10 9 /L; monocytes ≥10% of white blood cell count) for over three months, accompanied by dysplastic features in the bone marrow. 4,5 The only FDA-approved therapies currently available for CMML are hypomethylating agents, such as azacitidine, which achieve a complete response rate of just 7-17%. 2 ABOUT LILRB4 (also known as ILT3) LILRB4, also known as ILT3, is an immune-modulatory transmembrane protein found on monocytes and monocyte-derived cells. LILRB4 is expressed on certain hematologic cancer cells, such as myelomonocytic leukemia blasts, and on certain pathogenic cells involved in autoimmunity and inflammatory processes. ABOUT IO-202 IO-202 is a first-in-class IgG1 antibody with specific, high-affinity binding to LILRB4 and depletes LILRB4 positive cells via antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. As such, IO-202 is a targeted therapy with broad potential in blood cancers and autoimmune and inflammatory diseases. IO-202 has completed the dose escalation part of the first-in-human, multicenter, open-label Phase 1 study in the U.S., and the data was presented at the European Hematology Association (EHA) Congress in 2023. This Phase 1 trial has advanced to the dose expansion stage to evaluate IO-202 in combination with azacitidine ( NCT04372433 ) in patients with newly diagnosed chronic myelomonocytic leukemia (CMML) who have not received any hypomethylating agents (HMA). The U.S. Food and Drug Administration granted IO-202 Fast Track Designations for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) and relapsed or refractory CMML, respectively. The FDA has also granted IO-202 Orphan Drug Designations for the treatment of AML and CMML, respectively. ABOUT IMMUNE-ONC THERAPEUTICS, INC. Immune-Onc Therapeutics Inc. (“Immune-Onc”) is a private, clinical-stage biopharmaceutical company developing novel therapies in immunology and oncology by targeting myeloid cell inhibitory receptors. Immune-Onc has a differentiated pipeline with a current focus on targeting the Leukocyte Immunoglobulin-Like Receptor subfamily B (LILRB). Immune-Onc’s focused platform approach has led to the development of several promising therapeutics across various stages of development. Those include IO-108, an antagonist antibody targeting LILRB2 (also known as ILT4), in Phase 1b/2 clinical development for solid tumors, and IO-202, a first-in-class antibody targeting LILRB4 (also known as ILT3), in Phase 1b clinical development for the treatment of acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). Additional assets in Immune-Onc’s pipeline include IO-312 (a novel bispecific antibody targeting LILRB4 and CD3), IO-106 (first-in-class antagonist antibody targeting LAIR1), and undisclosed immunology and oncology programs. Immune-Onc has established agreements with leading biopharmaceutical companies, including BeiGene , Regeneron, and Roche , to support its global product development plans for IO-108 and IO-202. It has received research grants from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) and the California Institute for Regenerative Medicine (CIRM) and investment from The Leukemia & Lymphoma Society Therapy Acceleration Program® (LLS TAP®). Headquartered in Palo Alto, California, Immune-Onc has assembled a diverse team with deep expertise in drug development and proven track records of success at leading biopharmaceutical companies. For more information, please visit www.immune-onc.com and follow us on X and LinkedIn . SOURCE: Immune-Onc Therapeutics